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IV ketamine proves superior to active placebo in low, high doses
MIAMI – Intravenous ketamine in a range of doses is superior to active placebo, according to analyses from a study of the drug for treatment-resistant depression.
Most of the effect was attributable to differences recorded at Day 1 of the 3-day study, according to George I. Papakostas, MD, scientific director of the Massachusetts General Hospital Clinical Trials Network and Institute and coinvestigator of the study, who presented these findings at a meeting of the American Society of Clinical Psychopharmacology, formerly the New Clinical Drug Evaluation meeting.
The 99 adults with treatment-resistant depression – primarily white women in their mid-40s – were randomly assigned either to an active placebo group given 0.045 mg/kg of midazolam or to one of four treatment arms given a single infusion of intravenous ketamine at either 0.1 mg/kg, 0.2 mg/kg, 0.5 mg/kg, or 1.0 mg/kg.
Baseline scores on the 6-item Hamilton Depression Rating Scale (HAMD-6) ranged between 12.6 and 13.1 across the study.
To determine the efficacy of intravenous ketamine at different doses over the course of 72 hours, Dr. Papakostas, who also directs treatment-resistant depression studies at Massachusetts General, and his colleagues used multiple statistical models. The first analysis was a comparison of the effects of the active placebo and all ketamine groups combined at Day 1 and at Day 3.
At Day 1, the change in baseline HAMD-6 scores for all the ketamine arms combined, compared with the active placebo group, was statistically significant (P = .0278). At Day 3, the change in baseline HAMD-6 scores for the combined ketamine groups, compared with the active placebo arm, also was statistically significant (P = .0391).
A secondary analysis of the patient-reported Symptoms of Depression Questionnaire also showed a statistically significant improvement (P = .09) from baseline in the combined ketamine groups, compared with the active placebo group.
At Day 1, the combined ketamine groups’ changes from baseline HAMD-6 were –3.25 with an effect size of 0.86, a statistically significant finding. However, by the Day 3, the combined ketamine groups’ effects size fell away. “There is no longer a statistically significant difference, so it’s a rapid effect – like we’ve seen in the other studies for the combined doses – but it is not an effect that is sustained,” said Dr. Papakostas, also an associate professor of psychiatry at Harvard Medical School, Boston.
For the individual doses, compared with active placebo, the ketamine 0.1 mg/kg arm had an overall –0.35 change in baseline HAMD-6 scores, which Dr. Papakostas said had “a large effect size of 0.82.”
Dr. Papakostas also said the ketamine 0.2 mg/kg arm “did not really seem to move things around at all.” Meanwhile, the 0.5 mg/kg and 1.0 mg/kg arms each had “big differences” in baseline HAMD-6 scores, compared with active placebo, of –4.79 and –3.76, respectively. They also exhibited statistically significant effect sizes of 1.21 and 0.95 at Day 1, respectively. However, at Day 3, there were neither numerical nor statistical differences, indicating the effect is not sustained.
Changes in the Symptoms of Depression Questionnaire for the combined drug arms at Day 1 were statistically significant with an unadjusted P value of .07 and an adjusted P value of .13.
Results for the Clinician Administered Dissociative States Scale showed that neither the ketamine 0.1 mg/kg arm nor the ketamine 0.2 mg/kg arm separated from active placebo, while the ketamine 0.5 mg/kg arm and the ketamine 1.0 mg/kg arm were each different from active placebo to numerically and statistically significant degrees. Each of the 0.5 mg/kg and the 1.0 mg/kg ketamine arms were associated with rises in blood pressure, according to Dr. Papakostas.
“So, it seems as though the doses that caused a dissociation seemed to cause a clinical effect that is equivalent, whereas in the lower doses, there didn’t seem to be any dissociative effects or blood pressure effects,” Dr. Papakostas said. “If you combine the findings, in my opinion, there is a signal in the 0.1 mg/kg treatment arm, even though it just misses it on the P value.”
Dr. Papakostas said that, although more data are needed to determine optimal dosing and a clearer risk-benefit ratio, the results suggested that intravenous ketamine could offer transient, beneficial effects for patients with treatment-resistant depression.
Dr. Papakostas is the scientific director of the MGH Clinical Trials Network and Institute. This study’s coinvestigator, Maurizio Fava, MD, has numerous relevant financial ties to industry. This trial was part of the National Institute of Mental Health’s Rapidly-Acting Treatments for Treatment-Resistant Depression research program.
MIAMI – Intravenous ketamine in a range of doses is superior to active placebo, according to analyses from a study of the drug for treatment-resistant depression.
Most of the effect was attributable to differences recorded at Day 1 of the 3-day study, according to George I. Papakostas, MD, scientific director of the Massachusetts General Hospital Clinical Trials Network and Institute and coinvestigator of the study, who presented these findings at a meeting of the American Society of Clinical Psychopharmacology, formerly the New Clinical Drug Evaluation meeting.
The 99 adults with treatment-resistant depression – primarily white women in their mid-40s – were randomly assigned either to an active placebo group given 0.045 mg/kg of midazolam or to one of four treatment arms given a single infusion of intravenous ketamine at either 0.1 mg/kg, 0.2 mg/kg, 0.5 mg/kg, or 1.0 mg/kg.
Baseline scores on the 6-item Hamilton Depression Rating Scale (HAMD-6) ranged between 12.6 and 13.1 across the study.
To determine the efficacy of intravenous ketamine at different doses over the course of 72 hours, Dr. Papakostas, who also directs treatment-resistant depression studies at Massachusetts General, and his colleagues used multiple statistical models. The first analysis was a comparison of the effects of the active placebo and all ketamine groups combined at Day 1 and at Day 3.
At Day 1, the change in baseline HAMD-6 scores for all the ketamine arms combined, compared with the active placebo group, was statistically significant (P = .0278). At Day 3, the change in baseline HAMD-6 scores for the combined ketamine groups, compared with the active placebo arm, also was statistically significant (P = .0391).
A secondary analysis of the patient-reported Symptoms of Depression Questionnaire also showed a statistically significant improvement (P = .09) from baseline in the combined ketamine groups, compared with the active placebo group.
At Day 1, the combined ketamine groups’ changes from baseline HAMD-6 were –3.25 with an effect size of 0.86, a statistically significant finding. However, by the Day 3, the combined ketamine groups’ effects size fell away. “There is no longer a statistically significant difference, so it’s a rapid effect – like we’ve seen in the other studies for the combined doses – but it is not an effect that is sustained,” said Dr. Papakostas, also an associate professor of psychiatry at Harvard Medical School, Boston.
For the individual doses, compared with active placebo, the ketamine 0.1 mg/kg arm had an overall –0.35 change in baseline HAMD-6 scores, which Dr. Papakostas said had “a large effect size of 0.82.”
Dr. Papakostas also said the ketamine 0.2 mg/kg arm “did not really seem to move things around at all.” Meanwhile, the 0.5 mg/kg and 1.0 mg/kg arms each had “big differences” in baseline HAMD-6 scores, compared with active placebo, of –4.79 and –3.76, respectively. They also exhibited statistically significant effect sizes of 1.21 and 0.95 at Day 1, respectively. However, at Day 3, there were neither numerical nor statistical differences, indicating the effect is not sustained.
Changes in the Symptoms of Depression Questionnaire for the combined drug arms at Day 1 were statistically significant with an unadjusted P value of .07 and an adjusted P value of .13.
Results for the Clinician Administered Dissociative States Scale showed that neither the ketamine 0.1 mg/kg arm nor the ketamine 0.2 mg/kg arm separated from active placebo, while the ketamine 0.5 mg/kg arm and the ketamine 1.0 mg/kg arm were each different from active placebo to numerically and statistically significant degrees. Each of the 0.5 mg/kg and the 1.0 mg/kg ketamine arms were associated with rises in blood pressure, according to Dr. Papakostas.
“So, it seems as though the doses that caused a dissociation seemed to cause a clinical effect that is equivalent, whereas in the lower doses, there didn’t seem to be any dissociative effects or blood pressure effects,” Dr. Papakostas said. “If you combine the findings, in my opinion, there is a signal in the 0.1 mg/kg treatment arm, even though it just misses it on the P value.”
Dr. Papakostas said that, although more data are needed to determine optimal dosing and a clearer risk-benefit ratio, the results suggested that intravenous ketamine could offer transient, beneficial effects for patients with treatment-resistant depression.
Dr. Papakostas is the scientific director of the MGH Clinical Trials Network and Institute. This study’s coinvestigator, Maurizio Fava, MD, has numerous relevant financial ties to industry. This trial was part of the National Institute of Mental Health’s Rapidly-Acting Treatments for Treatment-Resistant Depression research program.
MIAMI – Intravenous ketamine in a range of doses is superior to active placebo, according to analyses from a study of the drug for treatment-resistant depression.
Most of the effect was attributable to differences recorded at Day 1 of the 3-day study, according to George I. Papakostas, MD, scientific director of the Massachusetts General Hospital Clinical Trials Network and Institute and coinvestigator of the study, who presented these findings at a meeting of the American Society of Clinical Psychopharmacology, formerly the New Clinical Drug Evaluation meeting.
The 99 adults with treatment-resistant depression – primarily white women in their mid-40s – were randomly assigned either to an active placebo group given 0.045 mg/kg of midazolam or to one of four treatment arms given a single infusion of intravenous ketamine at either 0.1 mg/kg, 0.2 mg/kg, 0.5 mg/kg, or 1.0 mg/kg.
Baseline scores on the 6-item Hamilton Depression Rating Scale (HAMD-6) ranged between 12.6 and 13.1 across the study.
To determine the efficacy of intravenous ketamine at different doses over the course of 72 hours, Dr. Papakostas, who also directs treatment-resistant depression studies at Massachusetts General, and his colleagues used multiple statistical models. The first analysis was a comparison of the effects of the active placebo and all ketamine groups combined at Day 1 and at Day 3.
At Day 1, the change in baseline HAMD-6 scores for all the ketamine arms combined, compared with the active placebo group, was statistically significant (P = .0278). At Day 3, the change in baseline HAMD-6 scores for the combined ketamine groups, compared with the active placebo arm, also was statistically significant (P = .0391).
A secondary analysis of the patient-reported Symptoms of Depression Questionnaire also showed a statistically significant improvement (P = .09) from baseline in the combined ketamine groups, compared with the active placebo group.
At Day 1, the combined ketamine groups’ changes from baseline HAMD-6 were –3.25 with an effect size of 0.86, a statistically significant finding. However, by the Day 3, the combined ketamine groups’ effects size fell away. “There is no longer a statistically significant difference, so it’s a rapid effect – like we’ve seen in the other studies for the combined doses – but it is not an effect that is sustained,” said Dr. Papakostas, also an associate professor of psychiatry at Harvard Medical School, Boston.
For the individual doses, compared with active placebo, the ketamine 0.1 mg/kg arm had an overall –0.35 change in baseline HAMD-6 scores, which Dr. Papakostas said had “a large effect size of 0.82.”
Dr. Papakostas also said the ketamine 0.2 mg/kg arm “did not really seem to move things around at all.” Meanwhile, the 0.5 mg/kg and 1.0 mg/kg arms each had “big differences” in baseline HAMD-6 scores, compared with active placebo, of –4.79 and –3.76, respectively. They also exhibited statistically significant effect sizes of 1.21 and 0.95 at Day 1, respectively. However, at Day 3, there were neither numerical nor statistical differences, indicating the effect is not sustained.
Changes in the Symptoms of Depression Questionnaire for the combined drug arms at Day 1 were statistically significant with an unadjusted P value of .07 and an adjusted P value of .13.
Results for the Clinician Administered Dissociative States Scale showed that neither the ketamine 0.1 mg/kg arm nor the ketamine 0.2 mg/kg arm separated from active placebo, while the ketamine 0.5 mg/kg arm and the ketamine 1.0 mg/kg arm were each different from active placebo to numerically and statistically significant degrees. Each of the 0.5 mg/kg and the 1.0 mg/kg ketamine arms were associated with rises in blood pressure, according to Dr. Papakostas.
“So, it seems as though the doses that caused a dissociation seemed to cause a clinical effect that is equivalent, whereas in the lower doses, there didn’t seem to be any dissociative effects or blood pressure effects,” Dr. Papakostas said. “If you combine the findings, in my opinion, there is a signal in the 0.1 mg/kg treatment arm, even though it just misses it on the P value.”
Dr. Papakostas said that, although more data are needed to determine optimal dosing and a clearer risk-benefit ratio, the results suggested that intravenous ketamine could offer transient, beneficial effects for patients with treatment-resistant depression.
Dr. Papakostas is the scientific director of the MGH Clinical Trials Network and Institute. This study’s coinvestigator, Maurizio Fava, MD, has numerous relevant financial ties to industry. This trial was part of the National Institute of Mental Health’s Rapidly-Acting Treatments for Treatment-Resistant Depression research program.
FROM THE ASCP ANNUAL MEETING
Key clinical point:
Major finding: Ketamine’s effect size and improvement from baseline depression scores showed significant separation from placebo in most analyses conducted in this study.
Data source: Multicenter, randomly controlled, double-blind study of 99 adults with treatment-resistant depression given active placebo or various doses of intravenous ketamine.
Disclosures: Dr. Papakostas is the scientific director of the Massachusetts General Hospital Clinical Trials Network and Institute. This study’s coinvestigator, Dr. Maurizio Fava, has numerous relevant financial ties to industry. This trial was part of the National Institute of Mental Health’s Rapidly-Acting Treatments for Treatment-Resistant Depression research program.
‘Motivational pharmacotherapy’ engages Latino patients with depression
MIAMI – Approaching treatment as a partnership between clinician and patient can help improve adherence in underserved members of racial/ethnic groups with depression, according to an expert.
“There is plenty of evidence that clinicians are less likely to engage minorities in a participatory way,” Roberto Lewis-Fernández, MD, said during a plenary session at a meeting of the American Society of Clinical Psychopharmacology, formerly the New Clinical Drug Evaluation Unit meeting. “They tend to ask fewer questions [of patients]. They tend to engage [patients] less in clinical decision making.”
This can lead to nonadherence or even discontinuation of therapy, said Dr. Lewis-Fernández, director of the New York State (NYS) Center of Excellence for Cultural Competence, as well as the Anxiety Disorders Clinic and the Hispanic Treatment Program at NYS Psychiatric Institute.
One solution for bridging what Dr. Lewis-Fernández calls the “power differential” between therapist and patient, and improving adherence rates, is to use “motivational pharmacotherapy,” a derivative of motivational interviewing, created by Dr. Lewis-Fernández and his colleagues. With motivational pharmacotherapy, patients are viewed as the experts in their challenges when meeting the needs of their treatment plan. The clinician is the expert partner in the technical aspects of care.
In a 12-week, open-trial pilot study for this intervention in 50 first-generation Latino patients diagnosed with major depressive disorder, Dr. Lewis-Fernández and his colleagues found that 20% of patients discontinued treatment, with a mean therapy duration of 74.2 out of 84 days (Psychiatry. 2013 Fall;76[3]:210-22).This was in comparison to reports in the literature of discontinuation rates among Latino patients ranging from 32% to 53%, and to rates between 36% and 46% in previous studies conducted at Dr. Lewis-Fernández’s own clinic, using similar medications and methods.
They also found that responder and remitter rates were 82% and 68%. The average length of the first clinical visit was 36.7 minutes, and 24.3 minutes for subsequent visits, which Dr. Lewis-Fernández said was compatible with community clinics.
Motivational pharmacotherapy relies on the psychotherapy components of motivational interviewing that address the need for behavioral change and for helping patients reduce their ambivalence about taking antidepressants. Those components are combined with manualized pharmacotherapy, said Dr. Lewis-Fernández, professor of clinical psychiatry at Columbia University, New York.
The language and tone of this kind of intervention must be empathetic and nonconfrontational, he said. “You can’t say to people who are ambivalent, ‘No, you’re wrong. Take your medication.’ Instead, [focus on] the discrepancy between the current situation and the desired state. Then medication can serve as the solution.”
This allows the patient to “roll with their resistance,” he said, rather than meet it head on. In turn, this approach emphasizes the patient’s capacity to advocate for himself or herself.
“You can’t do the treatment without the patient,” Dr. Lewis-Fernández said. “It’s essentially psychoeducation.”
Among some of the tips for conducting this intervention cited by Dr. Lewis-Fernández:
- Ask questions to elicit the patients’ cultural understanding about their illness and what troubles them most about their condition.
- Ask patients’ permission to show them the supportive data for the intervention.
- Ask them about their thoughts and feelings in response to learning the data.
- Use their understanding of the pros and cons of the medication to “negotiate” their engagement.
In previous studies, Dr. Lewis-Fernández said, he and his colleagues analyzed the reasons for nonadherence, which he said often were tied to the “chaos of their lives.” However, he said, there were improvements after the patients engaged in this psychoeducation-enriched intervention.
Not blaming minority patients for poor adherence is important, he said, since their ambivalence takes place in the context of having less access to quality care. Among the many obstacles these patients face in getting the care they need, insufficient clinician training in how to engage them should not have to be one of them, Dr. Lewis-Fernández said. “We should be doing something about this as a profession.”
Dr. Lewis-Fernández said he had no relevant disclosures. The study on motivational pharmacotherapy was sponsored by Pfizer and the National Institute of Mental Health.
On Twitter @whitneymcknight
MIAMI – Approaching treatment as a partnership between clinician and patient can help improve adherence in underserved members of racial/ethnic groups with depression, according to an expert.
“There is plenty of evidence that clinicians are less likely to engage minorities in a participatory way,” Roberto Lewis-Fernández, MD, said during a plenary session at a meeting of the American Society of Clinical Psychopharmacology, formerly the New Clinical Drug Evaluation Unit meeting. “They tend to ask fewer questions [of patients]. They tend to engage [patients] less in clinical decision making.”
This can lead to nonadherence or even discontinuation of therapy, said Dr. Lewis-Fernández, director of the New York State (NYS) Center of Excellence for Cultural Competence, as well as the Anxiety Disorders Clinic and the Hispanic Treatment Program at NYS Psychiatric Institute.
One solution for bridging what Dr. Lewis-Fernández calls the “power differential” between therapist and patient, and improving adherence rates, is to use “motivational pharmacotherapy,” a derivative of motivational interviewing, created by Dr. Lewis-Fernández and his colleagues. With motivational pharmacotherapy, patients are viewed as the experts in their challenges when meeting the needs of their treatment plan. The clinician is the expert partner in the technical aspects of care.
In a 12-week, open-trial pilot study for this intervention in 50 first-generation Latino patients diagnosed with major depressive disorder, Dr. Lewis-Fernández and his colleagues found that 20% of patients discontinued treatment, with a mean therapy duration of 74.2 out of 84 days (Psychiatry. 2013 Fall;76[3]:210-22).This was in comparison to reports in the literature of discontinuation rates among Latino patients ranging from 32% to 53%, and to rates between 36% and 46% in previous studies conducted at Dr. Lewis-Fernández’s own clinic, using similar medications and methods.
They also found that responder and remitter rates were 82% and 68%. The average length of the first clinical visit was 36.7 minutes, and 24.3 minutes for subsequent visits, which Dr. Lewis-Fernández said was compatible with community clinics.
Motivational pharmacotherapy relies on the psychotherapy components of motivational interviewing that address the need for behavioral change and for helping patients reduce their ambivalence about taking antidepressants. Those components are combined with manualized pharmacotherapy, said Dr. Lewis-Fernández, professor of clinical psychiatry at Columbia University, New York.
The language and tone of this kind of intervention must be empathetic and nonconfrontational, he said. “You can’t say to people who are ambivalent, ‘No, you’re wrong. Take your medication.’ Instead, [focus on] the discrepancy between the current situation and the desired state. Then medication can serve as the solution.”
This allows the patient to “roll with their resistance,” he said, rather than meet it head on. In turn, this approach emphasizes the patient’s capacity to advocate for himself or herself.
“You can’t do the treatment without the patient,” Dr. Lewis-Fernández said. “It’s essentially psychoeducation.”
Among some of the tips for conducting this intervention cited by Dr. Lewis-Fernández:
- Ask questions to elicit the patients’ cultural understanding about their illness and what troubles them most about their condition.
- Ask patients’ permission to show them the supportive data for the intervention.
- Ask them about their thoughts and feelings in response to learning the data.
- Use their understanding of the pros and cons of the medication to “negotiate” their engagement.
In previous studies, Dr. Lewis-Fernández said, he and his colleagues analyzed the reasons for nonadherence, which he said often were tied to the “chaos of their lives.” However, he said, there were improvements after the patients engaged in this psychoeducation-enriched intervention.
Not blaming minority patients for poor adherence is important, he said, since their ambivalence takes place in the context of having less access to quality care. Among the many obstacles these patients face in getting the care they need, insufficient clinician training in how to engage them should not have to be one of them, Dr. Lewis-Fernández said. “We should be doing something about this as a profession.”
Dr. Lewis-Fernández said he had no relevant disclosures. The study on motivational pharmacotherapy was sponsored by Pfizer and the National Institute of Mental Health.
On Twitter @whitneymcknight
MIAMI – Approaching treatment as a partnership between clinician and patient can help improve adherence in underserved members of racial/ethnic groups with depression, according to an expert.
“There is plenty of evidence that clinicians are less likely to engage minorities in a participatory way,” Roberto Lewis-Fernández, MD, said during a plenary session at a meeting of the American Society of Clinical Psychopharmacology, formerly the New Clinical Drug Evaluation Unit meeting. “They tend to ask fewer questions [of patients]. They tend to engage [patients] less in clinical decision making.”
This can lead to nonadherence or even discontinuation of therapy, said Dr. Lewis-Fernández, director of the New York State (NYS) Center of Excellence for Cultural Competence, as well as the Anxiety Disorders Clinic and the Hispanic Treatment Program at NYS Psychiatric Institute.
One solution for bridging what Dr. Lewis-Fernández calls the “power differential” between therapist and patient, and improving adherence rates, is to use “motivational pharmacotherapy,” a derivative of motivational interviewing, created by Dr. Lewis-Fernández and his colleagues. With motivational pharmacotherapy, patients are viewed as the experts in their challenges when meeting the needs of their treatment plan. The clinician is the expert partner in the technical aspects of care.
In a 12-week, open-trial pilot study for this intervention in 50 first-generation Latino patients diagnosed with major depressive disorder, Dr. Lewis-Fernández and his colleagues found that 20% of patients discontinued treatment, with a mean therapy duration of 74.2 out of 84 days (Psychiatry. 2013 Fall;76[3]:210-22).This was in comparison to reports in the literature of discontinuation rates among Latino patients ranging from 32% to 53%, and to rates between 36% and 46% in previous studies conducted at Dr. Lewis-Fernández’s own clinic, using similar medications and methods.
They also found that responder and remitter rates were 82% and 68%. The average length of the first clinical visit was 36.7 minutes, and 24.3 minutes for subsequent visits, which Dr. Lewis-Fernández said was compatible with community clinics.
Motivational pharmacotherapy relies on the psychotherapy components of motivational interviewing that address the need for behavioral change and for helping patients reduce their ambivalence about taking antidepressants. Those components are combined with manualized pharmacotherapy, said Dr. Lewis-Fernández, professor of clinical psychiatry at Columbia University, New York.
The language and tone of this kind of intervention must be empathetic and nonconfrontational, he said. “You can’t say to people who are ambivalent, ‘No, you’re wrong. Take your medication.’ Instead, [focus on] the discrepancy between the current situation and the desired state. Then medication can serve as the solution.”
This allows the patient to “roll with their resistance,” he said, rather than meet it head on. In turn, this approach emphasizes the patient’s capacity to advocate for himself or herself.
“You can’t do the treatment without the patient,” Dr. Lewis-Fernández said. “It’s essentially psychoeducation.”
Among some of the tips for conducting this intervention cited by Dr. Lewis-Fernández:
- Ask questions to elicit the patients’ cultural understanding about their illness and what troubles them most about their condition.
- Ask patients’ permission to show them the supportive data for the intervention.
- Ask them about their thoughts and feelings in response to learning the data.
- Use their understanding of the pros and cons of the medication to “negotiate” their engagement.
In previous studies, Dr. Lewis-Fernández said, he and his colleagues analyzed the reasons for nonadherence, which he said often were tied to the “chaos of their lives.” However, he said, there were improvements after the patients engaged in this psychoeducation-enriched intervention.
Not blaming minority patients for poor adherence is important, he said, since their ambivalence takes place in the context of having less access to quality care. Among the many obstacles these patients face in getting the care they need, insufficient clinician training in how to engage them should not have to be one of them, Dr. Lewis-Fernández said. “We should be doing something about this as a profession.”
Dr. Lewis-Fernández said he had no relevant disclosures. The study on motivational pharmacotherapy was sponsored by Pfizer and the National Institute of Mental Health.
On Twitter @whitneymcknight
EXPERT ANALYSIS FROM THE ASCP ANNUAL MEETING
More treatments becoming available for tardive dyskinesia
MIAMI – The pathophysiology of tardive dyskinesia remains a mystery, but patients with this involuntary movement disorder have new hope – thanks to recent approval of the first agent indicated for the condition and the anticipated approval of a second.
“These drugs actually work and are safe,” Ira D. Glick, MD, professor emeritus of psychiatry and behavioral sciences at Stanford (Calif.) University, said during a panel addressing the disorder at a meeting of the American Society of Clinical Psychopharmacology, formerly the New Clinical Drug Evaluation Unit meeting. 
The vesicular monoamine transport type 2 inhibitor valbenazine (Ingrezza, Neurocrine Biosciences) was approved earlier this year by the Food and Drug Administration, and a second VMAT2 inhibitor, deutetrabenazine (Teva), is scheduled for an FDA Prescription Drug User Fee Act review later this summer.
Those two novel agents downregulate the delivery of dopamine released by monoamine-containing presynaptic vesicles, thus decreasing the stimulation of the D2 receptors, and lessening the frequency and severity of involuntary movements associated with tardive dyskinesia (TD). The difference between them is that valbenazine converts to metabolites with no off-target affinities; deutetrabenazine modifies the pharmacokinetic pathway, slowing the rate of metabolization of the agent.
A phase 2, 6‐week dose‐titration study of valbenazine in 102 subjects with moderate to severe TD showed that the drug significantly reduced TD severity according to the Abnormal Involuntary Movement Scale (AIMS) when dosed at 25 mg and 75 mg, compared with placebo (P = .0005), and to the Clinical Global Impression of Change–Tardive Dyskinesia (P less than .0001) (Mov Disord. 2015 Oct;30[2]:1681-7).
Efficacy data from a pivotal 6-week, phase 3, double-blind, fixed-dosage, placebo-controlled, intention-to-treat study of 234 participants with moderate to severe antipsychotic-induced TD also showed favorable changes in AIMS scores in both the 80-mg and 40-mg groups, compared with placebo (P less than .05 for the valbenazine 40-mg group and P less than .001 for the 80-mg group) (Am J Psychiatry. 2017 May 1;174[5]:476-84). Both doses were efficacious and showed superiority over placebo with the 80-mg dose having a large effect size of 0.90. According to 52-week follow-up maintenance data presented by Dr. Glick, TD symptoms in the 80-mg group remitted until week 48, when patients were removed from their regimens.
“Here is what happens when you take patients off the drug: They relapse to where they were,” Dr. Glick said, noting that by week 52, the cohort essentially had returned to baseline AIMS scores. Somnolence is the main side effect, according to the drug’s package insert.
Clinical data for deutetrabenazine summarized by Dr. Glick indicated that in a 12-week trial in 117 people with moderate to severe TD, 24-mg and 36-mg doses of the drug separated “nicely” from placebo, had a robust efficacy profile in patients with worse symptoms, compared with placebo, a number needed to treat of 6, mild side effects, and no associated adverse events. Dr. Glick said phase 3 clinical trial data indicate that somnolence is once again the main side effect, that the drug was not associated with depression or suicidal ideation, and had low rates of psychiatric adverse events.
Although the exact pathophysiology of TD is unknown, according to panelist Leslie L. Citrome, MD, MPH, traditionally it was thought to be an associated adverse event of antidopaminergic use, particularly with first-generation antipsychotics. However, since TD also occurs with second-generation antipsychotics, and because symptoms frequently persist after antipsychotic use is discontinued, Dr. Citrome said the role of neurodegeneration, which can be exacerbated by oxidative stress and genetic vulnerability, also is implicated in the development of TD. The relationship between TD and decreased levels of brain-derived neurotropic factor, which contributes to the health of neurons, also is nascent in the literature, said Dr. Citrome, clinical professor of psychiatry and behavioral sciences at New York Medical College in Valhalla.
Until valbenazine’s approval, the most common treatment for TD was the orphan drug oral tetrabenazine, a reversible VMAT2 inhibitor that succeeded reserpine for TD treatment when it was discovered not to affect VMAT1, which occurs primarily in the peripheral nervous system. Reserpine irreversibly affects both VMAT1 and VMAT2. Tetrabenazine in the United States is indicated only for chorea in Huntington’s disease, making it highly expensive, according to Dr. Citrome, who also cited the drug’s short half-life and boxed warning for depression and suicidality as drawbacks.
“Its adverse events are problematic, and we don’t really have terrific evidence for its efficacy in TD,” he said.
However, of all the available TD treatments with any associated clinical data, including clonazepam, ginkgo biloba, branch chain amino acids, and amantadine, tetrabenazine’s wide acceptance made it the most “logical” starting point for a more effective treatment of TD, said Dr. Citrome.
The most well tolerated approach remains unclear, Dr. Citrome said. No head-to-head trials of valbenazine vs. deutetrabenazine have as yet been completed, and there are no prospective data. However, said Dr. Glick: “Think of your patients. They have schizophrenia, bipolar disease, terrible diseases. Then they get TD on top of that. How they suffer. Then you give them something that actually works.”
Dr. Glick disclosed that he has many industry ties, including with deutetrabenazine’s study sponsor Teva, as well as with Otsuka, and Takeda. Dr. Citrome disclosed that among his many pharmaceutical industry ties is Neurocrine Biosciences, manufacturer of valbenazine.
MIAMI – The pathophysiology of tardive dyskinesia remains a mystery, but patients with this involuntary movement disorder have new hope – thanks to recent approval of the first agent indicated for the condition and the anticipated approval of a second.
“These drugs actually work and are safe,” Ira D. Glick, MD, professor emeritus of psychiatry and behavioral sciences at Stanford (Calif.) University, said during a panel addressing the disorder at a meeting of the American Society of Clinical Psychopharmacology, formerly the New Clinical Drug Evaluation Unit meeting.
The vesicular monoamine transport type 2 inhibitor valbenazine (Ingrezza, Neurocrine Biosciences) was approved earlier this year by the Food and Drug Administration, and a second VMAT2 inhibitor, deutetrabenazine (Teva), is scheduled for an FDA Prescription Drug User Fee Act review later this summer.
Those two novel agents downregulate the delivery of dopamine released by monoamine-containing presynaptic vesicles, thus decreasing the stimulation of the D2 receptors, and lessening the frequency and severity of involuntary movements associated with tardive dyskinesia (TD). The difference between them is that valbenazine converts to metabolites with no off-target affinities; deutetrabenazine modifies the pharmacokinetic pathway, slowing the rate of metabolization of the agent.
A phase 2, 6‐week dose‐titration study of valbenazine in 102 subjects with moderate to severe TD showed that the drug significantly reduced TD severity according to the Abnormal Involuntary Movement Scale (AIMS) when dosed at 25 mg and 75 mg, compared with placebo (P = .0005), and to the Clinical Global Impression of Change–Tardive Dyskinesia (P less than .0001) (Mov Disord. 2015 Oct;30[2]:1681-7).
Efficacy data from a pivotal 6-week, phase 3, double-blind, fixed-dosage, placebo-controlled, intention-to-treat study of 234 participants with moderate to severe antipsychotic-induced TD also showed favorable changes in AIMS scores in both the 80-mg and 40-mg groups, compared with placebo (P less than .05 for the valbenazine 40-mg group and P less than .001 for the 80-mg group) (Am J Psychiatry. 2017 May 1;174[5]:476-84). Both doses were efficacious and showed superiority over placebo with the 80-mg dose having a large effect size of 0.90. According to 52-week follow-up maintenance data presented by Dr. Glick, TD symptoms in the 80-mg group remitted until week 48, when patients were removed from their regimens.
“Here is what happens when you take patients off the drug: They relapse to where they were,” Dr. Glick said, noting that by week 52, the cohort essentially had returned to baseline AIMS scores. Somnolence is the main side effect, according to the drug’s package insert.
Clinical data for deutetrabenazine summarized by Dr. Glick indicated that in a 12-week trial in 117 people with moderate to severe TD, 24-mg and 36-mg doses of the drug separated “nicely” from placebo, had a robust efficacy profile in patients with worse symptoms, compared with placebo, a number needed to treat of 6, mild side effects, and no associated adverse events. Dr. Glick said phase 3 clinical trial data indicate that somnolence is once again the main side effect, that the drug was not associated with depression or suicidal ideation, and had low rates of psychiatric adverse events.
Although the exact pathophysiology of TD is unknown, according to panelist Leslie L. Citrome, MD, MPH, traditionally it was thought to be an associated adverse event of antidopaminergic use, particularly with first-generation antipsychotics. However, since TD also occurs with second-generation antipsychotics, and because symptoms frequently persist after antipsychotic use is discontinued, Dr. Citrome said the role of neurodegeneration, which can be exacerbated by oxidative stress and genetic vulnerability, also is implicated in the development of TD. The relationship between TD and decreased levels of brain-derived neurotropic factor, which contributes to the health of neurons, also is nascent in the literature, said Dr. Citrome, clinical professor of psychiatry and behavioral sciences at New York Medical College in Valhalla.
Until valbenazine’s approval, the most common treatment for TD was the orphan drug oral tetrabenazine, a reversible VMAT2 inhibitor that succeeded reserpine for TD treatment when it was discovered not to affect VMAT1, which occurs primarily in the peripheral nervous system. Reserpine irreversibly affects both VMAT1 and VMAT2. Tetrabenazine in the United States is indicated only for chorea in Huntington’s disease, making it highly expensive, according to Dr. Citrome, who also cited the drug’s short half-life and boxed warning for depression and suicidality as drawbacks.
“Its adverse events are problematic, and we don’t really have terrific evidence for its efficacy in TD,” he said.
However, of all the available TD treatments with any associated clinical data, including clonazepam, ginkgo biloba, branch chain amino acids, and amantadine, tetrabenazine’s wide acceptance made it the most “logical” starting point for a more effective treatment of TD, said Dr. Citrome.
The most well tolerated approach remains unclear, Dr. Citrome said. No head-to-head trials of valbenazine vs. deutetrabenazine have as yet been completed, and there are no prospective data. However, said Dr. Glick: “Think of your patients. They have schizophrenia, bipolar disease, terrible diseases. Then they get TD on top of that. How they suffer. Then you give them something that actually works.”
Dr. Glick disclosed that he has many industry ties, including with deutetrabenazine’s study sponsor Teva, as well as with Otsuka, and Takeda. Dr. Citrome disclosed that among his many pharmaceutical industry ties is Neurocrine Biosciences, manufacturer of valbenazine.
MIAMI – The pathophysiology of tardive dyskinesia remains a mystery, but patients with this involuntary movement disorder have new hope – thanks to recent approval of the first agent indicated for the condition and the anticipated approval of a second.
“These drugs actually work and are safe,” Ira D. Glick, MD, professor emeritus of psychiatry and behavioral sciences at Stanford (Calif.) University, said during a panel addressing the disorder at a meeting of the American Society of Clinical Psychopharmacology, formerly the New Clinical Drug Evaluation Unit meeting.
The vesicular monoamine transport type 2 inhibitor valbenazine (Ingrezza, Neurocrine Biosciences) was approved earlier this year by the Food and Drug Administration, and a second VMAT2 inhibitor, deutetrabenazine (Teva), is scheduled for an FDA Prescription Drug User Fee Act review later this summer.
Those two novel agents downregulate the delivery of dopamine released by monoamine-containing presynaptic vesicles, thus decreasing the stimulation of the D2 receptors, and lessening the frequency and severity of involuntary movements associated with tardive dyskinesia (TD). The difference between them is that valbenazine converts to metabolites with no off-target affinities; deutetrabenazine modifies the pharmacokinetic pathway, slowing the rate of metabolization of the agent.
A phase 2, 6‐week dose‐titration study of valbenazine in 102 subjects with moderate to severe TD showed that the drug significantly reduced TD severity according to the Abnormal Involuntary Movement Scale (AIMS) when dosed at 25 mg and 75 mg, compared with placebo (P = .0005), and to the Clinical Global Impression of Change–Tardive Dyskinesia (P less than .0001) (Mov Disord. 2015 Oct;30[2]:1681-7).
Efficacy data from a pivotal 6-week, phase 3, double-blind, fixed-dosage, placebo-controlled, intention-to-treat study of 234 participants with moderate to severe antipsychotic-induced TD also showed favorable changes in AIMS scores in both the 80-mg and 40-mg groups, compared with placebo (P less than .05 for the valbenazine 40-mg group and P less than .001 for the 80-mg group) (Am J Psychiatry. 2017 May 1;174[5]:476-84). Both doses were efficacious and showed superiority over placebo with the 80-mg dose having a large effect size of 0.90. According to 52-week follow-up maintenance data presented by Dr. Glick, TD symptoms in the 80-mg group remitted until week 48, when patients were removed from their regimens.
“Here is what happens when you take patients off the drug: They relapse to where they were,” Dr. Glick said, noting that by week 52, the cohort essentially had returned to baseline AIMS scores. Somnolence is the main side effect, according to the drug’s package insert.
Clinical data for deutetrabenazine summarized by Dr. Glick indicated that in a 12-week trial in 117 people with moderate to severe TD, 24-mg and 36-mg doses of the drug separated “nicely” from placebo, had a robust efficacy profile in patients with worse symptoms, compared with placebo, a number needed to treat of 6, mild side effects, and no associated adverse events. Dr. Glick said phase 3 clinical trial data indicate that somnolence is once again the main side effect, that the drug was not associated with depression or suicidal ideation, and had low rates of psychiatric adverse events.
Although the exact pathophysiology of TD is unknown, according to panelist Leslie L. Citrome, MD, MPH, traditionally it was thought to be an associated adverse event of antidopaminergic use, particularly with first-generation antipsychotics. However, since TD also occurs with second-generation antipsychotics, and because symptoms frequently persist after antipsychotic use is discontinued, Dr. Citrome said the role of neurodegeneration, which can be exacerbated by oxidative stress and genetic vulnerability, also is implicated in the development of TD. The relationship between TD and decreased levels of brain-derived neurotropic factor, which contributes to the health of neurons, also is nascent in the literature, said Dr. Citrome, clinical professor of psychiatry and behavioral sciences at New York Medical College in Valhalla.
Until valbenazine’s approval, the most common treatment for TD was the orphan drug oral tetrabenazine, a reversible VMAT2 inhibitor that succeeded reserpine for TD treatment when it was discovered not to affect VMAT1, which occurs primarily in the peripheral nervous system. Reserpine irreversibly affects both VMAT1 and VMAT2. Tetrabenazine in the United States is indicated only for chorea in Huntington’s disease, making it highly expensive, according to Dr. Citrome, who also cited the drug’s short half-life and boxed warning for depression and suicidality as drawbacks.
“Its adverse events are problematic, and we don’t really have terrific evidence for its efficacy in TD,” he said.
However, of all the available TD treatments with any associated clinical data, including clonazepam, ginkgo biloba, branch chain amino acids, and amantadine, tetrabenazine’s wide acceptance made it the most “logical” starting point for a more effective treatment of TD, said Dr. Citrome.
The most well tolerated approach remains unclear, Dr. Citrome said. No head-to-head trials of valbenazine vs. deutetrabenazine have as yet been completed, and there are no prospective data. However, said Dr. Glick: “Think of your patients. They have schizophrenia, bipolar disease, terrible diseases. Then they get TD on top of that. How they suffer. Then you give them something that actually works.”
Dr. Glick disclosed that he has many industry ties, including with deutetrabenazine’s study sponsor Teva, as well as with Otsuka, and Takeda. Dr. Citrome disclosed that among his many pharmaceutical industry ties is Neurocrine Biosciences, manufacturer of valbenazine.
EXPERT ANALYSIS FROM The ASCP ANNUAL MEETING
Expert: Engage patients, clinicians as partners in research
MIAMI – Not all researchers are clinicians, but what if all clinicians were researchers? Clinical studies would yield more relevant data, resulting in better patient care, according to an expert.
“The clinical research enterprise is broken,” Andrew A. Nierenberg, MD, said during a keynote plenary session dedicated to serving diverse populations, at a meeting of the American Society of Clinical Psychopharmacology, formerly known as the New Clinical Drug Evaluation Unit meeting. “It’s a problem, because it really does not have an impact on the actual care we give, and it doesn’t answer the types of questions that patients care about.”
One persistent problem, Dr. Nierenberg said, is that often those who enroll in trials have unclear motives for doing so, but those motives usually are tied to incentives such as cash. “Who goes into these trials and why is absolutely critical to the signal,” he said.
Questionable intent is compounded by inadequate or nonexistent explanations to study participants about the researchers’ reasons for the trial, and no clear justification for why the participants should adhere to the protocols. This leads to medications often not being taken as directed, and poor attendance at follow-up points and psychosocial visits. The result overall, he said, is that clinical research amounts to symptomatic volunteers who are strangers to the investigator “doing weird things in places where they have never been before and [not really understanding] why they are doing them.” In practical terms, this means that the amount of evidence-based medicine practiced across the specialties is low – only about 15%, said Dr. Nierenberg, who cited a study that pinned blame for the “fragmented ‘nonsystem’ of [clinical research] on a lack of common goals, vision, and collaboration” (JAMA. 2009;301[8]:831-41).
The best solution would be integrating the clinical and the research enterprises into a single system – where patients and clinicians alike are engaged in the research process, he said.
“Transform clinicians into partners and collaborators. Engage them up front to help recruit, not just for your study but for all studies,” said Dr. Nierenberg, the incumbent holder of the Thomas P. Hackett, MD Endowed Chair in Psychiatry at Massachusetts General Hospital in Boston. “If someone comes in [seeking treatment], they can opt out of doing research, but the assumption is that they will collaborate and that we will expect them to collaborate.”
In his own work, Dr. Nierenberg helps run the MoodNetwork, a growing, nationwide database of patient-reported outcomes for those with mood disorders that he said is dedicated to filling knowledge gaps around those illnesses not easily gleaned from clinical response data alone. “Patients know what it is like to live with their illness more than we do,” said Dr. Nierenberg, also director of the Dauten Family Center for Bipolar Treatment Innovation in Boston.
The data from the MoodNetwork also feed into a nationwide network of databases run by the Patient-Centered Outcomes Research Institute network, originally created as part of the Affordable Care Act, and which, at least for now, Dr. Nierenberg said, appears safe from repeal. The network recently received $28 million to help create the necessary infrastructure for connecting research and clinical databases – including the electronic health records – from a variety of health institutions nationwide. “Most of you have your EHRs embedded into those networks even if you don’t know it,” Dr. Nierenberg said.
PCORInet’s resulting uber-database currently has patient-reported data on more than 122 million people. All of the data are queryable and available for use for virtually any study a clinical researcher or clinician would like to conduct into any aspect of any clinical specialty.
In his clinical practice, Dr. Nierenberg said, he is able to solicit patients in MoodNetwork studies by appealing to them as partners and collaborators from the moment they present in the clinic. He and his colleagues ensure that patients understand the importance of their participation not just to them as sufferers of an illness, but to the care of millions of others. Key to working together as partners is to use plain language when explaining treatment and research goals. It also is important to survey patients and listen to them when they share their experience of trials and treatment.
“We tend to suffer from the curse of knowledge,” Dr. Nierenberg said, referring to the amount of technical jargon that often separates study participants from researchers. “We are so embedded in our world; we can’t imagine not understanding it. It’s a failure to communicate, and it happens over and over again.”
Dr. Nierenberg’s talk generated buzz days after he gave it. During the meeting’s final regulatory plenary session, ASCP President Mark H. Rapaport, MD, chair of psychiatry and behavioral sciences at Emory University in Atlanta, invited Dr. Nierenberg to help clarify for Food and Drug Administration officials and attendees alike the extent to which point-of-care research could avoid numerous pitfalls, including expectation bias and an outsized placebo effect – two drawbacks that researchers typically avoid by purposefully not interacting with patients.
The way around those confounders, Dr. Nierenberg said, is to begin communicating with patients as soon as they enter the clinic. Randomize those who are seeking care from those who are willing to participate in research for a time-limited duration, and emphasize that there is continuity before and after the research with the same clinician providing the clinical care. “Be very explicit in saying to them that: ‘The study might affect your care and the care of others in the future, but that it is just as important to the study if you don’t respond as if you do [respond].’ ”
To avoid rater bias, he suggested blinding raters as to which clinicians gathered the data on which patients.
Incentivizing clinicians to change their work flows to accommodate becoming researchers requires seeing them as equals. As the current system of research is now, Dr. Nierenberg said, “clinicians get pushed aside.” Instead, he suggested, meet clinicians’ desires for access to the data to help care for their patients, or CMEs, and webinars – all resources and tools he said were possible to achieve with dashboards built into the information networks.
Dr. Nierenberg talked about the importance of teaching patients how to be collaborators, such as by having them respond to practice questions, asking whether they understand what is being asked of them, and presenting them with videos about what to expect.
Conversely, the patient can teach the researcher how to be a better collaborator. During the regulatory plenary session, Dr. Rapaport called upon David Sheehan, MD, a distinguished university health professor emeritus at University of South Florida in Tampa, now in private practice. His Sheehan Suicidality Tracking Scale was validated in a study that described the scale as having “excellent accuracy for suicidal ideation” (J Clin Psychiatry. 2015 Dec;76[12]:1676-82).
Throughout his career, Dr. Sheehan said, he has asked his patients to arrive early to their appointments to answer questions on scales of his own creation. He then reviews them with the patient in each visit and asks for their feedback. “Honestly, they gave me the best advice ...” Dr. Sheehan said. “It’s the way they phrase the questions that I would never would have thought up. They would say to me, ‘We would understand [the questions] if you put them this way, but if you don’t change the wording, a whole cohort of your patients will give you the wrong kind of answer.’ With decades of input like that, I realized it was the best way to go.”
Dr. Nierenberg described an alchemy of sorts that occurs when the power differential between the holder of the learned knowledge (the researcher) and the holder of experiential knowledge (the patient) is bridged. “What happens to your attitude when you’re working with a ‘collaborator’ compared to when you are working with a ‘patient’? You feel it, but you’re unaware of the bias. But if you think of them as your partners, and tell them that they are, you find they shift. They own it. It’s an authentic engagement over time.”
Ultimately, better research will lead to better patient care, he said.
Dr. Nierenberg had no relevant disclosures.
MIAMI – Not all researchers are clinicians, but what if all clinicians were researchers? Clinical studies would yield more relevant data, resulting in better patient care, according to an expert.
“The clinical research enterprise is broken,” Andrew A. Nierenberg, MD, said during a keynote plenary session dedicated to serving diverse populations, at a meeting of the American Society of Clinical Psychopharmacology, formerly known as the New Clinical Drug Evaluation Unit meeting. “It’s a problem, because it really does not have an impact on the actual care we give, and it doesn’t answer the types of questions that patients care about.”
One persistent problem, Dr. Nierenberg said, is that often those who enroll in trials have unclear motives for doing so, but those motives usually are tied to incentives such as cash. “Who goes into these trials and why is absolutely critical to the signal,” he said.
Questionable intent is compounded by inadequate or nonexistent explanations to study participants about the researchers’ reasons for the trial, and no clear justification for why the participants should adhere to the protocols. This leads to medications often not being taken as directed, and poor attendance at follow-up points and psychosocial visits. The result overall, he said, is that clinical research amounts to symptomatic volunteers who are strangers to the investigator “doing weird things in places where they have never been before and [not really understanding] why they are doing them.” In practical terms, this means that the amount of evidence-based medicine practiced across the specialties is low – only about 15%, said Dr. Nierenberg, who cited a study that pinned blame for the “fragmented ‘nonsystem’ of [clinical research] on a lack of common goals, vision, and collaboration” (JAMA. 2009;301[8]:831-41).
The best solution would be integrating the clinical and the research enterprises into a single system – where patients and clinicians alike are engaged in the research process, he said.
“Transform clinicians into partners and collaborators. Engage them up front to help recruit, not just for your study but for all studies,” said Dr. Nierenberg, the incumbent holder of the Thomas P. Hackett, MD Endowed Chair in Psychiatry at Massachusetts General Hospital in Boston. “If someone comes in [seeking treatment], they can opt out of doing research, but the assumption is that they will collaborate and that we will expect them to collaborate.”
In his own work, Dr. Nierenberg helps run the MoodNetwork, a growing, nationwide database of patient-reported outcomes for those with mood disorders that he said is dedicated to filling knowledge gaps around those illnesses not easily gleaned from clinical response data alone. “Patients know what it is like to live with their illness more than we do,” said Dr. Nierenberg, also director of the Dauten Family Center for Bipolar Treatment Innovation in Boston.
The data from the MoodNetwork also feed into a nationwide network of databases run by the Patient-Centered Outcomes Research Institute network, originally created as part of the Affordable Care Act, and which, at least for now, Dr. Nierenberg said, appears safe from repeal. The network recently received $28 million to help create the necessary infrastructure for connecting research and clinical databases – including the electronic health records – from a variety of health institutions nationwide. “Most of you have your EHRs embedded into those networks even if you don’t know it,” Dr. Nierenberg said.
PCORInet’s resulting uber-database currently has patient-reported data on more than 122 million people. All of the data are queryable and available for use for virtually any study a clinical researcher or clinician would like to conduct into any aspect of any clinical specialty.
In his clinical practice, Dr. Nierenberg said, he is able to solicit patients in MoodNetwork studies by appealing to them as partners and collaborators from the moment they present in the clinic. He and his colleagues ensure that patients understand the importance of their participation not just to them as sufferers of an illness, but to the care of millions of others. Key to working together as partners is to use plain language when explaining treatment and research goals. It also is important to survey patients and listen to them when they share their experience of trials and treatment.
“We tend to suffer from the curse of knowledge,” Dr. Nierenberg said, referring to the amount of technical jargon that often separates study participants from researchers. “We are so embedded in our world; we can’t imagine not understanding it. It’s a failure to communicate, and it happens over and over again.”
Dr. Nierenberg’s talk generated buzz days after he gave it. During the meeting’s final regulatory plenary session, ASCP President Mark H. Rapaport, MD, chair of psychiatry and behavioral sciences at Emory University in Atlanta, invited Dr. Nierenberg to help clarify for Food and Drug Administration officials and attendees alike the extent to which point-of-care research could avoid numerous pitfalls, including expectation bias and an outsized placebo effect – two drawbacks that researchers typically avoid by purposefully not interacting with patients.
The way around those confounders, Dr. Nierenberg said, is to begin communicating with patients as soon as they enter the clinic. Randomize those who are seeking care from those who are willing to participate in research for a time-limited duration, and emphasize that there is continuity before and after the research with the same clinician providing the clinical care. “Be very explicit in saying to them that: ‘The study might affect your care and the care of others in the future, but that it is just as important to the study if you don’t respond as if you do [respond].’ ”
To avoid rater bias, he suggested blinding raters as to which clinicians gathered the data on which patients.
Incentivizing clinicians to change their work flows to accommodate becoming researchers requires seeing them as equals. As the current system of research is now, Dr. Nierenberg said, “clinicians get pushed aside.” Instead, he suggested, meet clinicians’ desires for access to the data to help care for their patients, or CMEs, and webinars – all resources and tools he said were possible to achieve with dashboards built into the information networks.
Dr. Nierenberg talked about the importance of teaching patients how to be collaborators, such as by having them respond to practice questions, asking whether they understand what is being asked of them, and presenting them with videos about what to expect.
Conversely, the patient can teach the researcher how to be a better collaborator. During the regulatory plenary session, Dr. Rapaport called upon David Sheehan, MD, a distinguished university health professor emeritus at University of South Florida in Tampa, now in private practice. His Sheehan Suicidality Tracking Scale was validated in a study that described the scale as having “excellent accuracy for suicidal ideation” (J Clin Psychiatry. 2015 Dec;76[12]:1676-82).
Throughout his career, Dr. Sheehan said, he has asked his patients to arrive early to their appointments to answer questions on scales of his own creation. He then reviews them with the patient in each visit and asks for their feedback. “Honestly, they gave me the best advice ...” Dr. Sheehan said. “It’s the way they phrase the questions that I would never would have thought up. They would say to me, ‘We would understand [the questions] if you put them this way, but if you don’t change the wording, a whole cohort of your patients will give you the wrong kind of answer.’ With decades of input like that, I realized it was the best way to go.”
Dr. Nierenberg described an alchemy of sorts that occurs when the power differential between the holder of the learned knowledge (the researcher) and the holder of experiential knowledge (the patient) is bridged. “What happens to your attitude when you’re working with a ‘collaborator’ compared to when you are working with a ‘patient’? You feel it, but you’re unaware of the bias. But if you think of them as your partners, and tell them that they are, you find they shift. They own it. It’s an authentic engagement over time.”
Ultimately, better research will lead to better patient care, he said.
Dr. Nierenberg had no relevant disclosures.
MIAMI – Not all researchers are clinicians, but what if all clinicians were researchers? Clinical studies would yield more relevant data, resulting in better patient care, according to an expert.
“The clinical research enterprise is broken,” Andrew A. Nierenberg, MD, said during a keynote plenary session dedicated to serving diverse populations, at a meeting of the American Society of Clinical Psychopharmacology, formerly known as the New Clinical Drug Evaluation Unit meeting. “It’s a problem, because it really does not have an impact on the actual care we give, and it doesn’t answer the types of questions that patients care about.”
One persistent problem, Dr. Nierenberg said, is that often those who enroll in trials have unclear motives for doing so, but those motives usually are tied to incentives such as cash. “Who goes into these trials and why is absolutely critical to the signal,” he said.
Questionable intent is compounded by inadequate or nonexistent explanations to study participants about the researchers’ reasons for the trial, and no clear justification for why the participants should adhere to the protocols. This leads to medications often not being taken as directed, and poor attendance at follow-up points and psychosocial visits. The result overall, he said, is that clinical research amounts to symptomatic volunteers who are strangers to the investigator “doing weird things in places where they have never been before and [not really understanding] why they are doing them.” In practical terms, this means that the amount of evidence-based medicine practiced across the specialties is low – only about 15%, said Dr. Nierenberg, who cited a study that pinned blame for the “fragmented ‘nonsystem’ of [clinical research] on a lack of common goals, vision, and collaboration” (JAMA. 2009;301[8]:831-41).
The best solution would be integrating the clinical and the research enterprises into a single system – where patients and clinicians alike are engaged in the research process, he said.
“Transform clinicians into partners and collaborators. Engage them up front to help recruit, not just for your study but for all studies,” said Dr. Nierenberg, the incumbent holder of the Thomas P. Hackett, MD Endowed Chair in Psychiatry at Massachusetts General Hospital in Boston. “If someone comes in [seeking treatment], they can opt out of doing research, but the assumption is that they will collaborate and that we will expect them to collaborate.”
In his own work, Dr. Nierenberg helps run the MoodNetwork, a growing, nationwide database of patient-reported outcomes for those with mood disorders that he said is dedicated to filling knowledge gaps around those illnesses not easily gleaned from clinical response data alone. “Patients know what it is like to live with their illness more than we do,” said Dr. Nierenberg, also director of the Dauten Family Center for Bipolar Treatment Innovation in Boston.
The data from the MoodNetwork also feed into a nationwide network of databases run by the Patient-Centered Outcomes Research Institute network, originally created as part of the Affordable Care Act, and which, at least for now, Dr. Nierenberg said, appears safe from repeal. The network recently received $28 million to help create the necessary infrastructure for connecting research and clinical databases – including the electronic health records – from a variety of health institutions nationwide. “Most of you have your EHRs embedded into those networks even if you don’t know it,” Dr. Nierenberg said.
PCORInet’s resulting uber-database currently has patient-reported data on more than 122 million people. All of the data are queryable and available for use for virtually any study a clinical researcher or clinician would like to conduct into any aspect of any clinical specialty.
In his clinical practice, Dr. Nierenberg said, he is able to solicit patients in MoodNetwork studies by appealing to them as partners and collaborators from the moment they present in the clinic. He and his colleagues ensure that patients understand the importance of their participation not just to them as sufferers of an illness, but to the care of millions of others. Key to working together as partners is to use plain language when explaining treatment and research goals. It also is important to survey patients and listen to them when they share their experience of trials and treatment.
“We tend to suffer from the curse of knowledge,” Dr. Nierenberg said, referring to the amount of technical jargon that often separates study participants from researchers. “We are so embedded in our world; we can’t imagine not understanding it. It’s a failure to communicate, and it happens over and over again.”
Dr. Nierenberg’s talk generated buzz days after he gave it. During the meeting’s final regulatory plenary session, ASCP President Mark H. Rapaport, MD, chair of psychiatry and behavioral sciences at Emory University in Atlanta, invited Dr. Nierenberg to help clarify for Food and Drug Administration officials and attendees alike the extent to which point-of-care research could avoid numerous pitfalls, including expectation bias and an outsized placebo effect – two drawbacks that researchers typically avoid by purposefully not interacting with patients.
The way around those confounders, Dr. Nierenberg said, is to begin communicating with patients as soon as they enter the clinic. Randomize those who are seeking care from those who are willing to participate in research for a time-limited duration, and emphasize that there is continuity before and after the research with the same clinician providing the clinical care. “Be very explicit in saying to them that: ‘The study might affect your care and the care of others in the future, but that it is just as important to the study if you don’t respond as if you do [respond].’ ”
To avoid rater bias, he suggested blinding raters as to which clinicians gathered the data on which patients.
Incentivizing clinicians to change their work flows to accommodate becoming researchers requires seeing them as equals. As the current system of research is now, Dr. Nierenberg said, “clinicians get pushed aside.” Instead, he suggested, meet clinicians’ desires for access to the data to help care for their patients, or CMEs, and webinars – all resources and tools he said were possible to achieve with dashboards built into the information networks.
Dr. Nierenberg talked about the importance of teaching patients how to be collaborators, such as by having them respond to practice questions, asking whether they understand what is being asked of them, and presenting them with videos about what to expect.
Conversely, the patient can teach the researcher how to be a better collaborator. During the regulatory plenary session, Dr. Rapaport called upon David Sheehan, MD, a distinguished university health professor emeritus at University of South Florida in Tampa, now in private practice. His Sheehan Suicidality Tracking Scale was validated in a study that described the scale as having “excellent accuracy for suicidal ideation” (J Clin Psychiatry. 2015 Dec;76[12]:1676-82).
Throughout his career, Dr. Sheehan said, he has asked his patients to arrive early to their appointments to answer questions on scales of his own creation. He then reviews them with the patient in each visit and asks for their feedback. “Honestly, they gave me the best advice ...” Dr. Sheehan said. “It’s the way they phrase the questions that I would never would have thought up. They would say to me, ‘We would understand [the questions] if you put them this way, but if you don’t change the wording, a whole cohort of your patients will give you the wrong kind of answer.’ With decades of input like that, I realized it was the best way to go.”
Dr. Nierenberg described an alchemy of sorts that occurs when the power differential between the holder of the learned knowledge (the researcher) and the holder of experiential knowledge (the patient) is bridged. “What happens to your attitude when you’re working with a ‘collaborator’ compared to when you are working with a ‘patient’? You feel it, but you’re unaware of the bias. But if you think of them as your partners, and tell them that they are, you find they shift. They own it. It’s an authentic engagement over time.”
Ultimately, better research will lead to better patient care, he said.
Dr. Nierenberg had no relevant disclosures.
EXPERT ANALYSIS FROM THE ASCP ANNUAL MEETING
Patients’ profile deemed best criteria for LAIs in bipolar disorder
MIAMI – Expert clinicians endorsed long-acting injectables as a preferred treatment for bipolar I disorder on the basis of patient characteristics and treatment history, rather than on an assumed level of treatment adherence, according to a small survey.
“Just over three-quarters of the experts we surveyed said they were ‘somewhat’ or ‘not very’ confident about their ability to assess their patients’ adherence,” said Martha Sajatovic, MD, who presented the data during a poster session at a meeting of the American Society of Clinical Psychopharmacology, formerly the New Clinical Drug Evaluation Unit meeting.
The finding reflects a shift, according to Dr. Sajatovic, professor of psychiatry and neurology, and the Willard Brown Chair in Neurological Outcomes Research, at Case Western University in Cleveland.
The traditional view of using long-acting injectable antipsychotics (LAIs) for patients with bipolar I disorder is that they are appropriate only in certain cohorts, such as patients with very severe illness or at the more extreme spectrum in terms of risk, and those who are homeless or pose a risk to themselves or others, Dr. Sajatovic said. Also, when it comes to the use of LAIs, there is a lack of guidance – which might contribute to clinicians’ reluctance to prescribe or recommend them, she said.
In the survey, of the 42 experts contacted by Dr. Sajatovic and her colleagues, 34 responded. According to those respondents, 11% of their patients with bipolar disorder were being treated with LAIs, compared with one-third of all patients with schizophrenia/schizoaffective disorder.
Using a scale of 1-9, with 1 being “extremely inappropriate,” 2-3 being “usually inappropriate,” 4-6 being “sometimes appropriate,” 7-8 being “usually appropriate,” and 9 being “extremely appropriate,” all tended to favor patient characteristics and treatment history over adherence when rating criteria for treatment selection. This was true regardless of whether patients were newly diagnosed with bipolar disorder, or whether their diagnosis was established and treated with an antipsychotic for 2 or more years.
For comparison, Dr. Sajatovic and her colleagues also surveyed the expert panel members on their use of LAIs in established schizophrenia and schizoaffective disorder.
Patients with a history of two or more hospitalizations for bipolar relapses and those who were either homeless or had unstable housing were rated by most respondents as usually appropriate for LAIs as first-line treatment. For those with dubious treatment adherence, the profile was similar: LAIs were considered by a majority of respondents as usually appropriate if there was a history of two or more hospitalizations for bipolar relapses, as well as homelessness or an unstable housing situation. LAIs also were considered by a majority as usually appropriate in this cohort if there was a history of violence to others, and if patients had poor insight into their illness.
Spotty treatment adherence to medications was the most common treatment history characteristic cited for first-line prescription of LAIs in patients with an established bipolar disorder diagnosis. Other first-line LAI criteria cited by most respondents for this cohort were if they previously had done well on an LAI, and if they frequently missed clinic appointments.
Virtually all the criteria above applied to patients with established illness and questionable adherence, although the expert clinicians also largely cited a failure to respond to lithium or an anticonvulsant mood stabilizer, a predominant history of manic relapse, and a strong therapeutic alliance as additional reasons to view LAIs as usually appropriate.
Regardless of the assumption of adherence or nonadherence, in most cases in which patients had an established bipolar diagnosis, more than half of the expert panel said use of an LAI was extremely appropriate.
In patients with an established diagnosis of bipolar disorder with questionable treatment adherence, respondents strongly endorsed the idea that it was usually appropriate to use LAIs as first-line treatment if the patients had a history of two or more hospitalizations for bipolar relapses, homelessness or an otherwise unstable living arrangement, violence toward others, and poor insight into their illness.
The panel members were blinded to the study’s sponsor, which was Otsuka. All respondents had an average of 25 years of clinical experience and an average of 22 years of research experience, and all had extensive expertise in the use of two or more LAIs, although no specific antipsychotic brand names were included in the survey.
Just more than one-third of respondents reported spending all or most of their professional time seeing patients, and one-fifth reported that they saw patients half of the time. The average age of patients seen by the respondents was 35-65 years.
Dr. Sajatovic disclosed receiving research grants from the National Institutes of Health, Alkermes, Janssen, Merck, and several other pharmaceutical companies and foundations; serving as a consultant for numerous entities, including Otsuka; and receiving royalties from UpToDate, and several publishing companies.
MIAMI – Expert clinicians endorsed long-acting injectables as a preferred treatment for bipolar I disorder on the basis of patient characteristics and treatment history, rather than on an assumed level of treatment adherence, according to a small survey.
“Just over three-quarters of the experts we surveyed said they were ‘somewhat’ or ‘not very’ confident about their ability to assess their patients’ adherence,” said Martha Sajatovic, MD, who presented the data during a poster session at a meeting of the American Society of Clinical Psychopharmacology, formerly the New Clinical Drug Evaluation Unit meeting.
The finding reflects a shift, according to Dr. Sajatovic, professor of psychiatry and neurology, and the Willard Brown Chair in Neurological Outcomes Research, at Case Western University in Cleveland.
The traditional view of using long-acting injectable antipsychotics (LAIs) for patients with bipolar I disorder is that they are appropriate only in certain cohorts, such as patients with very severe illness or at the more extreme spectrum in terms of risk, and those who are homeless or pose a risk to themselves or others, Dr. Sajatovic said. Also, when it comes to the use of LAIs, there is a lack of guidance – which might contribute to clinicians’ reluctance to prescribe or recommend them, she said.
In the survey, of the 42 experts contacted by Dr. Sajatovic and her colleagues, 34 responded. According to those respondents, 11% of their patients with bipolar disorder were being treated with LAIs, compared with one-third of all patients with schizophrenia/schizoaffective disorder.
Using a scale of 1-9, with 1 being “extremely inappropriate,” 2-3 being “usually inappropriate,” 4-6 being “sometimes appropriate,” 7-8 being “usually appropriate,” and 9 being “extremely appropriate,” all tended to favor patient characteristics and treatment history over adherence when rating criteria for treatment selection. This was true regardless of whether patients were newly diagnosed with bipolar disorder, or whether their diagnosis was established and treated with an antipsychotic for 2 or more years.
For comparison, Dr. Sajatovic and her colleagues also surveyed the expert panel members on their use of LAIs in established schizophrenia and schizoaffective disorder.
Patients with a history of two or more hospitalizations for bipolar relapses and those who were either homeless or had unstable housing were rated by most respondents as usually appropriate for LAIs as first-line treatment. For those with dubious treatment adherence, the profile was similar: LAIs were considered by a majority of respondents as usually appropriate if there was a history of two or more hospitalizations for bipolar relapses, as well as homelessness or an unstable housing situation. LAIs also were considered by a majority as usually appropriate in this cohort if there was a history of violence to others, and if patients had poor insight into their illness.
Spotty treatment adherence to medications was the most common treatment history characteristic cited for first-line prescription of LAIs in patients with an established bipolar disorder diagnosis. Other first-line LAI criteria cited by most respondents for this cohort were if they previously had done well on an LAI, and if they frequently missed clinic appointments.
Virtually all the criteria above applied to patients with established illness and questionable adherence, although the expert clinicians also largely cited a failure to respond to lithium or an anticonvulsant mood stabilizer, a predominant history of manic relapse, and a strong therapeutic alliance as additional reasons to view LAIs as usually appropriate.
Regardless of the assumption of adherence or nonadherence, in most cases in which patients had an established bipolar diagnosis, more than half of the expert panel said use of an LAI was extremely appropriate.
In patients with an established diagnosis of bipolar disorder with questionable treatment adherence, respondents strongly endorsed the idea that it was usually appropriate to use LAIs as first-line treatment if the patients had a history of two or more hospitalizations for bipolar relapses, homelessness or an otherwise unstable living arrangement, violence toward others, and poor insight into their illness.
The panel members were blinded to the study’s sponsor, which was Otsuka. All respondents had an average of 25 years of clinical experience and an average of 22 years of research experience, and all had extensive expertise in the use of two or more LAIs, although no specific antipsychotic brand names were included in the survey.
Just more than one-third of respondents reported spending all or most of their professional time seeing patients, and one-fifth reported that they saw patients half of the time. The average age of patients seen by the respondents was 35-65 years.
Dr. Sajatovic disclosed receiving research grants from the National Institutes of Health, Alkermes, Janssen, Merck, and several other pharmaceutical companies and foundations; serving as a consultant for numerous entities, including Otsuka; and receiving royalties from UpToDate, and several publishing companies.
MIAMI – Expert clinicians endorsed long-acting injectables as a preferred treatment for bipolar I disorder on the basis of patient characteristics and treatment history, rather than on an assumed level of treatment adherence, according to a small survey.
“Just over three-quarters of the experts we surveyed said they were ‘somewhat’ or ‘not very’ confident about their ability to assess their patients’ adherence,” said Martha Sajatovic, MD, who presented the data during a poster session at a meeting of the American Society of Clinical Psychopharmacology, formerly the New Clinical Drug Evaluation Unit meeting.
The finding reflects a shift, according to Dr. Sajatovic, professor of psychiatry and neurology, and the Willard Brown Chair in Neurological Outcomes Research, at Case Western University in Cleveland.
The traditional view of using long-acting injectable antipsychotics (LAIs) for patients with bipolar I disorder is that they are appropriate only in certain cohorts, such as patients with very severe illness or at the more extreme spectrum in terms of risk, and those who are homeless or pose a risk to themselves or others, Dr. Sajatovic said. Also, when it comes to the use of LAIs, there is a lack of guidance – which might contribute to clinicians’ reluctance to prescribe or recommend them, she said.
In the survey, of the 42 experts contacted by Dr. Sajatovic and her colleagues, 34 responded. According to those respondents, 11% of their patients with bipolar disorder were being treated with LAIs, compared with one-third of all patients with schizophrenia/schizoaffective disorder.
Using a scale of 1-9, with 1 being “extremely inappropriate,” 2-3 being “usually inappropriate,” 4-6 being “sometimes appropriate,” 7-8 being “usually appropriate,” and 9 being “extremely appropriate,” all tended to favor patient characteristics and treatment history over adherence when rating criteria for treatment selection. This was true regardless of whether patients were newly diagnosed with bipolar disorder, or whether their diagnosis was established and treated with an antipsychotic for 2 or more years.
For comparison, Dr. Sajatovic and her colleagues also surveyed the expert panel members on their use of LAIs in established schizophrenia and schizoaffective disorder.
Patients with a history of two or more hospitalizations for bipolar relapses and those who were either homeless or had unstable housing were rated by most respondents as usually appropriate for LAIs as first-line treatment. For those with dubious treatment adherence, the profile was similar: LAIs were considered by a majority of respondents as usually appropriate if there was a history of two or more hospitalizations for bipolar relapses, as well as homelessness or an unstable housing situation. LAIs also were considered by a majority as usually appropriate in this cohort if there was a history of violence to others, and if patients had poor insight into their illness.
Spotty treatment adherence to medications was the most common treatment history characteristic cited for first-line prescription of LAIs in patients with an established bipolar disorder diagnosis. Other first-line LAI criteria cited by most respondents for this cohort were if they previously had done well on an LAI, and if they frequently missed clinic appointments.
Virtually all the criteria above applied to patients with established illness and questionable adherence, although the expert clinicians also largely cited a failure to respond to lithium or an anticonvulsant mood stabilizer, a predominant history of manic relapse, and a strong therapeutic alliance as additional reasons to view LAIs as usually appropriate.
Regardless of the assumption of adherence or nonadherence, in most cases in which patients had an established bipolar diagnosis, more than half of the expert panel said use of an LAI was extremely appropriate.
In patients with an established diagnosis of bipolar disorder with questionable treatment adherence, respondents strongly endorsed the idea that it was usually appropriate to use LAIs as first-line treatment if the patients had a history of two or more hospitalizations for bipolar relapses, homelessness or an otherwise unstable living arrangement, violence toward others, and poor insight into their illness.
The panel members were blinded to the study’s sponsor, which was Otsuka. All respondents had an average of 25 years of clinical experience and an average of 22 years of research experience, and all had extensive expertise in the use of two or more LAIs, although no specific antipsychotic brand names were included in the survey.
Just more than one-third of respondents reported spending all or most of their professional time seeing patients, and one-fifth reported that they saw patients half of the time. The average age of patients seen by the respondents was 35-65 years.
Dr. Sajatovic disclosed receiving research grants from the National Institutes of Health, Alkermes, Janssen, Merck, and several other pharmaceutical companies and foundations; serving as a consultant for numerous entities, including Otsuka; and receiving royalties from UpToDate, and several publishing companies.
AT THE ASCP ANNUAL MEETING
Key clinical point:
Major finding: Clinicians very strongly endorsed the use long-acting injectables as first-line treatment in patients with bipolar disorder who met several criteria, including having a history of two or more hospitalizations for bipolar relapses.
Data source: A blinded, consensus survey of 34 high-prescribing clinicians experienced in treating mood and psychotic disorders.
Disclosures: Dr. Sajatovic disclosed receiving research grants from the National Institutes of Health, Alkermes, Janssen, Merck, and several other pharmaceutical companies and foundations; serving as a consultant for numerous entities, including Otsuka, which sponsored the study; and receiving royalties from UpToDate, and several publishing companies.
Novel female sexual dysfunction drug effective, phase III studies show
MIAMI – Women distressed by a low desire for sex could have a novel pharmaceutical intervention soon.
Phase III results from the two Reconnect studies of 1,247 premenopausal women with hypoactive sexual desire disorder in stable relationships showed that bremelanotide was associated with statistically significant improvements in sexual desire and levels of distress about hyposexuality, compared with placebo. The phase III results confirm a phase IIb randomized, double-blind, multicenter trial showing that the drug boosts sexual arousal and desire in this population.
The phase III data were presented in a poster and during a session dedicated to new drugs in the pipeline at a meeting of the American Society of Clinical Psychopharmacology, formerly known as the New Clinical Drug Evaluation Unit meeting.
Bremelanotide, administered subcutaneously, is a novel cyclic 7-amino acid melanocortin-receptor agonist with a high affinity for the type-4 receptor. The mechanism of action is thought to be analogous to a peptide alpha-melanocyte–stimulating hormone that is thought to enhance dopamine and norepinephrine, said Dr. Clayton, the David C. Wilson Professor of Psychiatry and Neurobehavioral Sciences, and professor of clinical obstetrics and gynecology at UVA.
Women in the modified, intent-to-treat study were all given a 1-month, no-drug qualification month, followed by a 1-month single-blind placebo treatment, before they were randomly assigned to 24 weeks of either placebo or 1.75 mg bremelanotide. They could choose to use the drug at their discretion, whenever they anticipated that they would like to have sex.
“Women, on average, had sex about four times a month and used the product three times a month,” Dr. Clayton said in an interview. “We don’t have the answer for [why], but the likelihood is that they used it, and then, when they did, they had more desire and so didn’t need to [use it every time]. But, they could have used it every day of the month if they wanted.”
Changes in Female Sexual Function Index (FSFI) scores from baseline to study’s end were 0.24 in the 316 placebo group, compared with 0.54 in the 314 women in the study drug arm of the first study (P less than .0002). In the second study, the 290 women given placebo had a 0.21 improvement in FSFI scores, compared with a 0.63 improvement in the 282 study drug arm (P less than .0001). The FSFI is a validated, 19-item measure of female sexual function across several domains, including arousal and desire, from the past 30 days. Higher scores indicate better sexual function.
Reductions in distress levels as measured by the Female Sexual Distress Scale: Desire, Arousal, Orgasm (FSDS:DAO), item #13, were –0.35 in the placebo group of the first study, compared with –0.74 in the drug arm (P less than .0001). In the second study, the placebo arm had a –0.42 shift in scores from baseline, compared with –0.71 in the study drug arm (P less than .0057). The FSDS:DAO is a validated, 15-item Likert scale that measures aspects of distress surrounding aspects of sexual functioning in the past 30 days.
Across several secondary patient-reported outcomes study wide, when compared with placebo, the women who had been given bremelanotide reported higher levels of perceived benefit for having been in the study and higher levels of overall satisfaction with their sexual relations while taking the intervention. Changes in pain levels experienced during sex and differences from placebo in the number of satisfying sexual events, as defined by the individual woman, were not statistically significant. However, across the combined study arms, the reported number of satisfying sexual events was numerically better than placebo.
“That just means that ‘satisfying sexual events’ is not a very specific measure in studies of HSDD,” Dr. Clayton said, noting that the Food and Drug Administration no longer requires it as a primary endpoint in the most recent guidance on female sexual dysfunction. “[It’s] nonspecific. Some women think, ‘Yeah, I had a satisfying event because I had an orgasm. Others think it’s because they actually wanted to participate in sex, and that was so much better for them than going along with it but thinking, ‘Just get it over with.’ ”
Mild to moderate treatment-emergent adverse events led 18% of women in the combined drug study groups to either discontinue or interrupt treatment, mostly because of nausea, vomiting, flushing, or headaches. This was in comparison to discontinuation or interruption in 2% of the women in the combined placebo arms.
Because all study participants, whose average age was 39 years, were screened for depression and relationship problems, Dr. Clayton said the causes of HSDD in the study cohort were “biologically based” but that hypoactive sexual desire disorder is a biopsychosocial condition.
“These were women who were in a relationship for at least 6 months and had previously had at least 2 years of what they considered adequate or satisfactory sexual desire and function,” Dr. Clayton said. “My experience with these patients is that they are in love with their partners, they agree on their values, they communicate. But, what’s happened is they biologically and physiologically don’t desire sex anymore.”
In 2015, the FDA approved flibanserin (Addyi) a serotonin 1A receptor agonist and a serotonin 2A receptor antagonist, as the first treatment for hypoactive sexual desire disorder in premenopausal women. Flibanserin, a central acting medication that is taken as 100 mg daily, is marketed by Valeant.*
The bremelanotide studies were sponsored by Palatin Technologies, now with a licensing agreement with AMAG Pharmaceuticals. Dr. Clayton reported numerous financial disclosures, including ties with Palatin, Valeant, and S1 Biopharma. She also receives royalties from Guilford Publications and for her role in developing the Changes in Sexual Functioning Questionnaire.
wmcknight@frontlinemedcom.com
On Twitter @whitneymcknight
* Clarification, 6/21/2017: An earlier version of this story misstated the name of the company marketing Addyi and one of Dr. Clayton’s disclosures. The name of that company is Valeant.
MIAMI – Women distressed by a low desire for sex could have a novel pharmaceutical intervention soon.
Phase III results from the two Reconnect studies of 1,247 premenopausal women with hypoactive sexual desire disorder in stable relationships showed that bremelanotide was associated with statistically significant improvements in sexual desire and levels of distress about hyposexuality, compared with placebo. The phase III results confirm a phase IIb randomized, double-blind, multicenter trial showing that the drug boosts sexual arousal and desire in this population.
The phase III data were presented in a poster and during a session dedicated to new drugs in the pipeline at a meeting of the American Society of Clinical Psychopharmacology, formerly known as the New Clinical Drug Evaluation Unit meeting.
Bremelanotide, administered subcutaneously, is a novel cyclic 7-amino acid melanocortin-receptor agonist with a high affinity for the type-4 receptor. The mechanism of action is thought to be analogous to a peptide alpha-melanocyte–stimulating hormone that is thought to enhance dopamine and norepinephrine, said Dr. Clayton, the David C. Wilson Professor of Psychiatry and Neurobehavioral Sciences, and professor of clinical obstetrics and gynecology at UVA.
Women in the modified, intent-to-treat study were all given a 1-month, no-drug qualification month, followed by a 1-month single-blind placebo treatment, before they were randomly assigned to 24 weeks of either placebo or 1.75 mg bremelanotide. They could choose to use the drug at their discretion, whenever they anticipated that they would like to have sex.
“Women, on average, had sex about four times a month and used the product three times a month,” Dr. Clayton said in an interview. “We don’t have the answer for [why], but the likelihood is that they used it, and then, when they did, they had more desire and so didn’t need to [use it every time]. But, they could have used it every day of the month if they wanted.”
Changes in Female Sexual Function Index (FSFI) scores from baseline to study’s end were 0.24 in the 316 placebo group, compared with 0.54 in the 314 women in the study drug arm of the first study (P less than .0002). In the second study, the 290 women given placebo had a 0.21 improvement in FSFI scores, compared with a 0.63 improvement in the 282 study drug arm (P less than .0001). The FSFI is a validated, 19-item measure of female sexual function across several domains, including arousal and desire, from the past 30 days. Higher scores indicate better sexual function.
Reductions in distress levels as measured by the Female Sexual Distress Scale: Desire, Arousal, Orgasm (FSDS:DAO), item #13, were –0.35 in the placebo group of the first study, compared with –0.74 in the drug arm (P less than .0001). In the second study, the placebo arm had a –0.42 shift in scores from baseline, compared with –0.71 in the study drug arm (P less than .0057). The FSDS:DAO is a validated, 15-item Likert scale that measures aspects of distress surrounding aspects of sexual functioning in the past 30 days.
Across several secondary patient-reported outcomes study wide, when compared with placebo, the women who had been given bremelanotide reported higher levels of perceived benefit for having been in the study and higher levels of overall satisfaction with their sexual relations while taking the intervention. Changes in pain levels experienced during sex and differences from placebo in the number of satisfying sexual events, as defined by the individual woman, were not statistically significant. However, across the combined study arms, the reported number of satisfying sexual events was numerically better than placebo.
“That just means that ‘satisfying sexual events’ is not a very specific measure in studies of HSDD,” Dr. Clayton said, noting that the Food and Drug Administration no longer requires it as a primary endpoint in the most recent guidance on female sexual dysfunction. “[It’s] nonspecific. Some women think, ‘Yeah, I had a satisfying event because I had an orgasm. Others think it’s because they actually wanted to participate in sex, and that was so much better for them than going along with it but thinking, ‘Just get it over with.’ ”
Mild to moderate treatment-emergent adverse events led 18% of women in the combined drug study groups to either discontinue or interrupt treatment, mostly because of nausea, vomiting, flushing, or headaches. This was in comparison to discontinuation or interruption in 2% of the women in the combined placebo arms.
Because all study participants, whose average age was 39 years, were screened for depression and relationship problems, Dr. Clayton said the causes of HSDD in the study cohort were “biologically based” but that hypoactive sexual desire disorder is a biopsychosocial condition.
“These were women who were in a relationship for at least 6 months and had previously had at least 2 years of what they considered adequate or satisfactory sexual desire and function,” Dr. Clayton said. “My experience with these patients is that they are in love with their partners, they agree on their values, they communicate. But, what’s happened is they biologically and physiologically don’t desire sex anymore.”
In 2015, the FDA approved flibanserin (Addyi) a serotonin 1A receptor agonist and a serotonin 2A receptor antagonist, as the first treatment for hypoactive sexual desire disorder in premenopausal women. Flibanserin, a central acting medication that is taken as 100 mg daily, is marketed by Valeant.*
The bremelanotide studies were sponsored by Palatin Technologies, now with a licensing agreement with AMAG Pharmaceuticals. Dr. Clayton reported numerous financial disclosures, including ties with Palatin, Valeant, and S1 Biopharma. She also receives royalties from Guilford Publications and for her role in developing the Changes in Sexual Functioning Questionnaire.
wmcknight@frontlinemedcom.com
On Twitter @whitneymcknight
* Clarification, 6/21/2017: An earlier version of this story misstated the name of the company marketing Addyi and one of Dr. Clayton’s disclosures. The name of that company is Valeant.
MIAMI – Women distressed by a low desire for sex could have a novel pharmaceutical intervention soon.
Phase III results from the two Reconnect studies of 1,247 premenopausal women with hypoactive sexual desire disorder in stable relationships showed that bremelanotide was associated with statistically significant improvements in sexual desire and levels of distress about hyposexuality, compared with placebo. The phase III results confirm a phase IIb randomized, double-blind, multicenter trial showing that the drug boosts sexual arousal and desire in this population.
The phase III data were presented in a poster and during a session dedicated to new drugs in the pipeline at a meeting of the American Society of Clinical Psychopharmacology, formerly known as the New Clinical Drug Evaluation Unit meeting.
Bremelanotide, administered subcutaneously, is a novel cyclic 7-amino acid melanocortin-receptor agonist with a high affinity for the type-4 receptor. The mechanism of action is thought to be analogous to a peptide alpha-melanocyte–stimulating hormone that is thought to enhance dopamine and norepinephrine, said Dr. Clayton, the David C. Wilson Professor of Psychiatry and Neurobehavioral Sciences, and professor of clinical obstetrics and gynecology at UVA.
Women in the modified, intent-to-treat study were all given a 1-month, no-drug qualification month, followed by a 1-month single-blind placebo treatment, before they were randomly assigned to 24 weeks of either placebo or 1.75 mg bremelanotide. They could choose to use the drug at their discretion, whenever they anticipated that they would like to have sex.
“Women, on average, had sex about four times a month and used the product three times a month,” Dr. Clayton said in an interview. “We don’t have the answer for [why], but the likelihood is that they used it, and then, when they did, they had more desire and so didn’t need to [use it every time]. But, they could have used it every day of the month if they wanted.”
Changes in Female Sexual Function Index (FSFI) scores from baseline to study’s end were 0.24 in the 316 placebo group, compared with 0.54 in the 314 women in the study drug arm of the first study (P less than .0002). In the second study, the 290 women given placebo had a 0.21 improvement in FSFI scores, compared with a 0.63 improvement in the 282 study drug arm (P less than .0001). The FSFI is a validated, 19-item measure of female sexual function across several domains, including arousal and desire, from the past 30 days. Higher scores indicate better sexual function.
Reductions in distress levels as measured by the Female Sexual Distress Scale: Desire, Arousal, Orgasm (FSDS:DAO), item #13, were –0.35 in the placebo group of the first study, compared with –0.74 in the drug arm (P less than .0001). In the second study, the placebo arm had a –0.42 shift in scores from baseline, compared with –0.71 in the study drug arm (P less than .0057). The FSDS:DAO is a validated, 15-item Likert scale that measures aspects of distress surrounding aspects of sexual functioning in the past 30 days.
Across several secondary patient-reported outcomes study wide, when compared with placebo, the women who had been given bremelanotide reported higher levels of perceived benefit for having been in the study and higher levels of overall satisfaction with their sexual relations while taking the intervention. Changes in pain levels experienced during sex and differences from placebo in the number of satisfying sexual events, as defined by the individual woman, were not statistically significant. However, across the combined study arms, the reported number of satisfying sexual events was numerically better than placebo.
“That just means that ‘satisfying sexual events’ is not a very specific measure in studies of HSDD,” Dr. Clayton said, noting that the Food and Drug Administration no longer requires it as a primary endpoint in the most recent guidance on female sexual dysfunction. “[It’s] nonspecific. Some women think, ‘Yeah, I had a satisfying event because I had an orgasm. Others think it’s because they actually wanted to participate in sex, and that was so much better for them than going along with it but thinking, ‘Just get it over with.’ ”
Mild to moderate treatment-emergent adverse events led 18% of women in the combined drug study groups to either discontinue or interrupt treatment, mostly because of nausea, vomiting, flushing, or headaches. This was in comparison to discontinuation or interruption in 2% of the women in the combined placebo arms.
Because all study participants, whose average age was 39 years, were screened for depression and relationship problems, Dr. Clayton said the causes of HSDD in the study cohort were “biologically based” but that hypoactive sexual desire disorder is a biopsychosocial condition.
“These were women who were in a relationship for at least 6 months and had previously had at least 2 years of what they considered adequate or satisfactory sexual desire and function,” Dr. Clayton said. “My experience with these patients is that they are in love with their partners, they agree on their values, they communicate. But, what’s happened is they biologically and physiologically don’t desire sex anymore.”
In 2015, the FDA approved flibanserin (Addyi) a serotonin 1A receptor agonist and a serotonin 2A receptor antagonist, as the first treatment for hypoactive sexual desire disorder in premenopausal women. Flibanserin, a central acting medication that is taken as 100 mg daily, is marketed by Valeant.*
The bremelanotide studies were sponsored by Palatin Technologies, now with a licensing agreement with AMAG Pharmaceuticals. Dr. Clayton reported numerous financial disclosures, including ties with Palatin, Valeant, and S1 Biopharma. She also receives royalties from Guilford Publications and for her role in developing the Changes in Sexual Functioning Questionnaire.
wmcknight@frontlinemedcom.com
On Twitter @whitneymcknight
* Clarification, 6/21/2017: An earlier version of this story misstated the name of the company marketing Addyi and one of Dr. Clayton’s disclosures. The name of that company is Valeant.
AT THE ASCP ANNUAL MEETING
Key clinical point:
Major finding: Bremelanotide demonstrated statistical significance when meeting its coprimary endpoints of increased sexual desire and decreased distress over hyposexuality. The drug also was associated with significant improvements in overall sexual function.
Data source: Two phase III, multicenter studies of 1,247 premenopausal women with hypoactive sexual desire disorder (HSDD) without depression randomized to either placebo or bremelanotide 1.75 mg to use as needed for 24 weeks.
Disclosures: The bremelanotide studies were sponsored by Palatin Technologies, now with a licensing agreement with AMAG Pharmaceuticals. Dr. Clayton reported numerous financial disclosures, including ties with Palatin; Valeant* and S1 Biopharma. She also receives royalties from Guilford Publications and for her role in developing the Changes in Sexual Functioning Questionnaire.
Treatment response rates for psychotic bipolar depression similar to those without
MIAMI – Response rates for psychotic and nonpsychotic depression in bipolar disorder were statistically similar, regardless of treatment, an ad hoc analysis has shown.
Over a 6 month period, results from the multisite, randomized, controlled Bipolar CHOICE (Clinical Health Outcomes Initiative in Comparative Effectiveness for Bipolar Disorder) study showed that 482 patients anywhere on the bipolar spectrum, given either lithium or quetiapine, had similar treatment response rates over 6 months.
“When you look at the course of the improvement for those with psychosis, they had more severe disorder at baseline,and presented with these symptoms throughout the study. But, when we compare curves of improvement, those with severe disorder responded to treatment at the same pace [as those without psychosis],” Dr. Caldieraro said.
The overall scores for the Bipolar Inventory of Symptoms Scale (BISS) at baseline were 75.2 plus or minus 17.6 percentage points for those with psychosis, vs. 54.9 plus or minus 16.3 for those without (P less than .001). At 6 months, the scores were more in range with one another: 37.2 plus or minus 19.7 for those with psychosis and 26.3 plus or minus 18.0 for those without (P = .003). The BISS depression scores at baseline for those with psychosis were 29.5 plus or minus 7.0, compared with 24.9 plus or minus 8.0 for those without (P = .002). At study end, the scores were 13.0 plus or minus 8.6, vs. 10.9 plus or minus 9.5 (P = .253).
Overall Clinical Global Impressions (CGI) scores for bipolar disorder at baseline in the group with psychosis were 5.1 plus or minus 0.9, compared with 4.5 plus or minus 0.8 in those without (P less than .001). At 6 months, the scores were 3.4 plus or minus 1.3, vs. 2.8 plus or minus 1.3 (P = .032). The CGI scores for depression in the psychosis group at baseline were 4.9 plus or minus 0.9, compared with 4.4 plus or minus 0.9 in the nonpsychosis group (P = .006). At 6 months, the psychosis groups’ scores were 3.1 plus or minus 1.4, compared with 2.6 plus or minus 1.3 in the nonpsychosis group (P = .07).
In addition to either lithium or quetiapine, patients in the CHOICE study also received adjunctive personalized treatment. Patients who received lithium plus APT were not given second-generation antipsychotics, while those given quetiapine plus APT were not given lithium or any other second-generation antipsychotic.
In the quetiapine group, 21 people had psychotic depression at baseline. In the lithium group, there were 11. The time to remission was numerically, although not statistically, similar between the patients with psychosis in the lithium and the quetiapine groups.
Compared with the CHOICE study participants without psychosis, the subanalysis showed that the 32 people with psychotic features were far more likely to be single or never married (P = .036), employed at half the rate (P = .035), twice as likely to suffer from generalized anxiety disorder (P = .028), and more likely to have social phobias (P = .018). People with psychotic depression in the study also were more likely to suffer from agoraphobia.
One reason for his interest in the study, Dr. Caldieraro said, was that, despite the worse prognosis for people on the bipolar spectrum with psychotic depression, the literature on treatment outcomes for this cohort is scant.
“Ours is a small sample, so you could say that we didn’t have enough power, but we have some interesting results,” he said during his presentation. “The results need replication, but the study suggests that maybe, if we make the patient better, it doesn’t matter which medication we use.”
Dr. Caldieraro had no relevant disclosures. The Agency for Healthcare Research and Quality funded the CHOICE study, NCT01331304.
MIAMI – Response rates for psychotic and nonpsychotic depression in bipolar disorder were statistically similar, regardless of treatment, an ad hoc analysis has shown.
Over a 6 month period, results from the multisite, randomized, controlled Bipolar CHOICE (Clinical Health Outcomes Initiative in Comparative Effectiveness for Bipolar Disorder) study showed that 482 patients anywhere on the bipolar spectrum, given either lithium or quetiapine, had similar treatment response rates over 6 months.
“When you look at the course of the improvement for those with psychosis, they had more severe disorder at baseline,and presented with these symptoms throughout the study. But, when we compare curves of improvement, those with severe disorder responded to treatment at the same pace [as those without psychosis],” Dr. Caldieraro said.
The overall scores for the Bipolar Inventory of Symptoms Scale (BISS) at baseline were 75.2 plus or minus 17.6 percentage points for those with psychosis, vs. 54.9 plus or minus 16.3 for those without (P less than .001). At 6 months, the scores were more in range with one another: 37.2 plus or minus 19.7 for those with psychosis and 26.3 plus or minus 18.0 for those without (P = .003). The BISS depression scores at baseline for those with psychosis were 29.5 plus or minus 7.0, compared with 24.9 plus or minus 8.0 for those without (P = .002). At study end, the scores were 13.0 plus or minus 8.6, vs. 10.9 plus or minus 9.5 (P = .253).
Overall Clinical Global Impressions (CGI) scores for bipolar disorder at baseline in the group with psychosis were 5.1 plus or minus 0.9, compared with 4.5 plus or minus 0.8 in those without (P less than .001). At 6 months, the scores were 3.4 plus or minus 1.3, vs. 2.8 plus or minus 1.3 (P = .032). The CGI scores for depression in the psychosis group at baseline were 4.9 plus or minus 0.9, compared with 4.4 plus or minus 0.9 in the nonpsychosis group (P = .006). At 6 months, the psychosis groups’ scores were 3.1 plus or minus 1.4, compared with 2.6 plus or minus 1.3 in the nonpsychosis group (P = .07).
In addition to either lithium or quetiapine, patients in the CHOICE study also received adjunctive personalized treatment. Patients who received lithium plus APT were not given second-generation antipsychotics, while those given quetiapine plus APT were not given lithium or any other second-generation antipsychotic.
In the quetiapine group, 21 people had psychotic depression at baseline. In the lithium group, there were 11. The time to remission was numerically, although not statistically, similar between the patients with psychosis in the lithium and the quetiapine groups.
Compared with the CHOICE study participants without psychosis, the subanalysis showed that the 32 people with psychotic features were far more likely to be single or never married (P = .036), employed at half the rate (P = .035), twice as likely to suffer from generalized anxiety disorder (P = .028), and more likely to have social phobias (P = .018). People with psychotic depression in the study also were more likely to suffer from agoraphobia.
One reason for his interest in the study, Dr. Caldieraro said, was that, despite the worse prognosis for people on the bipolar spectrum with psychotic depression, the literature on treatment outcomes for this cohort is scant.
“Ours is a small sample, so you could say that we didn’t have enough power, but we have some interesting results,” he said during his presentation. “The results need replication, but the study suggests that maybe, if we make the patient better, it doesn’t matter which medication we use.”
Dr. Caldieraro had no relevant disclosures. The Agency for Healthcare Research and Quality funded the CHOICE study, NCT01331304.
MIAMI – Response rates for psychotic and nonpsychotic depression in bipolar disorder were statistically similar, regardless of treatment, an ad hoc analysis has shown.
Over a 6 month period, results from the multisite, randomized, controlled Bipolar CHOICE (Clinical Health Outcomes Initiative in Comparative Effectiveness for Bipolar Disorder) study showed that 482 patients anywhere on the bipolar spectrum, given either lithium or quetiapine, had similar treatment response rates over 6 months.
“When you look at the course of the improvement for those with psychosis, they had more severe disorder at baseline,and presented with these symptoms throughout the study. But, when we compare curves of improvement, those with severe disorder responded to treatment at the same pace [as those without psychosis],” Dr. Caldieraro said.
The overall scores for the Bipolar Inventory of Symptoms Scale (BISS) at baseline were 75.2 plus or minus 17.6 percentage points for those with psychosis, vs. 54.9 plus or minus 16.3 for those without (P less than .001). At 6 months, the scores were more in range with one another: 37.2 plus or minus 19.7 for those with psychosis and 26.3 plus or minus 18.0 for those without (P = .003). The BISS depression scores at baseline for those with psychosis were 29.5 plus or minus 7.0, compared with 24.9 plus or minus 8.0 for those without (P = .002). At study end, the scores were 13.0 plus or minus 8.6, vs. 10.9 plus or minus 9.5 (P = .253).
Overall Clinical Global Impressions (CGI) scores for bipolar disorder at baseline in the group with psychosis were 5.1 plus or minus 0.9, compared with 4.5 plus or minus 0.8 in those without (P less than .001). At 6 months, the scores were 3.4 plus or minus 1.3, vs. 2.8 plus or minus 1.3 (P = .032). The CGI scores for depression in the psychosis group at baseline were 4.9 plus or minus 0.9, compared with 4.4 plus or minus 0.9 in the nonpsychosis group (P = .006). At 6 months, the psychosis groups’ scores were 3.1 plus or minus 1.4, compared with 2.6 plus or minus 1.3 in the nonpsychosis group (P = .07).
In addition to either lithium or quetiapine, patients in the CHOICE study also received adjunctive personalized treatment. Patients who received lithium plus APT were not given second-generation antipsychotics, while those given quetiapine plus APT were not given lithium or any other second-generation antipsychotic.
In the quetiapine group, 21 people had psychotic depression at baseline. In the lithium group, there were 11. The time to remission was numerically, although not statistically, similar between the patients with psychosis in the lithium and the quetiapine groups.
Compared with the CHOICE study participants without psychosis, the subanalysis showed that the 32 people with psychotic features were far more likely to be single or never married (P = .036), employed at half the rate (P = .035), twice as likely to suffer from generalized anxiety disorder (P = .028), and more likely to have social phobias (P = .018). People with psychotic depression in the study also were more likely to suffer from agoraphobia.
One reason for his interest in the study, Dr. Caldieraro said, was that, despite the worse prognosis for people on the bipolar spectrum with psychotic depression, the literature on treatment outcomes for this cohort is scant.
“Ours is a small sample, so you could say that we didn’t have enough power, but we have some interesting results,” he said during his presentation. “The results need replication, but the study suggests that maybe, if we make the patient better, it doesn’t matter which medication we use.”
Dr. Caldieraro had no relevant disclosures. The Agency for Healthcare Research and Quality funded the CHOICE study, NCT01331304.
AT THE ASCP ANNUAL MEETING
Key clinical point:
Major finding: Patients with psychotic or nonpsychotic bipolar depression responded equally well to lithium and quetiapine when compared with response rates in patients without bipolar depression.
Data source: A secondary analysis of 32 patients from a multisite, randomized, controlled trial of 482 patients with bipolar disorder I or bipolar II and psychosis, assigned to receive either lithium or quetiapine for 6 months.
Disclosures: Dr. Caldieraro had no relevant disclosures. The Agency for Healthcare Research and Quality funded the CHOICE study, NCT01331304.
