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Efficacy of Quetiapine in PTSD
Bret A. Moore, PsyD, ABPP. Board-Certified Clinical Psychologist, San Antonio, TX
Dr. Moore has disclosed that he has no relevant financial or other interests in any commercial companies pertaining to this educational activity.
Review of: Villarreal G, Hamner MB, Cañive JM, et al. Efficacy of quetiapine monotherapy in posttraumatic stress disorder: a randomized, placebo-controlled trial. JAMA Psychiatry 2016:ahead of publication.
Study Type: Placebo-controlled, double-blinded clinical trial
Post-traumatic stress disorder (PTSD) is arguably one of the most difficult psychiatric disorders to treat. The two medications approved for the condition, sertraline and paroxetine, provide modest relief at best. This is particularly true for chronic and combat-related variants of the disorder. As a result, we are often forced to go off label—commonly with one of the atypical antipsychotics, even though the evidence for their efficacy is mixed. For example, some smaller studies have shown that risperidone is useful as an adjunctive treatment for PTSD. But, in a larger-scale study with nearly 300 veterans, the medication used as an adjunct did not outperform placebo (Krystal JH et al, JAMA 2011;306:493–502).
To further explore the utility of atypical antipsychotics, researchers randomly assigned 80 VA patients with PTSD to monotherapy with placebo or quetiapine. After a 1-week placebo run in period for all patients, 42 were assigned to placebo and 38 were assigned to quetiapine at a starting dose of 25 mg/day. The quetiapine was titrated to 800 mg/day as clinically indicated by the end of the study (average dose was 258 mg/day). Over 12 weeks, the patients’ progress was tracked with the Clinician-Administered PTSD Scale (CAPS) as well as with several non-PTSD measures.
Results
From baseline to study completion, CAPS scores for re-experiencing symptoms dropped from 20.66 to 11.71 for the quetiapine group and from 17.18 to 16.06 for placebo (better than placebo at p = 0.0004). A similar highly significant difference vs. placebo was noted for hyperarousal symptoms. Conversely, quetiapine did not fare any better than placebo for avoidance or negative symptoms. An unexpected, but welcomed finding is that patients taking quetiapine saw an improvement in their depression as assessed by the Hamilton Depression Rating Scale. This is important as there is a high comorbidity between depression and PTSD. More potential good news is that there were no differences in weight gain or blood pressure between the groups. However, this was only a 12-week study, and metabolic effects often show up later in treatment.
TCPR’s Take
Quetiapine outperformed placebo for symptoms of re-experience and hyperarousal in patients with PTSD. Although this was a well-designed, randomized, placebo-controlled trial, nearly one-third of the original sample dropped out for various reasons, and the final sample size was relatively small—limitations that should temper our confidence in the findings.
Practice implications
Quetiapine at fairly low doses (around 250 mg/day) is a reasonable option for your PTSD patients, especially those who haven’t responded to psychotherapy. As with any antipsychotic, make sure to get informed consent regarding the risks for weight gain and tardive dyskinesia, especially if you anticipate long-term treatment.
General PsychiatryStudy Type: Placebo-controlled, double-blinded clinical trial
Post-traumatic stress disorder (PTSD) is arguably one of the most difficult psychiatric disorders to treat. The two medications approved for the condition, sertraline and paroxetine, provide modest relief at best. This is particularly true for chronic and combat-related variants of the disorder. As a result, we are often forced to go off label—commonly with one of the atypical antipsychotics, even though the evidence for their efficacy is mixed. For example, some smaller studies have shown that risperidone is useful as an adjunctive treatment for PTSD. But, in a larger-scale study with nearly 300 veterans, the medication used as an adjunct did not outperform placebo (Krystal JH et al, JAMA 2011;306:493–502).
To further explore the utility of atypical antipsychotics, researchers randomly assigned 80 VA patients with PTSD to monotherapy with placebo or quetiapine. After a 1-week placebo run in period for all patients, 42 were assigned to placebo and 38 were assigned to quetiapine at a starting dose of 25 mg/day. The quetiapine was titrated to 800 mg/day as clinically indicated by the end of the study (average dose was 258 mg/day). Over 12 weeks, the patients’ progress was tracked with the Clinician-Administered PTSD Scale (CAPS) as well as with several non-PTSD measures.
Results
From baseline to study completion, CAPS scores for re-experiencing symptoms dropped from 20.66 to 11.71 for the quetiapine group and from 17.18 to 16.06 for placebo (better than placebo at p = 0.0004). A similar highly significant difference vs. placebo was noted for hyperarousal symptoms. Conversely, quetiapine did not fare any better than placebo for avoidance or negative symptoms. An unexpected, but welcomed finding is that patients taking quetiapine saw an improvement in their depression as assessed by the Hamilton Depression Rating Scale. This is important as there is a high comorbidity between depression and PTSD. More potential good news is that there were no differences in weight gain or blood pressure between the groups. However, this was only a 12-week study, and metabolic effects often show up later in treatment.
TCPR’s Take
Quetiapine outperformed placebo for symptoms of re-experience and hyperarousal in patients with PTSD. Although this was a well-designed, randomized, placebo-controlled trial, nearly one-third of the original sample dropped out for various reasons, and the final sample size was relatively small—limitations that should temper our confidence in the findings.
Practice implications
Quetiapine at fairly low doses (around 250 mg/day) is a reasonable option for your PTSD patients, especially those who haven’t responded to psychotherapy. As with any antipsychotic, make sure to get informed consent regarding the risks for weight gain and tardive dyskinesia, especially if you anticipate long-term treatment.
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