A review of atypical antipsychotic medications for posttraumatic stress disorder

William S. Middleton Memorial Veterans Hospital, University of Wisconsin, Madison, USA.
International clinical psychopharmacology (Impact Factor: 2.46). 07/2011; 26(4):193-200. DOI: 10.1097/YIC.0b013e3283473738
Source: PubMed


Posttraumatic stress disorder (PTSD) can be a chronic and disabling illness with a limited response to antidepressant treatment, particularly in the case of combat-induced PTSD. The purpose of this study is to review randomized controlled and open-label trials of atypical antipsychotics for the treatment of PTSD. We conducted PUBMED and PILOTS database searches for clinical trials of atypical antipsychotic medications for PTSD in May 2010. Eighteen clinical trials (10 double-blind placebo-controlled, eight open-label) of atypical antipsychotics for PTSD were found and reviewed. Effect sizes of double-blind placebo-controlled trials were small, but were positive for risperidone and quetiapine. Intrusive and hypervigilance symptom subscales showed the most improvement. We concluded that atypical antipsychotic medications have a modest benefit for the treatment of PTSD. Larger randomized controlled trials are needed to clarify the potential utility of these medications in the treatment of PTSD and more rigorous examination of metabolic side effects is warranted.

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    • "Moreover, a meta-analysis enables critical comparisons between studies and among competitive drugs as well as achievement of greater statistical power relative to individual trials (Huf et al., 2011). Several meta-analyses have reported favorable results in patients with PTSD following the use of AAs (Ahearn et al., 2011; Ipser and Stein, 2012; Pae et al., 2008a; Watts et al., 2013); however, the majority of large RCTs investigating PTSD (Krystal et al., 2011) failed to find an increased efficacy of risperidone compared to placebo. Furthermore, risperidone did not result in significant improvements in depression and anxiety compared to placebo in these studies. "
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    ABSTRACT: Despite the fact that the majority of currently available treatment guidelines propose antidepressants as the first-line pharmacological therapy for posttraumatic stress disorder (PTSD), a substantial portion of patients fail to show an adequate response following this type of treatment. In this context, a number of small, open-label studies and randomized controlled clinical trials (RCTs) have found atypical antipsychotics (AAs) to be a beneficial treatment for patients with PTSD. Thus, the present meta-analysis was conducted to enhance the sample size power and further the current understanding of the role of AAs for the treatment of PTSD. An extensive search of several databases identified 12 appropriate RCTs and available data from 9 of these (n = 497) were included in the final meta-analysis. AAs may have potential benefits for the treatment of PTSD as indicated by changes from baseline of the total score on the Clinician Administered PTSD Scale (CAPS; standardized mean difference [SMD] = -0.289, 95% confidence intervals [CIs] = -0.471, -0.106), P = 0.002). Additionally, AAs were found to be significantly more effective (P < 0.0001) than a placebo in terms of change from baseline for the intrusion sub-score on the CAPS (SMD = -0.373, 95% CIs = -0.568, -0.178) but there were no significant reductions for the avoidance and hyperarousal sub-symptoms. The responder rate and rate of improvement of depressive symptoms were also significantly higher in the AA group than the placebo group (P = 0.004 and P < 0.0001, respectively). However, the present results should be interpreted carefully and be translated into clinical practice only with due consideration of the limited quality and quantity of existing RCTs included in this analysis.
    Journal of Psychiatric Research 05/2014; 56(1). DOI:10.1016/j.jpsychires.2014.05.003 · 3.96 Impact Factor
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    • "Only one report of the usefulness of ziprasidone in the pharmacotherapy of PTSD have been published, revealing the efficacy of ziprasidone in two patients with chronic-combat related PTSD. [35] The level of evidence for the use of risperidone, olanzapine, and quetiapine in PTSD is at level B, with at least one positive double-blind placebo-controlled trial as well as open label trials with positive results [17] The other atypical antipsychotics have not yet demonstrated this level of evidence. The studies conducted showed that antipsychotic agents may be indicated as augmentation agents in treating PTSD, even if results are inconsistent. "
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    ABSTRACT: Introduction: Post-traumatic stress disorder (PTSD) is a frequent and disabling condition that occurs after exposure to a traumatic event, and Selective Serotonin Reuptake Inhibitors (SSRIs) are considered the first-line treatment approach for this disorder. However, a large proportion of patients remain symptomatic and other pharmacological agents have been investigated, based on the understanding of the underlying biological dysfunctions of PTSD. Methods: We conducted a review of the literature on the pharmacological options for PTSD other than the antidepressants, using MedLine and Web of Science databases, with search terms including the pharmacologic class of each agent plus PTSD, or pharmacotherapy, or fear conditioning. The literature review covered articles published until august 2012, including reviews and original articles. Results: Agents like antipsychotics, anticonvulsants, benzodiazepines, anti-adrenergic agents, have been studied in randomized clinical trials (RCTs), with general positive results for antipsychotics, especially as adjunct therapy, and for prazosin for sleep-related disturbances. However, one important target for novel medications is the modulation of the fear conditioning process, through the alteration of retrieval/reconsolidation or enhancement of fear extinction. This is traditionally targeted in prolonged exposure therapy, but pre-clinical findings from studies investigating agents like propanolol, clonidine, N-Methyl-D-aspartic Acid Receptor (NMDAR) compounds, 3,4-methylenedioxy-N-methylamphetamine (MDMA) and cannabinoids, indicate promising results in affecting the fear conditioning process and thus improving PTSD core symptoms. Discussion: Antipsychotics can be considered a reasonable alternative option to PTSD, with the largest body of evidence for risperidone, even though larger RCTs are warranted. Prazosin is also a promising agent, especially for sleep-related disturbances, while anticonvulsants and benzodiazepines lack empirical support. However, the most promising area for pharmacotherapy in PTSD is the modulation of the fear conditioning process, through agents used in adjunct to exposure therapy.
    02/2013; 10(2). DOI:10.2174/157488471002150723122127
    • "Our finding is in line with a recent systematic review of controlled data for the atypical antipsychotics risperidone and olanzapine, suggesting that they have potential to be effectively used in the treatment of PTSD (Ahearn et al., 2011). While our findings should still be interpreted with caution owing to the small sample, they nevertheless add to a body of accumulating evidence that support the use of the SGAs as a potentially useful strategy in the pharmacotherapy of PTSD (Pae et al., 2008; Canive et al., 2009). "
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    ABSTRACT: Although there have been important advances in the treatment of posttraumatic stress disorder (PTSD), many patients fail to respond to first-line pharmacotherapy. Limited evidence suggests that second generation antipsychotics may have a role to play as monotherapy in PTSD. We undertook a randomized, placebo-controlled study using flexible-dose olanzapine monotherapy for 8 weeks in 28 adult male and female participants (mean age: 40.75 ± 11.59 years) with non-combat related chronic PTSD. Data were analysed with repeated measures analysis of variance, using an intention to treat, last observation carried forward approach. The olanzapine group (n = 14) demonstrated significantly greater improvement on the Clinician Administered PTSD Scale from baseline to endpoint than the placebo group (n = 14) (F = 5.71, p = 0.018). Olanzapine was generally well tolerated, with no serious adverse events recorded. Substantial weight gain (6-10 kg) was, however, reported in 6/14 participants in the olanzapine group. To our knowledge, this is the first controlled evidence of the efficacy of olanzapine monotherapy in an exclusively non-combat related chronic PTSD group. Despite the small sample size, these data suggest that olanzapine may have a role in the treatment of PTSD. These findings warrant replication in a larger sample.
    Human Psychopharmacology Clinical and Experimental 07/2012; 27(4):386-91. DOI:10.1002/hup.2238 · 2.19 Impact Factor
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