A pilot randomized placebo-controlled trial of adjunctive aripiprazole for chronic PTSD in US military Veterans resistant to antidepressant treatment

Abstract

Many individuals with post-traumatic stress disorder (PTSD) experience persistent symptoms despite pharmacological treatment with antidepressants. Several open-label monotherapy and adjunctive studies have suggested that aripiprazole (a second-generation antipsychotic) may have clinical utility in PTSD. However, there have been no randomized placebo-controlled trials of aripiprazole use for PTSD. We thus conducted a pilot randomized controlled trial of adjunctive aripiprazole versus placebo among Veterans with chronic PTSD serving in the US military since 11 September 2001 to assess the feasibility, safety, tolerability, and therapeutic potential of aripiprazole. Sixteen Veterans were randomized, and 14 completed at least 4 weeks of the study; 12 completed the entire 8-week trial. Outcome measures included the Clinician-Administered PTSD Scale (CAPS), PTSD Checklist, Beck Depression Inventory, Second Edition, and Positive and Negative Syndrome Scale scores. Aripiprazole was well-tolerated in this cohort, and improvements in CAPS, PTSD Checklist, Beck Depression Inventory, Second Edition, and Positive and Negative Syndrome Scale scores were as hypothesized. Although CAPS change scores did not reach statistical significance, aripiprazole outperformed placebo by 9 points on the CAPS in the last observation carried forward analysis compared with the placebo group (n = 7 per group), and by 20 points in the group randomized to aripiprazole that completed the entire study (n = 5) compared with the placebo group (n = 7). Results suggest promise for aripiprazole as an adjunctive strategy for the treatment of PTSD.

Psychotherapy Versus Pharmacotherapy for Posttraumatic Stress Disorder: Systemic Review and Meta-Analyses to Determine First-Line Treatments

“…Three studies replicated data from other included studies, leaving 55 total studies. Interventions that met inclusion criteria and number of studies using them included aripiprazole (1), [30] brofaromine (2), [31,32] bupropion (1), [33] TF-CBT (2), [23,24,34] citalopram (1), [35] CPT (1), [36] divalproex (2), [37,38] EMDR (2), [39,40] fluoxetine (5), [25,26,[41][42][43][44] guanfacine (2), [45,46] IPT (1), [47] mirtazapine (1), [16] nefazodone (1), [48] olanzapine (3), [18,49,50] paroxetine (7), [51][52][53][54][55][56][57] PE with cognitive restructuring (PE/CR) (2), [58,59] PE (7), [40,47,[58][59][60][61][62] prazosin…”

“…Most medication studies and several psychotherapy studies reported outcome data selectively or in a misleading manner. Examples included partial/nonstandard reporting between text and charts, [19, 20, 22-27, 32-35, 37-39, 42, 44-46, 49, 52, 56, 58, 60, 62, 63, 65-69] switching between mean/mean change, [25, 26, 38, 43-45, 48, 50, 52, 66, 69, 71-75] switching be-tween standard deviations(SD)/confidence intervals/standard errors, [25,26,28,30,43,44,51,55,62,64,67,71,72] omitting baseline outcome data, [28,33,68] omitting variance measures completely, [28,31,68] omitting outcome measures at specific time points, [28,40,68] creation of nonstandard outcome measures by combining standard measures with other variables, [25,28,32,41,44,51,73] splitting outcome measures into subscales without providing total score, [39,58] failure to cross-reference data spread over several publications, [25,26,43,44] and including nonscaled graphs without providing corresponding means. [28,40,68] Data abstraction for most medication studies required mathematical conversion of provided data into mean total CAPS/SPRINT/PSS-I and SD.…”

The Post‐Deployment Mental Health (PDMH) study and repository: A multi‐site study of US Afghanistan and Iraq era veterans

“…Randomized 30 participants. Also see Table A2 for baseline analyses informing this trial. To recruit a target population for intervention study Naylor et al, 2015 Proof-of-concept randomized controlled trial of adjunctive aripiprazole in Operation Enduring Freedom (OEF)/Operation Iraqi Freedom (OIF) era veterans with PTSD resistant to antidepressant treatment. Randomized 16 participants. To recruit a target population for intervention study Other Brown, Strauss, et al, 2014 Compared 68 subjects with PTSD and 60 trauma-exposed non-PTSD controls.…”

Pharmacogenetics and Pharmacotherapy of Military Personnel Suffering from Post-traumatic Stress Disorder

“…This class of drugs exerts lower side effects compared to older antagonists. Aripiprazole was tested among military personnel as adjunctive therapy, if anti- depressants were ineffective [ 91 , 92 ]. The outcomes of these studies have been positive regarding reduction of overall symptoms and safety, but have to be supported by further studies with larger numbers of participants and placebo controls.…”