Randomized, double-blind comparison of sertraline and placebo for posttraumatic stress disorder in a Department of Veterans Affairs setting
Friedman MJ, Marmar CR, Baker DG, Sikes CR, Farfel GM;
Commented by , 29 Jun 2007
Aim of the study
Is sertraline superior to placebo in the treatment of post traumatic stress disorder (PTSD) in a predominately military (combat-related PTSD) population?
Method
Participants (N=169) were recruited from 10 Veterans Affairs medical centres in the United States between May 1994 to September 1996, and randomised to receive either placebo (n=83; 16 women) or sertraline (up to 200 mg/day; n= 86; 18 women) for 12 weeks following a 1 week placebo run-in, in a flexible dose, double-blind design.
Inclusion criteria
DSM-III-R diagnosis of PTSD as determined by Part 1 of the Clinician Administered PTSD Scale (CAPS-1), with a 6 month illness duration required; score > 50 on CAPS-2; over 18 years; literate.
Exclusion criteria included
Poor response to previous pharmacological treatment; positive urine screen for drugs at study entry; current Axis I mood or anxiety disorder, current or past schizophrenia/psychotic symptoms, physical illness, pregnant, personality disorder other than Cluster C; using other medications within 2 weeks (5 weeks for fluoxetine) of study commencing (except chloral hydrate for sleep); and current involvement in litigation associated with the traumatic event.
The primary efficacy measures included the mean change from baseline to week 12 in the total severity score of the CAPS-2, the Impact of Events Scale (IES), the Clinician Global Impressions - Severity and Clinician Global Impression – Improvement scales.
Results
Mean dose sertraline 135 mg/day. No significant differences were demonstrated between placebo and sertraline on any outcome measure. There were no consistent effects of gender, illness duration or past alcohol/substance abuse on primary outcome measures.
Dr Hood's and Prof Nutt's comments
SSRI antidepressants are first-line pharmacological treatments of PTSD (ref. 1, ref. 2) with robust effects seen in large previous studies of sertraline in civilian populations (ref. 3, ref. 4). This study by Friedman and colleagues failed to find evidence of efficacy of sertraline in a veterans population, despite a comprehensive analysis of potential moderator variables.
There was some evidence, however, of efficacy of sertraline in subjects with non-combat related traumas – prompting the possibility that sertraline is only effective in persons with civilian trauma. Whilst the authors make a decent case for why this is not true (including an argument for the treatment refractoriness of Vietnam veterans with PTSD), we are not entirely convinced and would like to see ongoing research to address this issue.
Such research into PTSD treatment predictors could complement findings such as that from Davidson and colleagues (ref. 5) that a marked improvement in anger/irritability after one week on sertraline may be a useful prognosticator of eventual response.
In the current academic climate we are pleased to see a large "negative" study such as this published in a major psychiatric journal, albeit delayed. Although the inclusion of such negative studies may be challenging to interpret and can raise more questions than they answer they do add a much needed balanced perspective.
References
1. Http://ipap.org/ptsd/contents.php. 20-5-2007
2. Ballenger JC, Davidson JR, Lecrubier Y, Nutt DJ, Marshall RD, Nemeroff CB, et al. Consensus statement update on posttraumatic stress disorder from the international consensus group on depression and anxiety. Journal of Clinical Psychiatry 2004 ;65 Suppl. 1; 55-62
3. Brady K, Pearlstein T, Asnis GM, Baker D, Rothbaum B, Sikes CR, et al. Efficacy and safety of sertraline treatment of posttraumatic stress disorder: a randomized controlled trial. JAMA 2000; 283(14);1837-1844
4. Davidson JR, Rothbaum BO, van der Kolk BA, Sikes CR, Farfel GM. Multicenter, double-blind comparison of sertraline and placebo in the treatment of posttraumatic stress disorder. Archives of General Psychiatry 2001; 58 (5); 485-492
5. Davidson J, Landerman LR, Clary CM Improvement of anger at one week predicts the effects of sertraline and placebo in PTSD. Journal of Psychiatric Research 2004; 38(5); 497-502