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Evidence-based pharmacotherapy of post-traumatic stress disorder (PTSD)

  • Jonathan C. Ipser (a1) and Dan J. Stein (a1)
Abstract
Abstract

Post-traumatic stress disorder (PTSD) is a prevalent and disabling disorder. Recognition of neurobiological abnormalities associated with this condition suggests the potential efficacy of medication in its treatment. Nevertheless, questions regarding the efficacy of medications remain, despite general endorsement by clinical practice guidelines of selective serotonin reuptake inhibitors (SSRIs) as first-line agents in treating PTSD. This paper reviews evidence from randomized controlled trials (RCTs) for the efficacy of acute and long-term pharmacotherapy for PTSD, including the treatment of refractory PTSD. In addition, we conducted a systematic meta-analysis to compare the efficacy of different medications in treating PTSD. The effects of methodological study features (including year of publication, duration, number of centres) and sample characteristics (proportion of combat veterans, gender composition) were also tested. The largest body of evidence for short- and long-term efficacy of medication currently exists for SSRIs, with promising initial findings for the selective noradrenergic reuptake inhibitor venlafaxine and the atypical antipsychotic risperidone. Treatment effect was predicted by number of centres and recency of the study, with little evidence that sample characteristics predicted response. Evidence for the effectiveness of benzodiazepines is lacking, despite their continued use in clinical practice. Finally, the α1 antagonist prazosin and the atypical antipsychotics show some efficacy in treatment-resistant PTSD. Adequately powered trials that are designed in accordance with best-practice guidelines are required to provide conclusive evidence of clinically relevant differences in efficacy between agents in treating PTSD, and to help estimate clinical and methodological predictors of treatment response.

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Corresponding author
Address for correspondence: Mr J. C. Ipser, Department of Psychiatry, University of Cape Town, Cape Town, South Africa. Tel.: +1 347 364 7366Fax: +27 21 448 8158Email: jonathanipser@gmail.com
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M Adamou , S Puchalska , W Plummer , AS Hale (2007). Valproate in the treatment of PTSD: systematic review and meta analysis. Current Medical Research and Opinion 23, 12851291.

DG Baker , BI Diamond , G Gillette , M Hamner , (1995). A double-blind, randomized, placebo-controlled, multi-center study of brofaromine in the treatment of post-traumatic stress disorder. Psychopharmacology (Berlin) 122, 386389.

B Bandelow , J Zohar , E Hollander , S Kasper , (2008). World federation of societies of biological psychiatry (WFSBP) guidelines for the pharmacological treatment of anxiety, obsessive-compulsive and post-traumatic stress disorders – first revision. World Journal of Biological Psychiatry 9, 248312.

G Bartzokis , PH Lu , J Turner , J Mintz , (2005). Adjunctive risperidone in the treatment of chronic combat-related posttraumatic stress disorder. Biological Psychiatry 57, 474479.

DD Blake , FW Weathers , LM Nagy , DG Kaloupek , (1995). The development of a clinician-Administered PTSD scale. Journal of Traumatic Stress 8, 7590.

K Brady , T Pearlstein , GM Asnis , D Baker , (2000). Efficacy and safety of sertraline treatment of posttraumatic stress disorder: a randomized controlled trial. Journal of the American Medical Association 283, 18371844.

KT Brady , S Sonne , RF Anton , CL Randall , (2005). Sertraline in the treatment of co-occurring alcohol dependence and posttraumatic stress disorder. Alcoholism: Clinical and Experimental Research 29, 395401.

N Breslau , RC Kessler , HD Chilcoat , LR Schultz , (1998). Trauma and posttraumatic stress disorder in the community: the 1996 detroit area survey of trauma. Archives of General Psychiatry 55, 626632.

N Brunello , JR Davidson , M Deahl , RC Kessler , (2001). Posttraumatic stress disorder: diagnosis and epidemiology, comorbidity and social consequences, biology and treatment. Neuropsychobiology 43, 150162.

MI Butterfield , ME Becker , KM Connor , S Sutherland , (2001). Olanzapine in the treatment of post-traumatic stress disorder: a pilot study. International Clinical Psychopharmacology 16, 197203.

J-M Cloos , V Ferreira (2009). Current use of benzodiazepines in anxiety disorders. Current Opinion in Psychiatry 22, 9095.

KM Connor , JR Davidson (1999). Further psychometric assessment of the TOP-8: a brief interview-based measure of PTSD. Depression and Anxiety 9, 135137.

KM Connor , JR Davidson , RH Weisler , W Zhang , (2006). Tiagabine for posttraumatic stress disorder: effects of open-label and double-blind discontinuation treatment. Psychopharmacology 184, 2125.

KM Connor , SM Sutherland , LA Tupler , ML Malik , (1999). Fluoxetine in post-traumatic stress disorder. randomised, double-blind study. British Journal of Psychiatry 175, 1722.

J Davidson , D Baldwin , DJ Stein , E Kuper , (2006 a). Treatment of posttraumatic stress disorder with venlafaxine extended release: a 6-month randomized controlled trial. Archives of General Psychiatry 63, 11581165.

J Davidson , H Kudler , R Smith , SL Mahorney , (1990). Treatment of posttraumatic stress disorder with amitriptyline and placebo. Archives of General Psychiatry 47, 259266.

J Davidson , T Pearlstein , P Londborg , KT Brady , (2001 a). Efficacy of sertraline in preventing relapse of posttraumatic stress disorder: results of a 28-week double-blind, placebo-controlled study. American Journal of Psychiatry 158, 19741981.

J Davidson , BO Rothbaum , P Tucker , G Asnis , (2006 b). Venlafaxine extended release in posttraumatic stress disorder: a sertraline- and placebo-controlled study. Journal of Clinical Psychopharmacology 26, 259267.

JR Davidson , SW Book , JT Colket , LA Tupler , (1997). Assessment of a new self-rating scale for post-traumatic stress disorder. Psychological Medicine 27, 153160.

JR Davidson , KM Connor , MA Hertzberg , RH Weisler , (2005). Maintenance therapy with fluoxetine in posttraumatic stress disorder: a placebo-controlled discontinuation study. Journal of Clinical Psychopharmacology 25, 166169.

JR Davidson , BO Rothbaum , BA van der Kolk , CR Sikes , (2001 b). Multicenter, double-blind comparison of sertraline and placebo in the treatment of posttraumatic stress disorder. Archives of General Psychiatry 58, 485492.

JR Davidson , RH Weisler , MI Butterfield , CD Casat , (2003). Mirtazapine vs. placebo in posttraumatic stress disorder: a pilot trial. Biological Psychiatry 53, 188191.

JRT Davidson , K Brady , TA Mellman , MB Stein , (2007). The efficacy and tolerability of tiagabine in adult patients with post-traumatic stress disorder. Journal of Clinical Psychopharmacology 27, 8588.

LL Davis , JR Davidson , LC Ward , A Bartolucci , (2008). Divalproex in the treatment of posttraumatic stress disorder: a randomized, double-blind, placebo-controlled trial in a veteran population. Journal of Clinical Psychopharmacology 28, 8488.

LL Davis , ME Jewell , S Ambrose , J Farley , (2004). A placebo-controlled study of nefazodone for the treatment of chronic posttraumatic stress disorder: a preliminary study. Journal of Clinical Psychopharmacology 24, 291297.

J Deeks , D Altman , M Bradburn (2001). Statistical methods for examining heterogeneity and combining results from several studies in meta-analysis. In: M Egger , SG Davey , DG Altman (Eds), Systematic Reviews in Health Care: Meta-Analysis in Context (pp. 285312). London: BMJ Publication Group.

R DerSimonian , N Laird (1986). Meta-analysis in clinical trials. Controlled Clinical Trials 7, 177188.

M Egger , GD Smith , M Schneider , C Minder (1997). Bias in meta-analysis detected by a simple, graphical test. British Medical Journal 315, 629634.

O Frans , P-A Rimmö , L Aberg , M Fredrikson (2005). Trauma exposure and post-traumatic stress disorder in the general population. Acta Psychiatrica Scandinavica 111, 291299.

MJ Friedman , CR Marmar , DG Baker , CR Sikes , (2007). Randomized, double-blind comparison of sertraline and placebo for posttraumatic stress disorder in a department of veterans affairs setting. Journal of Clinical Psychiatry 68, 711720.

MB Hamner , RA Faldowski , HG Ulmer , BC Frueh , (2003). Adjunctive risperidone treatment in post-traumatic stress disorder: a preliminary controlled trial of effects on comorbid psychotic symptoms. International Clinical Psychopharmacology 18, 18.

MA Hertzberg , MI Butterfield , ME Feldman , JC Beckham , (1999). A preliminary study of lamotrigine for the treatment of posttraumatic stress disorder. Biological Psychiatry 45, 12261229.

MA Hertzberg , ME Feldman , JC Beckham , HS Kudler , (2000). Lack of efficacy for fluoxetine in PTSD: a placebo controlled trial in combat veterans. Annals of Clinical Psychiatry 12, 101105.

JC Ipser , P Carey , Y Dhansay , N Fakier , (2006). Pharmacotherapy augmentation strategies in treatment-resistant anxiety disorders. Cochrane Database of Systematic Reviews. Issue No. 4. Art. No. CD005473.

Z Kaplan , M Amir , M Swartz , J Levine (1996). Inositol treatment of post-traumatic stress disorder. Anxiety 2, 5152.

RJ Katz , MH Lott , P Arbus , L Crocq , (1994). Pharmacotherapy of post-traumatic stress disorder with a novel psychotropic. Anxiety 1, 169174.

RC Kessler , P Berglund , O Demler , R Jin , (2005). Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the national comorbidity survey replication. Archives of General Psychiatry 62, 593602.

TR Kosten , JB Frank , E Dan , CJ McDougle , (1991). Pharmacotherapy for posttraumatic stress disorder using phenelzine or imipramine. Journal of Nervous and Mental Disease 179, 366370.

PD Londborg , MT Hegel , S Goldstein , D Goldstein , (2001). Sertraline treatment of posttraumatic stress disorder: results of 24 weeks of open-label continuation treatment. Journal of Clinical Psychiatry 62, 325331.

RD Marshall , KL Beebe , M Oldham , R Zaninelli (2001). Efficacy and safety of paroxetine treatment for chronic PTSD: a fixed-dose, placebo-controlled study. American Journal of Psychiatry 158, 19821988.

RD Marshall , R Lewis-Fernandez , C Blanco , HB Simpson , (2007). A controlled trial of paroxetine for chronic PTSD, dissociation, and interpersonal problems in mostly minority adults. Depression and Anxiety 24, 7784.

F Martenyi , EB Brown , CD Caldwell (2007). Failed efficacy of fluoxetine in the treatment of posttraumatic stress disorder: results of a fixed-dose, placebo-controlled study. Journal of Clinical Psychopharmacology 27, 166170.

F Martenyi , EB Brown , H Zhang , SC Koke , (2002 a). Fluoxetine v. placebo in prevention of relapse in post-traumatic stress disorder. British Journal of Psychiatry 181, 315320.

F Martenyi , EB Brown , H Zhang , A Prakash , (2002 b). Fluoxetine vs. placebo in posttraumatic stress disorder. Journal of Clinical Psychiatry 63, 199206.


PR Padala , J Madison , M Monnahan , W Marcil , (2006). Risperidone monotherapy for post-traumatic stress disorder related to sexual assault and domestic abuse in women. International Clinical Psychopharmacology 21, 275280.

SJ Penava , MW Otto , MH Pollack , JF Rosenbaum (1996). Current status of pharmacotherapy for PTSD: an effect size analysis of controlled studies. Depression and Anxiety 4, 240242.

RM Post , E Chalecka-Franaszek , CJ Hough (2003). Mechanisms of action of anticonvulsants and new mood stablizers. In: JC Soares , S Gershon (Eds), Handbook of Medical Psychiatry (pp. 767791). New York: Marcel Dekker Inc.

MA Raskind , ER Peskind , ED Kanter , EC Petrie , (2003). Reduction of nightmares and other PTSD symptoms in combat veterans by prazosin: a placebo-controlled study. American Journal of Psychiatry 160, 371373.

DB Reich , S Winternitz , J Hennen , T Watts , (2004). A preliminary study of risperidone in the treatment of posttraumatic stress disorder related to childhood abuse in women. Journal of Clinical Psychiatry 65, 16011606.

BO Rothbaum , TK Killeen , JR Davidson , KT Brady , (2008). Placebo-controlled trial of risperidone augmentation for selective serotonin reuptake inhibitor-resistant civilian posttraumatic stress disorder. Journal of Clinical Psychiatry 69, 520525.

S Seedat , MB Stein , PP Oosthuizen , RA Emsley , (2003). Linking posttraumatic stress disorder and psychosis: a look at epidemiology, phenomenology, and treatment. Journal of Nervous and Mental Disease 191, 675681.

M Shestatzky , D Greenberg , B Lerer (1988). A controlled trial of phenelzine in posttraumatic stress disorder. Psychiatry Research 24, 149155.

SM Stahl , MM Grady , C Moret , M Briley (2005). SNRIs: the pharmacology, clinical efficacy, and tolerability in comparison with other classes of antidepressants. CNS Spectrums 10, 732747.

DJ Stein , JC Ipser , S Seedat (2006). Pharmacotherapy for post traumatic stress disorder (PTSD). Cochrane Database of Systematic Reviews. Issue No. 1. Art. No. CD002795.

MB Stein , NA Kline , JL Matloff (2002). Adjunctive olanzapine for SSRI-resistant combat-related PTSD: a double-blind, placebo-controlled study. American Journal of Psychiatry 159, 17771779.

C Stewart , T Wrobel (2009). Evaluation of the efficacy of pharmacotherapy and psychotherapy in treatment of combat-related post-traumatic stress disorder: a meta-analytic review of outcome studies. Military Medicine 174, 460469.

FB Taylor , P Martin , C Thompson , J Williams , (2008). Prazosin effects on objective sleep measures and clinical symptoms in civilian trauma posttraumatic stress disorder: a placebo-controlled study 22. Biological Psychiatry 63, 629632.

P Tucker , RP Trautman , DB Wyatt , J Thompson , (2007). Efficacy and safety of topiramate monotherapy in civilian posttraumatic stress disorder: a randomized, double-blind, placebo-controlled study. Journal of Clinical Psychiatry 68, 201206.

P Tucker , R Zaninelli , R Yehuda , L Ruggiero , (2001). Paroxetine in the treatment of chronic posttraumatic stress disorder: results of a placebo-controlled, flexible-dosage trial. Journal of Clinical Psychiatry 62, 860868.

BA van der Kolk , D Dreyfuss , M Michaels , D Shera , (1994). Fluoxetine in posttraumatic stress disorder. Journal of Clinical Psychiatry 55, 517522.

BA van der Kolk , J Spinazzola , ME Blaustein , JW Hopper , (2007). A randomized clinical trial of eye movement desensitization and reprocessing (EMDR), fluoxetine, and pill placebo in the treatment of posttraumatic stress disorder: treatment effects and long-term maintenance. Journal of Clinical Psychiatry 68, 3746.

ML Van Etten , S Taylor (1998). Comparative efficacy of treatments for post-traumatic stress disorder: a meta-Analysis. Clinical Psychology and Psychotherapy 5, 126144.

W Viechtbauer (2010). Conducting meta-analyses in R with the metafor package. Journal of Statistical Software 36, 148.

J Zohar , D Amital , C Miodownik , M Kotler , (2002). Double-blind placebo-controlled pilot study of sertraline in military veterans with posttraumatic stress disorder. Journal of Clinical Psychopharmacology 22, 190195.

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