Pharmacotherapy for posttraumatic stress disorder in adults
- Murray B Stein, MD, MPH
Murray B Stein, MD, MPH
- Editor-in-Chief — Psychiatry
- Section Editor — Anxiety Disorders
- Professor of Psychiatry and Family Medicine & Public Health
- University of California San Diego
Posttraumatic stress disorder (PTSD) is a severe, often chronic and disabling disorder, which develops in some persons following exposure to a traumatic event involving actual or threatened injury to themselves or others. PTSD is characterized by intrusive thoughts, nightmares and flashbacks of past traumatic events, avoidance of reminders of trauma, hypervigilance, and sleep disturbance, all of which lead to considerable social, occupational, and interpersonal dysfunction.
Effective treatments for PTSD include medications and psychotherapies. However, a substantial proportion of patients have symptoms resistant to treatment. It is often necessary to switch or combine treatments to achieve a satisfactory therapeutic response.
The pharmacological treatment of PTSD is addressed in this topic. The epidemiology, pathophysiology, clinical manifestations, and diagnosis of PTSD are discussed separately, as is psychotherapy for PTSD. The epidemiology, pathophysiology, clinical manifestations, diagnosis, and treatment of acute stress disorder are also discussed separately. (See "Posttraumatic stress disorder in adults: Epidemiology, pathophysiology, clinical manifestations, course, assessment, and diagnosis" and "Psychotherapy for posttraumatic stress disorder in adults" and "Acute stress disorder in adults: Epidemiology, pathogenesis, clinical manifestations, course, and diagnosis" and "Treatment of acute stress disorder in adults".)
Treatment should optimally be initiated shortly after diagnosis. The diagnosis of PTSD is made after persistence of symptoms for at least four weeks following the trauma, but most patients present for treatment many months, or sometimes years, later. In theory, early treatment of PTSD may prevent chronicity, but this not been shown empirically, particularly for pharmacotherapy .
The therapeutic goals of pharmacologic therapy are to decrease intrusive thoughts and images, phobic avoidance, pathological hyperarousal, hypervigilance, irritability and anger, and depression. Drug therapies have generally been most effective in decreasing hyperarousal and mood (irritability, anger, depression) symptoms, and somewhat less effective for the symptoms of re-experiencing, emotional numbing, and behavioral avoidance, but individual differences in response generally outweigh treatment-specific differences. There is a great deal of variation in response to pharmacologic treatment, with few robust individual predictors of response available [2,3]. Some ancillary symptoms of PTSD, such as sleep disturbance, can be particularly difficult to treat, and are among the symptoms that result in the use of polypharmacy that is so common in the treatment of PTSD [4,5].
- Ursano RJ, Bell C, Eth S, et al. Practice guideline for the treatment of patients with acute stress disorder and posttraumatic stress disorder. Am J Psychiatry 2004; 161:3.
- Ravindran LN, Stein MB. Pharmacotherapy of PTSD: premises, principles, and priorities. Brain Res 2009; 1293:24.
- Ravindran LN, Stein MB. Anxiety Disorders: Somatic Treatment. In: Kaplan and Sadock Comprehensive Textbook of Psychiatry, 9th ed, Sadock BJ, Sadock VA, Ruiz P. (Eds), Lippincott Williams & Wilkins, Philadelphia, PA 2009. p.1906.
- Mohamed S, Rosenheck RA. Pharmacotherapy of PTSD in the U.S. Department of Veterans Affairs: diagnostic- and symptom-guided drug selection. J Clin Psychiatry 2008; 69:959.
- Harpaz-Rotem I, Rosenheck RA, Mohamed S, Desai RA. Pharmacologic treatment of posttraumatic stress disorder among privately insured Americans. Psychiatr Serv 2008; 59:1184.
- Stein DJ, Ipser JC, Seedat S. Pharmacotherapy for post traumatic stress disorder (PTSD). Cochrane Database Syst Rev 2006; :CD002795.
- Committee on Treatment of Posttraumatic Stress Disorder (Institute of Medicine). Treatment of Posttraumatic Stress Disorder: An Assessment of the Evidence, The National Academies Press, Washington, DC 2007.
- Davidson J, Baldwin D, Stein DJ, et al. Treatment of posttraumatic stress disorder with venlafaxine extended release: a 6-month randomized controlled trial. Arch Gen Psychiatry 2006; 63:1158.
- Davidson J, Rothbaum BO, Tucker P, et al. Venlafaxine extended release in posttraumatic stress disorder: a sertraline- and placebo-controlled study. J Clin Psychopharmacol 2006; 26:259.
- Villarreal G, Hamner MB, Cañive JM, et al. Efficacy of Quetiapine Monotherapy in Posttraumatic Stress Disorder: A Randomized, Placebo-Controlled Trial. Am J Psychiatry 2016; 173:1205.
- Carey P, Suliman S, Ganesan K, et al. Olanzapine monotherapy in posttraumatic stress disorder: efficacy in a randomized, double-blind, placebo-controlled study. Hum Psychopharmacol 2012; 27:386.
- Padala PR, Madison J, Monnahan M, et al. Risperidone monotherapy for post-traumatic stress disorder related to sexual assault and domestic abuse in women. Int Clin Psychopharmacol 2006; 21:275.
- Krystal JH, Rosenheck RA, Cramer JA, et al. Adjunctive risperidone treatment for antidepressant-resistant symptoms of chronic military service-related PTSD: a randomized trial. JAMA 2011; 306:493.
- Reich DB, Winternitz S, Hennen J, et al. A preliminary study of risperidone in the treatment of posttraumatic stress disorder related to childhood abuse in women. J Clin Psychiatry 2004; 65:1601.
- Rothbaum BO, Killeen TK, Davidson JR, et al. Placebo-controlled trial of risperidone augmentation for selective serotonin reuptake inhibitor-resistant civilian posttraumatic stress disorder. J Clin Psychiatry 2008; 69:520.
- Stein MB, Kline NA, Matloff JL. Adjunctive olanzapine for SSRI-resistant combat-related PTSD: a double-blind, placebo-controlled study. Am J Psychiatry 2002; 159:1777.
- Taylor FB, Martin P, Thompson C, et al. Prazosin effects on objective sleep measures and clinical symptoms in civilian trauma posttraumatic stress disorder: a placebo-controlled study. Biol Psychiatry 2008; 63:629.
- Raskind MA, Peskind ER, Hoff DJ, et al. A parallel group placebo controlled study of prazosin for trauma nightmares and sleep disturbance in combat veterans with post-traumatic stress disorder. Biol Psychiatry 2007; 61:928.
- Raskind MA, Peskind ER, Kanter ED, et al. Reduction of nightmares and other PTSD symptoms in combat veterans by prazosin: a placebo-controlled study. Am J Psychiatry 2003; 160:371.
- Raskind MA, Peterson K, Williams T, et al. A trial of prazosin for combat trauma PTSD with nightmares in active-duty soldiers returned from Iraq and Afghanistan. Am J Psychiatry 2013; 170:1003.
- Singh B, Hughes AJ, Mehta G, et al. Efficacy of Prazosin in Posttraumatic Stress Disorder: A Systematic Review and Meta-Analysis. Prim Care Companion CNS Disord 2016.
- Steenen SA, van Wijk AJ, van der Heijden GJ, et al. Propranolol for the treatment of anxiety disorders: Systematic review and meta-analysis. J Psychopharmacol 2016; 30:128.
- Rothbaum BO, Price M, Jovanovic T, et al. A randomized, double-blind evaluation of D-cycloserine or alprazolam combined with virtual reality exposure therapy for posttraumatic stress disorder in Iraq and Afghanistan War veterans. Am J Psychiatry 2014; 171:640.
- Davidson JR, Brady K, Mellman TA, et al. The efficacy and tolerability of tiagabine in adult patients with post-traumatic stress disorder. J Clin Psychopharmacol 2007; 27:85.
- Tucker P, Trautman RP, Wyatt DB, et al. Efficacy and safety of topiramate monotherapy in civilian posttraumatic stress disorder: a randomized, double-blind, placebo-controlled study. J Clin Psychiatry 2007; 68:201.
- Lindley SE, Carlson EB, Hill K. A randomized, double-blind, placebo-controlled trial of augmentation topiramate for chronic combat-related posttraumatic stress disorder. J Clin Psychopharmacol 2007; 27:677.
- Yeh MS, Mari JJ, Costa MC, et al. A double-blind randomized controlled trial to study the efficacy of topiramate in a civilian sample of PTSD. CNS Neurosci Ther 2011; 17:305.
- Davis LL, Davidson JR, Ward LC, et al. Divalproex in the treatment of posttraumatic stress disorder: a randomized, double-blind, placebo-controlled trial in a veteran population. J Clin Psychopharmacol 2008; 28:84.
- Hamner MB, Faldowski RA, Robert S, et al. A preliminary controlled trial of divalproex in posttraumatic stress disorder. Ann Clin Psychiatry 2009; 21:89.
- Feder A, Parides MK, Murrough JW, et al. Efficacy of intravenous ketamine for treatment of chronic posttraumatic stress disorder: a randomized clinical trial. JAMA Psychiatry 2014; 71:681.
- Davidson J, Pearlstein T, Londborg P, et al. Efficacy of sertraline in preventing relapse of posttraumatic stress disorder: results of a 28-week double-blind, placebo-controlled study. Am J Psychiatry 2001; 158:1974.
- Shalev AY, Ankri Y, Israeli-Shalev Y, et al. Prevention of posttraumatic stress disorder by early treatment: results from the Jerusalem Trauma Outreach And Prevention study. Arch Gen Psychiatry 2012; 69:166.
- Hetrick SE, Purcell R, Garner B, Parslow R. Combined pharmacotherapy and psychological therapies for post traumatic stress disorder (PTSD). Cochrane Database Syst Rev 2010; :CD007316.
- Rothbaum BO, Cahill SP, Foa EB, et al. Augmentation of sertraline with prolonged exposure in the treatment of posttraumatic stress disorder. J Trauma Stress 2006; 19:625.
- Simon NM, Connor KM, Lang AJ, et al. Paroxetine CR augmentation for posttraumatic stress disorder refractory to prolonged exposure therapy. J Clin Psychiatry 2008; 69:400.
- Schneier FR, Neria Y, Pavlicova M, et al. Combined prolonged exposure therapy and paroxetine for PTSD related to the World Trade Center attack: a randomized controlled trial. Am J Psychiatry 2012; 169:80.
- Norberg MM, Krystal JH, Tolin DF. A meta-analysis of D-cycloserine and the facilitation of fear extinction and exposure therapy. Biol Psychiatry 2008; 63:1118.
- Zatzick D, Jurkovich G, Rivara FP, et al. A randomized stepped care intervention trial targeting posttraumatic stress disorder for surgically hospitalized injury survivors. Ann Surg 2013; 257:390.
- Selective serotonin reuptake inhibitors
- - Administration
- Serotonin-norepinephrine reuptake inhibitors
- Other antidepressants
- Second-generation antipsychotics
- - Efficacy
- - Administration
- Alpha-adrenergic receptor blockers
- Beta-adrenergic receptor blockers
- Mood stabilizers
- COMPARING PHARMACOTHERAPY AND PSYCHOTHERAPY
- COMBINING PHARMACOTHERAPY AND PSYCHOTHERAPY
- SSRI antidepressants
- Stepped care in trauma surgery center
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS