Treatment of posttraumatic stress disorder
INTRODUCTION — Posttraumatic stress disorder (PTSD) has been described as "the complex somatic, cognitive, affective and behavioral effects of psychological trauma" . 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 psychotherapy. 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 treatment of PTSD is addressed in this topic. The epidemiology, pathophysiology, clinical manifestations, and diagnosis of PTSD are discussed separately.
TREATMENT — Due to the complex nature of the disorder, individuals with PTSD may benefit most from long-term multifaceted treatment . Initial treatment can consist of either medication or psychotherapy based on patient preference and treatment availability; neither has consistenly been shown to be superior to the other in clinical trials. Combined medication and psychotherapy should be offered to patients who do not respond adequately to either modality individually.
The diagnosis of PTSD is made after persistence of symptoms for at least four weeks after the trauma. Ideally, treatment should be initiated shortly after diagnosis. Early treatment of PTSD may prevent chronicity .
Pharmacologic therapy — The therapeutic goals of pharmacologic therapy are to decrease intrusive thoughts and images, phobic avoidance, pathological hyperarousal, vigilance, impulsivity, and depression. Drug therapies have been most effective in decreasing arousal and the reexperiencing of symptoms such as nightmares and flashbacks (positive symptoms of PTSD), and generally less effective for the symptoms of avoidance, numbing, and withdrawal (negative symptoms).
If effective, medication should be continued for at least a year to prevent relapse or recurrence.
Serotonin reuptake inhibitors — Selective serotonin reuptake inhibitors (SSRIs) are first-line medications for the treatment of PTSD. In a meta-analysis of seven randomized trials, patients treated with SSRIs were more likely to experience improvement in symptoms and functioning than the group receiving placebo (RR 1.59, 95% CI 1.39 to 1.82) . Symptoms of PTSD responsive to SSRIs include flashbacks, arousal, and avoidance [5-7].
Research indicates that continuing the SSRI for at least six months in patients who respond to the medication reduces the rate of relapse .
SSRIs are typically started at the low end of their therapeutic range and titrated up gradually if the patient does not respond to the initial dose. Lower starting doses are used for patients who may be more sensitive to side effects. Usual starting doses, low starting doses, and therapeutic dose ranges for commonly used SSRIs are shown in a table (table 1).
SSRI oral dosage (adult) for treatment of post-traumatic stress disorder (PTSD)
|Usual starting dose, mg||Low starting dose, mg||Therapeutic dose (daily), mg|
|Paroxetine||20||5 to 10||20 to 60|
|Sertraline||50||12.5 to 25||50 to 200|
|Fluvoxamine||50||25||100 to 300*|
|Fluoxetine||20||5||20 to 60|
|Citalopram||20||10||20 to 60|
* If an immediate release preparation of fluvoxamine is used, dose shown in table should be given in two divided doses.
Common side effects include jitteriness, restlessness, agitation, headache, gastrointestinal symptoms (diarrhea and nausea), and insomnia. As many as half of men and women develop sexual side effects after several weeks or months of SSRI therapy . These adverse effects can lead to medication discontinuation. The management of SSRI-induced sexual dysfunction is discussed separately.
Other antidepressants — Tricyclic antidepressants decrease intrusive nightmares and flashbacks . They are generally poor for treating avoidance and numbing, although amitriptyline improved avoidance symptoms in one study . Treatment of coexisting depression will improve most symptoms of PTSD, particularly avoidance and numbing. Tricyclics are generally less well tolerated than SSRIs and not considered first-line agents. Side effects include sedation, weight gain, sexual dysfunction, orthostasis, and exacerbation of problems with cardiac conduction.
Monoamine oxidase inhibitors are effective in decreasing intrusive thoughts, nightmares, and flashbacks . However, side effects and dietary restrictions limit their use to cases with an inadequate response to other antidepressants.
Atypical antipsychotics — Patients with symptoms refractory to SSRIs can be treated with atypical antipsychotics [2,12]. A meta-analysis of seven randomized trials suggest that atypical antipsychotic medications reduce PTSD compared to placebo [4,13]. The trials were small (an average of 16 patients) and studied a mix of monotherapy and different adjunctive combinations.
Benzodiazepines — Benzodiazepines are generally ineffective in PTSD, which is surprising considering the constellation of anxiety, jitteriness, hyperarousal, and autonomic instability commonly observed in these patients. One study comparing alprazolam and placebo found a modest reduction of anxiety in patients with PTSD, although symptoms specific to PTSD were not changed . Given the prevalence of comorbid substance abuse in patients with PTSD and the lack of efficacy, benzodiazepines should generally be avoided.
Mood stabilizers — Anticonvulsant medications with demonstrated mood-stabilizing properties for other psychiatric disorders, includingcarbamazepine, valproic acid, and lamotrigine, may be effective in treating impulsive behavior, hyperarousal, and flashbacks in patients with PTSD . Adequately powered, randomized trials have not been conducted.
Alpha blockers — In several, small randomized trials, prazosin decreased nightmares, but did not substantially affect other symptoms of PTSD [16-18]. Side effects include orthostasis, headache, and lethargy.
Psychotherapy — Several types of psychotherapy have been shown to reduce symptoms of PTSD, including trauma-focused cognitive-behavioral therapy (CBT), stress management, and eye movement desensitization and reprocessing (EMDR) [2,19,20].
Trauma-focused cognitive behavioral therapy — Cognitive components of trauma-focused CBT involve helping the patient identify and challenge distorted thinking patterns related to themselves and the trauma they experienced. Behavioral interventions include gradual re-exposure to memories or reminders of the trauma, with resulting desensitization to them. In a meta-analysis of 14 randomized trials, patients showed a greater reduction of PTSD symptoms from trauma-focused CBT than patients receiving usual care . Trauma-focused CBT has been found to be effective when delivered to individuals or groups. Research studies have also demonstrated the effectiveness of cognitive therapy or behavioral therapy when these components are delivered separately [1,20].
Stress management — Stress management includes various therapies that have cognitive and/or behavioral components but do not focus on the patient's traumatic experiences. In three trials involving 86 patients, stress management reduced PTSD symptoms more effectively than usual care .
Eye movement desensitization and reprocessing — Eye movement desensitization and reprocessing (EMDR) involves the patient recalling and visualizing the traumatic experience while making repeated eye movements. EMDR has been found to reduce PTSD symptoms compared to usual care in five trials with a total of 162 patients . The treatment has raised controversy, and evidence suggests exposure is the effective component of the therapy, and eye movements may not be necessary [20,21].
Psychodynamic psychotherapy — Psychodynamic therapy draws on psychoanalysis, object relations, and other conceptual foundations to help patients explore their distress, development, and relationships, and examine their motives, needs, and defenses. Psychodynamic psychotherapy has not been adequately studied in randomized trials. Based on clinician experience and observational trials, American Psychiatric Association practice guidelines suggest that psychodynamic psychotherapy may be helpful for PTSD .
Combined medication and psychotherapy — Although widely used, the combination of medication and psychotherapy for PTSD has not been compared to either modality alone in randomized trials .
Conceptually, the combination of treatments may be complementary. As described above, medications are most effective for "positive symptoms" of PTSD, eg, arousal, nightmares, and flashbacks, while psychotherapy can be effective for associated, "negative symptoms" including avoidance, numbing, and withdrawal.
PREVENTION — Pharmacologic and psychological interventions have been tested for use in the aftermath of traumatic events, but neither has been shown to prevent onset of PTSD in randomized trials.
Morphine — A recent observational study examined use of morphine early in the treatment of trauma. A retrospective study of 696 US military personnel who experienced physical trauma compared the rate of morphine use during early trauma care between those who subsequently developed PTSD and those who did not. Subjects with PTSD were less likely to have received morphine (OR 0.48, 95% CI 0.34 - 0.68) . These results need replication in both observational and double blind trials. A similar, dose-related association between morphine use and subsequent development of PTSD was observed in an earlier analysis of 24 children who received inpatient medical care for treatment of acute burns .
Other medications — In small, preliminary investigations of a preventative role for other agents, evidence for propranolol was mixed [24,25] and studies of benzodiazepines  and gabapentin  were negative.
Psychological debriefing — Despite extensive use following disasters and other traumatic events, psychological debriefing has been found to be ineffective in preventing PTSD [27,28]. Also known as "critical incident stress debriefing", the intervention involves recollecting, articulating, and reworking of the traumatic event. Meta-analyses of numerous clinical trials found no evidence of effectiveness for either the initial, single-session intervention  or for subsequent, multiple-session versions .
SUMMARY AND RECOMMENDATIONS
- We recommend treatment of PTSD with either selective serotonin reuptake inhibitors (SSRIs) or trauma-focused cognitive behavioral therapy (CBT) (Grade 1A). Because clinical trials do not support one modality over the other, the selection between SSRIs and CBT should be determined by patient preference and treatment availability.
- Combined treatment with SSRIs and trauma-focused CBT has not been shown to be superior to the individual treatments for Posttraumatic stress disorder (PTSD). However, combined treatment can be considered for patients with an inadequate response to a single modality.
- We suggest prescribing SSRIs for PTSD before other pharmacotherapies with evidence of efficacy for the disorder, including mood stabilizers, prazosin, and atypical antipsychotics (Grade 2B) .
- In addition to trauma-focused CBT, stress management and EMDR are effective psychotherapies for PTSD, although the role of eye movements in EMDR is a subject of controversy.
- Psychological debriefing in the aftermath of a traumatic event has been found to be ineffective in preventing the development of PTSD.
- Holbrook, TL, Galarneau, MR, Dye, JL, et al. Morphine use after combat injury in Iraq and post-traumatic stress disorder. N Engl J Med 2010; 362:110.
- 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.
- Ballenger, JC, Davidson, JR, Lecrubier, Y, et al. Consensus statement update on posttraumatic stress disorder from the international consensus group on depression and anxiety. J Clin Psychiatry 2004; 65 Suppl 1:55.
- Stein, DJ, Ipser, JC, Seedat, S. Pharmacotherapy for post traumatic stress disorder (PTSD). Cochrane Database Syst Rev 2006; :CD002795.
- McDougle, CJ, Southwick, SM, Charney, DS, St James, RL. An open trial of fluoxetine in the treatment of posttraumatic stress disorder. J Clin Psychopharmacol 1991; 11:325.
- Kline, NA, Dow, BM, Brown, SA, Matloff, JL. Sertraline efficacy in depressed combat veterans with posttraumatic stress disorder. Am J Psychiatry 1994; 151:621.
- Brady, K, Pearlstein, T, Asnis, GM, et al. Efficacy and safety of sertraline treatment of posttraumatic stress disorder: a randomized controlled trial. JAMA 2000; 283:1837.
- 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.
- Ekselius, L, von Knorring, L. Effect on sexual function of long-term treatment with selective serotonin reuptake inhibitors in depressed patients treated in primary care. J Clin Psychopharmacol 2001; 21:154.
- Frank, JB, Kosten, TR, Giller EL, Jr, Dan, E. A randomized clinical trial of phenelzine and imipramine for posttraumatic stress disorder. Am J Psychiatry 1988; 145:1289.
- Davidson, J, Kudler, H, Smith, R, et al. Treatment of posttraumatic stress disorder with amitriptyline and placebo. Arch Gen Psychiatry 1990; 47:259.
- Vieweg, WV, Julius, DA, Fernandez, A, et al. Posttraumatic stress disorder: clinical features, pathophysiology, and treatment. Am J Med 2006; 119:383.
- Pae, CU, Lim, HK, Peindl, K, et al. The atypical antipsychotics olanzapine and risperidone in the treatment of posttraumatic stress disorder: a meta-analysis of randomized, double-blind, placebo-controlled clinical trials. Int Clin Psychopharmacol 2008; 23:1.
- Braun, P, Greenberg, D, Dasberg, H, Lerer, B. Core symptoms of posttraumatic stress disorder unimproved by alprazolam treatment. J Clin Psychiatry 1990; 51:236.
- Berlin, HA. Antiepileptic drugs for the treatment of post-traumatic stress disorder. Curr Psychiatry Rep 2007; 9:291.
- 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.
- Miller, LJ. Prazosin for the treatment of posttraumatic stress disorder sleep disturbances. Pharmacotherapy 2008; 28:656.
- 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.
- Bradley, R, Greene, J, Russ, E, et al. A multidimensional meta-analysis of psychotherapy for PTSD. Am J Psychiatry 2005; 162:214.
- Bisson, J, Andrew, M. Psychological treatment of post-traumatic stress disorder (PTSD). Cochrane Database Syst Rev 2005; :CD003388.
- Davidson, PR, Parker, KC. Eye movement desensitization and reprocessing (EMDR): a meta-analysis. J Consult Clin Psychol 2001; 69:305.
- Black, DW. Efficacy of combined pharmacotherapy and psychotherapy versus monotherapy in the treatment of anxiety disorders. CNS Spectr 2006; 11:29.
- Saxe, G, Stoddard, F, Courtney, D, et al. Relationship between acute morphine and the course of PTSD in children with burns. J Am Acad Child Adolesc Psychiatry 2001; 40:915.
- Vaiva, G, Ducrocq, F, Jezequel, K, et al. Immediate treatment with propranolol decreases posttraumatic stress disorder two months after trauma. Biol Psychiatry 2003; 54:947.
- Stein, MB, Kerridge, C, Dimsdale, JE, Hoyt, DB. Pharmacotherapy to prevent PTSD: Results from a randomized controlled proof-of-concept trial in physically injured patients. J Trauma Stress 2007; 20:923.
- Gelpin, E, Bonne, O, Peri, T, et al. Treatment of recent trauma survivors with benzodiazepines: a prospective study. J Clin Psychiatry 1996; 57:390.
- Rose, S, Bisson, J, Churchill, R, Wessely, S. Psychological debriefing for preventing post traumatic stress disorder (PTSD). Cochrane Database Syst Rev 2002; :CD000560.
- Roberts, NP, Kitchiner, NJ, Kenardy, J, Bisson, J. Multiple session early psychological interventions for the prevention of post-traumatic stress disorder. Cochrane Database Syst Rev 2009; :CD006869.