Posttraumatic stress disorder (PTSD) is an anxiety disorder that occurs after severe psychological stress, eg, assault, combat, natural disasters, terrorism, or other stressors. The stressor induces intense fear or helplessness in the patient. Three symptom clusters are included in DSM-IV criteria for PTSD: re-experiencing the traumatic event, avoidance of reminders of the event and psychological numbing, and hyperarousal symptoms.
Re-experiencing symptoms may include intrusive memories of the trauma, nightmares, sudden acting or feeling as if the trauma were recurring, and psychological or physiological reactivity on exposure to reminders of the trauma. Avoidance symptoms may include avoidance of people, places, or situations that remind the individual of the traumatic event: psychological numbing, feelings of detachment from others, and a sense of a foreshortened future. Hyperarousal symptoms may include irritability, insomnia, difficulty concentrating, exaggerated startle responses, and hypervigilance. By definition, these symptoms should be present for at least 1 month after the trauma. Shorter duration of symptoms may be consistent with acute stress disorder.
Chronic PTSD potentially leads to significant disability with impairment in social and occupational function. The estimated lifetime prevalence of PTSD is about 7% to 8% in the United States.1 Two SSRIs are currently FDA-approved for the treatment of PTSD: sertraline and paroxetine. Both antidepressants demonstrated efficacy and tolerability in most of the regulatory trials. In fact, most antidepressants, including the tricyclics, monoamine oxidase inhibitors, other SSRIs, serotonin/norepinephrine reuptake inhibitors (SNRIs), and atypical antidepressants such as mirtazapine, have demonstrated efficacy at least in open-label studies.2
Given the heterogeneity of PTSD symptoms, as well as the potential for comorbidity (Figure), a number of other classes of psychotropics have been used alone or in combination with antidepressants. These include anticonvulsants, putative mood stabilizers, adrenergic blockers, anxiolytic medications, and second-generation antipsychotics.
The customary treatment of PTSD involves a combination of psychosocial interventions with medication management. Psychosocial therapy may include group therapy, education, supportive therapy, family therapy, and cognitive-behavioral psychotherapy (CBT) or prolonged exposure therapy (PE). To date, CBT or PE appear to be the most effective forms of psychotherapy for patients with PTSD. These modalities may be delivered either in group or individual settings.
To my knowledge, there is no commonly accepted definition of long-term treatment in PTSD. A duration of at least 3 months is a DSM-IV criterion for chronic PTSD. For the purposes of this article, treatment studies that exceeded 12 weeks were included.
Davis and colleagues2 have recently reviewed the literature on long-term pharmacological therapy of PTSD. This article summarizes those studies as well as some more recently published trials. Psychotherapeutic interventions alone or in combination with medication are also discussed.
Davidson and colleagues3 assessed the efficacy of sertraline compared with placebo in 96 patients who had completed a 12-week double-blind, placebo-controlled trial followed by a 24-week open-label treatment-continuation period. The study length was 28 weeks, and dosages of sertraline were flexible in the range of 50 to 200 mg daily. Forty-six patients were randomly selected to receive sertraline (78% were women) and 50 to receive placebo (62% were women).
Outcome measures included the Clinician-Administered PTSD Scale (CAPS), the Impact of Events Scale, and the Clinical Global Impression severity and improvement scales. Outcome parameters included rate of relapse and discontinuation because of clinical deterioration.
There were lower PTSD relapse rates in the group that received sertraline (5%) than in the placebo group (26%). Those in the placebo group were more than 6 times as likely to relapse as those receiving sertraline. All 3 PTSD symptom clusters remained improved in patients who did not relapse, and Kaplan-Meier analyses were consistent with an extended time in remission for the sertraline group.
Early response to treatment greatly reduced the risk for relapse in the placebo group. The mean dosage of 137 mg of sertraline daily was well tolerated. This study suggests that sertraline was helpful in the long-term prevention of relapse in patients with PTSD.
Rapaport and colleagues4 assessed quality of life (QOL) variables in patients with PTSD who were treated with sertraline over a 64-week treatment period. These data were derived from the study by Davidson and colleagues.3 Primary assessments included the Quality of Life Enjoyment and Satisfaction Questionaire (Q-LES-Q), emotional role functioning and mental health subscales of the Medical Outcomes Study 36-Item Short Form Survey, and occupational and social function items from the CAPS. At the end of the acute (12-week) treatment phase, 58% of sertraline responders had improvement in QOL measures (ie, had obtained a Q-LES-Q score within 20% of community norms). Compared with baseline, 24 weeks of continuation treatment resulted in an additional 10% improvement in QOL measures. Double-blind discontinuation of sertraline resulted in worsening QOL measures. These data support the notion that continuation and maintenance treatment with sertraline may not only improve symptoms of PTSD and prevent relapse but may also improve associated occupational and social impairment and quality of life.
1. Kessler RC, Sonnega A, Bromet E, et al. Posttraumatic stress disorder in the National Comorbidity Survey. Arch Gen Psychiatry. 1995;52:1048-1060.
2. Davis LL, Frazier EC, Williford RB, Newell JM. Long-term pharmacotherapy for post-traumatic stress disorder. CNS Drugs. 2006;20:465-476.
3. 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 study. Am J Psychiatry. 2001;158:1974-1981.
4. Rapaport MH, Endicott J, Clary CM. Posttraumatic stress disorder and quality of life: results across 64 weeks of sertraline treatment. J Clin Psychiatry. 2002; 63:59-65.
5. Davidson J, Rothbaum BO, Tucker P, et al. Venlafaxine extended release in posttraumatic stress disorder: a setraline- and placebo-controlled study [published correction appears in J Clin Psychopharmacol. 2006;26:473. Dosage error in text]. J Clin Psychopharmacol. 2006; 26:259-267.
6. 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;63:1158-1165.
7. Vermetten E, Vythilingam M, Southwick SM, et al. Long-term treatment with paroxetine increases verbal declarative memory and hippocampal volume in posttraumatic stress disorder.Biol Psychiatry. 2003;54: 693-702.
8. Martenyi F, Brown EB, Zhang H, et al. Fluoxetine v. placebo in prevention of relapse in posttraumatic stress disorder. Br J Psychiatry. 2002;181:315-320.
9. Hertzberg MA, Feldman ME, Beckman JC, et al. Three- to four-year follow-up to an open trial of nefazodone for combat-related posttraumatic stress disorder. Ann Clin Psychiatry. 2002;14:215-221.
10. Kim W, Pae CU, Chae JH, et al. The effectiveness of mirtazapine in the treatment of posttraumatic stress disorder: a 24-week continuation therapy. Psychiatry Clin Neurosci. 2005;59:743-747.
11. 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; 19:625-638.
12. van der Kolk BA, Spinazzola J, Blaustein ME, et al. 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. J Clin Psychiatry. 2007;68:37-46.
13. Bryant RA, Sackville T, Dang ST, et al. Treating acute stress disorder: an evaluation of cognitive behavior therapy and supportive counseling techniques. Am J Psychiatry. 1999;156:1780-1786
14. Connor KM, Davidson JR, Weisler RH, et al. Tiagabine for posttraumatic stress disorder: effects of open-label and discontinuation treatment. Psychopharmacology. 2006;184:21-25.
15. Wheatley M, Plant J, Reader H, et al. Clozapine treatment of adolescents with posttraumatic stress disorder and psychotic symptoms. J Clin Psychopharmacol. 2004; 24:167-173.
16. Bartzokis G, Lu PH, Turner J, et al. Adjunctive risperidone in the treatment of chronic combat-related posttraumatic stress disorder. Biol Psychiatry. 2005;57: 474-479.
17. 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;61:928-934.
18. Hamner MB, Robert S, Frueh BC. Treatment-resistant posttraumatic stress disorder: strategies for intervention. CNS Spectr. 2004;10:740-752.