Efficacy and Safety of Sertraline Treatment of Posttraumatic Stress Disorder: A Randomized Controlled Trial | Psychiatry | JAMA | JAMA Network
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1.
Kessler RC, Sonnega A, Bromet E, Hughes M, Nelson CB. Posttraumatic stress disorder in the National Comorbidity Survey.  Arch Gen Psychiatry.1995;52:1048-1060.Google Scholar
2.
Breslau N, Davis GC, Peterson EL, Schultz L. Psychiatric sequelae of posttraumatic stress disorder in women.  Arch Gen Psychiatry.1997;54:81-87.Google Scholar
3.
Grillon C, Southwick SM, Charney DS. The psychobiological basis of posttraumatic stress disorder.  Mol Psychiatry.1996;1:278-297.Google Scholar
4.
Breslau N, Davis GC, Andreski P, Peterson E. Traumatic events and posttraumatic stress disorder in an urban population of young adults.  Arch Gen Psychiatry.1991;48:216-222.Google Scholar
5.
Resnick HS, Kilpatrick DG, Dansky BS, Saunders BE, Best CL. Prevalence of civilian trauma and posttraumatic stress disorder in a representative national sample of women.  J Consult Clin Psychol.1993;61:984-991.Google Scholar
6.
Breslau N, Davis GC. Posttraumatic stress disorder in an urban population of young adults: risk factors for chronicity.  Am J Psychiatry.1992;149:671-675.Google Scholar
7.
Davidson JR, Hughes D, Blazer DG, George LK. Post-traumatic stress disorder in the community: an epidemiological study.  Psychol Med.1991;21:713-721.Google Scholar
8.
Mellman TA, Randolph CA, Brawman-Mintzer O, Flores LP, Milanes FJ. Phenomenology and course of psychiatric disorders associated with combat-related posttraumatic stress disorder.  Am J Psychiatry.1992;149:1568-1574.Google Scholar
9.
Resnick HS, Kilpatrick DG, Lipovsky JA. Assessment of rape-related posttraumatic stress disorder: stressor and symptom dimensions.  J Consult Clin Psychol.1991;13:561-572.Google Scholar
10.
Davidson JR, Kudler HS, Saunders WB, Smith RD. Symptom and comorbidity patterns in World War II and Vietnam veterans with posttraumatic stress disorder.  Compr Psychiatry.1990;31:162-170.Google Scholar
11.
Solomon SD, Davidson JR. Trauma: prevalence, impairment, service use, and cost.  J Clin Psychiatry.1997;58(suppl 9):5-11.Google Scholar
12.
Zatzick DF, Marmar CR, Weiss DS.  et al.  Posttraumatic stress disorder and functioning and quality of life outcomes in a nationally representative sample of male Vietnam veterans.  Am J Psychiatry.1997;154:1690-1695.Google Scholar
13.
Friedman MJ, Schnurr PP. The relationship between trauma, posttraumatic stress disorder, and physical health. In: Friedman MJ, Charney DS, Deutch AY, eds. Neurobiological and Clinical Consequences of Stress: From Normal Adaptation to Post-Traumatic Stress Disorder. Philadelphia, Pa: Lippincott-Raven Publishers; 1995:507-524.
14.
Kimerling R, Calhoun KS. Somatic symptoms, social support, and treatment seeking among sexual assault victims.  J Consult Clin Psychol.1994;62:333-340.Google Scholar
15.
Golding JM, Stein JA, Siegel JM, Burnham MA, Sorenson SB. Sexual assault history and use of health and mental health services.  Am J Community Psychol.1988;16:625-644.Google Scholar
16.
Davidson JR, Hughes D, Blazer DG, George LK. Post-traumatic stress disorder in the community: an epidemiological study.  Psychol Med.1991;21:713-721.Google Scholar
17.
Solomon SD, Gerrity ET, Muff AM. Efficacy of treatments for posttraumatic stress disorder: an empirical review.  JAMA.1992;268:633-638.Google Scholar
18.
Shestatzky M, Greenberg D, Lerer B. A controlled trial of phenelzine in posttraumatic stress disorder.  Psychiatry Res.1988;24:149-155.Google Scholar
19.
Frank JB, Kosten TR, Giller Jr EL, Dan E. A randomized clinical trial of phenelzine and imipramine for posttraumatic stress disorder.  Am J Psychiatry.1988;145:1289-1291.Google Scholar
20.
Reist C, Kauffmann CD, Haier RJ.  et al.  A controlled trial of desipramine in 18 men with posttraumatic stress disorder.  Am J Psychiatry.1989;146:513-516.Google Scholar
21.
Davidson J, Kudler H, Smith R.  et al.  Treatment of posttraumatic stress disorder with amitriptyline and placebo.  Arch Gen Psychiatry.1990;47:259-266.Google Scholar
22.
Braun P, Greenberg D, Dasberg H, Lerer B. Core symptoms of posttraumatic stress disorder unimproved by alprazolam treatment.  J Clin Psychiatry.1990;51:236-238.Google Scholar
23.
Katz RJ, Lott MH, Arbus P.  et al.  Pharmacotherapy of post-traumatic stress disorder with a novel psychotropic.  Anxiety.1994-1995;1:169-174.Google Scholar
24.
Baker DG, Diamond BI, Gillette G.  et al.  A double-blind, randomized, placebo-controlled, multi-center study of brofaromine in the treatment of post-traumatic stress disorder.  Psychopharmacology (Berl).1995;122:386-389.Google Scholar
25.
van der Kolk BA, Dreyfuss D, Michaels M.  et al.  Fluoxetine in posttraumatic stress disorder.  J Clin Psychiatry.1994;55:517-522.Google Scholar
26.
Heym J, Koe BK. Pharmacology of sertraline: a review.  J Clin Psychiatry.1988;49(suppl):40-45.Google Scholar
27.
Yehuda R, Antelman SM. Criteria for rationally evaluating animal models of posttraumatic stress disorder.  Biol Psychiatry.1993;33:479-486.Google Scholar
28.
Foa EB, Zinbarg R, Rothbaum BO. Uncontrollability and unpredictability in post-traumatic stress disorder: an animal model.  Psychol Bull.1992;112:218-238.Google Scholar
29.
Brady KT, Sonne SC, Roberts JM. Sertraline treatment of comorbid posttraumatic stress disorder and alcohol dependence.  J Clin Psychiatry.1995;56:502-505.Google Scholar
30.
Rothbaum BO, Ninan PT, Thomas L. Sertraline in the treatment of rape victims with posttraumatic stress disorder.  J Trauma Stress.1996;9:865-871.Google Scholar
31.
Fabre LF, Abuzzahab FS, Amin M.  et al.  Sertraline safety and efficacy in major depression: a double-blind fixed-dose comparison with placebo.  Biol Psychiatry.1995;38:592-602.Google Scholar
32.
Reimherr FW, Chouinard G, Cohn CK.  et al.  Antidepressant efficacy of sertraline: a double-blind, placebo- and amitriptyline-controlled, multicenter comparison study in outpatients with major depression.  J Clin Psychiatry.1990;51(suppl B):18-27.Google Scholar
33.
Keller MB, Kocsis JH, Thase ME.  et al.  Maintenance phase efficacy of sertraline for chronic depression: a randomized controlled trial.  JAMA.1998;280:1665-1672.Google Scholar
34.
Londborg PD, Wolkow R, Smith WT.  et al.  Sertraline in the treatment of panic disorder: a multi-site, double-blind, placebo-controlled, fixed-dose investigation.  Br J Psychiatry.1998;173:54-60.Google Scholar
35.
Pollack MH, Otto MW, Worthington JJ, Manfro GG, Wolkow R. Sertraline in the treatment of panic disorder: a flexible-dose multicenter trial.  Arch Gen Psychiatry.1998;55:1010-1016.Google Scholar
36.
Pohl RB, Wolkow RM, Clary CM. Sertraline in the treatment of panic disorder: a double-blind multicenter trial.  Am J Psychiatry.1998;155:1189-1195.Google Scholar
37.
Greist J, Chouinard G, DuBoff E.  et al.  Double-blind parallel comparison of three dosages of sertraline and placebo in outpatients with obsessive-compulsive disorder.  Arch Gen Psychiatry.1995;52:289-295.Google Scholar
38.
Hoehn-Saric R, Harrison W, Clary C. Obsessive-compulsive disorder with comorbid major depression: a comparison of sertraline and desipramine treatment [abstract].  Eur Neuropsychopharmacol.1997;7:S180.Google Scholar
39.
Weathers FW, Litz BT. Psychometric properties of the Clinician-Administered PTSD Scale, CAPS-1.  PTSD Res Q.1994;5:2-6.Google Scholar
40.
Blake DD, Weathers FW, Nagy LM.  et al.  A clinician rating scale for assessing current and lifetime PTSD: the CAPS-1.  Behav Therapist.1990;13:187-188.Google Scholar
41.
Horowitz M, Wilner N, Alvarez W. Impact of Event Scale: a measure of subjective stress.  Psychosom Med.1979;41:209-218.Google Scholar
42.
Zilberg NJ, Weiss DS, Horowitz MJ. Impact of Event Scale: a cross-validation study and some empirical evidence supporting a conceptual model of stress response syndromes.  J Consult Clin Psychol.1982;50:407-414.Google Scholar
43.
Guy W. ECDEU Assessment Manual for PsychopharmacologyWashington, DC: National Institute of Mental Health, US Dept of Health, Education, and Welfare; 1976:76-338.
44.
Davidson JR, Book SW, Colket JT.  et al.  Assessment of a new self-rating scale for post-traumatic stress disorder.  Psychol Med.1997;27:153-160.Google Scholar
45.
Zlotnick C, Davidson J, Shea MT, Pearlstein T. Validation of the Davidson Trauma Scale in a sample of survivors of childhood sexual abuse.  J Nerv Ment Dis.1996;184:255-257.Google Scholar
46.
Hamilton MA. A rating scale for depression.  J Neurol Neurosurg Psychiatry.1960;23:56-62.Google Scholar
47.
Endicott J, Nee J, Harrison W, Blumenthal R. Quality of Life Enjoyment and Satisfaction Questionnaire: a new measure.  Psychopharmacol Bull.1993;29:321-326.Google Scholar
48.
Brady KT. Posttraumatic stress disorder and comorbidity: recognizing the many faces of PTSD.  J Clin Psychiatry.1997;58(suppl 9):12-15.Google Scholar
49.
Yehuda R, McFarlane AC. Conflict between current knowledge about posttraumatic stress disorder and its original conceptual basis.  Am J Psychiatry.1995;152:1705-1713.Google Scholar
50.
Davidson JR, Rothbaum BO, van der Kolk BA, Sikes CR, Farfel GM. Multi-center, double-blind comparison of sertraline and placebo in the treatment of posttraumatic stress disorder. Paper presented at: The International Society for Traumatic Stress Studies; November 21, 1998; Washington, DC.
Original Contribution
April 12, 2000

Efficacy and Safety of Sertraline Treatment of Posttraumatic Stress Disorder: A Randomized Controlled Trial

Author Affiliations

Author Affiliations: Departments of Psychiatry, Medical University of South Carolina, Charleston (Dr Brady), Butler Hospital, Providence, RI (Dr Pearlstein), Montefiore Medical Center, Bronx, NY (Dr Asnis), Emory University, Atlanta, Ga (Dr Rothbaum); Posttraumatic Stress Disorder Unit, Cincinnati Veterans Affairs Medical Center, Cincinnati, Ohio (Dr Baker); and Pfizer Inc, New York, NY (Drs Sikes and Farfel).

JAMA. 2000;283(14):1837-1844. doi:10.1001/jama.283.14.1837
Abstract

Context Despite the high prevalence, chronicity, and associated comorbidity of posttraumatic stress disorder (PTSD) in the community, few placebo-controlled studies have evaluated the efficacy of pharmacotherapy for this disorder.

Objective To determine if treatment with sertraline hydrochloride effectively diminishes symptoms of PTSD of moderate to marked severity.

Design Twelve-week, double-blind, placebo-controlled trial preceded by a 2-week, single-blind placebo lead-in period, conducted between May 1996 and June 1997.

Setting Outpatient psychiatric clinics in 8 academic medical centers and 6 clinical research centers.

Patients A total of 187 outpatients with a Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition diagnosis of PTSD and a Clinician Administered PTSD Scale Part 2 (CAPS-2) minimum total severity score of at least 50 at baseline (mean age, 40 years; mean duration of illness, 12 years; 73% were women; and 61.5% experienced physical or sexual assault).

Intervention Patients were randomized to acute treatment with sertraline hydrochloride in flexible daily dosages of 50 to 200 mg/d, following 1 week at 25 mg/d (n=94); or placebo (n=93).

Main Outcome Measures Baseline-to-end-point changes in CAPS-2 total severity score, Impact of Event Scale total score (IES), and Clinical Global Impression–Severity (CGI-S), and CGI-Improvement (CGI-I) ratings, compared by treatment vs placebo groups.

Results Sertraline treatment yielded significantly greater improvement than placebo on 3 of the 4 primary outcome measures (mean change from baseline to end point for CAPS-2 total score, −33.0 vs −23.2 [P=.02], and for CGI-S, −1.2 vs −0.8 [P=.01]; mean CGI-I score at end point, 2.5 vs 3.0 [P=.02]), with the fourth measure, the IES total score, showing a trend toward significance (mean change from baseline to end point, −16.2 vs −12.1; P=.07). Using a conservative last-observation-carried-forward analysis, treatment with sertraline resulted in a responder rate of 53% at study end point compared with 32% for placebo (P=.008, with responder defined as >30% reduction from baseline in CAPS-2 total severity score and a CGI-I score of 1 [very much improved], or 2 [much improved]). Significant (P<.05) efficacy was evident for sertraline from week 2 on the CAPS-2 total severity score. Sertraline had significant efficacy vs placebo on the CAPS-2 PTSD symptom clusters of avoidance/numbing (P=.02) and increased arousal (P=.03) but not on reexperiencing/intrusion (P=.14). Sertraline was well tolerated, with insomnia the only adverse effect reported significantly more often than placebo (16.0% vs 4.3%; P=.01).

Conclusions Our data suggest that sertraline is a safe, well-tolerated, and effective treatment for PTSD.

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