Adjunctive risperidone treatment for antidepressant-resistant symptoms of chronic
military service-related PTSD: a randomized trial.
Author(s): Krystal JH, Rosenheck RA, Cramer JA, Vessicchio JC, Jones KM, Vertrees JE, Horney
RA, Huang GD, Stock C; Veterans Affairs Cooperative Study No. 504 Group.
Collaborators: Canive J, Calais L, Smith A, Nye E, Duncan E, Skelton K, Bradley
R, Tabb K, Sergent T, Daugherty M, Russ E, Denny N, Arnemann K, Lauren-Rusnack J,
Schillac J, Batten S, Dixon L, Santanello A, Bell L, Duncan J, Carney S, Kavanagh
G, Parker P, McCall K, Rathmell S, Kaloupek D, Aguayo G, Ryngala D, Collins A,
Hamner M, Agbor-Tabi D, Timmerman M, Brown M, Robert S, Coleman S, Fore P, Tepper
T, Yount J, Konicki E, Nero V, Smith E, Huhra-Grassel R, Suris A, North C,
Whitman J, Wiley E, Hertzberg M, Biddix R, Becker M, Grieder T, Feigel C, Vo T,
Wolf P, Garza R, Murphy C, Melton B, Ahearn E, Johnson C, Mussey M, Smith T,
David D, Junco-Valladares J, Slone P, Giron A, Westermeyer J, Spring M, Ferrier
A, Eakin M, Wolkin A, Woo C, Kramer M, Erhman R, Marquez K, Fornish A, Khan A,
Zakai A, Frank H, Kikuchi J, Stock C, Carpenter L, Plumb S, Allen S, Olsen C,
Greenwell M, Casada J, Polanco J, Benson T, Baker D, Shah P, Gorman P, Perin T,
Kelada A, Cooley J, Pittman J, Madra N, Schoenfeld F, Schmitz M, Coeshott R, Tong
H, Davis L, Garner C, Newell J, Hicks P, Justice S, Lippe B, Saunders C,
Goldstein D, Ereshefsky S, Melnick A, Urbaitis M, Affleck S, Beam M, Spence E,
Briones D, Dixon S, Howell C, Lu X, Conner D, Haakenson C, Grieger T, Blake D,
Dickerson K, Thase M, Harvey P, Jones K, Vertrees J, Stein M, Stock C, Hertzberg
M, Duncan E, Gelernter J, Ciraulo D, Kaloupek D, Stein M, Bartzokis G, Rasmusson
A, Davidson J, Marmar C, Lavori P, Berkowitz S, O'Leary T, Schuster B, Jones K,
Collins J, Howell C, Vertrees J, Bradham D, Friedman M.
Affiliation(s): Clinical Neuroscience Division, Department of Veterans Affairs National Center
for PTSD, VA Connecticut Healthcare System, West Haven, USA.
john.krystal@yale.edu
Publication date & source: 2011, JAMA. , 306(5):493-502
CONTEXT: Serotonin reuptake-inhibiting (SRI) antidepressants are the only
FDA-approved pharmacotherapies for the treatment of posttraumatic stress disorder
(PTSD).
OBJECTIVE: To determine efficacy of the second-generation antipsychotic
risperidone as an adjunct to ongoing pharmacologic and psychosocial treatments
for veterans with chronic military-related PTSD.
DESIGN, SETTING, AND PARTICIPANTS: A 6-month, randomized, double-blind,
placebo-controlled multicenter trial conducted between February 2007 and February
2010 at 23 Veterans Administration outpatient medical centers. Of the 367
patients screened, 296 were diagnosed with military-related PTSD and had ongoing
symptoms despite at least 2 adequate SRI treatments, and 247 contributed to
analysis of the primary outcome measure.
INTERVENTION: Risperidone (up to 4 mg once daily) or placebo.
MAIN OUTCOME MEASURES: The Clinician-Administered PTSD Scale (CAPS) (range,
0-136). Other measures included the Montgomery-Asberg Depression Rating Scale
(MADRS), Hamilton Anxiety Scale (HAMA), Clinical Global Impression scale (CGI),
and Veterans RAND 36-Item Health Survey (SF-36V).
RESULTS: Change in CAPS scores from baseline to 24 weeks in the risperidone group
was -16.3 (95% CI, -19.7 to -12.9) and in the placebo group, -12.5 (95% CI, -15.7
to -9.4); the mean difference was 3.74 (95% CI, -0.86 to 8.35; t = 1.6; P = .11).
Mixed model analysis of all time points also showed no significant difference in
CAPS score (risperidone: mean, 64.43; 95% CI, 61.98 to 66.89, vs placebo: mean,
67.16; 95% CI, 64.71 to 69.62; mean difference, 2.73; 95% CI, -0.74 to 6.20; P =
.12). Risperidone did not reduce symptoms of depression (MADRS mean difference,
1.19; 95% CI, -0.29 to 2.68; P = .11) or anxiety (HAMA mean difference, 1.16; 95%
CI, -0.18 to 2.51; P = .09; patient-rated CGI mean difference, 0.20; 95% CI,
-0.06 to 0.45; P = .14; observer-rated CGI mean difference, 0.18; 95% CI, 0.01 to
0.34; P = .04), or increase quality of life (SF-36V physical component mean
difference, -1.13, 95% CI, -2.58 to 0.32; P = .13; SF-36V mental component mean
difference, -0.26; 95% CI, -2.13 to 1.61; P = .79). Adverse events were more
common with risperidone vs placebo, including self-reported weight gain (15.3% vs
2.3%), fatigue (13.7% vs 0.0%), somnolence (9.9% vs 1.5%), and hypersalivation
(9.9% vs 0.8%), respectively.
CONCLUSION: Among patients with military-related PTSD with SRI-resistant
symptoms, 6-month treatment with risperidone compared with placebo did not reduce
PTSD symptoms.
TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00099983.
|
