Skip to main content Accessibility help
×
Home

Comparative efficacy and acceptability of pharmacological treatments for post-traumatic stress disorder in adults: a network meta-analysis

  • Andrea Cipriani (a1), Taryn Williams (a2), Adriani Nikolakopoulou (a3), Georgia Salanti (a3), Anna Chaimani (a4), Jonathan Ipser (a2), Phil J. Cowen (a1), John R. Geddes (a1) and Dan J. Stein (a2)...

Abstract

Background

Guidelines about post-traumatic stress disorder (PTSD) recommend broad categories of drugs, but uncertainty remains about what pharmacological treatment to select among all available compounds.

Methods

Cochrane Central Register of Controlled Trials register, MEDLINE, PsycINFO, National PTSD Center Pilots database, PubMed, trial registries, and databases of pharmaceutical companies were searched until February 2016 for double-blind randomised trials comparing any pharmacological intervention or placebo as oral therapy in adults with PTSD. Initially, we performed standard pairwise meta-analyses using a random effects model. We then carried out a network meta-analysis. The main outcome measures were mean change on a standardised scale and all-cause dropout rate. Acute treatment was defined as 8-week follow up.

Results

Desipramine, fluoxetine, paroxetine, phenelzine, risperidone, sertraline, and venlafaxine were more effective than placebo; phenelzine was better than many other active treatments and was the only drug, which was significantly better than placebo in terms of dropouts (odds ratio 7.50, 95% CI 1.72–32.80). Mirtazapine yielded a relatively high rank for efficacy, but the respective value for acceptability was not among the best treatments. Divalproex had overall the worst ranking.

Conclusions

The efficacy and acceptability hierarchies generated by our study were robust against many sources of bias. The differences between drugs and placebo were small, with the only exception of phenelzine. Considering the small amount of available data, these results are probably not robust enough to suggest phenelzine as a drug of choice. However, findings from this review reinforce the idea that phenelzine should be prioritised in future trials in PTSD.

Copyright

Corresponding author

Author for correspondence: Andrea Cipriani, E-mail: andrea.cipriani@psych.ox.ac.uk

References

Hide All
Altman, DG and Bland, JM (1996) Detecting skewness from summary information. British Medical Journal 313, 1200.
American Psychiatric Association (2004) Practice Guideline for the Treatment of Patients with Acute Stress Disorder and Posttraumatic Stress Disorder. Arlington: American Psychiatric Publishing.
Aurora, RN, Zak, RS, Auerbach, SH, Casey, KR, Chowdhuri, S, Karippot, A et al. Standards of Practice Committee; American Academy of Sleep Medicine (2010) Best practice guide for the treatment of nightmare disorder in adults. Journal of Clinical Sleep Medicine 6, 389401.
Chaimani, A, Higgins, JPT, Mavridis, D, Spyridonos, P and Salanti, G (2013 a) Graphical tools for network meta-analysis in STATA. PLoS ONE 8, e76654.
Chaimani, A and Salanti, G (2012) Using network meta-analysis to evaluate the existence of small-study effects in a network of interventions. Research Synthesis and Methods 3, 161176.
Chaimani, A, Vasiliadis, HS, Pandis, N, Schmid, CH, Welton, NJ and Salanti, G (2013 b) Effects of study precision and risk of bias in networks of interventions: a network meta-epidemiological study. International Journal of Epidemiology 42, 11201131.
Cipriani, A, Barbui, C, Salanti, G, Rendell, J, Brown, R, Stockton, S et al. (2011) Comparative efficacy and acceptability of antimanic drugs in acute mania: a multiple-treatments meta-analysis. Lancet 378, 13061315.
Cipriani, A, Furukawa, TA, Salanti, G, Geddes, JR, Higgins, JP, Churchill, R et al. (2009) Comparative efficacy and acceptability of 12 new-generation antidepressants: a multiple-treatments meta-analysis. Lancet 373, 746758.
Cipriani, A, Higgins, JP, Geddes, JR and Salanti, G (2013) Conceptual and technical challenges in network meta-analysis. Annals of Internal Medicine 159, 130137.
Cohen, J (1988) Statistical Power Analysis for the Behavioral Sciences, 2nd edn. Hillsdale: Lawrence Erlbaum Associates.
DerSimonian, R and Laird, N (1986) Meta-analysis in clinical trials. Controlled Clinical Trials 7, 177188.
Dohrenwend, BP, Turner, JB, Turse, NA, Adams, BG, Koenen, KC and Marshall, R (2006) The psychological risks of Vietnam for U.S. veterans: a revisit with new data and methods. Science 313, 979982.
Furukawa, TA, Barbui, C, Cipriani, A, Brambilla, P and Watanabe, N (2006) Imputing missing standard deviations in meta-analyses can provide accurate results. Journal of Clinical Epidemiology 59, 710.
Germain, A (2013) Sleep disturbances as the hallmark of PTSD: where are we now? American Journal of Psychiatry 170, 372382.
Higgins, JP and Green, S (2011) Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated September 2011]. Available at http://www.cochrane-handbook.org.
Higgins, JP, Thompson, SG, Deeks, JJ and Altman, DG (2003) Measuring inconsistency in meta-analyses. British Medical Journal 327, 557560.
Higgins, JPT, Jackson, D, Barrett, JK, Lu, G, Ades, AE and White, IR (2012) Consistency and inconsistency in network meta-analysis: concepts and models for multi-arm studies. Research Synthesis and Methods 3, 98110.
Hoskins, M, Pearce, J, Bethell, A, Dankova, L, Barbui, C, Tol, WA et al. (2015) Pharmacotherapy for post-traumatic stress disorder: systematic review and meta-analysis. British Journal of Psychiatry 206, 93100.
Huwiler-Müntener, K, Jüni, P, Junker, C and Egger, M (2002) Quality of reporting of randomized trials as a measure of methodologic quality. Journal of American Medical Association 287, 28012804.
Jackson, D, Barrett, JK, Stephen, R, White, IR and Higgins, JPT (2014) A design-by-treatment interaction model for network meta-analysis with random inconsistency effects. Statistics in Medicine 33, 36393654.
Jansen, JP and Naci, H (2013) Is network meta-analysis as valid as standard pairwise meta-analysis? It all depends on the distribution of effect modifiers. BMC Medicine 11, 159.
Johnson, MR, Lydiard, RB and Ballenger, JC (1994) MAOIs in panic disorder and agoraphobia. In Kennedy, SH (ed.). Clinical Advances in Monoamine Oxidase Inhibitor Therapies. Washington, DC: American Psychiatric Press, pp. 205224.
Jonas, DE, Cusack, K, Forneris, CA, Wilkins, TM, Sonis, J, Middleton, JC et al. (2013) Psychological and Pharmacological Treatments for Adults With Posttraumatic Stress Disorder (PTSD). Rockville (MD): Agency for Healthcare Research and Quality (US). Report No.: 13-EHC011-EF.
Katzman, MA, Bleau, P, Blier, P, Chokka, P, Kjernisted, K, Van Ameringen, M; Canadian Anxiety Guidelines Initiative Group on behalf of the Anxiety Disorders Association of Canada/Association Canadienne des troubles anxieux and McGill University et al. (2014) Canadian clinical practice guidelines for the management of anxiety, posttraumatic stress and obsessive-compulsive disorders. BMC Psychiatry 14, S1.
Kessler, RC, Aguilar-Gaxiola, S, Alonso, J, Angermeyer, MC, Anthony, JC and Brugha, TS et al. (2011) Prevalence and severity of mental disorders in the world mental health survey initiative. In Kessler, RC and Ustun, B (eds). The WHO World Mental Health Surveys: Global Perspectives on the Epidemiology of Mental Disorders. Cambridge: Cambridge University Press, pp. 511521.
Krysinska, K and Lester, D (2010) Post-traumatic stress disorder and suicide risk: a systematic review. Archives of Suicide Research 14, 123.
Landolt, HP, Raimo, EB, Schnierow, BJ, Kelsoe, JR, Rapaport, MH and Gillin, JC (2001) Sleep and sleep electroencephalogram in depressed patients treated with phenelzine. Archives of General Psychiatry 58, 268276.
Leucht, S, Cipriani, A, Spineli, L, Mavridis, D, Orey, D, Richter, F et al. (2013) Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis. Lancet 382, 951962.
Leucht, S, Hierl, S, Kissling, W, Dold, M and Davis, JM (2012) Putting the efficacy of psychiatric and general medicine medication into perspective: review of meta-analyses. British Journal of Psychiatry 200, 97106.
Mellman, TA, Pigeon, WR, Nowell, PD and Nolan, B (2007) Relationships between REM sleep findings and PTSD symptoms during the early aftermath of trauma. Journal of Traumatic Stress 20, 893901.
Miura, T, Noma, H, Furukawa, TA, Mitsuyasu, H, Tanaka, S, Stockton, S et al. (2014) Comparative efficacy and acceptability of pharmacological treatments in the maintenance treatment of bipolar disorder: a network meta-analysis. Lancet Psychiatry 1, 351359.
National Institute for Health and Care Excellence (2005) Post-traumatic stress disorder (PTSD). The management of PTSD in adults and children in primary and secondary care. NICE clinical guideline 26. Available at http://www.nice.org.uk/guidance/cg26/resources/guidance-posttraumatic-stress-disorder-ptsd-pdf.
National Institute for Health and Care Excellence (2011) Generalised anxiety disorder and panic disorder (with or without agoraphobia) in adults. Management in primary, secondary and community care. NICE clinical guideline 113. Available at http://www.nice.org.uk/guidance/cg113/resources/guidance-generalised-anxiety-disorder-and-panic-disorder-with-or-without-agoraphobia-in-adults-pdf.
National Institute for Health and Care Excellence (2013) Social anxiety disorder: recognition, assessment and treatment. NICE clinical guideline 159. Available at http://www.nice.org.uk/guidance/cg159/resources/guidance-social-anxiety-disorder-recognition-assessment-and-treatment-pdf.
Norris, F and Sloane, LB (2007) The epidemiology of trauma and PTSD. In Friedman, MJ, Keane, TM and Resick, PA (eds). Handbook of PTSD: Science and Practice. New York: Guilford Press, pp. 7898.
Phoenix Australia - Centre for Posttraumatic Mental Health (2013) Australian Guidelines for the Treatment of Acute Stress Disorder and Posttraumatic Stress Disorder. Melbourne, Victoria: Phoenix Australia. Available at http://phoenixaustralia.org/wp-content/uploads/2015/03/Phoenix-ASD-PTSD-Guidelines.pdf.
Rhodes, KM, Turner, RM and Higgins, JP (2015) Predictive distributions were developed for the extent of heterogeneity in meta-analyses of continuous outcome data. Journal of Clinical Epidemiology 68, 5260.
Rosso, IM, Weiner, MR, Crowley, DJ, Silveri, MM, Rauch, SL and Jensen, JE (2014) Insula and anterior cingulate GABA levels in posttraumatic stress disorder: preliminary findings using magnetic resonance spectroscopy. Depression and Anxiety 31, 115123.
Salanti, G (2012) Indirect and mixed-treatment comparison, network, or multiple-treatments meta-analysis: many names, many benefits, many concerns for the next generation evidence synthesis tool. Research Synthesis and Methods 3, 8097.
Salanti, G, Ades, AE and Ioannidis, JP (2011) Graphical methods and numerical summaries for presenting results from multiple-treatment meta-analysis: an overview and tutorial. Journal of Clinical Epidemiology 64, 163171.
Salanti, G, Del Giovane, C, Chaimani, A, Caldwell, DM and Higgins, JP (2014) Evaluating the quality of evidence from a network meta-analysis. PLoS ONE 9, e99682.
Seal, KH, Bertenthal, D, Miner, CR, Sen, S and Marmar, C (2007) Bringing the war back home: mental health disorders among 103788 US veterans returning from Iraq and Afghanistan seen at Department of Veterans Affairs facilities. Archives of Internal Medicine 167, 476482.
Sharpley, AL and Cowen, PJ (1995) Effect of pharmacologic treatments on the sleep of depressed patients. Biological Psychiatry 37, 8598.
Sheehan, DV, Ballenger, J and Jacobsen, G (1980) Treatment of endogenous anxiety with phobic, hysterical and hypochondrial symptoms. Archives of General Psychiatry 37, 5159.
Song, F, Altman, DG, Glenny, AM and Deeks, JJ (2003) Validity of indirect comparison for estimating efficacy of competing interventions: empirical evidence from published meta-analyses. British Medical Journal 326, 472.
StataCorp (2015) Stata Statistical Software: Release 14. College Station, TX: StataCorp LP.
Steel, Z, Chey, T, Silove, D, Marnane, C, Bryant, RA and van Ommeren, M (2009) Association of torture and other potentially traumatic events with mental health outcomes among populations exposed to mass conflict and displacement: a systematic review and meta-analysis. Journal of the American Medical Association 302, 537549.
Turner, RM, Davey, J, Clarke, MJ, Thompson, SG and Higgins, JP (2012) Predicting the extent of heterogeneity in meta-analysis, using empirical data from the Cochrane Database of Systematic Reviews. International Journal of Epidemiology 41, 818827.
Veroniki, AA, Vasiliadis, HS, Higgins, JP and Salanti, G (2013) Evaluation of inconsistency in networks of interventions. International Journal of Epidemiology 42, 332345.
Watts, BV, Schnurr, PP, Mayo, L, Young-Xu, Y, Weeks, WB and Friedman, MJ (2013) Meta-analysis of the efficacy of treatments for posttraumatic stress disorder. Journal of Clinical Psychiatry 74, e541e550.
White, IR (2011) Multivariate random-effects meta-regression: updates to mvmeta. The STATA Journal 11, 255270.
White, IR, Barrett, JK, Jackson, D and Higgins, JPT (2012) Consistency and inconsistency in network meta-analysis: model estimation using multivariate meta-regression. Research Synthesis and Methods 3, 111125.
Wood, L, Egger, M, Gluud, LL, Schulz, KF, Jüni, P, Altman, DG et al. (2008) Empirical evidence of bias in treatment effect estimates in controlled trials with different interventions and outcomes: meta-epidemiological study. British Medical Journal 336, 601605.
Wyatt, RJ, Fram, DH, Kupfer, DJ and Snyder, F (1971) Total prolonged drug-induced REM sleep suppression in anxious-depressed patients. Archives of General Psychiatry 24, 145155.

Keywords

Type Description Title
UNKNOWN
Supplementary materials

Cipriani et al supplementary material
Appendices 1-16

 Unknown (949 KB)
949 KB

Metrics

Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed