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#136 Atypical antipsychotics for anxiety: Worth worrying about?

Are atypical antipsychotics (alone or added to antidepressants) effective in managing anxiety disorders?

Atypical antipsychotics have similar efficacy to antidepressants in generalized anxiety disorder (GAD), but are more poorly tolerated and do not improve response rates when added to antidepressants. In obsessive-compulsive disorder (OCD), approximately one in 4-8 people will have a response when antipsychotics are added to antidepressants, while one in nine will stop due to adverse effects.   

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All included results statistically significant unless mentioned. 
  • GAD: Highest quality systematic review of nine randomized controlled trials (RCTs) (4,387 patients).1 
    • Quetiapine versus placebo (four RCTs, 2,262 patients): 
      • ResponseNumber Needed to Treat (NNT)=6. Inconsistent results. 
      • Remission: NNT=10. Inconsistent results. 
      • Withdrawal due to adverse events: Number Needed to Harm (NNH)=9. 
    • Quetiapine versus antidepressants (two RCTs, 858 patients):  
      • Similar efficacy but quetiapine more withdrawal due to adverse effects NNH=11.  
    • Quetiapine (one RCT, 22 patients)risperidone (two RCTs, 457 patients), or olanzapine (one RCT, 24 patients) versus placebo added to antidepressants:  
      • No differences except olanzapine one improved anxiety rating.  
  • OCD: Highest quality systematic review of 11 RCTs (396 patients):2 
    • Antipsychotic versus placebo added to antidepressants: 
      • Olanzapine: Not different. 
      • Quetiapine: Response NNT=8 (borderline significance p=0.07). 
        • Stopping early due to adverse effects NNH=9 over 12 weeks.  
      • Risperidone: ResponsNNT=4. 
        • No difference in stopping early for adverse effects. 
    • No RCTs versus placebo or antidepressants. 
  • Other reviews found similar results.3-10 Aripiprazole may be beneficial in OCD, based on two RCTs (79 patients).7  
  • Limitations: Short-term (≤16 weeks); all manufacturer-sponsored, often small sample sizes, unclear randomization and blinding procedures in most studies.1,2  
  • No evidence for panic and too little evidence (two RCTs, 27 patients) for social phobia.1  
  • NNT~5-over 10-13 weeks for response from antidepressants in GAD and OCD.11,12 
  • For depression, atypical antipsychotics have stronger evidence for augmentation of antidepressants than therapy alone.13 
  • Canadian guidelines recommend atypical antipsychotics typically 3rd line (alone or adjunct) for most anxiety disorders, with risperidone and aripiprazole 1st line adjuncts in OCD.14 

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  • Adrienne J Lindblad BSP ACPR PharmD
  • Lisa Freeman BSc(Hon) MD CCFP

1. Depping AM, Komossa K, Kissling W, et al. Cochrane Database Syst Rev. 2010; 12:CD008120.

2. Komossa K, Depping AM, Meyer M, et al. Cochrane Database Syst Rev. 2010; 12:CD008141.

3. LaLonde CD, Van Lieshout RJ. J Clin Psychopharmacol. 2011; 31(3):326-33.

4. Maglione M, Maher AR, Hu J, et al. Rockville (MD): Agency for Healthcare Research and Quality (US); 2011 Sep. Report No.: 11-EHC087-EF.

5. Maher AR, Maglione M, Bagley S, et al. JAMA. 2011; 306(12):1359-69.

6. Dold M, Aigner M, Lanzenberger R, et al. Int J Neuropsychopharmacol. 2013; 16:557-74.

7. Veale D, Miles S, Smallcombe N, et al. BMC Psychiatry. 2014; 14(1):317. [Epub ahead of print]

8. Bloch MH, Landeros-Weisenberger A, Kelmindi B, et al. Mol Psychiatry. 2006; 11:622-32.

9. Skapinakis P, Papatheodorou T, Mavreas V. Eur Neuropsychopharmacol. 2007; 17:79-93.

10. Soomro GS. BMJ Clin Evid. 2012. pii: 1004.

11. Kapczinski FFK, Silva de Lima M, dos Santos Souza JJSS, et al. Cochrane Database Syst Rev. 2003; 2:CD003592.

12. Soomro GM, Altman DG, Rajagopal S, et al. Cochrane Database System Rev. 2008; 1:CD001765.

13. Turgeon R, Allan GM. [Publication on the Internet] Tools for Practice, Alberta College of Family Physicians. 2012 January 23. Last accessed April 9, 2015.

14. Katzman MA, Bleau P, Blier P, et al. BMC Psychiatry. 2014; 14 Suppl 1:S1.

Authors do not have any conflicts to disclose.