Credits Earned (2024) Crédits obtenus

Redeem Prepaid Membership

Tools for Practice Outils pour la pratique

#60 Antipsychotics for depression: An acceptable risk/benefit profile?

Are antipsychotics, either added to standard antidepressants or as monotherapy, effective for the treatment of depression without psychotic features?

Second-generation antipsychotics appear effective in treating depression when given to augment antidepressants.  One antipsychotic (quetiapine) appears effective in treating depression alone but equivalence to antidepressants is uncertain.  The evidence has a high risk of bias and adverse events are common.  

CFPCLearn Logo

Reading Tools for Practice Article can earn you MainPro+ Credits

La lecture d'articles d'outils de pratique peut vous permettre de gagner des crédits MainPro+

Join Now S’inscrire maintenant

Already a CFPCLearn Member? Log in

Déjà abonné à CMFCApprendre? Ouvrir une session

2010 Cochrane review1 (28 trials, 8487 patients):  
  • Antipsychotic versus antidepressant: Equivalence is uncertain. 
    • Olanzapine (five trials, 779 patients): Two of five olanzapine studies found antidepressants superior (three found no difference). 
    • Quetiapine (one trial, 309 patients): Equivalent but only one trial.   
  • Antipsychotic versus placebo: Only quetiapine (four trials, 2,069 patients) was studied in depression without psychosis: 
    • Response (Number Needed to Treat (NNT)=8) and remission (NNT=17) 
  • Antipsychotic added t(augmenting) antidepressants: 12 trials using aripiprazole, olanzapine, quetiapine, or risperidone: 
    • Response (NNT=7-12) and remission (NNT=7-12). 
  • Adverse events were common, and typical of the antipsychotic studied (example 4 kg weight gain with olanzapine). 
    • More patients stopped due to adverse events in the antipsychotic group: Number Needed to Harm (NNH)=6-13 when used alone and NNH=12-50 when used as augmentation.  
  • Insufficient evidence to determine if one antipsychotic is superior to others. 
Newer systematic reviews found similar.2-5     Context:  
  • Trials in systematic reviews have a high risk of bias including unclear allocation concealment, selective reporting and short trial duration (22 of 28 studies <12 weeks) 
    • Although not assessed, selective publication (not publishing negative studies)6 and sponsorship bias7 are common concerns in the literature.  
  • Canadian8 and American9 depression guidelines include the option of second-generation antipsychotics alone or as augmentation therapy in patients who have failed first-line antidepressants. 
  • Efficacy of second-generation antipsychotics is minimal in some anxiety conditions (like Generalized Anxiety Disorder) but may help others (like Obsessive Compulsive Disorder).10 
updated June 9 2015 by ricky

Greg Sherman January 8, 2024

Good refresher

Latest Tools for Practice
Derniers outils pour la pratique

#369 Remind me, do medications that target brain amyloid improve my dementia?

Are amyloid-targeting monoclonal antibodies safe and effective for mild cognitive impairment or Alzheimer’s dementia?
Read Lire 0.25 credits available Crédits disponibles

#368 Sodium Restriction in Heart Failure: Beneficial or pouring salt in the wound?

Does sodium restriction improve outcomes in patients with chronic heart failure?
Read Lire 0.25 credits available Crédits disponibles

#367 Oral Calcitonin Gene-related Peptide Antagonists: A painfully long name for the acute treatment of migraines

What are the risks and benefits of ubrogepant for the acute treatment of episodic migraines?
Read Lire 0.25 credits available Crédits disponibles

This content is certified for MainPro+ Credits, log in to access

Ce contenu est certifié pour les crédits MainPro+, Ouvrir une session

  • G. Michael Allan MD CCFP
  • Ricky Turgeon BSc Pharm

1. Komossa K, Depping AM, Gaudchau A, et al. Cochrane Database Syst Rev. 2010 Dec 8; (12):CD008121.

2. Wen XJ, Wang LM, Liu ZL, et al. Braz J Med Biol Res. 2014 Jul; 47(7):605-16.

3. Spielmans GI, Berman MI, Linardatos E, et al. PLoS Med. 2013; 10(3):e1001403.

4. Zhou X, Keitner GI, Qin B, et al. Int J Neuropsychopharmacol. 2015 May 25. pii: pyv060. doi: 10.1093/ijnp/pyv060. [Epub ahead of print]

5. Edwards SJ, Hamilton V, Nherera L, et al. Health Technol Assess. 2013 Nov; 17(54):1-190.

6. Turner EH, Matthews AM, Linardatos E, et al. N Engl J Med. 2008 Jan 17; 358(3):252-60.

7. Heres S, Davis J, Maino K, et al. Am J Psychiatry. 2006; 163:185–194.

8. Kennedy SH, Lam RW, Parikh SV, et al. J Affect Disord. 2009; 117 Suppl 1:S26-43.

9. Gelenberg AJ, Freeman MP, Markowitz, et al. Practice guideline for the treatment of major depressive disorder. Available at: Last accessed June 9, 2015.

10. Lindblad AJ, Freeman L. Tools for Practice. April 15, 2015. Available at: Last accessed June 9, 2015.

Authors do not have any conflicts of interest to declare.

Les auteurs n’ont aucun conflit d’intérêts à déclarer.

Most recent review: 09/06/2015

By: Adrienne J Lindblad BSP ACPR PharmD


Evidence Updated: 5 systematic reviews added, context updated; Bottom Line: Unchanged.

Learning at a glance
Yearly credits
Acquired ()
Your content by topic
Cardiology Dermatology Emergency
My Bookmarks