Combination of Pharmacologic and Nonpharmacologic Therapies

The combination of pharmacologic and nonpharmacologic therapies, such as regular exercise, adequate sleep, and stress reduction techniques, should be considered, according to the authors,1 as it has been shown to improve outcomes in BPAD.18

Tips for Managing Patients Taking SGAs for Bipolar Depression

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The authors recommend several important measures to take prior to and during treatment with SGAs for bipolar depression.

  • Conduct a thorough workup prior to initiating treatment and monitor carefully and regularly for adverse effects. (Tables 1, 2)
  • When initiating medications during an acute depressive episode, consider the long-term plan for maintenance therapy (eg, lithium, valproate, lamotrigine, olanzapine, and aripiprazole)
  • Simplify the medication regimen after the episode resolves
  • Monitor the patient’s depressive symptoms for remission to recognize appropriate time to discontinue OFC, quetiapine, or lurasidone and switch to maintenance therapy
  • In designing a long-term treatment program, take into account patient preference, treatment response, and potential long-term adverse effects


The authors emphasize that there is “now an undeniably increasing role for primary care practitioners in the treatment of bipolar depression” and that collaborative care is very important. They add that management of bipolar depression “may require a complex, multimodal approach.”


1.      Avery LM, Drayton SJ. Bipolar depression: Managing patients with second generation antipsychotics. Int J Psychiatry Med. 2016;51(2):145-59.

2.      Miller S, Dell’Osso B, Ketter TA. The prevalence and burden of bipolar depression. J Affect Disord. 2014 Dec;169 Suppl 1:S3-11.

3.      Rihmer Z, Rihmer A, Dome P. Suicidal behaviour in patients with mood disorders. Evid Based Psychiatr Care. 2015;1:19-26.

4.      Grunze H, Vieta E, Goodwin GM, et al. The World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for the Biological Treatment of Bipolar Disorders: Update 2010 on the treatment of acute bipolar depression. World J Biol Psychiatry. 2010 Mar;11(2):81-109.

5.      Geddes JR, Calabrese JR, Goodwin GM. Lamotrigine for treatment of bipolar depression: independent meta-analysis and meta-regression of individual patient data from five randomised trials. Br J Psychiatry. 2009 Jan;194(1):4-9.

6.      Sachs GS, Nierenberg AA, Calabrese JR, et al. Effectiveness of adjunctive antidepressant treatment for bipolar depression. N Engl J Med. 2007 Apr 26;356(17):1711-22.

7.      Sidor MM, Macqueen GM. Antidepressants for the acute treatment of bipolar depression: a systematic review and meta-analysis. J Clin Psychiatry. 2011 Feb;72(2):156-67.

8.      Leverich GS, Altshuler LL, Frye MA, et al. Risk of switch in mood polarity to hypomania or mania in patients with bipolar depression during acute and continuation trials of venlafaxine, sertraline, and bupropion as adjuncts to mood stabilizers. Am J Psychiatry. 2006 Feb;163(2):232-9.

9.      Tohen M, Vieta E, Calabrese J et al. Efficacy of olanzapine and olanzapine-fluoxetine combination in the treatment of bipolar I depression. Arch Gen Psychiatry. 2003 Nov;60(11):1079-88.

10.  Corya SA, Perlis RH, Keck PE Jr, et al. A 24-week open-label extension study of olanzapine-fluoxetine combination and olanzapine monotherapy in the treatment of bipolar depression. J Clin Psychiatry. 2006 May;67(5):798-806.

11.  Calabrese JR, Keck PE, Jr, Macfadden W, et al. A randomized, double-blind, placebo-controlled trial of quetiapine in the treatment of bipolar I or II depression. Am J Psychiatry. 2005;162(7):1351–1360.

12.  Thase ME, Macfadden W, Weisler RH, et al. Efficacy of quetiapine monotherapy in bipolar I and II depression: a double-blind, placebo-controlled study (the BOLDER II study). J Clin Psychopharmacol. 2006;26(6):600–609.

13.  Young AH, McElroy SL, Bauer M, et al. A double-blind, placebo-controlled study of quetiapine and lithium monotherapy in adults in the acute phase of bipolar depression (EMBOLDEN I). J Clin Psychiatry. 2010;71(2):150–162.

14.  McElroy SL, Weisler RH, Chang W, et al. A double-blind, placebo-controlled study of quetiapine and paroxetine as monotherapy in adults with bipolar depression (EMBOLDEN II). J Clin Psychiatry. 2010;71(2):163–174.

15.  Suppes T, Datto C, Minkwitz M, et al. Effectiveness of the extended release formulation of quetiapine as monotherapy for the treatment of acute bipolar depression. J Affect Disord. 2010;121(1-2):106–115.

16.  Loebel A, Cucchiaro J, Silva R, et al. Lurasidone as adjunctive therapy with lithium or valproate for the treatment of bipolar I depression: a randomized, double-blind, placebo-controlled study. Am J Psychiatry. 2014;171(2):169–177.

17.  Loebel A, Cucchiaro J, Silva R, et al. Lurasidone monotherapy in the treatment of bipolar I depression: a randomized, double-blind, placebo-controlled study. Am J Psychiatry. 2014;171(2):160–168.

18.  Parikh SV, Hawke LD, Velyvis V, et al. Combined treatment: impact of optimal psychotherapy and medication in bipolar disorder. Bipolar Disord. 2015 Feb;17(1):86-96.