For years, lithium and the antiepileptics were the mainstay for treatment of bipolar disorder. In recent years, numerous antipsychotics have also been utilized.

Essential Questions and References

What is the evidence for combination of lithium and valproic acid in treatment of bipolar disorder?

BALANCE

  1. BALANCE investigators and collaborators, Geddes J, Goodwin GM , et al. Lithium plus valproate combination therapy versus monotherapy for relapse prevention in bipolar I disorder (BALANCE): a randomised open-label trial. Lancet. 2010;375(9712):385-95. [PubMed]

What is the evidence for lithium or divalproex in treatment of mania in geriatric patients with bipolar disorder?

GERI-BD

  1. Young RC, Mulsant BH, Sajatovic M, Gildengers AG, Gyulai L, AL Jurdi RK, et al. GERI-BD: A randomized double-blind controlled trial of lithium and divalproex in the treatment of mania in older patients with bipolar disorder. Am J Psychiatry. 2017;174(11):1086-93. [PubMed]

What is the evidence to support use of antipsychotics for management of bipolar disorder?

BOLDER (BipOLar DEpRession)

  1. Calabrese JR, Keck PE, 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):1351-60. [PubMed]

  2. Thase ME, Macfadden W, Weisler RH, et al. Efficacy of quetiapine monotherapy in bipolar I and II depression: a double-blind, placebo-controlled study (BOLDER II study). J Clin Psychopharmacol. 2006;26(6):600-9. [PubMed]

EMBOLDEN I and II

  1. 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):150-62.  [PubMed]
  2. 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):163-74. [PubMed]

STEP-BD (Systematic Treatment Enhancement Program for Bipolar Disorder)

  1. Nierenberg AA, Ostacher MJ, Calabrese JR, et al. Treatment-resistant bipolar depression: a STEP-BD equipoise randomized effectiveness trial of antidepressant augmentation with lamotrigine, inositol, or risperidone. Am J Psychiatry. 2006;163(2):210-6.[PubMed]

Should antidepressants be used to treat bipolar depression?

EMBOLDEN I and II

  1. 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):163-74. [PubMed]

STEP-BD (Systematic Treatment Enhancement Program for Bipolar Disorder)

  1. Nierenberg AA, Ostacher MJ, Calabrese JR, et al. Treatment-resistant bipolar depression: a STEP-BD equipoise randomized effectiveness trial of antidepressant augmentation with lamotrigine, inositol, or risperidone. Am J Psychiatry. 2006;163(2):210-6.[PubMed]
  2. Sachs GS, Nierenberg AA, Calabrese JR, et al. Effectiveness of adjunctive antidepressant treatment for bipolar depression. N Engl J Med. 2007;356(17):1711-22. [PubMed]
  3. Ghaemi SN, Ostacher MM, El-Mallakh RS, et al. Antidepressant discontinuation in bipolar depression: a Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) randomized clinical trial of long-term effectiveness and safety. J Clin Psychiatry. 2010;71(4):372-80. [PubMed]