A review of FDA-approved treatment options in bipolar depression.
OBJECTIVE
Herein we review the evidence supporting Food and Drug Administration (FDA) approved and emerging treatments for bipolar depression.


METHODS
A PubMed search of all English-language articles published up to July 2013 was conducted. The search terms were quetiapine, olanzapine-fluoxetine, olanzapine, lurasidone, ketamine, modafinil/armodafinil, and lamotrigine. The search was augmented with a manual review of relevant article reference lists, as well as posters presented at national and international meetings. Articles selected for review were based on the adequacy of sample size, the use of standardized diagnostic instruments, validated assessment measures, and overall manuscript quality.


RESULTS
Olanzapine-fluoxetine combination (OFC), quetiapine, and lurasidone are FDA-approved for the acute treatment of bipolar depression. Lurasidone is the most recently approved agent for bipolar depression. Olanzapine-fluoxetine combination and quetiapine are approved as single modality therapies while lurasidone is approved as a monotherapy and as an adjunct to lithium or divalproex. The overall effect size of the 3 treatments in mitigating depressive symptoms is similar. Clinically significant weight gain and metabolic disruption as well as sedation are significant limitations of OFC and quetiapine. The minimal propensity for weight gain as well as the metabolic neutrality of lurasidone in the bipolar population is a clinically significant advantage. Evidence also supports lamotrigine with compelling evidence as an adjunct to lithium and in recurrence prevention paradigm; suggested evidence also exists for ketamine and modafinil/armodafinil; notwithstanding, these treatments remain investigational.


CONCLUSIONS
Relatively few agents are FDA-approved for bipolar depression. The selection and sequencing of agents in bipolar depression should give primacy to those agents that are FDA-approved. Further refinement of the selection process will need to pay careful attention to the relative hazards of weight gain and metabolic disruption in this highly susceptible population. Other agents with differential mechanisms (eg, ketamine) offer a promising alternative in bipolar depression.
1 Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
Roger S
RS
McIntyre
3 Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, Ontario, Canada.
Danielle S
DS
Cha
3 Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, Ontario, Canada.
Rachael D
RD
Kim
3 Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, Ontario, Canada.
Rodrigo B
RB
Mansur
D000928:Antidepressive Agents / Q000627:therapeutic use*; D018687:Antidepressive Agents, Second-Generation / Q000627:therapeutic use; D014150:Antipsychotic Agents / Q000627:therapeutic use; D001559:Benzhydryl Compounds / Q000627:therapeutic use; D001569:Benzodiazepines / Q000627:therapeutic use; D001714:Bipolar Disorder / Q000188:drug therapy*; D000697:Central Nervous System Stimulants / Q000627:therapeutic use; D003866:Depressive Disorder / Q000188:drug therapy*; D003987:Dibenzothiazepines / Q000627:therapeutic use; D017277:Drug Approval; D004338:Drug Combinations; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use; D005473:Fluoxetine / Q000627:therapeutic use; D006801:Humans; D054833:Isoindoles / Q000627:therapeutic use; D007649:Ketamine / Q000627:therapeutic use; D000077213:Lamotrigine; D000069056:Lurasidone Hydrochloride; D000077408:Modafinil; D000069348:Quetiapine Fumarate; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use; D013844:Thiazoles / Q000627:therapeutic use; D014227:Triazines / Q000627:therapeutic use; D014481:United States; D014486:United States Food and Drug Administration
D000928:Antidepressive Agents; D018687:Antidepressive Agents, Second-Generation; D014150:Antipsychotic Agents; D001559:Benzhydryl Compounds; D001569:Benzodiazepines; D000697:Central Nervous System Stimulants; D003987:Dibenzothiazepines; D004338:Drug Combinations; D018691:Excitatory Amino Acid Antagonists; D005473:Fluoxetine; D054833:Isoindoles; D007649:Ketamine; D000077213:Lamotrigine; D000069056:Lurasidone Hydrochloride; D000077408:Modafinil; D000069348:Quetiapine Fumarate; D017367:Selective Serotonin Reuptake Inhibitors; D013844:Thiazoles; D014227:Triazines; C492572:olanzapine-fluoxetine combination