A Randomized Add-on Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Bipolar Depression

Abstract

Bipolar disorder (BPD) is one of the most severe psychiatric disorders and ranks in the top 10 causes of medical disability worldwide. The lifetime prevalence is approximately 4% in the United States,¹ with depressive symptomatology dominating the longitudinal course of the illness.² Currently approved treatments for bipolar depression include lithium, quetiapine, and the combination olanzapine and fluoxetine. Other treatments used during the depressive phase of the illness include lamotrigine, antidepressants, and atypical antipsychotics. However, many patients with bipolar depression do not respond adequately to these medications despite adequate trials.^2-4 Another limitation of existing therapeutics is that they are associated with a considerable lag of onset; only a fraction of patients meet response criteria by the end of the first week of treatment.^5-7 This delayed onset of antidepressant effects can result in considerable morbidity, including increased suicide risk.^8,9 Therefore, rapid-onset pharmacological strategies with pronounced and sustained effects would have an enormous impact on public health; this is particularly true because BPD is perhaps the psychiatric disorder with the highest mortality rate.¹⁰