Treatment-refractory bipolar disorder: classification to aid in clinical management.

Bipolar disorder is an illness with complex symptomatology that encompasses severe symptoms of mood and thought disorder and can limit the cognitive range of human brain functioning. The Diagnostic and Statistical Manual, 4th edition and International Classification of Mental Disorder recommend subgroups of bipolar disorder based on symptoms, illness severity, and frequency of episodes. Pharmacological agents commonly used in the management of bipolar disorder include lithium; anticonvulsants, such as valproate, carbamazepine and lamotrigine; and recent years have witnessed increasing use of atypical antipsychotics. There are several intra- and inter-class differences in these compounds, especially relating to polarity of mood episode under consideration. Monotherapy trials have focused on efficacy of the compounds; few have explored combination therapy, especially in patients failing to respond or inadequately responding to one agent. Clinicians have frequently prescribed two or more compounds to stabilize moods. Monotherapy treatment of bipolar manic episode with various compounds including atypical antipsychotics, mood stabilizers such as lithium, valproic acid and carbamazepine yielded response rates of 50%. However, combination therapy of atypical antipsychotics with valproic acid or lithium offered an additional 20% improvement in the response rates. The article will review published data on augmentation studies, comment on case reports published in treatment-refractory bipolar disorder, and propose a new classification guideline for staging treatment-refractory bipolar disorder.