Pharmacological Treatments for Bipolar Disorder: An Update

Abstract

Bipolar Disorder (ED) is a heterogeneous group of conditions marked by the onset of mood episodes in adolescence and early adulthood and varying presentations, course, and response to treatment. It is commonly associated with coexisting alcohol and substance abuse, anxiety disorders, psychotic symptoms, and medical disorders. Although Bipolar I Disorder (BD), with clear interepisode intervals, has been the center of classical descriptions of the condition, Bipolar II Disorder, mixedstates, andvarioustypesofaccelerated cycling are being increasingly recognized as common. Untreated BD isassociatedwith high recurrence rates; deterioration in psychological, interpersonal, and scholastic or work functioning; suicide; and increased rates of medical conditions-particularly cardiovascular disease. Clinicians have long recognized what research has shown: Only a few patients with BD achieve full remission with monotherapy, and most patients will need-and likely benefit from-judicious use of combined medications, at least during different phases of the disorder. Moreover, what works in acute phases of mania or depression maynot be effective in prophylaxis and relapse prevention, particularly in the case of depressive breakthroughs. Finally, the side effects and tolerability of medications have a profound impact on treatment adherence and thus on morbidity. Despite this knowledge, much work has, until recently, focusedon the elusive search foran ideal monotherapy-an effective treatment for all types and phases of the disorder. The attitudes and expectations of major regulatory authorities in North America and Europe have driven monotherapyresearch at the cost of more clinically meaningful studies of combination treatments. (Interestingly enough, suchstudieshavebeenacceptedin thedevelopment of antiepileptic treatment.) Further, although nobody would doubt lithium’s remarkable efficacy in treating both mania and depression, as well as for prophylaxis in a subgroup of bipolar patients, the standardsandrigor of scientific research methodology and ethics have changedsinceitsfirst approval. Thisposes significant challenges to designing and satisfactorilycompletingstudieswith new medications, particularlyformaintenance orprophylactic treatment. Finally, thereis both considerable interest in medications that offer symptomatic relief when treating BD and a surge of interest in their neuroprotective effects-not onlyin regard to the newer medications but also in regard to lithium in particular. Acute Mania Different studies have shown that lithium (Bowden, Brugger, Swann et al., 1994; Maggs, 1963), valproate (Bowden et al., 1994), and carbamazepine (Post, Uhde, Roy-Byme et al., 1987) are superior to placebo. In addition, a randomized open study has shown their effectiveness for adolescents with BD (Kowatch, Suppes, Carmody et al., 2000). There is considerable evidence that moodstabilizersmaybe sufficient in dealing with some psychotic symptoms and that benzodiazepines, such as lorazepam (Bowde et. al., 1994), when added to mood stabilizers, effectively manage behavioral dyscontrol in a subgroup of manic patients. Valproate and carbamazepine are likely more effective than lithium in treating mixed mania. Becausetheyact rapidly, havesignificant antimanic and antipsychotic efficacy, and can be administered parenterally, typical neurolepticsare widelyused-particularly for aggressive, agitated, or psychotic patients-despite concerns about extrapyramidal side effects and the risk of tardive dyskinesia during long-term use. The advent of atypical neuroleptics has offered the clinician newand effective choices in the treatment of mania. The followinghave been shown to be efficacious in controlled studies of both