Treatment options for acute mania include lithium(Drug information on lithium), divalproex, carba-mazepine, and atypical antipsychotics. There is no compelling evidence suggesting that the overall response or remission rate with any of these categories of treatments is superior to the others. This largely reflects an absence of comparative data rather than proven noninferiority. Research re- sults that agree with clinical experience do, however, indicate that some treatment options may exert a faster onset of action (eg, atypical antipsychotics) for some symptom domains (eg, agitation) compared with other treatment choices (eg, lithium).
All treatment options have been shown to be effective in bipolar mania, while fewer have been established as efficacious in mixed-state presentations. The combination of lithium or divalproex and several atypical antipsychotic drugs (eg, risperidone(Drug information on risperidone), olanzapine(Drug information on olanzapine), and quetiapine(Drug information on quetiapine)) has proved to be more effective than lithium or divalproex monotherapy in the management of acute mania.25 The relative efficacy of atypical antipsychotic medications as monotherapy versus their combination with lithium and divalproex is currently unknown.
Although it is perceived that the presence of psychotic symptoms would invite the need for an atypical antipsychotic, trials that have compared the efficacy of divalproex with olanzapine have failed to establish that divalproex is inferior in the treatment of psychotic mania.25 Nevertheless, most experts would recommend the use of an atypical antipsychotic drug alone or adjunctively in the management of a patient who is manic with psychotic features.
Clinicians often receive conflicting messages regarding benzodiazepine use in the management of BD. Ben- zodiazepines with intermediate half-lives (eg, lorazepam(Drug information on lorazepam)) are routinely included as "rescue medications" in acute mania trials. They are prescribed to treat residual symptoms (eg, anxiety, agitation, and insomnia) and also as antidotes for treatment-emergent adverse events. Generally speaking, judicious use of a benzodiazepine with an intermediate half-life for the short-term treatment of mania may be warranted in carefully selected patients. The long-term use of benzodiazepines is generally discouraged and is associated with several tolerability and safety concerns.Acute bipolar depression
Episodes of depressive symptoms dominate the course of BD. Nevertheless, established treatments for bipolar depression remain woefully inadequate. During the next several years, practitioners will be exposed to several new treatment options for the management of bipolar depression. The Texas Implementation of Medication Algorithms guidelines for bipolar depression recommend the use of lithium, lamotrigine(Drug information on lamotrigine), or atypical antipsychotics as first- and second-stage treatments for bipolar depression.
Conventional unimodal antidepressant medications (with the exception of the combination of olanzapine and fluoxetine(Drug information on fluoxetine)) have been relegated to later stages in situations in which patients are nonresponsive to and/or intolerant of previous medications. This positioning of antidepressants reflects the concern regarding antidepressant-induced hypomania and cycle acceleration in BD. It should be mentioned, however, that a consensus on the sequencing of antidepressants or of their appropriateness in BD does not currently exist.Maintenance treatment of bipolar disorder
If an ideal maintenance therapy for BD existed (ie, one that completely eliminated any chance of recurrence and provided a restoration of full functioning), then acute therapies would not be needed. Unfortunately, the intermediate and long-term prognosis of BD remains rather disappointing. Results from the Systematic Treatment Enhancement Program for Bipolar Disorder, which combined psychosocial interventions with pharmacotherapy, indicated that about half of the patients with BD who recovered from an index episode experienced a recurrence within 18 months of prospective follow-up.26
The FDA has currently given its approval to lithium, olanzapine, aripiprazole(Drug information on aripiprazole), and lamotrigine for the maintenance treatment of bipolar illness. The selection of a treatment should be based on patient profile, preference, comorbidity, cost, tolerability, and safety. Atypical antipsychotic drugs, as a class of treatment, are increasingly conceptualized as mood-stabilizing therapies for patients with BD. Clinicians are encouraged to familiarize themselves with the profile of efficacy and tolerability for each agent across multiple phases of BD (Table, see Psychiatric Times, October, p 51).Bipolar II disorder
Relatively few treatments for bipolar II disorder have been proven to be efficacious. This is all the more disconcerting in light of the prevalence of bipolar II disorder and its burden of illness, which is estimated to be similar to, and perhaps to exceed that of, bipolar I disorder. The treatment of bipolar II disorder has often been with the application of therapies already established to be efficacious in bipolar I disorder. Although intuitive, this approach may not always be valid in light of evidence indicating that bipolar II disorder may be distinct from bipolar I disorder in its course, outcome, and treatment re- sponse characteristics.27
Treatment options for bipolar II disorder with proven efficacy in randomized controlled trials include lithium, carbamazepine(Drug information on carbamazepine), lamotrigine (rapid-cycling bipolar II), and quetiapine (bipolar depression).25 The Canadian Network for Mood and Anxiety Treatments guidelines provide a starting point for considering treatment options in bipolar II disorder. We expect that new treatment studies will lead to significant changes in the selection and sequencing of treatments for bipolar II disorder.CONCLUSION
BD is a complex, multidimensional medical condition associated with substantial morbidity and mortality. The encompassing aim of managing a patient with BD is to bring about wellness. A CDMM is encouraged as a framework for organizing and integrating systems and treatments for individuals and groups of persons with BD. The use of evidence-based guidelines as a vehicle to select and sequence treatment alternatives in BD is part of any CDMM. A related key element in managing chronic medical conditions is the identification of critical end points and measurement of patient progress.
A working definition for remission in BD has been proposed. Until this and other definitions are validated, measurement-based care is supported by research evidence and will increasingly be a standard of care in the future.
Dr McIntyre is associate professor in the department of psychiatry and pharmacology, University of Toronto, and head of the mood disorders psychopharmacology unit, University Health Network in Toronto. Dr McIntyre is a consultant and speaker for AstraZeneca, Eli Lilly, Janssen-Ortho, Organon, Wyeth, Lundbeck, GlaxoSmithKline, Oryx Pharmaceuticals, Biovail, Pfizer, and Prestwick. He has received research funding from Wyeth, GlaxoSmithKline, Merck, Servier, and AstraZeneca.
Ms Soczynska is a research coordinator in the mood disorders psychopharmacology unit, University Health Network in Toronto. Mr Konarski is director of neuroimaging in the mood disorders psychopharmacology unit, University Health Network in Toronto. Both authors report no conflicts of interest to disclose regarding the subject matter of this article.