New treatment guidelines developed for bipolar disorder

An update in practice guidelines by the American Psychiatric Association (APA) now offers more options to psychiatry healthcare professionals caring for bipolar patients. The APA's original guidelines, published in 1994, were updated based on new data regarding the efficacy of newer anticonvulsants, such as Lamictal (lamotrigine, GlaxoSmith-Kline), and atypical antipsychotics, such as Zyprexa (olanzapine, Novartis) and Risperdal (risperidone, Janssen) in treating bipolar disorders.

Medications previously unstudied for use in treating the disorder are now known to be effective and are incorporated into the new guidelines. While there is no cure for bipolar disorder, proper treatment can lower the associated morbidity and mortality, including the rate of suicide.

The new publication contains three principal parts: treatment recommendations; background information and review of available (published and unpublished) evidence; and suggestions for future research needs.

For treatment of an acute manic or mixed (manic and depressive) episode, the guidelines suggest lithium plus an antipsychotic agent, or valproate plus an antipsychotic. For patients less ill, monotherapy with lithium, valproate, or an atypical antipsychotic, such as olanzapine or risperidone, may be sufficient. Controlling symptoms, such as agitation, aggression, and impulsivity, and ensuring the safety of patients and those around them is the goal of therapy in treating a manic or mixed episode.

Atypical antipsychotics are preferred to the older, typical antipsychotics because of a favorable side-effect profile—fewer extrapyramidal effects, lower incidence of tardive dyskinesia, and less sedation. Short-term adjunctive treatment with a benzodiazepine may also be beneficial during an acute episode.

The previous guidelines suggested lithium alone or in combination with an antidepressant for treating acute episodes of bipolar depression. Lithium and lamotrigine are now considered the first-line agents; antidepressant therapy is not recommended initially, except in some severely ill patients. For those not responding to first-line agents at optimal doses, adding lamotrigine, bupropion, or paroxetine is the next step. Alternatives include the addition of antidepressants, such as a selective serotonin reuptake inhibitor, venlafaxine, or a monoamine oxidase inhibitor.

"I agree with the use of lamotrigine for the treatment of an acute episode of bipolar depression," said Luriko Ajari, pharmacy manager at the Langley Porter Psychiatric Institute at the University of California San Francisco (UCSF) and assistant clinical professor at the UCSF school of pharmacy. "The antidepressant effects of lithium can take up to two months, and since the depressive phase of bipolar disorder is associated with considerable morbi-dity, newer recommendations were needed." Ajari believes there are many patients who cannot take lithium, due to its side effects. She further noted that lamotrigine had stabilized many of her patients who relapsed when they could no longer tolerate lithium because of reduced kidney function or other adverse events. Lithium and lamotrigine each exhibit antidepressant properties without inducing switches to mania or rapid cycling.

Rapid cycling refers to four or more episodes (major depressive, mixed, manic, or hypomanic) that occur within one year. The episodes must be separated by at least two months or switch to an episode of the opposite polarity (e.g., from major depressive to manic). The APA suggests identifying and eliminating certain conditions or situations that can lead to rapid cycling, such as hypothyroidism, drug or alcohol abuse, or the use of antidepressants.

The initial treatment for rapid cycling should include lithium or valproate. Lamotrigine may be used as an alternative treatment. Combinations of medication are often required. Although lamotrigine is being used more often in her practice, Ajari said psychiatrists may be reluctant to prescribe the drug because slow titration is necessary to achieve an optimal dosage, and extra monitoring is needed due to a potential for severe skin rash (including Stevens-Johnson syndrome) and drug interactions.

Because bipolar disorder is a chronic illness, the APA emphasizes the importance of maintenance treatment. "Many patients may not receive adequate maintenance treatment for several reasons," said Elizabeth A. Winans, Pharm.D., BCPP, clinical assistant professor, University of Illinois College of Pharmacy and department of psychiatry, Psychiatric Clinical Research Center. Bipolar patients are often noncompliant with medications and may not understand the continued need for them, she said. She also believes a clinician's practice may differ from the guidelines, specifically in the duration of maintenance therapy for the less severely ill patient.

After remission of an acute episode, bipolar patients are at high risk for relapse for up to six months, and the APA recommends using lithium or valproate as "continuation treatment." Alternatives include lamotrigine, carbamazepine, or oxcarbazepine. If one of these was used to achieve remission from the most recent acute episode, it should generally be continued into the maintenance phase.

Maintenance therapy is always recommended for patients with bipolar I disorder (history of at least one episode of mania) and usually recommended for bipolar II disorder (history of major depressive episodes and one or more hypomanic episodes).

The need for antipsychotic agents should be reassessed before continuing their use into the maintenance phase, and these agents should often be discontinued unless they are needed to control psychosis. Atypical antipsychotics during the maintenance phase may be considered, according to the APA.

Medication dosages should be optimized for patients who experience a breakthrough manic or depressive episode despite ongoing maintenance treatment. Serum drug levels should be monitored to ensure that they fall within the therapeutic range. Patients still not responding may require additional medications.

While the APA acknowledges that the guidelines are meant only as recommendations, and treatment of bipolar patients must always be tailored to the individual, "most clinicians are already treating patients in a manner that closely resembles the guidelines," said Winans.

According to the APA, the goal is to provide practicing healthcare professionals with the current evidence on treatment approaches so they may integrate recent findings into their daily practices.

The final version of the guidelines will be published as a supplement to the American Journal of Psychiatry and will be available this month at the APA's annual meeting in Philadelphia.