Focus
on Bipolar Disorder Treatment: |
| A new publication and a recent medical meeting addressed the long-term management of bipolar disorder. The latest volume in the Review of Psychiatry series, volume 24: Advances in Treatment of Bipolar Disorder (American Psychiatric Publishing, Inc., 2005), includes a chapter by Charles L. Bowden, M.D., and Vivek Singh, M.D., entitled “Long-Term Management of Bipolar Disorder.” In it, the authors describe 3 paradigm shifts that have occurred in the treatment of bipolar disorder: (1) a growing awareness that bipolar disorder is a chronic illness and needs long-term maintenance treatment, (2) a realization that the focus of treatment needs to be on the illness itself, not individual episodes, and (3) the recognition that full functional recovery, not just symptomatic recovery, should be the goal of treatment. Achieving these objectives when treating a patient with bipolar disorder calls for a careful combination of psychosocial and pharmacologic strategies on the part of the health care provider. An important aspect of long-term management that directly affects the effectiveness of treatment is the patient's adherence to his or her treatment regimen. Although adherence can be affected by many different factors, one major factor is tolerability of treatment. A treatment's tolerability profile can be a result of dosing strategies—with divalproex and lithium, for example, it is important to keep the dosage as low as possible to prevent adverse effects. Another part of the long-term management of bipolar disorder is the recognition of what Bowden and Singh call “signal events.” These events indicate whether a patient has either returned to a premorbid level of functioning, such as when a patient shows renewed interest in a hobby, or is at risk for relapse or recurrence, such as when a patient reports an increased level of personal stress. Taking these signal events into account can help the clinician tailor treatment to meet the patient's needs. At the foundation of a long-term treatment plan for a patient with bipolar disorder is pharmacotherapy. Few long-term placebo-controlled studies have been conducted, so the evidence base for treatment recommendations is still narrow. Bowden and Singh again emphasized the importance of choosing a medication that will be well-tolerated over the long term because discontinuation and noncompliance are directly related to adverse side effects. Using the lowest therapeutic dose, thus minimizing the chance of severe side effects, and educating the patient about what to expect from his or her medication can help encourage adherence. The authors then reviewed available evidence for medications often used in bipolar disorder, including lithium, valproate, carbamazepine, lamotrigine, antipsychotics, and antidepressants. Only 2 medications, lithium and lamotrigine, are approved by the U.S. Food and Drug Administration for maintenance treatment of bipolar disorder. Many patients with bipolar disorder are treated with more than one medication. The authors reviewed combination therapy, distinguishing between add-on therapy and cotherapy. With add-on therapy, a patient starts taking one medication and has another added at a later date, and with cotherapy, a patient initiates treatment with 2 medications at the same time. The evidence is stronger in support of add-on therapy, but the cotherapy model may be useful in patients who present with severe symptoms of differing types and who need those symptoms controlled immediately. [top]
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| Data regarding maintenance combination therapy is limited, with little evidence dictating whether a patient can be on combination therapy for the long term or whether one agent should be tapered after the patient is stable. Long-term treatment of bipolar disorder was also addressed at the 2005 annual meeting of the American Psychiatric Association (APA). In a scientific session, Peselow and associates reported on the risk of relapse among patients who continued lithium treatment versus those who discontinued treatment (Scientific and Clinical Report Session 15). All patients had been stable for 4 years on lithium therapy. After an additional 3 years, 77% of patients in the continuation group had remained well, compared with only 26% of patients in the discontinuation group (p < .0001). Several new research posters reported long-term results as well. Warrington et al. evaluated the long-term efficacy of ziprasidone in bipolar mania or mixed episodes, with or without psychotic symptoms, in an open-label, 52-week extension study (NR299). By the study's end, mean Mania Rating Scale (MRS) scores and Clinical Global Impressions-Severity scale scores were significantly lower (p < .005) than at baseline, regardless of the presence of psychotic symptoms. Houston and colleagues reported results on olanzapine versus lithium prophylaxis of bipolar disorder (NR377). Euthymic patients were randomly assigned to maintenance treatment with olanzapine or lithium, and in this post hoc analysis, they were grouped according to the number of previous manic episodes. For patients with early-stage bipolar disorder, i.e., with 2 or fewer previous manic episodes, olanzapine-treated patients had a significantly lower rate of recurrence than did lithium-treated patients (2.1% vs. 26.4%; p = .008). For patients with intermediate- and late-stage bipolar disorder, the difference between the prophylactic effect of these 2 agents narrowed (13.3% vs. 23.8% and 23.9% vs. 33.3%, respectively). The management of subsyndromal symptoms is a major concern in the long-term treatment of bipolar disorder. Yatham and coworkers analyzed pooled data from 2 large maintenance trials to determine whether the polarity of the previous episode predicted the polarity of subsyndromal symptoms (NR305). Subsyndromal symptoms of depression were 12.5 times more frequent than subsyndromal manic symptoms in patients with an index episode of depression, and subsyndromal manic symptoms were 1.4-fold more frequent than subsyndromal depressive symptoms in patients with a previous manic episode. Dr. Bowden commented on the importance of these findings, noting that the reports summarized in this article and similar recent data from bipolar studies emphasize subset differences, rather than treating findings on bipolar disorder as fully applicable to all bipolar patients. For example, this is the case in studies differentiating mixed mania from euphoric mania in symptoms, illness course, and treatment responsiveness. He suggests that even further subdivisions make sense and will further refine ways that we think about causes and treatments of bipolar disorder. For example, there is evidence that mixed mania includes at least 2 subtypes, one principally anxious and depressed, another principally irritable. He observed that a positive benefit of such finer-grained analyses is that most can be applied by clinicians to improve their current care of patients with bipolar disorders. Take the CME test online Download the CME test as a PDF Return to the main Brief Reports page |
| Drug names: carbamazepine (Equetro, Tegretol, and others), divalproex (Depakote), lamotrigine (Lamictal), lithium (Eskalith, Lithobid, and others), olanzapine (Zyprexa), ziprasidone (Geodon). Supported by an educational grant from GlaxoSmithKline.
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