Friday, December 1, 2023
As an organization accredited by the ACCME, Medscape, LLC requires everyone who is in a position to control the content of an education activity to disclose all relevant financial relationships with any commercial interest. The ACCME defines "relevant financial relationships" as financial relationships in any amount, occurring within the past 12 months, including financial relationships of a spouse or life partner, that could create a conflict of interest.
Medscape, LLC encourages Authors to identify investigational products or off-label uses of products regulated by the US Food and Drug Administration, at first mention and where appropriate in the content.
Resident in Psychiatry, Emory University, Atlanta, Georgia
Reunette W. Harris Professor and Chairman, Department of Psychiatry & Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia
processing....
Data from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD), a large NIMH-sponsored multicenter study designed to determine optimal acute and chronic pharmacologic and behavioral interventions for the treatment of bipolar disorder, has started to become publicly available. After enrollment in the study, patients received evaluations every 3 months during their first year and then every 6 months thereafter. As this study first started enrolling patients in 1998, the usage pattern of the agents, in particular the newer anticonvulsants and/or second generation antipsychotics, may have subsequently changed. The most commonly prescribed class of medications at study entry, the standard mood stabilizers like lithium, valproate, or carbamazepine, were taken by 72% of patients. The newer anticonvulsants (lamotrigine, gabapentin, and topiramate) were taken by 32% of patients. Nearly 41% of patients were treated with antidepressants, and 27% were taking second-generation atypical antipsychotics. Only 11% of patients were treated with mood stabilizer monotherapy.[30]
STEP-BD was designed as a hybrid to include patients in both naturalistic long-term follow-up along with those in randomized, placebo-controlled clinical trials. The overall study included patients with bipolar disorder of all subtypes, severity, and demographic groups. All study clinicians received a minimum of 20 hours of treatment-related study in the management of bipolar disorder[31] based on expert opinion consensus guidelines.[32] They were encouraged to offer patients treatments from "Menus of Reasonable Choices" and were not forced to adhere to a formal treatment algorithm within the naturalistic part of the study. The study designers intended for STEP-BD to serve well-characterized bipolar subjects who could enter both clinical trials and randomized pathways for acute depression, refractory depression, and relapse prevention. The randomized care pathways generally had more rigorous inclusion criteria than did the naturalistic arm of the study and were primarily designed to compare one of several psychotropic medication regimens considered first-line treatment options.[32]
The significant relapse rates seen in the STEP-BD population further highlight the need for newer and better behavioral and pharmacologic interventions. Of interest, over a 24-month follow-up of 1469 patients who were symptomatic at study entry, only 58% achieved recovery, defined as 2 or fewer syndromal features of mania, hypomania, or depression for at least 8 weeks. However, 49% of these patients had a recurrence of symptoms after being free of symptoms for 8 or more weeks: 35% of patients relapsed into a depression, and 14% of patients relapsed into a mania.[33] Data from this study are available at www.stepbd.org.
Despite the advances in the management of acute mania, the treatment of bipolar depression remains a formidable challenge. There is increasing evidence that the largest part of the disability of bipolar disorder stems from the depressive phase of the illness. A long-term longitudinal study of patients with bipolar I disorder followed over a 12-year period is of interest.[34] Patients were symptomatically ill approximately 47% of the time over the 12-year period they were followed, spending nearly 3-fold more time experiencing syndromal or subsyndromal depressive symptoms as compared with manic or hypomanic symptoms. Currently, a clear demonstration of the efficacy of the atypical antipsychotics, with the exception of quetiapine and the olanzapine/fluoxetine combination, in the treatment of bipolar depression is still lacking. There is evidence that lamotrigine,[35] quetiapine,[18,36] olanzapine, and the fluoxetine-olanzapine combination[37] are effective in the treatment of bipolar depression, as are various antidepressants and electroconvulsive therapy, though a number of failed trials have been reported.[38] Of note, lamotrigine, which was approved by the FDA for the prevention of recurring episodes of bipolar disorder, is not effective in the treatment of acute mania. Other monotherapy trials with anticonvulsants, including gabapentin, oxcarbazepine, and topiramate, also have failed to document efficacy for the management of acute mania.[39,40]
A review of the literature highlights the significant unmet needs in the treatment of bipolar disorder. Even in the most recent studies described above, clinical remission rates are suboptimal. Although this is in part related to the relatively brief observation period of 21 days for the majority of acute mania, long-term maintenance studies have also demonstrated a high rate of relapse within the 6- to 18-month observation period usual in many of these studies. Although monotherapy would be ideal, it is not realistic for a sizeable percentage of bipolar patients. Like cancer and hypertension, bipolar disorder requires considerable pharmacologic management coupled with psychotherapeutic intervention to achieve the highest rates of remission. Until we obtain a better understanding of the pathophysiology of bipolar disorder, we must be guided by evidence of the best current treatment of this devastating disorder.
Supported by an independent educational grant from GlaxoSmithKline.
