Daniel J. Rapport

Predictors of valproate response in bipolar rapid cycling

Multiple regression/discriminant analyses were separately conducted to generate predictors of acute and prophylactic antimanic and depressive outcome in 101 valproate-treated bipolar rapid cyclers. Predictors of good antimanic response included decreasing or stable episode frequencies and nonpsychotic mania. Predictors of good antidepressant response included nonpsychotic mania worsening over the years of the illness and absence of borderline personality disorder comorbidity. This report confirms prior findings that indicate that valproate possesses marked acute and prophylactic antimanic and antimixed effects with only poor to moderate antidepressant properties.

Current research on rapid cycling bipolar disorder and its treatment

Rapid cycling is a pattern of presentation of bipolar disorder that specifies the course of the illness and is associated with a greater morbidity. The validity of rapid cycling as a distinct course modifier for bipolar disorder has been demonstrated and the term has been incorporated into the DSM-IV. The phenomenon of rapid cycling tends to appear late in the course of the disorder, occurs more frequently among females, and is more frequently seen in patients with bipolar type II disorder. Stimulants such as cocaine may also play some role in rapid-cycling. It is generally accepted that a recent history of rapid cycling predicts non-response to monotherapy with lithium and probably carbamazepine as well; however it is also possible that concurrent use of antidepressants may play a role in destabilizing the illness course under these agents. Thus, clinical considerations suggest that discontinuing antidepressants may facilitate the recovery process. Among clinically available monotherapies, valproate and lamotrigine appear to be the most useful clinically. However, other treatments such as lithium, carbamazepine, the atypical antipsychotic agents, thyroid hormone, and bupropion are frequently needed augmentation strategies. Electroconvulsive therapy may also prove efficacious in selected cases. The present paper provides a critical review of the evidence for the foregoing clinical issues in rapid cycling.

Controlled trials in bipolar I depression: focus on switch rates and efficacy

Until recently, the rate at which patients switch from bipolar depression to the manic or hypomanic phase of the disorder during treatment with antidepressant medications was poorly defined. The completion of three large-scale, double-blind controlled trials in bipolar I depression has improved understanding of this phenomenon. The low switching rates observed in these studies of lamotrigine, paroxetine and moclobemide may indicate a special application of these drugs in the management of patients prone to antidepressant-induced switching. These studies also confirm prior suggestions that tricyclic antidepressants present the highest risk of switching. At present there is no consensus over the optimal definition of switching. Standardising the definition may lead to improvements in the clinical management of bipolar disorder.

Clinical Studies on the Use of Lamotrigine in Bipolar Disorder

New mood stabilizers that possess efficacy in the depressed phase of bipolar disorder are needed. The use of marketed antidepressants puts bipolar patients at some increased risk for drug-induced hypomania/mania and rapid cycling. During the development of the antiepileptic, lamotrigine, the drug was observed to improve mood, alertness, and social interactions in some patients with epilepsy. These early observations provided the rationale for investigations into lamotrigine’s potential efficacy in bipolar disorder. There are now 14 open clinical reports involving a total of 207 lamotrigine-treated patients with bipolar disorder that suggest this drug possesses a broad spectrum of efficacy in the management of the depressed, hypomanic, manic, and mixed phases of bipolar disorder. In an attempt to replicate and extend these preliminary open-label prospective findings, a series of multicenter, double-blind, placebo-controlled studies evaluating the efficacy and dose-response relationships of lamotrigine in the various phases of the illness, including both acute and maintenance designs in both bipolar I and II disorder, is ongoing.

Primary care for the developmentally disabled adult.

ConclusionsIt is important to appreciate that as the U.S. population matures, the number of middle-aged and elderly developmentally disabled adults living in the community will increase. This population may constitute a larger proportion of the primary care physician’s practice. Although this population carries a heavier burden of chronic illness than their nondisabled counterparts, studies indicate that the vast majority of their problems can be handled well by primary care physicians. We hope more information will become available to clinicians over the next few years as more controlled studies are performed to define the physical and mental health needs of the developmentally disabled. Providing primary care for the developmentally disabled is challenging but rewarding. Physicians need to accept the challenges of this aspect of medicine and contribute their efforts and expertise to this field.

Emotional Status of Third Year Medical Students and Their Responses to a Brief Intervention

Three classes of entering third-year medical students answered questions regarding emotional and physical stress responses and self care behaviors and were screened for anxious and depressive symptoms. The most common stress response was emotional and the majority of students felt the most tension in their neck and shoulders. Students’ primary self care behavior was exercise. Sixteen percent screened positive for depressive symptoms as assessed by the Patient Health Questionnaire-2 (PHQ-2) and 24% screened positive for anxiety as assessed by the Generalized Anxiety Disorder-2 (GAD-2) scale. A brief relaxation exercise was offered to students and resulted in statistically significant increases in perceived relaxation, lower tension, and increased skin temperature, a physiological indicator of relaxation. While a short relaxation intervention can produce significant improvements in stress-related symptoms, some students may be at risk for emotional disorders during medical school and need further evaluation and treatment.

A Descriptive Analysis of Factors Leading to a 1-Year Remission in Bipolar Disorder.

Background: Bipolar spectrum disorders are associated with symptomatic and functional disability in many patients. Other studies have examined predictors of outcome with variable results. The goal of this retrospective study was to identify medications associated with a minimum of 12 consecutive months of symptomatic, functional, and syndromal remission. Methods: The charts of 121 patients with confirmed bipolar disorder were reviewed. Data on medical regimen and demographic and adherence factors were gathered using standardized data collection sheets approved by the University of Toledo Institutional Review Board. The criterion for improvement was set at 12 consecutive months of Clinical Global Impressions Improvement ratings of ⩽2, which is a far higher standard of syndromal and functional remissions than the usual 8 consecutive weeks used by the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision. Results: In this sample of 121 patients, 43.8% achieved a minimum of 12 consecutive months of remission, whereas 56.2% did not. When bipolar disorder was divided into its subtypes, 45.5% of our cohort were diagnosed with bipolar I disorder, 27.3% were diagnosed with bipolar II disorder, and 27.3% were diagnosed with bipolar disorder, not otherwise specified. Of the 55 patients with bipolar I disorder, 27 remitted and 28 did not. Of the 33 patients with bipolar II disorder, 12 remitted and 21 did not. Of the 33 patients with bipolar disorder, not otherwise specified, 14 remitted and 19 did not. The treatment regimen that was most closely associated with remission was a combination of atypical antipsychotics (primarily aripiprazole), mood stabilizers (primarily lamotrigine), and an antidepressant. In addition, the patients who achieved remission were more likely to be adherent to medication and with appointments. Conclusions: The chart review showed that 12 consecutive months of symptomatic remission was achieved in our clinic in 43.8% of patients with bipolar disorder when they were treated with tailored medication regimens. The remainder (56.2%) failed to achieve 12 consecutive months of remission based on real-time Clinical Global Impressions Improvement ratings. The combination of an atypical antipsychotic, a mood stabilizer, and an antidepressant was highly correlated with 1-year remission.