S. Nassir Ghaemi

Is bipolar disorder still underdiagnosed? Are antidepressants overutilized?

BACKGROUND Previous studies have suggested that bipolar disorder may be underdiagnosed, and that antidepressants may be over-utilized in its treatment. METHODS Consecutively admitted patients (n =48) diagnosed with DSM-IV bipolar disorder, type I, (n = 44) or schizoaffective disorder, bipolar type, (n = 4) were interviewed systematically and their charts were reviewed to confirm diagnosis before admission. They were then treated according to systematic structured interview diagnoses. These data reflect the changes in diagnoses and treatment. RESULTS 40% (19/48) were identified with previously undiagnosed bipolar disorder, all previously diagnosed with unipolar major depressive disorder. A period of 7.5+/-9.8 years elapsed in this group before bipolar diagnosis was made. Antidepressant use was high on admission (38%) and was reduced with acceptable treatment response rates. The adjunctive use of risperidone appeared to be a good treatment alternative. LIMITATIONS While diagnoses were made prospectively, treatment response was assessed retrospectively, and was based on non-randomized, naturalistic therapy. CONCLUSIONS Systematic application of DSM-IV criteria identified previously undiagnosed bipolar disorder in 40% of a referred population of patients with mood disorders, all previously misdiagnosed as unipolar major depressive disorder. Antidepressants appeared overutilized and risperidone was an effective alternative adjunctive therapy agent.

The International Society for Bipolar Disorders (ISBD) Task Force Report on Antidepressant Use in Bipolar Disorders

OBJECTIVE The risk-benefit profile of antidepressant medications in bipolar disorder is controversial. When conclusive evidence is lacking, expert consensus can guide treatment decisions. The International Society for Bipolar Disorders (ISBD) convened a task force to seek consensus recommendations on the use of antidepressants in bipolar disorders. METHOD An expert task force iteratively developed consensus through serial consensus-based revisions using the Delphi method. Initial survey items were based on systematic review of the literature. Subsequent surveys included new or reworded items and items that needed to be rerated. This process resulted in the final ISBD Task Force clinical recommendations on antidepressant use in bipolar disorder. RESULTS There is striking incongruity between the wide use of and the weak evidence base for the efficacy and safety of antidepressant drugs in bipolar disorder. Few well-designed, long-term trials of prophylactic benefits have been conducted, and there is insufficient evidence for treatment benefits with antidepressants combined with mood stabilizers. A major concern is the risk for mood switch to hypomania, mania, and mixed states. Integrating the evidence and the experience of the task force members, a consensus was reached on 12 statements on the use of antidepressants in bipolar disorder. CONCLUSIONS Because of limited data, the task force could not make broad statements endorsing antidepressant use but acknowledged that individual bipolar patients may benefit from antidepressants. Regarding safety, serotonin reuptake inhibitors and bupropion may have lower rates of manic switch than tricyclic and tetracyclic antidepressants and norepinephrine-serotonin reuptake inhibitors. The frequency and severity of antidepressant-associated mood elevations appear to be greater in bipolar I than bipolar II disorder. Hence, in bipolar I patients antidepressants should be prescribed only as an adjunct to mood-stabilizing medications.

The International Society for Bipolar Disorders (ISBD) Task Force report on the nomenclature of course and outcome in bipolar disorders.

OBJECTIVES Via an international panel of experts, this paper attempts to document, review, interpret, and propose operational definitions used to describe the course of bipolar disorders for worldwide use, and to disseminate consensus opinion, supported by the existing literature, in order to better predict course and treatment outcomes. METHODS Under the auspices of the International Society for Bipolar Disorders, a task force was convened to examine, report, discuss, and integrate findings from the scientific literature related to observational and clinical trial studies in order to reach consensus and propose terminology describing course and outcome in bipolar disorders. RESULTS Consensus opinion was reached regarding the definition of nine terms (response, remission, recovery, relapse, recurrence, subsyndromal states, predominant polarity, switch, and functional outcome) commonly used to describe course and outcomes in bipolar disorders. Further studies are needed to validate the proposed definitions. CONCLUSION Determination and dissemination of a consensus nomenclature serve as the first step toward producing a validated and standardized system to define course and outcome in bipolar disorders in order to identify predictors of outcome and effects of treatment. The task force acknowledges that there is limited validity to the proposed terms, as for the most part they represent a consensus opinion. These definitions need to be validated in existing databases and in future studies, and the primary goals of the task force are to stimulate research on the validity of proposed concepts and further standardize the technical nomenclature.

Pramipexole augmentation in the treatment of unipolar and bipolar depression : A Retrospective chart review

Objective: To assess the effectiveness and safety of pramipexole as an adjunctive medication in refractory bipolar and unipolar depression in a naturalistic setting. Methods: Retrospective chart review by psychiatrists on staff at a university hospital identified all patients who had received pramipexole. Response was based on moderate to marked improvement in the Clinical Global Impression-Improvement (CGI-I) scale. Results: Pramipexole (mean dose 0.70 mg/d, mean duration 24.4 weeks) was effective in 6/12 (50.0%) of patients with bipolar depression, and 8/20 (40%) of patients with unipolar depression, mean duration of follow-up of 24.4 weeks. One case of transient hypomania was noted. Eight patients discontinued pramipexole due to lack of response and four due to side effects. Conclusions: Pramipexole, used as an adjunct to antidepressants or mood stabilizers, appeared to be effective and safe in the treatment of unipolar and bipolar depression. These uncontrolled, retrospective, naturalistic pilot data require confirmation by controlled research before conclusions can be made.

Lack of insight in bipolar disorder : the acute manic episode

This study examined the clinical correlates of lack of insight in bipolar disorder. In 28 acutely manic patients interviewed upon hospitalization and/or discharge, mean scores on the Insight and Treatment Attitudes Questionnaire (ITAQ) improved only slightly, from 12.0 on admission to 15.5 on discharge (p = .08), despite marked improvement in other psychiatric symptoms. A reciprocal relationship was found between higher ITAQ scores and involuntary hospitalization (r = -.38). Like schizophrenia, bipolar disorder appears to be a condition in which poor insight is a prominent characteristic.

Side effects of atypical antipsychotics: extrapyramidal symptoms and the metabolic syndrome.

In this article we examine the two major classes of side effects with atypical antipsychotics: extrapyramidal symptoms (EPS) and the metabolic syndrome (the triad of diabetes, dyslipidemia, and hypertension, with associated obesity). We conclude that atypical antipsychotics continue to have notable risks of EPS, particularly akathisia, and that these agents also appear to increase the risk of the metabolic syndrome, though this effect seems most marked with clozapine and olanzapine. Novel conclusions based on this review are as follows: we provide a classification scheme based on low versus high D2 binding affinity (which is, to our knowledge, a new means of classifying atypical antipsychotics); we emphasize that the akathisia risk is likely equal among agents and that tardive dyskinesia is an early, and not late, risk in treatment (a common misconception); we make the methodological point that in randomized clinical trials, there is a high risk of false-negatives regarding side effects; we raise the issue of confounding bias in epidemiological studies of metabolic syndrome; and we stress the need to compare side effects in the same studies and not different studies. Future prospective observational cohort studies must target side effects and be designed to collect and analyze data on confounding factors.

Diagnostic guidelines for bipolar disorder: a summary of the International Society for Bipolar Disorders Diagnostic Guidelines Task Force Report

The Diagnostic Guidelines Task Force of the International Society for Bipolar Disorders (ISBD) presents in this document and this special issue a summary of the current nosological status of bipolar illness, a discussion of possible revisions to current DSM-IV and ICD-10 definitions, an examination of the relevant literature, explication of areas of consensus and dissensus, and proposed definitions that might guide clinicians in the most valid approach to diagnosis of these conditions given the current state of our knowledge.

Is insight in mania state-dependent? A meta-analysis

In the first meta-analysis of studies assessing insight in mania, we sought to determine whether insight in mania is state-dependent or a trait-like condition. In schizophrenia, insight is a trait-like condition. If state-dependent, insight in mania would differ from insight in schizophrenia, and different treatment and research implications would follow. Seven reports using standardized insight rating scales in mania were identified through a MEDLINE literature search. Four longitudinal studies were included in a meta-analysis. The meta-analysis found that insight appears to be state-dependent. Insight showed a 20% improvement (95% confidence intervals, 7% to 34%) after recovery from acute mania (p = .003). Insight improves in bipolar disorder with resolution of the acute manic episode, suggesting that insight is state-dependent in bipolar disorder. We suggest that impaired insight be considered as part of the diagnostic picture of acute mania.

Cognitive impairment in bipolar disorder and schizophrenia: a systematic review

Aims: Previous comparisons of cognitive decline among patients with bipolar disorder (BD) and schizophrenia (SZ) have found somehow quite similar profiles of deficits, but results have varied between studies. Therefore an extensive and thoughtful systematic review of the matter is warranted. Methods: Studies were found through systematic search (PubMed) following PRISMA guidelines. To be included, studies must have assessed the following cognitive functions: executive functions, memory, IQ, attention-concentration, and perceptuomotor function. In order to make comparison between the two entities, studies should include BD patients with operationally defined euthymia, schizophrenic patients in remission, and third group of healthy control patients. Comparisons were made after controlling for years of schooling and residual affective symptoms. Results: We found that overall both SZ and BD patients present deficits on all neurocognitive measures compared to healthy controls. In particular, SZ patients show more severe and pervasive cognitive deficits while BD patients present a milder and more confined impairment. In addition, evidence from the literature suggests that SZ and BD patients share a similar cognitive impairment profile with different degrees of deficits. Therefore, the difference between the two groups seems to be more quantitative (degree of deficit) rather than qualitative (profile), supporting a dimensional approach to the two clinical entities. Limitations of the present review includes the impossibility to control for effects of medication, varying time required for assessment across studies, illness diagnosis reliability, and course severity. Conclusion: Patients with BD might exhibit a cognitive impairment that could be similar to SZ in terms of their profile, although patients with SZ may have more severe and widespread impairments.

Acute treatment of bipolar disorder with adjunctive risperidone in outpatients.

Objective: To test the hypothesis that, although typical neuroleptics are commonly used in the treatment of bipolar disorder, newer atypical antipsychotic agents, like risperidone, may be more effective and better-tolerated. Method: The effectiveness of risperidone was evaluated in 14 outpatients with bipolar disorder, type I, who received risperidone for 6.4 ± 2.7 weeks at 2.75 ± 1.8 mg/day. Results: Nine (64%) patients were much improved based on Clinical Global Impression (CGI) scores, and mean Global Assessment of Functioning (GAF) scores improved from 48.2 ± 4.9 to 58.8 ± 7.3 (t = 4.49, P = 0.0006, paired t test). Treatment was well tolerated, and no patient experienced worsening of mood symptoms while receiving risperidone. Conclusion: This open series suggests risperidone is beneficial in the treatment of outpatients with bipolar disorder.