Carlos A. Zarate

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

OBJECTIVEnThe 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.nnnMETHODnAn 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.nnnRESULTSnThere 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.nnnCONCLUSIONSnBecause 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 McLean-Harvard first-episode project: 6-month symptomatic and functional outcome in affective and nonaffective psychosis.

BACKGROUNDnThe McLean-Harvard First-Episode Project recruited affective and nonaffective patients at their first lifetime psychiatric hospitalization.nnnMETHODSnBaseline evaluation and 6-month follow-up in 257 cases yielded recovery outcomes defined by syndromal (absence of DSM-IV criteria for a current episode) and functional (vocational and residential status at least at baseline levels) status. Time to recovery was assessed by survival analysis, and risk factors by multivariate logistic regression.nnnRESULTSnSyndromal recovery was attained by 77% of cases over an average of 84 days. By diagnostic group, syndromal recovery rates ranked (p = .001) major affective disorders (81%) > nonaffective acute psychoses (74%) > schizoaffective disorders (70%) > schizophrenia (36%). Functional recovery was significantly associated to syndromal recovery, diagnosis, shorter hospitalization normalized to year, and older age at onset. Average hospital stay declined across the study period, but recovery did not vary with year of entry.nnnCONCLUSIONSnSyndromal recovery was achieved by nearly one half of patients within 3 months of a first lifetime hospitalization for a psychotic illness, but functional recovery was not achieved by 6 months in nearly two thirds of patients who had attained syndromal recovery.

The effect of comorbid substance use disorders on the course of bipolar disorder: a review.

&NA; Population‐based studies have documented that among all patients with major psychiatric disorders, those with bipolar disorder have the highest prevalence of comorbid substance abuse and dependence. The cause of this high comorbidity rate has not been clearly established, and the relationship is probably bidirectional. Articles published in English from 1980 through 1997 containing the terms comorbidity, mania, outcome, and substance use were identified by searching Medline and then the bibliographies of the articles identified in this search. The literature review showed several risk factors to be associated with comorbid substance use disorders in bipolar disorder patients: early age of onset, gender, family history of substance use disorders, and presence of mixed mania. Methodological enhancements that have helped to advance understanding in this area include distinguishing between primary and secondary disorders, between the different subtypes of bipolar disorder, and between first and subsequent episodes of illness. In order to determine the temporal sequence of onset, longitudinal studies initiated at the onset of either illness need to be pursued. Increased understanding of the association between bipolar disorder and comorbid substance use disorder will facilitate improved detection and intervention, as well as more‐effective preventive measures that could improve outcome for patients with bipolar disorder.

Is There a Relationship Between Clozapine and Obsessive-Compulsive Disorder?: A Retrospective Chart Review

The emergence of obsessive-compulsive symptoms during clozapine treatment has been reported in recent case studies, yet the incidence and significance of this finding is still unclear pending reliable data from a larger sample of patients. Hospital records of 142 randomly selected inpatients started on clozapine treatment at McLean Hospital before July 1, 1992, were reviewed retrospectively. Based on a limited retrospective chart review, there were no definitive cases of patients who developed obsessive-compulsive disorder (OCD) or whose OCD worsened as a result of clozapine treatment. Although some fluctuation of OCD symptoms may have occurred in two cases, it is unclear whether those symptoms were related to treatment with clozapine (or other psychotropic drugs) or to undulations in the natural history of OCD. No definitive relationship between OCD symptoms and clozapine treatment could be established in this limited study. Further clarification of this matter awaits outcome research using prospective methodologies.

A meta-analysis of the use of typical antipsychotic agents in bipolar disorder

BACKGROUNDnThe potential benefits of typical antipsychotic agents in bipolar disorder are offset by serious treatment-associated side effects. Despite these concerns and the availability of mood stabilizing agents, the treatment of bipolar disorder with typical antipsychotic agents appears to be widespread.nnnMETHODSnA Medline search identified 16 publications that outlined medication use among 2378 bipolar disorder patients. Meta-analysis was used to estimate a weighted average of the relative proportions of the treatment use, where the weights were the reciprocals of the estimated variances for each study.nnnRESULTSnOverall, 84.7% of bipolar patients received typical antipsychotic agents, with a loading toward a greater in-patient (90.7%) relative to out-patient (65.3%) use. Monotherapy accounted for 53.8% of typical antipsychotic use, and typical antipsychotic/mood stabilizer combination therapy accounted for 47.4%. In four studies where length of treatment data were available, the median of minimum typical antipsychotic use was 2.5 months, with 96.0% of the patients receiving typical antipsychotic agents.nnnLIMITATIONSnThe meta-analytic technique employed in this analysis is limited by the possible inclusion of studies with unreliable study designs or biased treatment practices, publication bias in which some studies may not have been reported, and possible lack of identification of all relevant studies.nnnCONCLUSIONSnTypical antipsychotic agents are commonly used in the treatment of bipolar disorder, possibly due to dissatisfaction with mood stabilizer monotherapy especially in psychotic mania, the high prevalence of psychotic symptoms in acute mania, inappropriate continuation of typical antipsychotic agents after initial stabilization, and/or unavailability or unfamiliarity with new treatments. These findings also suggest that typical antipsychotics may have not only antipsychotic effects in mania but perhaps also antimanic properties.

Telephone versus in-person clinical and health status assessment interviews in patients with bipolar disorder.

&NA; We evaluated the correspondence between in‐person‐ and telephone interview‐derived data on affective symptoms, health‐related quality of life, disability days, and medication compliance in patients with bipolar disorder. Twenty‐eight outpatients with DSM‐III‐R‐documented bipolar disorder were randomly assigned to an initial in‐person or telephone interview. An average of 4.0 days later, they were reassessed by the other interview method. Results indicate good to excellent agreement between telephone and in‐person interviews on measures of mania (intraclass correlation coefficient (ICC) = 0.92) and depression symptoms (ICC = 0.90), suicide risk (k = 0.80), and alcohol use (k = 0.61), scores on the Medical Outcomes Study 36‐Item Short‐Form Health Survey (ICCs = 0.66–0.92), and medication compliance (ICCs = 0.50–0.66). Measures of bed disability days (ICC = 0.34) and restricted activity days (ICC = 0.66) showed less agreement. Telephone interviews are feasible and reliable for collecting data on psychiatric and other health‐related outcomes in bipolar disorder patients.

Combined valproate or carbamazepine and electroconvulsive therapy.

This pharmacoepidemiological study was undertaken to determine if the combination of elec-troconvulsive therapy (ECT) and the anticonvulsants valproate (VPA) or carbamazepine (CBZ) is safe and efficacious. The charts of seven patients receiving ECT and VPA or CBZ (ECT–anticonvulsant group) concurrently between May 8, 1989, and May 9, 1993, were reviewed to determine the indication for each treatment, the number and type of ECT treatments, the seizure duration, adverse events, and the efficacy of the combination. The ECT–anticonvulsant group was compared to patients not treated with anticonvulsants (ECT-alone group) to determine if there were any differences in the two groups. Three patients had a marked clinical improvement, two a moderate response, one a minimal response, and one no response. The ECT–AC group, compared to the control group, had a shorter duration of seizures when unilateral treatments were used. However, there were no differences in the other variables compared. One patient had moderate confusion, and the other mild confusion and hypomania. This small case series suggests that the combination of ECT and anticonvulsants is safe and may be considered in patients for whom prophylaxis with anticonvulsant drugs is planned. Further controlled studies are needed to confirm our findings.

First-episode schizophreniform disorder : comparisons with first-episode schizophrenia

BACKGROUNDnSchizophreniform disorder remains poorly understood and has been reported probably to be a heterogeneous group of psychotic disorders.nnnMETHODnThis study compared first-episode schizophreniform disorder (N=12) and schizophrenia (N=18) patients. The authors propose that schizophreniform disorder has a different type of onset and outcome than schizophrenia. Patients were given extensive assessments at initial evaluation, 6 month follow-up, and 24 month follow-up. Comparisons between the two groups were made on type of onset, demographic, clinical ratings and outcome variables.nnnRESULTSnPatients with schizophreniform disorder compared to patients with schizophrenia were more likely to have an acute onset (P=0.003), and have recovered by 6 months (P=0.03). However, there were no differences in outcome at 24 months. Furthermore, all schizophreniform cases except for two were re-diagnosed at 24 months as having schizophrenia.nnnCONCLUSIONSnThe findings suggest that the initial differences of schizophreniform disorder compared to schizophrenia were not apparent at 24 months follow-up. Schizophreniform disorder did not emerge as a highly distinctive and stable form of psychosis that merits a diagnostic classification separate from schizophrenia.

Shifts in hospital diagnostic frequencies: bipolar disorder subtypes, 1981–1993

Annual rates of bipolar and schizoaffective disorder (SA) subtypes from 1981 to 1993 at a private university psychiatric hospital were reviewed. Annual total diagnostic rates for all bipolar disorders (BPD) remained constant between 1981 and 1993, (22%), while the frequency of SA rose 6-fold, from 1.4% to 8.7%. Rates of BPD, not otherwise specified increased 7-fold, while that for the other BPD subtypes fell in the same period of time. Several factors may have influenced these trends including changes in diagnostic criteria used, treatment-oriented diagnostic bias and indirect effects of sharply falling length of stay.

The Danger of Hopefulness: A Clozapine “Cure” of Chronic Psychosis

Julie is a 22-year-old white female with paranoid schizophrenia, seen in weekly outpatient psychotherapy by the same clinician over the past 5 years. She is followed separately for psychopharmacological treatment. She lives with her mother, adoptive stepfather, and sister. Her biological father also suffers from schizophrenia. By the age of 17, Julie had had seven psychiatric admissions. Following her first hospitalization at age 12, she returned to school and again achieved good grades for several years. By 14, however, she was abusing a wide range of substances, including alcohol, marijuana, cocaine, LSD, and opiates. A year-long drug rehabilitation program had little impact. Bizarre and sometimes violent behavior led to several more hospitalizations. A variety of antipsychotic medications proved ineffective in tempering either her delusional thinking or her outbursts of violent behavior. By the age of 16, an intricate network of delusions had begun to crystallize. Since that time, Julie has maintained that she is the reincarnation of various deceased artists and performers, among them John Lemon, Billie Holiday, Jackson Pollock, Leonard0 da Vinci, and Edith Piaf. Because of her belief that she is these individuals, she has attempted to enlist the support of lawyers to collect the money due for her concerts, films, and artwork. Outpatient psychotherapy was seen as a supportive intervention in which Julie could slowly move toward acceptance of her schizophrenia and begin developing skills to strengthen her relationships with family members and peers. She adamantly rejected the recommendation of