Kate V. Fogarty

Weight loss in overweight patients maintained on atypical antipsychotic agents

Background:Weight gain and associated medical morbidity offset the reduction of extrapyramidal side effects associated with atypical antipsychotics. Efforts to control weight in antipsychotic-treated patients have yielded limited success.Methods:We studied the impact of an intensive 24-week program of diet, exercise, and counseling in 17 chronically psychotic patients (10 women, seven men) who entered at high average body weight (105.0±18.4 kg) and body mass index (BMI) (36.6±4.6 kg/m2). A total of 12 subjects who completed the initial 24 weeks elected to participate in an additional 24-week, less intensive extension phase.Results:By 24 weeks, weight-loss/patient averaged 6.0 kg (5.7%) and BMI decreased to 34.5 (by 5.7%). Blood pressure decreased from 130/83 to 116/74 (11% improvement), pulse fell slightly, and serum cholesterol and triglyceride concentrations changed nonsignificantly. With less intensive management for another 24 weeks, subjects regained minimal weight (0.43 kg).Conclusions:These findings add to the emerging view that weight gain is a major health problem associated with modern antipsychotic drugs and that labor-intensive weight-control efforts in patients requiring antipsychotic treatment yield clinically promising benefits. Improved treatments without weight-gain risk are needed.

Duloxetine in the treatment of irritable bowel syndrome: an open-label pilot study†

To assess the efficacy of duloxetine for irritable bowel syndrome (IBS).

Memantine in the treatment of binge eating disorder: An open-label, prospective trial†

OBJECTIVE To assess preliminarily the efficacy of memantine in binge eating disorder. METHOD This was an open-label, 12-week, flexible-dose (5-20 mg/day) trial of memantine in binge eating disorder. The primary outcome was frequency of binge days. Secondary outcomes included frequency of binge episodes, body-mass index (BMI), weight, Clinical Global Impressions Severity (CGI-S), Three Factor Eating Questionnaire (TFEQ), Montgomery-Asberg Depression Rating Scale (MADRS), Hamilton Anxiety Rating Scale (HAM-A), and Sheehan Disability Scale (SDS). Longitudinal random regression analysis was performed for frequency of binge days and episodes, BMI, weight, and CGI-S; analysis of baseline to endpoint change was performed for all outcomes. RESULTS Sixteen individuals received memantine; 15 completed at least one postbaseline evaluation, 9 completed the study. Mean dose at endpoint was 18.3 mg/day. Memantine was associated with significant reductions in frequency of binge days and episodes, severity of illness (p < .001 for both analyses), disinhibition on the TFEQ (p = .015), and disability on the SDS (p < .05 for three subscales). There was no significant change in BMI, weight, MADRS, HAM-A, and TFEQ cognitive restraint and hunger. CONCLUSION In this open-label trial, memantine was well tolerated and effective in reducing binge eating, severity of illness, and disability, but had little effect on BMI and weight.

Aripiprazole: initial clinical experience with 142 hospitalized psychiatric patients.

Background: Aripiprazole is the first dopamine D2 receptor partial-agonist approved for treatment of schizophrenia. Its apparently benign adverse-effect profile encourages broader use in other disorders, especially to limit weight gain associated with other antipsychotic or antimanic agents. We considered the first 6 months of experience with aripiprazole in psychiatric inpatients with a range of disorders. Methods: We analyzed data obtained from medical records of patients treated with aripiprazole who were hospitalized at McLean Hospital (for 19 ± 18 days) between December 2002 and June 2003 to evaluate dosing, tolerability, and clinical effects of this new agent in patients diagnosed with DSM-IV psychotic, major affective, or other disorders. Results: Out of a sample of 2766 adult inpatients (65.5% women), 142 were given aripiprazole (mean final daily dose, 16.1 ± 6.2 mg, 0.20 ± 0.09 mg/kg body weight) for major affective disorders (52%), primary psychotic disorders (40%), and dementia (8%). CGI ratings improved by 20% on average. Adverse effects were infrequent (15.5%), were three times more likely among women, and most often involved moderate behavioral activation or nausea, with no new episodes of mania. Of the patients who were given aripiprazole, 83% continued it at discharge. Many patients were obese when they were admitted, and obesity was associated with relatively low mg/kg doses of aripiprazole. Conclusions: Aripiprazole was used in a range of disorders and was generally well tolerated. Adverse effects may reflect its unique dopamine partial-agonist activity. Since aripiprazole is likely to be considered for obese patients, body weight should be considered in establishing adequate doses. Controlled trials of this antipsychotic agent in disorders other than schizophrenia are needed.

Ziprasidone: first year experience in a hospital setting.

Background: The antipsychotic drug ziprasidone, FDA-approved and introduced in the United States in February 2001 for the treatment of schizophrenia, appears to have similar efficacy but better tolerability than older antipsychotics and requires further evaluation under clinical conditions. Methods: We analyzed medical records of McLean Hospital inpatients treated with ziprasidone between March 2001 and February 2002, gathering data on DSM-IV diagnoses, presenting symptoms, dosing, concomitant psychotropic medications, clinical changes, adverse effects, and electrocardiographic (ECG) findings. Results: Ziprasidone was given to 151 inpatients (3.4% of admissions; 108 women, 43 men), aged 37.5 ± 11.4 years, who presented with depression (n = 79), psychosis (n = 46), mania (n = 18), bipolar mixed-states (n = 4), or other conditions (n = 4). Daily doses averaged 49.8 ± 34.1 mg initially and 83.2 ± 46.3 mg at discharge; the greatest dose increases during hospitalization (by a mean of 61%) were in patients with schizoaffective disorder (n = 46; 30% of cases). In 41 cases (27%), ziprasidone was the only antipsychotic at discharge; in 61 (40%) it was used with other antipsychotics. Ziprasidone was discontinued during hospitalization in 49 cases (32.5%), due to lack of efficacy (n = 26; 17.2%), adverse effects (n = 13, 8.6%), or reasons not stated (n = 10, 6.6%). Of 70 patients for whom ECG data were obtained during treatment with ziprasidone, 8 (11%) had QTc intervals > 450 msec during treatment, but none of the 39 patients with ECGs both before and during ziprasidone treatment showed clinically meaningful increases in QTc intervals. Ziprasidone was discontinued in 4 patients (2.6%) due to concern about QTc intervals, but in no case was the QTc interval ≥ 500 msec or associated with clinical cardiac toxicity. Improvements in CGI and GAF scores from admission to discharge were similar across diagnoses and unrelated to length of stay or ziprasidone dose. Conclusions: Ziprasidone was well tolerated by hospitalized patients with various major psychiatric disorders and may be of value in conditions other than schizophrenia.