Atypical antipsychotic-induced weight gain

Introduction of a new group of antipsychotic drugs, called atypical because of the proprieties differing them from classical neuroleptics, gave hope for the beginning of a new era in treatment of psychoses, including schizophrenia. Different mechanisms of action not only resulted in a broader spectrum of action and high efficacy but also in a relative lack of extrapiramidal symptoms. However, atypical neuroleptics are not totally free from adverse effects. Symptoms such as sedation, metabolic changes and weight gain, often very quick and severe - present also in the case of classical drugs, but put to the background by extrapiramidal symptoms--have become prominent. Weight gain is important both from the clinical and subjective point of view--as associated with serious somatic consequences and as a source of enormous mental distress. These problems are addressed in this review, with the focus on weight gain associated with the use of specific atypical neuroleptics.     

Self-weighing in weight gain prevention and weight loss trials

Background: Although self-monitoring is a central tenet of behavioral approaches to changing health behavior, clinical and public health recommendations for better controlling body weight do not emphasize weight self-monitoring. Purpose: The objective was to determine whether more frequent self-weighing exerts a positive influence on weight loss or weight gain prevention. Methods: This study examined cross-sectional and longitudinal associations between self-weighing frequency and weight in two distinct groups: 1,226 adults who were enrolled in a weight gain prevention trial, and 1,800 adults who were enrolled in a weight loss trial. Results: Although the samples differed significantly in weight and baseline demographic characteristics, the distribution of baseline weighing frequencies did not differ by study. In both groups, more frequent self-weighing at baseline was associated with greater age, lower fat intake, White ethnicity, current nonsmoking status, a greater history of dieting to lose weight, and lower current body mass index. Despite similar weighing instructions, differential patterns of weighing frequency over time were observed: Weight loss dieters increased weighing over time regardless of treatment group (control or intervention), whereas weight gain preventers decreased weighing over time in the control group and increased weighing over time in intervention groups. Most important, higher weighing frequency was associated with greater 24month weight loss or less weight gain. Conclusions: Results support the idea that daily weighing is valuable to individuals trying to lose weight or prevent weight gain. Daily self-weighing should be emphasized in clinical and public health messages about weight control. Experimental studies on the effects of weighing frequency in these contexts are recommended. This research was supported by National Institute of Diabetes and Digestive and Kidney Diseases Grants 1R01-DK45361 and 1R01-DK53826     

Chronic imipramine treatment and weight gain

A study of weight change in subjects treated with imipramine was performed on recurrent depressive outpatients. The patients (n = 52) were treated with imipramine (200-250 mg/day) and psychotherapy for 16 weeks. Each individual was weighed upon entry to the study (drug-free) and then weekly thereafter for 16 weeks. Of the 44 women (85%) and 8 men (15%) in the study, 60% of the total group had a weight gain or loss less than 5 pounds (mean = 1.1 pounds) over this time. A weight gain of 6-10 pounds was observed in 19% of subjects, while 9% of the group gained 11-15 pounds. Only 6% (3 subjects) gained more than 15 pounds. Three subjects (6%) lost 6-10 pounds. No correlations were observed between a change in weight and the subject's age, sex, prior weight, or response to medication.     

Lithium treatment and weight gain.

The problem of lithium maintenance treatment and weight gain was examined in 70 manic-melancholic patients who had been in treatment for 2 to 10 years. Their case records were reviewed and they answered a questionnaire. Out of 70 patients, 45 increased in weight with a mean weight gain of about 10 kg. The patients who increased in weight during the treatment were overweight already before the start and reached a weight about 20% higher than their ideal weight. They nearly all found themselves overweight and took measures to slim. No connection between a history of infant obesity and weight gain was found. Increase in appetite was only found in one third of the patients and had only a weak influence on the degree of weight gain. Nearly all the patients felt an increased thirst, and a very clear correlation between liquid intake and weight gain was found. It is recommended that all patients are repeatedly warned of the risks involved in satisfying their increased thirst on lithium by fluids rich in calories.     

Reversal of antipsychotic-associated weight gain

BACKGROUND: Given growing concern about weight gain associated with treatment with antipsychotic agents, we performed a retrospective chart review of patients who reversed weight gain associated with antipsychotic treatment to determine the prevalence of reversal and both the course and methods used. METHOD: Prevalence of weight gain reversal was determined by surveying clinicians. Of 53 patients who gained >/= 20 lb (9 kg) during antipsychotic treatment, an initial sample of 12 patients (23%) who subsequently lost >/= 10 lb (5 kg) was identified. These 12 patients were combined with additional patients, identified by the authors, who met the same criteria for reversal of antipsychotic-associated weight gain to form a total sample of 35 patients. Course and methods of weight loss were determined by reviewing these patients' charts. Information about interventions and both antipsychotic and other medications was collected. RESULTS: At the point of maximum weight gain, the total sample of 35 patients had gained a mean of 29.36 kg (64.73 lb) over a mean of 33 months. At the point of greatest weight loss (56 months), these patients were a mean of 10.86 kg (23.94 lb) over their baseline weight. The most recent weight for patients (63 months) indicated they were 14.81 kg (32.65 lb) over baseline. The most frequent weight loss interventions were regular dietician visits (42.9% [N = 15]), self-directed diet (28.6% [N = 10]), and weight loss as a treatment goal (25.7% [N = 9]). The least frequent interventions were no intervention (5.7% [N = 2]), psychiatrist addressing weight loss (5.7% [N = 2]), and surgery (2.9% [N = 1]). No significant change in medications prescribed was found. CONCLUSION: Some patients who gain weight while taking antipsychotic medications are able to stop gaining and lose weight over time, largely through behavioral interventions. While patients' weight fluctuated, this group sustained a loss of approximately half their initial gain. Dietary interventions appear promising and should be explored further to prevent and reverse weight gain.     

Memantine-associated reversal of clozapine-induced weight gain

INTRODUCTION: Weight gain is a frequently observed adverse event in the treatment with atypical antipsychotics that significantly affects the patients' physical health and treatment compliance. METHODS: We report on a treatment-resistant schizophrenic patient who received an add-on treatment with the low-affinity NMDA antagonist memantine because of cognitive disturbances. RESULTS: During this treatment we observed a marked decrease of clozapine-induced weight gain. The causal relationship to memantine could be demonstrated using an on-off-on design with a significant increase of weight after discontinuation and again a substantial weight loss after re-exposition with memantine. Beside weight, also negative symptoms improved. DISCUSSION: Prospective controlled trials evaluating the safety and possible positive effects of memantine on antipsychotic induced weight gain are needed.     

Diurnal weight gain in chronic psychosis

We found diurnal weight gain to be abnormal among 93 chronically psychotic patients, most of whom had schizophrenia. They were weighed at 7 a.m. and 4 p.m. weekly for 3 weeks. We normalized the diurnal weight gain (NDWG) as a percentage by subtracting the 7 a.m. weight from the 4 p.m. weight, multiplying the difference by 100, and dividing the result by the 7 a.m. weight. NDWG was 1.7 +/- 1.0 percent for the study sample, 0.6 +/- 0.4 percent for 16 acutely psychotic controls, and 0.5 +/- 0.4 percent for 29 normals. More than 60 percent of the study sample had abnormal NDWG values. NDWG related to antipsychotic drug dose (r = 0.290, p = 0.005) with variability in drug dose accounting for 8 percent of the variability in NDWG. This report provides yet another piece of evidence that disordered water balance is common in chronic psychiatric patients. The etiology is unknown, but it may relate to subtle brain abnormalities in the regulation of fluid intake and excretion.