Atypical antipsychotics and diabetic ketoacidosis: a review.

RATIONALE: Atypical antipsychotics have been linked to weight gain and type 2 diabetes, but are also associated with diabetic ketoacidosis (DKA), which can occur more acutely and in the absence of weight gain. OBJECTIVES: Our aim was to review current case reports of DKA in the context of atypical antipsychotic treatment to better understand (a) the scope of the problem, (b) its relationship to different atypical agents, (c) risk factors, (d) long-term outcome, and (e) putative mechanisms of action. METHOD: Searches in PubMed/Medline, as well as the University of Toronto's Scholar Portal, were performed for all relevant articles/abstracts in English. RESULTS: Sixty reports, yielding 69 cases, affirm that DKA is a rare but serious risk with almost all atypical antipsychotics; however, liability seems to vary between agents, at least partially mirroring risk of weight gain. Mean age of onset was 36.9 years (range 12-80), with 68 % of cases occurring in males, and 41 % in individuals of African American or African Caribbean descent. Over one third of cases present with either no weight gain or weight loss, and 61 % of these require ongoing treatment for glycemic control. Death occurred in 7.25 % of cases. CONCLUSION: While the underlying mechanisms are not well understood, antipsychotic-related DKA can occur soon after treatment onset and in the absence of weight gain. Although rare, clinicians must remain vigilant given its acute onset and potential lethality.

Smoking cessation in women with severe mental illness: exploring the role of exercise as an adjunct treatment.

OBJECTIVE: The aim of this study was to investigate the potential role of exercise in smoking cessation in women with severe mental illness (SMI). METHODS: Semistructured interviews with 12 women diagnosed with SMI receiving smoking cessation treatment were conducted. RESULTS: Participants perceived three roles for exercise in assisting smoking cessation--addressing fears with preexisting chronic health conditions, emotion management and distraction, and weight management. Most participants identified health care providers (HCPs) as needing to play a supportive role in integrating exercise into smoking cessation attempts. CONCLUSION: Findings support a potential role for exercise in facilitating smoking cessation among women with SMI. PRACTICE IMPLICATIONS: HCPs should consider developing referral links with exercise specialists to facilitate smoking cessation in women with SMI.

Psychiatric illness and obesity: recognizing the "obesogenic" nature of an inpatient psychiatric setting.

OBJECTIVE: The prevalence of obesity and obesity-related diseases is higher among individuals with psychiatric illness than in the general population. This study examined environmental factors that contribute to obesity in one psychiatric hospital in Canada. METHODS: Semistructured interviews were conducted with 25 key stakeholders from multiple professional disciplines at the hospital. Transcribed interviews were analyzed through content analysis with the analysis grid for environments linked to obesity (ANGELO) framework as a categorical template. RESULTS: Factors contributing to obesity in this setting were related to increased energy intake, such as easy access to high-calorie snacks and beverages, and reduced energy expenditure, such as lack of access to staircases. CONCLUSIONS: Psychiatric settings may contribute to the high prevalence of obesity among individuals with psychiatric illness. Ecologically framed interventions are required to address obesity in this population.

Insulin resistance and decreased glucose-stimulated insulin secretion after acute olanzapine administration.

The newer atypical antipsychotics, as a class, have been associated with an increased risk of weight gain and metabolic abnormalities. The mechanisms underlying this phenomenon are currently unclear, but there are data to suggest the possibility of an immediate (as opposed to chronic) effect of these drugs. The aim of the present study was to assess the acute effects of olanzapine on specific measures of insulin sensitivity and secretion. Healthy animals were tested in either the hyperinsulinemic-euglycemic or the hyperglycemic clamp. After reaching steady state in the hyperinsulinemic-euglycemic clamp, rats were injected with olanzapine (3 mg/kg sc) and monitored for an additional 130 minutes. In the hyperglycemic clamp, olanzapine was injected approximately 90 minutes before receiving a glucose bolus, and hyperglycemia was maintained via exogenous glucose infusion for an additional 90 minutes. Insulin and C-peptide levels were monitored throughout this clamp.Acute administration of olanzapine significantly lowered the glucose infusion rate due to an increase in hepatic glucose production and a decrease in glucose utilization. Olanzapine pretreatment induced hyperglycemia and markedly decreased plasma insulin and C-peptide in response to the glucose challenge. These findings indicate that olanzapine can directly induce metabolic changes that occur rapidly and well in advance of the changes that might be anticipated as a result of its weight-gain liability. We present novel findings highlighting an olanzapine-induced deficit in beta-cell functioning.

Metabolic monitoring for patients treated with antipsychotic medications.

OBJECTIVES: Metabolic side effects of antipsychotic treatment include weight gain, dyslipidemia and increased susceptibility to diabetes. Patients with schizophrenia have increased coronary heart disease mortality and reduced life expectancy. There is an urgent clinical need to monitor antipsychotic-treated patients for metabolic disturbance. Our objectives were to review published international monitoring guidelines, establish goals for metabolic monitoring, and make recommendations for practice. METHOD: We reviewed the major published consensus guidelines for metabolic monitoring of patients treated with antipsychotic medications and selectively reviewed practice guidelines for the management of diabetes, dyslipidemia, and hypertension. RESULTS: Patients with serious mental illness have markedly elevated rates of metabolic disturbance and limited access to general medical care. Monitoring, but not necessarily medical treatment of metabolic disorder, falls within the scope of psychiatric practice and should include screening for metabolic disturbance as well as tracking the effects of antipsychotic treatment. In addition, psychiatrists and psychiatric services should work toward facilitating patients' access to medical care. There is considerable consensus in the published guidelines. Areas of dissent include which patients to monitor, the utility of glucose tolerance testing, and the point at which to consider switching antipsychotics. CONCLUSION: We encourage clinicians to adopt a structured system for conducting and recording metabolic monitoring and to develop collaborations with family physicians, diabetes specialists, dieticians, and recreation therapists to facilitate appropriate medical care for antipsychotic-treated patients.

Pharmacologic and nonpharmacologic strategies for weight gain and metabolic disturbance in patients treated with antipsychotic medications.

OBJECTIVES: To provide an overview of pharmacologic and nonpharmacologic strategies for antipsychotic-associated weight gain and metabolic disturbance, to identify important areas for future research, and to make practice recommendations based on current knowledge. METHODS: We undertook a selective review of interventions for weight gain and metabolic disturbance in the general population and in individuals treated with antipsychotic medications, focusing on randomized controlled trials in schizophrenia. RESULTS: Pharmacologic strategies include medication choice, medication dosage and formulation, choice of concomitant psychotropic medications, medication switching, medication addition to effect weight loss or prevent weight gain, and medications to increase insulin sensitivity. Medication choice and medication switching may have the most potent influence on weight and metabolic parameters. Modest short-term weight loss can occur with the addition of selective medications and (or) lifestyle interventions. However, more rigorous and longer-term studies are needed. CONCLUSIONS: Although difficult, the prevention of weight gain and the promotion of weight loss are possible for individuals treated with antipsychotic medications. Further research, including diabetes prevention studies, is required. We suggest a pathway for the management of weight gain and emerging metabolic disturbance.

Insulin resistance and adiponectin levels in drug-free patients with schizophrenia: A preliminary report.

OBJECTIVE: To compare the insulin sensitivity and adiponectin levels of medication-free patients suffering from schizophrenia or schizoaffective disorder with that of matched healthy volunteers. METHOD: We evaluated 9 nondiabetic patients aged 26.6 years (median 26 years, range 17 to 41 years) and matched volunteers, using the frequently sampled intravenous glucose tolerance test, minimal model analysis, and fasting adiponectin levels. RESULTS: The mean insulin sensitivity index of the patients was 42% lower than that of the healthy volunteers (P = 0.026), with inadequate compensation in insulin secretion. Patients with schizophrenia tended to have reduced adiponectin levels (P = 0.055). CONCLUSIONS: By direct measurement, this study provides evidence of insulin resistance and susceptibility to type 2 diabetes in patients with schizophrenia who are free of antipsychotic drugs.