Peter Manu

Does antipsychotic polypharmacy increase the risk for metabolic syndrome

OBJECTIVE To determine whether the coprescribing of two or more antipsychotics, a relatively frequent practice with little data to support its safety and efficacy, is associated with an increased prevalence of metabolic syndrome. METHODS 364 newly admitted adults treated with second-generation antipsychotics underwent assessments evaluating antipsychotic polytherapy, and of the presence of metabolic syndrome and triglycerides/high-density lipoprotein cholesterol ratio>3.5 (TG/HDL), a sensitive marker of insulin resistance. The correlates of antipsychotic polytherapy and associations with metabolic syndrome and TG/HDL were determined by univariate comparisons and multiple logistic regression analyses. RESULTS Antipsychotic polytherapy was present in 70 patients (19.2%) and was significantly more likely in patients with schizophrenia and those treated with clozapine, quetiapine or ziprasidone (p<0.0001). Compared with antipsychotic monotherapy, polytherapy was associated with elevated rates of metabolic syndrome (50.0% vs. 34.3%, p=0.015) and TG/HDL (50.7% vs. 35.0%, p=0.016). However, in logistic regression analyses, metabolic syndrome was significantly associated with higher body mass index (BMI), older age, a diagnosis of bipolar disorder or schizophrenia, and cotreatment with a first-generation antipsychotic (r(2): 0.25, p<0.0001). The TG/HDL marker of insulin resistance was associated with higher BMI, male sex, Caucasian race and absence of aripiprazole treatment (r(2): 0.14, p<0.0001). Antipsychotic polypharmacy dropped out of both multivariate models. CONCLUSIONS Compared with patients receiving antipsychotic monotherapy, patients on antipsychotic polytherapy have higher rates of metabolic syndrome and lipid markers of insulin resistance. However, antipsychotic polytherapy is not independently associated with the prevalence of these abnormalities, which are related to known demographic, clinical and anthropometric risk factors.

Equally increased risk for metabolic syndrome in patients with bipolar disorder and schizophrenia treated with second‐generation antipsychotics

OBJECTIVE Although second-generation antipsychotics (SGAs) are widely used in treating schizophrenia and bipolar disorder, their effects on dyslipidemia, glucose intolerance, metabolic syndrome (MetS), and coronary heart disease (CHD) risk are less well documented for bipolar disorder. We compared bipolar disorder and schizophrenia patients receiving SGAs to determine whether MetS prevalence is influenced by the primary psychiatric diagnosis or concomitant mood stabilizer treatment. METHODS Admission assessment of MetS criteria (abdominal obesity, fasting hypertriglyceridemia, low high-density lipoprotein cholesterol, hyperglycemia, arterial hypertension) and the calculated 10-year CHD risk in bipolar disorder and schizophrenia patients treated with SGAs and closely matched for age, sex, and race. RESULTS Compared to schizophrenia patients (n = 111), those with bipolar disorder (n = 74) had lower body mass index (27.1 +/- 5.3 versus 29.9 +/- 8.1, p = 0.0053), were more likely treated with mood stabilizers (60.8 versus 36.0, p = 0.0009), and less likely treated with clozapine (1.3% versus 15.3%, p = 0.0017) or two antipsychotics (10.8% versus 34.2%, p = 0.0003). Despite these differences, bipolar disorder and schizophrenia patients had comparable rates of MetS (43.2% versus 45.9%, p = 0.71) and predicted CHD events (10-year risk >10%: 18.9% versus 23.4%, p = 0.47). Using >or=100 mg/dL as the adapted glucose criterion, MetS rates were 54.0% in both diagnostic groups (p = 1.0). Mood stabilizer co-treatment was not associated with MetS or its individual criteria. CONCLUSIONS Patients with bipolar disorder and schizophrenia who are treated with SGAs have similarly high rates of MetS. These findings suggest a shared susceptibility to antipsychotic-related metabolic dysregulations that is not primarily related to psychiatric diagnosis or concomitant mood stabilizer treatment.

Predictors of insulin resistance in the obese with metabolic syndrome

BACKGROUND In the obese, the metabolic syndrome (MetS) is assumed to reflect insulin resistance. OBJECTIVE To determine the predictors of insulin resistance in obese subjects with MetS. DESIGN We used the 90th percentile of the homeostasis model assessment (HOMA) to define insulin resistance in 4958 nondiabetic adults evaluated in the National Health and Nutrition Examination Surveys, 1999-2004, and compared the 373 obese subjects who were insulin-resistant (HOMA 9.52+/-5.73) to a control group of 373 obese who had the highest sensitivity to insulin (HOMA 1.79+/-0.44). MEASUREMENTS MetS was present in 312 (83.6%) obese with insulin resistance and in 156 (41.8%) obese from the insulin-sensitive control group. Demographic, metabolic, and lifestyle variables were analyzed with logistic regression. RESULTS In a logistic model of insulin resistance given the presence of MetS, the significant predictors were triglycerides (P=0.0021), body mass index (P=0.0096), HDL-cholesterol (P=0.0098), age (P=0.0242) and smoking (P=0.0366). LIMITATIONS Cross-sectional design prevents elucidation of causality for the association between insulin resistance and MetS. CONCLUSIONS Insulin resistance is not an obligatory correlate of MetS in the obese. Its likelihood can be predicted by cigarette smoking and by the severity of obesity and dyslipidemia.

Low-density lipoprotein cholesterol in patients treated with atypical antipsychotics: missed targets and lost opportunities.

BACKGROUND The treatment of psychotic disorders with second-generation antipsychotics (SGAs) has been linked to an increased risk of coronary heart disease (CHD). Lowering low-density lipoprotein-cholesterol (LDL-C) to individualized targets of 100, 130 or 160 mg/dl reduces the risk of CHD. We determined the prevalence of above-target LDL-C and its management during psychiatric hospitalization. METHODS 364 hospitalized adults receiving SGAs underwent LDL-C target assessments. Records of patients with above-target LDL-C were searched for dietary or pharmacologic treatments and referrals for medical consultation. RESULTS Above-target LDL-C levels were present in 100 (27.5%) patients and were associated with higher total cholesterol, lower high-density lipoprotein cholesterol, older age, higher systolic blood pressure, smoking and male gender (r(2): 0.53; p<0.0001). Only 32.0% of these patients received appropriate interventions during hospital stays of 27.6+/-23.3 days. CONCLUSIONS A substantial number of SGA-treated patients have above-target LDL-C, but do not receive interventions to reduce the risk of CHD.

Reply: To PMID 24354448.

age of 75 mg clozapine, we thought it would be possible to raise the dose by 12.5 mg to 87.5 mg, but then Mr. D complained for the first time of side-effects. We apologized for being too hasty and reduced the dosage by 6.25 mg to 81.25 mg a day. At the time of writing, 9 weeks after starting clozapine, Mr. D shows no side-effects or suicidality and is more satisfied with his life, less psychotic, and willing to continue clozapine. We recommend choosing the titration scheme for clozapine on an individual basis: For belligerent, agitated in-patients with florid positive symptoms and potential for harming themselves or others (like the patients of Ifteni and his colleagues), a rapid titration may be adequate and some patients may even need compulsory treatment with clozapine injections (4), whereas for an out-patient who was difficult to persuade of the possible benefits of clozapine, a cautious titration may be advisable, beginning with 6.25 mg and daily dose increments of 12.5 mg at the discretion of the patient and psychiatrist. Needless to say, elderly patients or patients with Parkinson’s disease need an even slower titration scheme starting with even lower doses.