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.
Correll
Christoph U
CU
The Zucker Hillside Hospital, North Shore-Long Island Jewish Health System, Glen Oaks, NY 11004, United States. ccorrell@lij.edu
Frederickson
Anne M
AM
Kane
John M
JM
Manu
Peter
P
D000328:Adult; D000367:Age Factors; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D000068180:Aripiprazole; D001714:Bipolar Disorder / Q000097:blood / Q000188:drug therapy*; D015992:Body Mass Index; D008076:Cholesterol, HDL / Q000097:blood; D003024:Clozapine / Q000009:adverse effects / Q000627:therapeutic use; D003430:Cross-Sectional Studies; D003987:Dibenzothiazepines / Q000009:adverse effects / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000139:chemically induced* / Q000175:diagnosis; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000069348:Quetiapine Fumarate; D015363:Quinolones / Q000009:adverse effects / Q000627:therapeutic use; D012307:Risk Factors; D012559:Schizophrenia / Q000097:blood / Q000188:drug therapy*; D013844:Thiazoles / Q000008:administration & dosage / Q000627:therapeutic use; D014280:Triglycerides / Q000097:blood
D014150:Antipsychotic Agents; D008076:Cholesterol, HDL; D003987:Dibenzothiazepines; D010879:Piperazines; D015363:Quinolones; D013844:Thiazoles; D014280:Triglycerides; D000069348:Quetiapine Fumarate; C092292:ziprasidone; D000068180:Aripiprazole; D003024:Clozapine