Hyperlipidemia Following Treatment With Antipsychotic Medications

Department of Psychiatry, Columbia University, NY State Psychiatric Institute, 1051 Riverside Dr., Unit 24, New York, NY 10032, USA.
American Journal of Psychiatry (Impact Factor: 12.3). 11/2006; 163(10):1821-5. DOI: 10.1176/appi.ajp.163.10.1821
Source: PubMed


This study attempted to estimate the relative risk of developing hyperlipidemia after treatment with antipsychotics in relation to no antipsychotic treatment.
A matched case-control analysis was performed with pharmacy and claims data from California Medicaid (Medi-Cal). Patients were excluded if they were treated for medical disorders or prescribed medications known to increase their risk of hyperlipidemia. Cases were ages 18 to 64 years with schizophrenia, major depression, bipolar disorder, or other affective psychoses and incident hyperlipidemia. Cases were matched to up to six control subjects by age, sex, race, and psychiatric diagnosis. Both groups were prescribed either no antipsychotic medication or had two or more prescriptions for one and only one antipsychotic medication during the 60 days prior to the first indication of hyperlipidemia (cases) or matched index date (controls) in the billing record. Conditional logistic regressions were used to derive odds ratios and 95% confidence intervals (95% CIs) of each antipsychotic medication in relation to no antipsychotic medication.
A total of 13,133 incident cases of hyperlipidemia were matched to 72,140 control subjects. As compared with no antipsychotic medication, treatment with clozapine (odds ratio: 1.82, 95% CI: 1.61-2.05), risperidone (odds ratio: 1.53, 95% CI: 1.43-1.64), quetiapine (odds ratio: 1.52, 95% CI: 1.40-1.65), olanzapine (odds ratio: 1.56, 95% CI: 1.47-1.67), ziprasidone (odds ratio: 1.40, 95% CI: 1.19-1.65), and first-generation antipsychotics (odds ratio: 1.26, 95% CI: 1.14-1.39), but not aripiprazole (odds ratio: 1.19, 95% CI: 0.94-1.52) was associated with a significant increase in risk of incident hyperlipidemia.
These findings suggest that most commonly prescribed antipsychotic medications increase the risk of developing hyperlipidemia in patients with schizophrenia or mood disorders.

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    • "Although we were unable to follow these patients long enough to determine how the course of their weight gain may continue to change over time, it is possible these patients’ weight trajectory may follow that of other patients with increasing metabolic disturbance occurring during the course of treatment. The weight gain observed in this analysis is comparable to that observed in previous short-term PP studies, where moderate weight gain (0.9-1.5 kg) was observed over a 13-week period [18-20]. Similar findings were also seen in long-term studies with oral paliperidone extended–release, which showed a mean (SD) increase in body weight of 1.2 (5.16) kg from OLE baseline to OLE endpoint [28]. "
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    ABSTRACT: There is a strong association between weight gain and metabolic events in patients with schizophrenia receiving many of the second-generation antipsychotic agents. We explored the relationship between body mass index (BMI) and metabolic events in patients with schizophrenia receiving long-acting injectable paliperidone palmitate (PP) in a long-term trial. We conducted a post hoc analysis of data from a PP study that included a 33-week open-label transition (TR) and maintenance phase; a variable duration, randomized, double-blind (DB), placebo-controlled phase and a 52-week open-label extension (OLE) phase. Overall, 644 patients received PP continuously from study entry through discontinuation or study completion and were grouped by baseline BMI (kg/m2): underweight (BMI <19; n = 29, 4.5%), normal-weight (BMI 19- < 25; n = 229, 35.6%), overweight (BMI 25- < 30; n = 232, 36.0%) and obese (BMI >=30; n = 154, 23.9%). Metabolic treatment-emergent adverse events (TEAEs) and changes in related laboratory results from TR baseline were analyzed. PP exposure was similar across BMI groups; overall mean (SD) dose/month was 70.3 (17.17) mg eq. [109.6 (26.78) mg]; median duration of exposure was 204 days (6 to 1009 days). Occurrences of metabolic TEAEs overall by group were 0% (underweight), 14.9% (normal-weight), 14.7% (overweight), and 24.0% (obese). The most common (>=2%) metabolic TEAE were weight gain and elevated blood levels of glucose, lipids, and insulin. Mean BMI and weight increased in normal-weight and overweight groups at DB endpoint, and in underweight, normal-weight and overweight groups at OLE endpoint (p <=0.05). No consistent trend for increased metabolic-related laboratory values by baseline BMI group was observed. Homeostatic model assessments for insulin resistance indicated preexisting insulin resistance at baseline, with minimal changes at OLE endpoint across baseline BMI groups. Occurrences of metabolic-related TEAEs trended with greater BMI status in patients with schizophrenia treated with PP; consistent trends in metabolic-related laboratory values were not observed.Trial registration: This study is registered at (NCT 00518323).
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    • "To our knowledge, there is no proven link between the prescription of baclofen and an increased blood level of triglycerides. Risperidone, and more generally atypical antipsychotics, widely used in schizophrenia and bipolar disorder, is known to cause an increase in triglycerides (Weinbrenner et al., 2009), but this increase is usually small and below 2 g/l (Olfson et al., 2006). We report here an original case of a patient treated with atypical antipsychotic (risperidone) for a type 1 bipolar disorder and high-dose baclofen (HDB) for alcohol dependence who presented a rapid and severe elevation of his blood level of triglycerides. "

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    • "There have been striking expansions in the rate of antidepressant medication prescribing (Olfson & Marcus 2009) and the prescription of off-label antipsychotic medication (Comer et al. 2011). The growth in off-label antipsychotic prescribing in outpatient mental health care is of particular concern, given the associated metabolic, endocrine, and cerebrovascular risks that have been well documented (Olfson et al. 2006). Since the introduction of second-generation antipsychotic medications in the early 1990s, these powerful medications have become increasingly common in the outpatient management of diverse clinical populations. "
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