To the editor: Second-generation antipsychotics are frequently associated with metabolic adverse effects, such as weight gain and elevations of triglyceride or total cholesterol levels (3). Although minor changes in lipid levels have previously been reported during risperidone treatment (2), we observed the following case of pronounced risperidone-induced hypertriglyceridemia.
“Mr. A” was a 27-year-old man who suffered from DSM-IV paranoid schizophrenia for 9 years and had been previously treated with perazine and flupentixole. Upon his hospitalization, the patient presented with normal triglyceride (97 mg/dl) and total cholesterol (121 mg/dl) levels (body weight: 98 kg; body mass index: 30.25 kg/m2). His exacerbated psychotic syndrome remitted after risperidone was increased to 8 mg per day (serum level: 6.4 μg/L). His scores on the Positive and Negative Syndrome Scale (PANSS) were as follows: positive subscale, 9; negative subscale, 11; and global psychopathology subscale, 19. After 12 weeks, we observed an exceptional increase in his triglyceride levels, up to 627 mg/dl, and a marked rise in his total cholesterol levels, up to 249 mg/dl. Mr. A’s uric acid level was slightly elevated, at 8.1 mg/dl. His fasting serum leptin was 14 μg/L, and his insulin level was 11 mU/L. His C-peptide level was 0.78 nmol/L, and his HbA1c level was 5.4%, both of which were normal. The patient’s body weight increased to 112 kg (body mass index: 34.57 kg/m2). After switching to aripiprazole, 45 mg per day, he experienced no change in body weight. However, significantly lower triglyceride and total cholesterol levels were observed during the subsequent 8 weeks (triglyceride level: 263 mg/dl; total cholesterol level: 104 mg/dl). Unfortunately, the patient’s symptoms worsened, with a PANSS global psychopathology subscale score of 60, a positive subscale score of 29, and negative subscale score of 39.
After intensive consultation, Mr. A agreed to the reintroduction of risperidone, 8 mg/day, and his psychosis remitted (PANSS scores: positive subscale=10; negative subscale=8; global subscale=18), but his lipid levels re-increased (triglyceride level: 512 mg/dl; total cholesterol level: 278 mg/dl), with his body weight at 114 kg and a body mass index of 35.18 kg/m2. Consequently, we suggested adding bezafibrate, a fibrate drug for reducing hyperlipidemia.
Although other studies have described risperidone-induced increases in triglycerides levels of 20% (2), our patient experienced an elevation of 600%. We were unable to detect excessive eating behavior or abnormal leptin levels or glucose metabolism. The general explanations of second-generation antipsychotic-induced metabolic disturbances implicate the antiserotonergic and antihistaminergic effects of drugs such as clozapine and olanzapine (3). However, risperidone interacts particularly with serotonin 5-HT2A receptors—and only to a lower extent with 5-HT2C receptors—and the drug has very low affinity to histamine H1-receptors, rendering observations in our patient somewhat unexplained.
In light of recommendations to switch patients with second-generation antipsychotic-induced hypertriglyceridemia to risperidone (1), careful individual decisions appear to be necessary. We recommend general metabolic monitoring and dietary consultation for patients with psychotic disorders.
1.Garman PM, Ried LD, Bengtson MA, Hsu C, McConkey JR: Effect on lipid profiles of switching from olanzapine to another second-generation antipsychotic agent in veterans with schizophrenia. J Am Pharm Assoc 2007; 47:373–3782.Khalili H, Dashti-Khavidaki S, Okhovatpour H, Ghaeli P: Effects of risperidone on lipid profile. Ann Pharmacother 2007; 41:899–9003.Meyer JM, Koro CE: The effects of antipsychotic therapy on serum lipids: a comprehensive review. Schizophr Res 2004; 70:1–17
Dr. Zink has received scientific and speaker grants and travel expense and consultant fees from AstraZeneca, Bristol-Myers Squib, the European Research Advisory Board (ERAB), Janssen Cilag, Pfizer Pharma GmbH, and Otsuka. Susanne Englisch has received travel expense and consultant fees from AstraZeneca, Bristol-Myers Squibb, Janssen Cilag, Pfizer Pharma GmbH, and Otsuka. Drs. Weinbrenner, Peus, and Inta report no competing interests.
This letter (doi: 10.1176/appi.ajp.2008.08081169) was accepted for publication in October 2008.