Dose-dependent acute excessive weight gain and metabolic changes in a drug-naive patient on risperidone are reversible with discontinuation: a case report

Atypical antipsychotics are first-line drugs to treat schizophrenia with a reduced rate of extrapyramidal effects [1]. However, studies have also noted their capacity to cause obesity in addition to metabolic abnormalities [2]. This is also true of risperidone, which has been observed to increase weight by a mean of 2.10 kg [3] and to maintain the same weight at 1 year. This weight gain has been noted to be extreme, persistent and, in some cases, may be irreversible with atypical antipsychotics [4, 5] including risperidone [6]. However, the risk is lower when compared with olanzapine and clozapine [6]. Risperidone also has controversial effects on metabolic parameters, with the majority of studies showing an increase in weight and triglyceride concentrations [3, 7], whereas others have demonstrated a decrease in overall body mass index (BMI) [8] as well as a reversal of other antipsychotic-induced hypertriglyceridaemia [9].

We present the case of a drug-naive schizophrenic patient who, while being treated with risperidone over 6 weeks, experienced changes in lipid profile with an overall increase in BMI and excessive gain in weight which returned to baseline on discontinuation.

A White 32-year-old married woman with a diagnosis of paranoid schizophrenia (International Classification of Diseases 10), who had been drug-naive for the previous 8 months, was admitted and started on risperidone 3 mg day⁻¹. The severity of psychotic symptoms was assessed using the Brief Psychiatric Rating Scale (BPRS). Family history was negative for psychiatric illness, obesity and diabetes mellitus. On day 1 (BPRS = 34), her BMI was 17.7 (height 150 cm, weight 40 kg, waist circumference 69 cm). Baseline fasting serum lipid profile and glucose were: cholesterol 104 mg dl⁻¹ (range 150–200 mg dl⁻¹), triglycerides 86 mg dl⁻¹ (range 60–150 mg dl⁻¹), low density lipoprotein (LDL) 87 mg dl⁻¹ (range 0–100 mg dl⁻¹), very low density lipoproteins (VLDL) 18 mg dl⁻¹ (range 12–33 mg dl⁻¹) and fasting blood glucose (FBS) 100 mg%.

At the end of first 2 weeks, a modest improvement in psychotic symptoms was observed (BPRS score = 20), with modest weight gain (3 kg, BMI 19) and an increase in waist circumference to 74 cm.

During the next 2 weeks, she gained another 3 kg (BMI 20.4; waist circumference 80 cm), complained of increased appetite and carbohydrate cravings and was noted to be eating voraciously. As there was minimal improvement in her psychotic symptoms (BPRS score = 18), risperidone was gradually increased to 6 mg day⁻¹ without signs of adverse effects. However, she continued to gain weight (weight 48 kg, BMI 21.4; waist circumference 86 cm) over the next 2 weeks (weeks 4–6). All attempts to reduce her weight by restricting her diet and increasing her activity failed. A repeat biochemistry revealed elevated concentrations of cholesterol (194 mg dl⁻¹), triglyceride (99 mg dl⁻¹), LDL (133 mg dl⁻¹) and VLDL (40 mg dl⁻¹), with normal FBS (86 mg%). A decision to discontinue risperidone was taken in view of persisting psychotic symptoms and adverse metabolic parameters (Naranjo algorithm evaluation obtained a score of 6, which indicates that it is ‘probable’ that the adverse reaction was due to the drug) and she was started on haloperidol along with depot fluphenazine.

At 1 month's follow-up, she had reduced her weight (42 kg) and waist circumference (70 cm) with reduction to almost baseline concentrations in all metabolic parameters (cholesterol 110 mg dl⁻¹, triglyceride 94 mg dl⁻¹, LDL 97 mg dl⁻¹, VLDL 27 mg dl⁻¹ and FBS 90 mg%), which was maintained at 3 months' follow-up. The patient had no abnormalities of thyroid function or her menstrual cycle during the 6 weeks of treatment with risperidone. It is worth noting that she complied well with pharmacotherapy, as assessed by pill count.

Risperidone-induced weight gain is more pronounced in the young, men, those with lower BMI and of non-White race [10]. Weight change of 7% above baseline is taken as clinically significant. Moreover, short-term weight gain has been associated with a good clinical response [2]. However, our patient was female and had significant weight gain of 20% above baseline, which was, however, associated with poor clinical response. Metabolic changes, as seen by dose-dependent elevations of cholesterol, triglyceride, LDL and VLDL concentrations within 6 weeks of risperidone therapy, are other atypical features seen in our patient. The combination of increasing weight along with abdominal adiposity and dyslipidaemic changes may herald the onset of metabolic syndrome. Furthermore, the increase in BMI from 17 to 21 within 6 weeks may also signal the beginning of obesity, as BMI >22 has been defined as being overweight for Asians and Indians [11–13]. However, all these changes were rapidly reversible on discontinuation of the drug, making it imperative that clinicians identify early and monitor susceptible patients on antipsychotics, so that progression to metabolic syndrome may be prevented.