Weight gain in a patient with schizophrenia switched from quetiapine to amisulpride

EXISTING EVIDENCE HAS shown that amisulpride is superior to other second-generation antipsychotics in that it generates comparable treatment efficacy and, on the other hand, confers lower risk for weight gain and metabolic syndrome.1 We report a case in which switching from quetiapine to amisulpride induced excessive weight gain. A 40-year-old woman was treated with quetiapine 400 mg/day for paranoid schizophrenia over a period of 3 years with satisfactory symptom control. Moderate weight gain (from 75 kg to 79 kg) was noted in the first 3 months of quetiapine treatment, but her bodyweight stabilized after that. Other than being overweight (body mass index [BMI] = 29), all laboratory data, such as lipid profile, blood sugar and prolactin level, were within normal limits during treatment with quetiapine. Unfortunately, her psychotic symptoms flared up in February 2007, after her husband's frequent business traveling during that period. The dose of quetiapine was increased to 600 mg/day initially, but she could not tolerate the sedative effect and requested for alternative medication. Quetiapine was replaced with amisulpride 400 mg/day. Her psychotic symptoms responded well to amisulpride monotherapy in the first 2 weeks, but hyperphagia, dramatic weight increase (5 kg in the first month and 3 kg in the second month) and missing periods followed. Two months after introducing amisulpride, laboratory data showed hypertriglyceridemia (triglyceride 206 mg/dL) and hyperprolactinemia (prolactin 112.5 ng/mL). Her fasting glucose was within the normal range. Because of increased risk for metabolic syndrome and the patient's request to switch back to quetiapine, amisulpride was discontinued and quetiapine was re-introduced. In 1 month her hyperphagia disappeared and her bodyweight decreased by 2 kg. Her period as well as prolactin level were back to normal 2 months after re-introduction of quetiapine. Although she suffered from mild daytime sleepiness, her psychotic symptoms were under favorable control on quetiapine 600 mg/day. In the present case hyperphagia, prominent weight gain, amenorrhea, dyslipidemia, and increased prolactin levels developed within the first 2 months of switching from quetiapine to amisulpride. Discontinuation of amisulpride was associated with disappearance of hyperphagia, resumption of menstruation and decrease of bodyweight. To our knowledge this is the first report regarding paradoxical weight gain after switching from quetiapine to amisulpride. Presumably, being obviously overweight during quetiapine treatment, the present patient would have benefited from switching to amisulpride in terms of the side-effect profile of metabolic syndrome. Paradoxically, she continued to gain weight quickly after shifting from quetiapine to amisulpride; furthermore, her triglyceride level increased in a very short period of time. The phenomenon hints that mechanisms for weight gain might differ between amisulpride and other serotonin–dopamine antagonists (SDA). Serotonergic and histaminergic systems have been reported to play key roles in bodyweight gain associated with SDA treatments.2 Amisulpride, a selective D2/D3 antagonist, has no affinity for either serotonergic or histaminergic receptors; this property may be related to its lower risk for weight gain.3, 4 But the dopaminergic system per se may be related to feeding regulation. Several animal studies have shown that local injection of dopamine into the lateral hypothalamus led to decreased feeding. Injection of sulpride, another D2/D3 antagonist, to the lateral–perifornical hypothalamus induced strong feeding and drinking behaviors in satiated rats.5-8 Previous observations also indicate that dopamine-D2-receptor availability is negatively correlated with BMI in obese people.9 It is speculated that lower D2 receptor availability results in greater dopamine release and thus induces a stronger rewarding effect toward food.10 Because D2 receptor occupancy is approximately 56–82% for amisulpride,11 while quetiapine induces relatively low occupancy (31% at 450 mg/day),12 differential D2 receptor occupancy may explain the moderate weight gain experienced by the present patient under quetiapine 400 mg/day and the continued increase in weight on amisulpride 400 mg/day. One other important reason for the excessive weight gain was the increased prolactin level, because hyperprolactinemia has been linked to weight gain, hyperphagia and increased adiposity.13, 14 The mechanism may act through direct stimulation of the feeding center in the central nervous system, or through interaction with the gonadal steroids and eating-stimulatory neuropeptides.13 Hyperprolactinemia has also been shown to impair insulin sensitivity and consequently to promote fat deposition.15 In the present case the prolactin level was within the normal range (22.3 ng/mL) on quetiapine treatment, but increased to 112.5 ng/mL when treatment was switched to amisulpride; concomitant hyperphagia was also noted. The prolactin level returned to normal (23.5 ng/mL) 2 months after the discontinuation of amisulpride and so did the symptoms of hyperphagia. We report a case of excessive weight gain, dyslipidemia and hyperprolactinemia after switching from quetiapine to amisulpride. As described in the discussion, prolactin and dopaminergic system may have played an important role in bodyweight gain in the present case. Prior studies on the mechanism associated with antipsychotic-induced bodyweight gain have placed more emphasis on the serotonergic and histaminergic system; the role of prolactin and the dopaminergic system, however, have been less frequently addressed. This case calls for the need to further understand the pharmacologic mechanisms behind metabolic syndromes of different antipsychotic agents, in order to select more appropriate and customized antipsychotics.