Some Effects of Risperidone and Quetiapine on Growth Parameters and Hormone Levels in Young Pigtail Macaques

Abstract

Objective: Atypical antipsychotic drugs are prescribed to young children for a number of symptoms, some with no Food and Drug Administration approval for children. Effects on growth of children have received little experimental study. We assessed the effects of two atypicals, risperidone and quetiapine, on growth, prolactin, and thyroid hormones of young pigtail macaques (macaca nemestrina), modeling potential effects on 4-8-year-old children. Methods: Subjects were studied blindly after random assignment to risperidone (N ¼ 10), quetiapine (N ¼ 10), or placebo (N ¼ 20). Four phases were studied: (1) predrug, 9-12 months of age; (2) low dose (risperidone 0.025 mg/kg, quetiapine 2 mg/ kg), 13-16 months; (3) high dose (risperidone 0.05 mg/kg, quetiapine 4 mg/kg), 17-20 months; (4) postdrug, 21-24 months. Body weight was measured daily, skeletal dimension monthly, and bone mineralization and hormones bimonthly. Results: Our primary result showed that, compared with placebo, neither drug had detrimental effects on body weight, skeletal dimensions, or thyroid hormones. However, in a transient effect, bone density was lower following low-dose risperidone than either quetiapine or placebo. In both drug phases, risperidone prolactin was higher than the other groups, which did not differ. The higher prolactin of the risperidone group may partially explain the bone density effect. Conclusion: This 16-month study of young, developing pigtail macaques given risperidone at doses from 0.025 to 0.05 mg/kg or quetiapine at doses from 2 to 4 mg/kg suggests that these drugs are safe for normal body weight and skeletal growth in young pigtail macaques given an adequate diet, although these drugs are known to cause significant weight gain and other metabolic changes in some children, adolescents, and adult humans. In addition, the results, although transient in our study, also suggest that research in children on bone mineralization effects of risperidone, and possibly other antipsychotic drugs, may be warranted.

Immunoendocrine Peripheral Effects Induced by Atypical Antipsychotics

“…The changes in hormone levels related with risperidone treatment are also evident in animal models. In a pigtail macaque model, PRL was higher at low (0.025 mg/Kg) and high doses (0.05 mg/Kg) of risperidone during 4-month consumption, with a gradual decline until reaching placebo levels in the post-drug phase (149). In an animal model, male Wistar rats showed reduced α-MSH, agouti-related protein (AgRP), and cocaineand amphetamine-regulated transcript (CART) concentrations and increased leptin levels vs. the vehicle group after 4 weeks of treatment (2 mg/kg/day) (150).…”

Is antipsychotic treatment linked to low bone mineral density and osteoporosis? A review of the evidence and the clinical implications

“…It follows from this that people taking antipsychotic drugs are likely to be at increased risk of osteoporosis. Recent animal studies in macaques and rats have found that antipsychotic treatment was associated with reduced bone mineralisation (Sackett et al , ; Kunimatsu et al , ). In the rat study, the significant reductions in femoral BMD were linked to the effects of prolactin elevation and decreased oestradiol levels during antipsychotic treatment (Kunimatsu et al , ).…”

Four decades of leading‐edge research in the reproductive and developmental sciences: The Infant Primate Research Laboratory at the University of Washington National Primate Research Center

“…Recently, atypical antipsychotic drugs with less severe side effects have been used in pediatric clinical treatment but the safety and efficacy of these drugs for children and adolescents has not been well-established. A project at the IPRL was undertaken to evaluate the effects of two drugs in this class, risperidone and quetiapine , in young, normally developing male Macaca nemestrina monkeys [Sackett et al, 2010]. Males received a daily dose of risperidone (0.25 mg/kg) or quetiapine (2 mg/kg) for 4 months.…”

“…Recently, atypical antipsychotic drugs with less severe side effects have been used in pediatric clinical treatment but the safety and efficacy of these drugs has not been well established. A project at the IPRL was undertaken to evaluate the effects of two drugs in this class, risperidone and quetiapine, in young, normally developing male M. nemestrina monkeys [Sackett et al, 2010]. Subjects were tested on a comprehensive developmental test battery that included measures of (1) social, cognitive, emotional, perceptual and motor behavior; (2) physical assessments of health, somatic growth, bone mineralization, and hormonal function; and (3) highresolution anatomical and chemical magnetic resonance brain imaging.…”