Weight gain from antipsychotics

With respect to other ethnic groups, African Americans may have a differential sensitivity to weight gain on clozapine (de Leon etal, 2007). They may also require lower doses than Caucasians (Kelly et al, 2006) and inter-individual as well as ethnic responsiveness maybe partly explained by differences in dopamine receptor polymorphisms (Hwang et al, 2005). It is conceivable that side effects may also be differentially expressed based on pharmacodynamic differences resulting from polymorphisms in other receptor types (histaminergic, muscarinic, etc.). This area remains largely unexplored with respect to ethnic differences in antipsychotic side effects. 

Kim, S.F., Huang, A.S., Snowman, A.M., Teuscher, C. and Snyder, S.H. (2007) From the coven Antipsychotic drug-induced weight gain mediated by histamine HI receptor-linked activation of hypothalamic AMP-kinase. Proceedings of the National Academy of Sciences of the United States of America, 104 (9), 3456-3459. 

Besides weight gain, probably the most common side effect from antipsychotics in young people is sedation. Histamine receptor blockade appears to mediate this side effect. Excessive sleepiness can interfere with a youth s academic performance, cause sluggishness, and cause a child to appear drugged to their peers and family. 

Data from short-term clinical trials (6 weeks) suggest that quetiapine may be useful for the management of psychotic disorders in patients who do not tolerate the adverse effects of the typical antipsychotic drugs or clozapine (3). The most common adverse effects of quetiapine were dizziness, hypotension, somnolence, and weight gain. Raised hepatic enzymes have also been reported. In addition, two patients with idiopathic Parkinson s disease and psychosis were treated with quetiapine for 52 weeks (4). Psychotic symptoms were successfully controlled without worsening of motor disability. 

Mechanism of any possible weight gain is unknown weight gain is not common with aripiprazole and may thus have a different mechanism from atypical antipsychotics for which weight gain is common or problematic... 

Observational studies The use of antipsychotic drugs in children and adolescents is of particular concern. In a 24-week, multicenter, open study supported by Eli-Lilly, the marketing authorization holder, 96 adolescents with schizophrenic disorder (mean age 16 years 68% boys) were given olanzapine 10 mg/day [83 ]. BPRS scores fell from baseline to week 6 by a mean of 17. The most common adverse events were weight gain and increased prolactin. Weight... 

Observational studies An open-label, long-term study of patients switched to oral paliperidone from either risperidone or other antipsychotics found that extrapyramidal symptoms improved significantly for all patients [192 ]. Akathisia and weight gain were the main adverse events, and increased prolactin levels in female patients from the nonrisperidone group. 

On the contrary, JNJ-37822681 (230) is a D2 highly selective receptor antagonist and hence acts in a mode analogous to that of most marketed antipsychotics [212], JNJ-37822681 is characterized by a rapid dissociation rate from the dopamine D2 receptor, which was hypothesized to confer antipsychotic efficacy and improved tolerability [213]. Clinical studies in patients with an acute exacerbation of schizophrenia showed that JNJ-37822681 had similar biological activity but lesser tendency to induce weight gain compared to a known antipsychotic drug. Olanzapine (242) [214] (Fig. 8). 

Four patients developed tardive dyskinesia while taking conventional antipsychotic drugs and were switched to sertindole (5). Three apparently recovered from the movement disorder. In the other patient sertindole monotherapy was not sufficient to reduce the movement effects, but combination treatment with tetrabe-nazine resulted in a greater reduction in extrapyramidal symptoms. There was no evidence of QTC prolongation in these patients, but one patient gained 8 kg in weight. 

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