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The aim of this study was to evaluate long-term weight gain associated with clozapine, olanzapine, and risperidone treatment and its clinical risk factors in children and adolescents. At four child and adolescent psychiatric departments, the weight and body mass index of initially hospitalized patients (aged 9.0-21.3 years) treated with clozapine (n = 15), olanzapine (n = 8), and risperidone (n = 10) were prospectively monitored for 45 weeks. Clinical risk factors (age, gender, baseline weight, dosage, drug-naivety) were tested for their association with weight gain in the three groups. All three groups experienced significant weight gain between baseline and endpoint. The absolute and percentage average weight gains were significantly higher for the olanzapine group (16.2 +/- 8.8 kg; 30.1 +/- 18.9%) than for the clozapine (9.5 +/- 10.4 kg; 14.8 +/- 15.8%) and the risperidone (7.2 +/- 5.3 kg; 11.5 +/- 6.0%) groups. Olanzapine is associated with extreme long-term weight gain in children and adolescents that, in addition, is much higher than that expected in adults. Clozapine and risperidone are associated with a less marked weight gain in children and adolescents but also much higher than that expected in adults. These differences may affect compliance with medication and health risk.

The study was aimed at the evaluation of weight gain associated with atypical antipsychotics and its clinical risk factors in children and adolescents. Weight and body mass index (BMI) of initially hospitalised patients treated with clozapine (n = 15), olanzapine (n = 15), and risperidone (n = 15) were prospectively monitored on a weekly basis for the first 6 weeks. Different clinical risk factors were tested for their association with weight gain in the three groups. All three groups experienced significant weight gain between baseline and endpoint (p < 0.0001). For all weight measures, planned comparisons were all significant between olanzapine vs. clozapine and risperidone, respectively. Average weight gain was significantly higher for the olanzapine group (mean = 4.6 kg, SD = 1.9) than for the risperidone (mean = 2.8 kg, SD = 1.3) and clozapine (mean = 2.5 kg, SD = 2.9) groups. Olanzapine and risperidone, but not clozapine, caused a disproportionately higher weight gain in children and adolescents in comparison to adults.

Objective: The aim of this study was to improve and evaluate the practibility of a method for the assessment of drug-associated side effects, and we implemented a clinical drug monitoring for atypical neuroleptics., Methods: Side effects of initially hospitalized patients treated with clozapine (n = 16), olanzapine (n = 16), and risperidone (n = 19) were prospectively monitored on a weekly basis for the first 3 weeks. In the case of stable medication, measurements of all variables were made every 4 weeks or upon discharge. We used the Dosage Record Treatment Emergent Symptom Scale (DOTES) in a supplemented version to measure the presence and severity of side effects., Results: Drowsiness and decreased motor activity were common, especially in the first 2 weeks. Orthostatic hypotension, increased salivation, constipation, and nasal congestion were seen in more than 30% to 60% of patients treated with clozapine and were less common in adolescents treated with olanzapine and risperidone. Rigidity, tremor, and dystonia were seen in 5% to 15% of patients treated with risperidone and olanzapine. The average weight gain after 6 weeks of treatment with the atypical neuroleptics was significantly higher for the olanzapine group (4.6 +/- 1.9 kg) than for the risperidone (2.8 +/- 1.3 kg) and clozapine (2.5 +/- 2.9 kg) groups., Conclusions: The authors' supplemented DOTES version is generally applicable to clinical use in mental health centers. The differences among the side effects of these three agents may affect compliance with medication and medical risks of metabolic syndrome, diabetes, and cardiovascular disease. More research on the short- and long-term safety of psychotropic drugs in children and adolescents, using standardized methods, should be considered.

Clozapine is a dibenzodiazepine derivative with established antipsychotic efficacy in adult patients with schizophrenic psychoses. There are more than 15 studies that have also demonstrated the antipsychotic efficacy of clozapine in childhood and adolescent schizophrenia. The main advantages of clozapine treatment in this age group in comparison with typical antipsychotics are: (i) high antipsychotic efficacy during an acute schizophrenic episode; (ii) better improvement in chronic cases with a high load of negative symptoms; and (iii) markedly fewer extrapyramidal adverse effects and, therefore, fairly good tolerability. However, because of its possible adverse effects on the haemopoetic system (granulocytopenia, agranulocytosis), clozapine should not be used as first-line antipsychotic medication. Other adverse effects are related to the cardiovascular system (hypotonia, tachycardia or arrhythmia), the central nervous system (epileptic seizures, fever) and liver function (transient increases in levels of hepatic transaminases). Two other frequent adverse effects are hypersalivation and body-weight gain, which may present a particular problem in adolescents and young adults. Careful monitoring of haematological parameters and other adverse effects are preconditions for a successful treatment programme.