The metabolic syndrome and its constituting variables in atypical antipsychotic-treated subjects: comparison with other drug treatments, drug-free psychiatric patients, first-degree relatives and the general population in Venezuela.

BACKGROUND: Few studies on the association between atypical antipsychotic drug (AAP) administration and metabolic dysfunction have concurrently evaluated the general population (GP), other psychotropic drug treatments and drug-free psychiatric patients. METHODS: We assessed the frequency of the metabolic syndrome (MS) according to the National Cholesterol Education Program criteria (NCEP) and its constituting variables in a GP sample (n=271) and in patients receiving, for at least three consecutive months, antiepileptic drugs (n=93), olanzapine (n=162), clozapine (n=105), typical antipsychotics (n=117), other AAP (n=58), other psychotropic drugs (n=185), and drug-free individuals (n=636). Subjects were clinically classified as schizophrenia, bipolar or other axis I disorders (DSM-IV-RT), and as first-degree relatives of each diagnostic group. RESULTS: The MS was detected in 26.6% of the GP (95% confidence interval: 21.5-31.8). No diagnostic or treatment group had a significantly higher age-adjusted frequency than the GP (p>0.05). Treatment duration did not significantly affect the results. However, significant differences were observed in the frequency of abnormal MS constituting variables in comparison to the GP. For example, schizophrenia patients and their relatives, bipolar subjects and olanzapine- and clozapine-treated patients had higher abnormal waist circumference values. In addition, bipolar patients and their relatives and subjects treated with olanzapine and other AAPs had higher frequencies of abnormal glucose levels. Neither schizophrenia nor bipolar patients in the diagnostic categories nor the olanzapine or the clozapine groups displayed higher proportions of abnormal triglycerides, high density cholesterol or blood pressure levels than the GP. CONCLUSIONS: While we did not demonstrate an increased frequency of the MS in AAP-treated subjects, our results confirm that specific metabolic variables must be monitored in psychiatric patients. Besides they stress the importance, in epidemiological studies, of concurrently comparing the figures recorded in AAP-treated patients with those obtained in the local GP, other drug treatment groups and drug-free subjects when referring to the magnitude of the metabolic effects of specific antipsychotic agents.

Frequency of abnormal correlation between leptin and the body mass index during first and second generation antipsychotic drug treatment.

BACKGROUND: Leptin dysregulation has been implicated in the body weight gain and metabolic dysfunction observed with the second generation antipsychotic drugs (SGAD) olanzapine and clozapine. METHODS: This study quantified the frequency of subjects with abnormal correlation between leptin and the body mass index controlling for gender (defined as being out of the upper or lower 95% confidence interval in the regression line when combining each group with the drug-free subjects) after prolonged treatment with olanzapine (n=126), clozapine (n=62), first generation antiypsychotics (n=91), other SGAD (n=22), other psychotropic drugs (n=65) and drug-free subjects (n=229). RESULTS: None of the analysis was significant (p>0.05). In fact, in 17 out of 20 comparisons, the drug-free group had numerically higher frequencies of outliers than the corresponding treatment group. There were 28 outliers (4.7% of the total sample). In agreement with previous studies, cross-sectional analysis did not report gross alterations in serum leptin levels during olanzapine or clozapine administration. CONCLUSIONS: Longitudinal studies should focus on leptin regulation early on treatment, on the frequency of abnormal leptin receptor sensitivity and/or specific polymorphisms in the leptin allele and on several confounding factors in order to design personalized preventive and therapeutic measures.

Pharmacological management of atypical antipsychotic-induced weight gain.

Excessive bodyweight gain was reported during the 1950s as an adverse effect of typical antipsychotic drug treatment, but the magnitude of bodyweight gain was found to be higher with the atypical antipsychotic drugs that were introduced after 1990. Clozapine and olanzapine produce the greatest bodyweight gain, ziprasidone and aripiprazole have a neutral influence, and quetiapine and risperidone cause an intermediate effect. In the CATIE study, the percentage of patients with bodyweight gain of >7% compared with baseline differed significantly between the antipsychotic drugs, i.e. 30%, 16%, 14%, 12% and 7% for olanzapine, quetiapine, risperidone, perphenazine (a typical antipsychotic) and ziprasidone, respectively (p<0.001). Appetite stimulation is probably a key cause of bodyweight gain, but genetic polymorphisms modify the bodyweight response during treatment with atypical antipsychotics. In addition to nutritional advice, programmed physical activity, cognitive-behavioural training and atypical antipsychotic switching, pharmacological adjunctive treatments have been assessed to counteract excessive bodyweight gain. In some clinical trials, nizatidine, amantadine, reboxetine, topiramate, sibutramine and metformin proved effective in preventing or reversing atypical antipsychotic-induced bodyweight gain; however, the results are inconclusive since few randomized, placebo-controlled clinical trials have been conducted. Indeed, most studies were short-term trials without adequate statistical power and, in the case of metformin, nizatidine and sibutramine, the results are contradictory. The tolerability profile of these agents is adequate. More studies are needed before formal recommendations on the use of these drugs can be made. Meanwhile, clinicians are advised to use any of these adjunctive treatments according to their individual pharmacological and tolerability profiles, and the patient's personal and family history of bodyweight gain and metabolic dysfunction.