Clozapine, Diabetes Mellitus, Weight Gain, and Lipid Abnormalities: A Five-Year Naturalistic Study

Henderson, David C.

doi:10.1176/appi.ajp.157.6.975

Cited by 635 publications

(456 citation statements)

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“…In keeping with this, body weight was not affected when haloperidol was administered orally to male rats for three or six weeks (Minet-Ringuet et al, 2005; Pouzet et al, 2003), and was even suppressed under the longer treatment period of 80 weeks (Yoshida et al, 1995 51(7--8): 1129--1136, 2006 adipose tissue under the influence of hormonal changes such as increased serum levels of insulin (Cusin et al, 1990), corticosterone (Guillaume-Gentil et al, 1993) and growth hormone (Ho et al, 1996) and reduced serum levels of thyroid hormones (Kyle et al, 1966), IGF-1 (Shaw et al, 2003), and testosterone (Mudali and Dobs, 2004). However, our data show that not only does chronic haloperidol administration to male rats have no effect on body weight or food intake, it also has no effect on adiposity or the serum levels of many of the hormones that modulate body composition.…”

Section: Effect Of Haloperidol or Risperidone On Body Tissue Compositionmentioning

confidence: 83%

“…Moreover, atypical antipsychotic drugs have been increasingly used for the clinical management of other conditions such as mania, bipolar disorder, dementia, and severe anxiety (Hellewell, 2006 andNemeroff, 2005). However, one serious disadvantage of atypical antipsychotic drugs is an increased propensity of excessive weight gain and diabetes mellitus associated with their use (Conley and Kelly, 2005, Green et al, 2000and Henderson, 2001, although the degree of weight gain induced by the different atypical agents may range significantly. For example, the atypical antipsychotics clozapine and olanzapine have been reported to induce substantial weight gain of approximately 4 kg over ten weeks period while others like sertindole and risperidone had more modest effects with mean weight gain of 2.92 kg and 2.10 kg respectively after ten weeks of treatment (Allison et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

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Distinct endocrine effects of chronic haloperidol or risperidone administration in male rats

et al. 2006

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Antipsychotic drugs have been used effectively for the treatment of schizophrenia symptoms, but they are often associated with metabolic side effects such as weight gain and endocrine disruptions. To investigate the possible mechanisms of antipsychotic-induced metabolic effects, we studied the impact of chronic administration of a typical antipsychotic drug (haloperidol) and an atypical antipsychotic (risperidone) to male rats on food intake, body weight, adiposity, and the circulating concentrations of hormones and metabolites that can influence energy homeostasis. Chronic (28 days) haloperidol administration had no effect on food intake, weight gain or adiposity in male rats, whereas risperidone treatment resulted in a transient reduction in food intake and significantly reduced body weight gain compared to vehicle-treated control rats. Whereas neither antipsychotic had any effect on serum lipid profiles, glucose tolerance or the circulating concentrations of hormones controlled by the hypothalamo-pituitary-thyroid (free T4), -adrenal (corticosterone), -somatotropic (IGF-1), orgonadotropic axes (testosterone), haloperidol increased circulating insulin levels and risperidone increased serum glucagon levels. This finding suggests that haloperidol or risperidone induce distinct metabolic effects. Since metabolic disorders such as obesity and type 2 diabetes mellitus represent serious health issues, understanding antipsychotic-induced endocrine and metabolic effects may ultimately allow better control of these side effects.

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Section: Effect Of Haloperidol or Risperidone On Body Tissue Compositionmentioning

confidence: 83%

Section: Introductionmentioning

confidence: 99%

Distinct endocrine effects of chronic haloperidol or risperidone administration in male rats

et al. 2006

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“…It was suggested that psychotropic drugs which cause weight gain, activate the TNF-α system (14) and thus the TNF-α system is an early and sensitive indicator of weight gain (15 (17). (20) (19,(23)(24)(25)(26).…”

Section: Methodsmentioning

confidence: 99%

Nutritional Approach to Metabolic Changes Arising Out of Schizophrenia Therapy: Case Report

et al. 2007

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“…4 In another study, patients who already had diabetes required to be switched from an oral hypoglycaemic agent to insulin or alternatively for their insulin dosage to be increased approximately two-fold. 5 Where diabetes occurs in association with these drugs, it usually presents soon after commencement of treatment -59% of cases within three months and 84% within six months -and resolves once the drug is withdrawn. 12 Where DKA has occurred, the majority of cases were within six months of commencing treatment and resolved upon withdrawal of the drug.…”

Section: The Association Between Atypical Antipsychotic Drugs and Diamentioning

confidence: 99%

“…[3][4][5][6][7][8][9][10][11] There have been numerous case reports in the literature of new-onset diabetes following the commencement of atypical antipsychotics, particularly clozapine and olanzapine. Many other cases have been reported through the clozapine patient monitoring service.…”

Section: The Association Between Atypical Antipsychotic Drugs and Diamentioning

confidence: 99%

Atypical antipsychotic drugs and diabetes

Livingstone¹,

Rampes

2003

Pract Diab Int

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Atypical antipsychotic drugsSchizophrenia is a syndrome characterised by a broad range of cognitive, emotional and behavioural problems, the prevalence of which is estimated at 0.2-1.0% in the general population. Its symptoms are classified into positive (hallucinations, delusions, formal thought disorder and bizarre behaviour) and negative (flattening of mood, emotional apathy, social withdrawal, lack of motivation and loss of pleasure). Schizophrenia has been treated largely using conventional antipsychotic drugs. However, over the last 10 years, the atypical, also known as novel or secondgeneration, antipsychotics have increasingly been used. The British National Formulary currently lists amisulpride, clozapine, olanzapine, quetiapine, risperidone, sertindole and zotepine as atypical antipsychotic drugs. From a pharmacological perspective, they are distinguished by their dual action of serotonin 2A receptor and dopamine D2 receptor antagonism as compared to the conventional antipsychotic drugs, which have an antagonistic action mainly on the D2 receptor.The atypical antipsychotics are indicated both for the treatment of schizophrenia and related disorders in which psychosis is a defining feature. However, they can also be used to quieten patients whatever the underlying psychopathology, e.g. brain damage, severe anxiety, toxic delirium or agitated depression. From a clinical perspective, atypical antipsychotic drugs have a lower incidence of extrapyramidal adverse effects than the conventional antipsychotic drugs and are more efficacious in the treatment of negative symptoms of schizophrenia. Recently, the National Institute Clinical Excellence has published guidance on the use of atypical antipsychotic drugs for the treatment of schizophrenia. 1 It is recommended that they are used as firstline treatments for individuals with newly diagnosed schizophrenia and should also be used for those patients whose management has been unsatisfactory on conventional drugs or who have experienced unacceptable adverse effects. The following two prescribing restrictions should be noted. Sertindole is available on a named patient supply only due to its cardiac adverse effects and clozapine is restricted to individuals who are intolerant or unresponsive to conventional antipsychotic drugs. The association between atypical antipsychotic drugs and diabetesIt has long been recognised that hyperglycaemia and type 2 diabetes mellitus are more common in patients with schizophrenia than in the general population. In one recent study the prevalence of diabetes in a sample population of patients with schizophrenia was 15.8% as opposed to 3.2% in the general population. 2 Type 2 diabetes is itself becoming a commoner condition in the population as a whole.Since the introduction of the atypical antipsychotic drugs it has become apparent that their use is associated with metabolic adverse effects (Table 1) diabetes. 4 In another study, patients who already had diabetes required to be switched from an oral hypoglycaemic agent to insulin o...

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Clozapine, Diabetes Mellitus, Weight Gain, and Lipid Abnormalities: A Five-Year Naturalistic Study

Abstract: The results support the hypotheses that patients treated with clozapine experience significant weight gain and lipid abnormalities and appear to be at increased risk for developing diabetes.

Cited by 635 publications

References 40 publications

Distinct endocrine effects of chronic haloperidol or risperidone administration in male rats

Distinct endocrine effects of chronic haloperidol or risperidone administration in male rats

Nutritional Approach to Metabolic Changes Arising Out of Schizophrenia Therapy: Case Report

Atypical antipsychotic drugs and diabetes

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