Antipsychotic-induced body weight gain: Predictors and a systematic categorization of the long-term weight course

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Abstract

Objective

To explore the impact of premorbid and baseline body mass indices (BMIs) as well as BMI of patient’s parents and associated variables on the prediction of antipsychotic-induced body weight gain.

Methods

Retrospective/cross-sectional data of 65 patients receiving clozapine, olanzapine and/or risperidone were assessed according to a systematic categorization of the long-term (7.3 ± 9.2 years) weight course and evaluated using descriptive, explorative correlation and regression analyses.

Results

Increased values of parents’ BMI (p = 0.041) and patients’ BMI at premorbid stage (p = 0.039) and prior to first antipsychotic treatment (p = 0.032) as well as female gender (p = 0.012), younger age (p = 0.005) and non-smoking (p = 0.047) have the most predictive value on body weight gain under antipsychotic treatment including pre-treatment with typical antipsychotics. Weight gain under atypical antipsychotics (pre-treatment excluded) is predicted by an increased premorbid BMI (p = 0.019). Conversely, a low BMI prior to first antipsychotic treatment predicts a higher acceleration of BMI change (p = 0.008) in vulnerable individuals, but not total BMI change itself. Furthermore, a diagnosis of a schizophrenia spectrum disorder showed a trend towards the prediction of an increased atypical ΔBMI (p = 0.067), possibly due to a longer treatment duration with atypical antipsychotics (p < 0.001).

Discussion

The study indicates increased parents’ BMI and patients’ premorbid BMI, female gender, younger age and – as a trend – the diagnosis of a schizophrenia spectrum disorder to be predictors for antipsychotic-induced body weight gain involving atypical antipsychotics. Data contribute to the assumption of a strong impact of predispositional factors on weight gain, besides treatment-related factors.

Introduction

Weight gain is a major side effect of antipsychotic treatment, in particular with atypical antipsychotics. Though a short-term weight gain directly after initiation of treatment can often be observed, the consequences of a long-term treatment are far more relevant. They comprise overweight, obesity, metabolic disturbances (e.g. lipid abnormalities, diabetes) with increased risk for cardiovascular diseases as well as psychological distress including reduced treatment compliance. A high impact on body weight gain is obviously represented by pharmacological factors including medication choice with clozapine and olanzapine having the strongest effect (Allison et al., 1999) as well as dosage, formulation and choice of concomitant psychotropic medications (Frankenburg et al., 1998).

The mechanisms underlying weight gain are still unknown. There are remarkable interindividual differences of antipsychotic-induced weight gain suggesting a high impact of genetic factors (Theisen et al., 2005b, Gebhardt et al., in press). Actual genetic studies focus on more than 300 candidate genes, especially concerning receptors of the central serotonin and histamine system, as well as peripheral metabolic regulation processes including leptin, pro-melanin concentrating hormone and insulin-induced gene 2 (Chagnon, 2006, Basile et al., 2001, Basile et al., 2002, Chagnon et al., 2007, Ellingrod et al., 2007, Le Hellard et al., 2008). Research results on potential metabolic predictors (e.g., leptin, ghrelin) are ambiguous (Martin et al., 2004; Murashita et al., 2005, Murashita et al., 2007, Palik et al., 2005, Theisen et al., 2005a, Hosojima et al., 2006, Popovic et al., 2007, Esen-Danacı et al., 2008, Perez-Iglesias et al., 2008).

Due to a lack of genetic or metabolic prediction tests, clinicians still rely on clinical predictors. According to the current state of research antipsychotic-induced body weight gain correlates mostly with a low baseline body mass index (BMI, kg/m2), adolescent and also higher adult age, female gender, non-smoking, in part increased dosage, a diagnosis of undifferentiated schizophrenia, nonwhite ethnicity and in case of bipolar disorder nonrapid cycling and psychotic features (Baptista, 1999, Blin and Micalle, 2001, Russell and Mackell, 2001, Homel et al., 2002, Safer, 2004, Lipkovich et al., 2006, Strassnig et al., 2007, Saddichha et al., 2008). After initiation of antipsychotic treatment, a strong increase of appetite is combined with immediate substantial weight gain (Theisen et al., 2003, Gebhardt et al., 2007).

The current study aimed to identify clinical predictors on body weight gain under antipsychotic treatment, especially the atypical antipsychotics clozapine, olanzapine and/or risperidone, which possess a comparably similar chemical structure. Because comparison of studies on antipsychotic-induced weight gain is hampered by the use of different definitions of weight gain, of different measures (e.g., kg, kg/m2, pounds) with diverging time points of measurement during course of weight, we present in this study a systematic categorization of the long-term weight course under consideration of (pre-)treatment periods.

Given the retrospective/cross-sectional design of this study, it is not possible to test a priori hypotheses; however, there were three main topics, which were explored in this study:

  • (1)

    the predictive impact of BMI of the patients’ parents on antipsychotic-induced weight gain.

  • (2)

    the predictive impact of patients’ BMI (premorbid and prior to typical/atypical antipsychotic treatment) on weight gain including the role of appetite in this context.

  • (3)

    the predictive impact of additional variables concerning weight gain such as age, gender, diagnosis, smoking, pre-treatment and treatment duration.

Section snippets

Subjects

Of 127 patients in part examined for other research questions by our study group in the past (see also Theisen et al., 2005b, Gebhardt et al., 2007, Gebhardt et al., in press), 94 patients participated in the study and fulfilled the following inclusion criteria: (1) duration of treatment with either clozapine, olanzapine or risperidone for at least four weeks, (2) treatment of psychotic symptoms in the context of a schizophrenia spectrum or other psychiatric disorders [per DSM-IV] and (3) no

Descriptive data and group differences

Descriptive data on age and BMI at the different time points are shown in Table 1.

Medication. 76.2% of the NSCZ patients were treated with olanzapine, whereas the antipsychotic drug spectrum in SCZ patients was much more differentiated (olanzapine monotherapy in only 20.5%). ANOVA revealed differences in both total ΔBMI (p < 0.001) and atypical ΔBMI (p = 0.023) among the used antipsychotic drugs. Post-hoc tests displayed a higher total ΔBMI in patients who had treatments with clozapine and

Discussion

The percentage of overweight/obese patients rose from 10.8/6.6% to 36.9/32.3% of the total study sample during an average time period of 5.0 ± 7.4 years under antipsychotic treatment (of this 2.1 ± 2.8 years with atypical antipsychotics) indicating the high impact of body weight gain as side effect. The three main topics investigated in this study comprise the predictive value of (1) parents’ BMI, (2) patients BMI and (3) additional variables on antipsychotic induced weight gain.

  • (1)

    To our knowledge,

Conclusion

The results suggest that especially young non-smoking females with a schizophrenia spectrum disorder who report a high BMI of their parents, a high premorbid BMI and – in case of not being treated so far with typical antipsychotics – a high BMI directly prior to antipsychotic treatment are at particular risk for antipsychotic-induced body weight gain. Clinicians should carefully evaluate the use of atypical antipsychotics in these patients. Further, a low BMI prior to first antipsychotic

Conflict of interest statement

All other authors declare that they have no conflicts of interest.

Role of funding source

This study was supported by the “Bundesministerium für Bildung und Forschung” (BMBF: National Genome Research Network 01GS0118, “Molecular mechanisms underlying weight alterations upon treatment with centrally acting drugs”) and the “Deutsche Forschungsgemeinschaft” (DFG; Re 471/11-2). These organizations had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication.

References (42)

  • T. Baptista

    Body weight gain induced by antipsychotic drugs: Mechanisms and mangagement

    Acta psychiatrica Scandinavica

    (1999)
  • V.S. Basile et al.

    Genetic dissection of atypical antipsychotic-induced weight gain: novel preliminary data on the pharmacogenetic puzzle

    Journal of Clinical Psychiatry

    (2001)
  • O. Blin et al.

    Antipsychotic-associated weight gain and clinical outcome parameters

    Journal of Clinical Psychiatry

    (2001)
  • C. Bouchard et al.

    The response to long-term overfeeding in identical twins

    New England Journal of Medicine

    (1990)
  • M. Cabanac et al.

    Sensory feedback in regulation of body weight: is there a ponderostat?

    Nature

    (1971)
  • Y.C. Chagnon

    Susceptibility genes for the side effect of antipsychotics on body weight and obesity

    Current Drug Targets

    (2006)
  • Y.C. Chagnon et al.

    Possible association of the pro-melanin-concentrating hormone gene with a greater body mass index as a side effect of the antipsychotic olanzapine

    American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics

    (2007)
  • V.L. Ellingrod et al.

    Leptin and leptin receptor gene polymorphisms and increases in body mass index (BMI) from olanzapine treatment in persons with schizophrenia

    Psychopharmacology Bulletin

    (2007)
  • C. Fleischhaker et al.

    Weight gain associated with clozapine, olanzapine and risperidone in children and adolescents

    Journal of Neural Transmission

    (2007)
  • S. Gebhardt et al.

    Clozapine/olanzapine-induced recurrence or deterioration of binge eating-related eating disorders

    Journal of Neural Transmission

    (2007)
  • Gebhardt S, Theisen FM, Haberhausen M, Heinzel-Gutenbrunner M, Wehmeier PM, Krieg JC, et al. Body weight gain induced...
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