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Non-pharmacological management of antipsychotic-induced weight gain: Systematic review and meta-analysis of randomised controlled trials

  • Mario Álvarez-Jiménez (a1), Sarah E. Hetrick (a2), César González-Blanch (a3), John F. Gleeson (a4) and Patrick D. McGorry (a2)...
Abstract
Background

Antipsychotic-induced weight gain is a major concern in the treatment of psychosis. The efficacy of non-pharmacological interventions as well as the optimal intervention approach for this side-effect remain unclear.

Aims

To determine the effectiveness of non-pharmacological interventions and specific treatment approaches to control antipsychotic-induced weight gain in patients with firstepisode or chronic schizophrenia.

Method

Systematic review and meta-analysis of randomised controlled trials.

Results

Ten trials were included in the meta-analysis. Adjunctive non-pharmacological interventions, either individual or group interventions, or cognitive-behavioural therapy as well as nutritional counselling were effective in reducing or attenuating antipsychotic-induced weight gain compared with treatment as usual, with treatment effects maintained over follow-up.

Conclusions

Non-pharmacological weight-management interventions should be a priority, particularly during the early stages of antipsychotic treatment. Preventive approaches have the potential to be more effective, acceptable, cost-efficient and beneficial.

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Copyright
Corresponding author
Dr Mario Álvarez-Jiménez, ORYGEN Research Centre, 35 Poplar Road, Parkville 3054, Victoria, Melbourne, Australia. Email: malvarez@unimelb.edu.au
Footnotes
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Declaration of interest

None.

Funding detailed in Acknowledgments.

Footnotes
References
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Non-pharmacological management of antipsychotic-induced weight gain: Systematic review and meta-analysis of randomised controlled trials

  • Mario Álvarez-Jiménez (a1), Sarah E. Hetrick (a2), César González-Blanch (a3), John F. Gleeson (a4) and Patrick D. McGorry (a2)...
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eLetters

In research, aces don�t win the match!

Mario �lvarez-Jim�nez, Research Fellow & Clinical Psychologist
25 October 2008

We would like to thank George et al. for their comments on our manuscript. However, we believe that some clarification is needed regarding the outcomes and procedures of our meta-analysis.

First, we agree that percentage of weight gain is a more appropriate measure to assess weight gain compared with body weight change. In fact, somewhere else we have pointed to “the importance of reporting percentage of weight gain, as absolute body weight changes may be deceptive, concealing the real extent of this side effect on those who experience weight gain” (1). To put it more simply, research shows that up to 80% of individuals being treated with antipsychotics suffer significant gain in body weight. As a result, patients taking antipsychotics are more likely to gain 20 kg than they are to lose 20 kg. Indeed weight management interventions do not usually produce weight loss but they attenuate antipsychotic-induced weight gain (2). For these reasons data on weight change is unlikely to overestimate the effectiveness of weight management interventions as George et al contend. To illustrate this further, in a previous randomized controlled trial (RCT) of weight management interventions we assessed the proportion of patients that gained more than7% of their baseline body weight. Patients in the control group gained 6.9kg compared with 3.9 kg in the intervention group. These absolute gains were translated into 78.8% in the control group increasing their baseline weight by more than 7% vs. 39.9% in the intervention group (3).

George et al. also commented on the quality of the included trials asa potential threat for the reliability of the results. Firstly, it should be pointed out that only RCTs were included – in three of them we were able to pool relevant data with the help of the authors. Secondly, we performed several sensitivity analyses to determine the robustness of our findings to the exclusion of low-quality trials and exclusion of small trials (4). The exclusion of these studies affected the overall effect size and confidence intervals only marginally. Importantly, there was notable consistency across all study estimates, which was reflected in therobustness of the findings across analytic methods. Thus, our findings areunlikely to be biased by these issues.

After examining all the available evidence it is now possible to conclude that large scale pragmatic trials with longer follow up are needed to make further progress in this area as George et al. state.

References

1.Alvarez-Jimenez M, Gonzalez-Blanch C, Crespo-Facorro B, Hetrick S,Rodriguez-Sanchez JM, Perez-Iglesias R, et al. Antipsychotic-induced weight gain in chronic and first-episode psychotic disorders: a systematiccritical reappraisal. CNS Drugs 2008;22(7):547-62.2.Alvarez-Jimenez M, Hetrick SE, Gonzalez-Blanch C, Gleeson JF, McGorry PD. Non-pharmacological management of antipsychotic-induced weight gain: systematic review and meta-analysis of randomised controlled trials. Br J Psychiatry 20;193(2):101-7.3.Alvarez-Jimenez M, Gonzalez-Blanch C, Vazquez-Barquero JL, Perez-Iglesias R, Martinez-Garcia O, Perez-Pardal T, et al. Attenuation of antipsychotic-induced weight gain with early behavioral intervention in drug-naive first-episode psychosis patients: A randomized controlled trial. Journal of Clinical Psychiatry 2006 Aug;67(8):1253-60.4.Egger M, Smith GD, Phillips AN. Meta-analysis: Principles and procedures. British Medical Journal. 1997;315(7121):1533-7.

Declaration of interest: None
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Conflict of interest: None Declared

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One ace and three faults don�t win the set!

Dimple George, Academic CT3
24 September 2008

This well written paper by Álvarez-Jiménez et al attempts to address a major concern in the management of psychosis namely weight gain with antipsychotic medication which has an overarching impact on the managementof psychosis.The question it purports to answer is clearly focussed and the search strategy thorough and systematic.

However, the description of the conduct of included trials and assessment of the risk of bias presented in table DS2, it becomes clear that several poor quality trials were included with only 2/10 having used an intention to treat analysis and 1/10 disclosing allocation concealment.

Proper randomisation is particularly important in small trials as it is relied upon to produce groups with similar baseline characteristics. Poor quality randomisation would instead produce unequal groups with questionable validity of the results.

The attrition rate is particularly high (up to 50%) for the control group in this case. Empirical evidence suggests that participants who adhere tend to do better than those who do not adhere, even after adjustment for all known prognostic factors and irrespective of assignmentto active treatment or placebo.

In the absence of an intention to treat analysis, the results are biased in an unpredictable manner, compounded by the small size of the trials.Similar problems extend to the subgroup analysis .The authors confirm thatthe effect size is reduced in the better quality studies. 3 out of 4 trials in the nutritional therapy subgroup analysis were of poor quality .Similarly 4 out of 5 studies in the comparison of individual versus grouptherapy. Hence by including poor quality trials with larger treatment effects in the analysis, the beneficial effect of the intervention has been overestimated.

The choice of mean weight change as an outcome measure is an interesting one as it actually masks the heterogeneity between subjects insmall trials. In simple terms, if 1 individual in the intervention arm of the trial , loses 20kgs it skews the results in favour of the interventioneven if the other 5 individuals gained 2 kgs each, giving a group mean weight loss of 10kgs. It would perhaps have been more appropriate to have chosen a dichotomous definition of significant weight change (say 5 %), sothat it would be clear how many individuals actually benefitted from the intervention.

The reviewers could have chosen to request the raw data from individual trials as it would allow them opportunity to account for dropouts, redo the intention to treat analysis and calculate dichotomous weight change outcomes. This however would still not resolve the basic problem with regard to quality in individual studies. Well designed, largescale pragmatic trials with longer periods of follow up are needed before undertaking further review in this area, an implication which has been acknowledged by the authors.

References:

Non-pharmacological management of antipsychotic-induced weight gain: systematic review and meta-analysis of randomised controlled trials. MarioÁlvarez-Jiménez et al. The British Journal of Psychiatry (2008); 193: 101-107.

What is meant by intention to treat analysis? Survey of published randomised controlled trials. S.Hollis et al. BMJ (1999); 319:670-674
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