Role of Antipsychotic Medication In Weight Gain

Do Antipsychotic Medication Cause Weight Gain?

Prevalence of weight gain is a common in psychotic patients. Individuals with schizophrenia have more intra-abdominal fat. Therefore, these patients are at greater risk of complications of obesity. There are several lifestyle factors such as poor diet, smoking and a sedentary lifestyle which further increase its risk. Prevalence of obesity and metabolic disturbances has increased significantly after the discovery of atypical antipsychotics.

 Antipsychotic-induced weight gain

Weight gain is associated with significant physical and psychological diseases. Weight gain increases the risk of diabetes, cardiovascular disease and stroke. Coronary heart disease risk and metabolic syndrome is commonly prevalent in patients that are treated with antipsychotics. Obesity is associated with depression, low self-esteem, guilt and shame. Weight gain impaired quality of life and increases the risk of depression. It is also associated with noncompliance of medication as well

Mechanisms of antipsychotic weight gain

Weight gain induced by Antipsychotics is a complex side-effect with several mechanisms.

Effect on energy expenditure and energy intake

Weight gain is caused by a reduced rate of energy expenditure. This shows that weight management strategies should focus to increase energy consumption by exercise rather than strategies to reduce energy intake e.g. diet or food intake. One of the reason of weight gain with antipsychotics is associated with increased food intake and sedentary lifestyle.

Effects on receptors and neurotransmitters

The two receptors that are most associated with weight gain are

• Serotonin 2C (5-HT2C)

Serotonin transmission reduces food intake. On the other hand, antagonism of serotonin receptors induces food intake in spite of satiety leading to weight gain.

• Histamine (H1) receptors.

Histamine receptor antagonism increases energy intake centrally by increasing appetite.

The weight gain with antipsychotic is dependent on the affinity of these drugs with serotonin and histamine receptors. Clozapine and olanzapine have the greatest affinity for 5-HT2C and H1 receptor, that why they have greatest potential for weight gain. In contrast, risperidone has lesser affinity for the 5-HT2C and H1 receptors and thus has lesser chances of weight gain than olanzapine or clozapine.

Pharmacogenetics and weight gain

There are  certain fundamental biological factors that make some  patients more prone to weight gain. Patients having low Body Mass Index are at greater risk of weight gain and that early. In the first few weeks of treatment, rapid weight gain predicts long-term weight gain. Sometimes, the weight gain is irreversible and even discontinuation or switching antipsychotics therapy does not reduce weight. A 5-HT2C receptormpolymorphism has strong associations with weight gain and increased risk of metabolic syndrome in people taking antipsychotics.

Neuroendocrinal mechanisms

Other mechanisms include the effect of antipsychotics in increasing prolactin. Hyperprolactinemia can affect circulating levels of gonadal hormones and impair insulin sensitivity that leads to weight gain.

Weight gain by effect on glucose and lipids

Hyperlipidemia and Hyperglycemia are often thought to be result of weight gain. There is independent associations of antipsychoticswith hyperglycemia and dyslipidemia. Olanzapine and clozapinehave the greatest impact in increasing blood glucose and lipids independent of adiposity. Psychosis and antipsychotics are both independently linked with an increased risk of diabetes and worsening blood sugar control. Atypical antipsychotics are more likely to produce this effect than the first-generation antipsychoticagents.

Management strategies for weight gain

Management strategies are divided into choice of antipsychotic, pharmacological and psychological treatments for promoting weight loss and switching strategies.

Choice of antipsychotic

The most important parameter in the prevention of weight gain is the choice of antipsychotic but optimal treatment of psychosis is a priority. There are a number of factors that should be considered when choosing an antipsychotic, which includes

• nature and severity of the illness
• the past response of the patient
• patient and family preference
• psychiatric and medical comorbidity
• effectiveness of the medication
• Potential for extrapyramidal and metabolic side effects.
•  

Pharmacological management

The main pharmacological agents investigated for antipsychotic-induced weight gain are H2 receptor antagonists, topiramate, amantadine, metformin, antidepressants, fenfluramine and phenylpropanolamine.

Orlistat, sibutramine and rimonabant are effective in weight reduction. Orlistat is a lipase inhibitor which reduces the absorption of dietary fat.

Psychological strategies

The main psychological strategies in antipsychotic induced weight gain are

• Cognitive behavioural therapy
• Behavioural therapy
• Nutritional interventions

Psychological strategies may result in weight loss. The most important are behavioural interventions that emphasizes on lifestyle modifications and physical activity.

Antipsychotic switching

One option to reverse weight gain is to switch antipsychotics with a lower propensity to cause weight gain or dyslipidemia caused by previous antipsychotic treatment. Switching to ziprasidone is an effective strategy in individuals on olanzapine and produced reductions in lipids and weight.

Lifestyle modifications for weight loss

• Limit foods high in saturated fat  by substituting with unsaturated fat
• Increasing intake of fibre
• Limit salt  and alcohol intake
• A moderate decrease in caloric intake
• Increase physical exercise 
•  

References

McIntyre RS, Mancini DA, Basile VS. Mechanisms of antipsychotic-induced weight gain. J Clin Psychiatry 2001; 62:23_29.

Ryan MCM, Flanagan S, Kinsella U, Keeling F, Thakore JH. Atypical antipsychotics and visceral fat distribution in first episode, drug-naı¨ve patients with schizophrenia. Life Sci 2004; 74:1999_2008.

Connolly M, Kelly C. Lifestyle and physical health in schizophrenia. Adv Psychiatr Treat 2005; 11:125_132.

Reist C, Mintz J, Albers L, Jamal MM, Szabo S, Ozdemir V. Second-generation antipsychotic exposure and metabolicrelated disorders in patients with schizophrenia: an observational pharmacoepidemiology study from 1988 to 2002. J Clin Psychopharmacol 2007; 27:46_51.

Newcomer JW. Second generation (atypical) antipsychotics and metabolic effects: a comprehensive literature review. CNS Drugs 2005; 19:1_93.

Lieberman JA, Stroup TS, McEvoy JP et al. Effectiveness of antipsychotic drugs in patients with schizophrenia. N Engl J Med 2005; 353:1209_1223.

Allison DB, Mentore LJ, Heo M et al. Antipsychoticinduced weight gain: a comprehensive research synthesis. Am J Psychiatry 1999; 156:1686_1696.

Mond J, Morice R, Owen C, Korten A. Use of antipsychotic medications in Australia between July 1995 and December 2001. Aust N Z J Psychiatry 2003; 37:55_61.

Meltzer HY, Perry E, Jayathilake K. Clozapine-induced weight gain predicts improvement in psychopathology. Schizophr Res 2003; 59:19_27.

Bai YM, Lin CC, Chen JY, Lin CY, Su TP, Chou P. Association of initial antipsychotic response to clozapine and long-term weight gain. Am J Psychiatry 2006; 163:1276_ 1279.

International Diabetes Federation. IDF Consensus worldwide definition of the metabolic syndrome 2006. Belgium: International Diabetes Foundation. [cited 3 October 2007.]

Available from URL: http://www.idf.org/webdata/docs/ MetS_def_update2006.pdf

Newcomer JW, Haupt DW. The metabolic effects of antipsychotic medications. Can J Psychiatry 2006; 51:480_491.

Bobes J, Arango C, Aranda P et al. Cardiovascular and metabolic risk in outpatients with schizophrenia treated with antipsychotics: results of the CLAMORS study. Schizophr Res 2007; 90:162_173.

Read More:

Alcohol Use in Men What You Need to Knowl

Antihypertensive Drugs – Lowdown – Pharmacology

Liver Disease in Men What You Need to Know

How to Eat Your Way to Your Goal Weight