Atypical Antipsychotics should go with Metformin and Lifestyle Intervention

A recent study indicates that lifestyle intervention and metformine in combination has the greatest effect on weight loss and increases insulin sensitivity for patients taking atypical antipsychotics. These methods result in a decrease of 1.8 of the BMI, an increase in insulin resistance index of 3.6 and the waist circumference decreases with 2.0 cm. This is important because all antipsychotics but especially the atypical antipsychotics have weight gain as a common side-effect. Clozapine and olanzapine produce the most weight gainfollowed by quetiapine and risperidone. Ziprasidone and aripiprazole produce the least weight gain.
Metformin alone was more effective than lifestyle intervention alone in increasing insulin sensitivity and reversing weight gain.

Why is this important?
Weight gain influences adherence to drug therapy. Overweight is an important risk factor for cardiovascular disease such as hypertension, diabetes and heart disease.
Outpatient mental health clinics should also provide these measures to their patients when they are on atypical antipsychotics

The mechanism underlying weight gain resulting from atypical antipsychotics is not fully understood. It could be caused by influencing brain receptors that can lead to increase in appetite. It can also impair metabolic regulation and alteration of insulin sensitivity.

The Treatment
Metformin inhibits hepatic glucose production. It is well tolerated and prevents continual weight gain while it decreases measures of insulin resistance. Insulin resistance is a risk factor for diabetes type II.
The lifestyle intervention included psycho-education, dietary, and exercise programs.
The psycho-education focused on eating and activity and how these can influence weight management.
The diet prescribed was less than 30% of total calories from fat (<7% satured fat and <200 mg of vcholesterol); 55% from carbohydrates; and more than 15% from protein daily with an increase in fiber intake to at least 15 gr per 1000 kcal. The so called American Hearty Association step 2 diet
Exercise for at least 30 minutes per day. It consisted of walking bicycling, jogging ball games. The therapists and patients collaboratively developed individual programs of gradual assignment of exercise.

BMI=body mass index:
The BMI is one of the most accurate ways to determine whether an adult is overweight. It is a gauge of total body fat, calculated by dividing the person’s weight (in kilograms) by his or her height (in square meters). A person with a BMI of 25 or greater is considered to be overweight and with a BMI of 30 or greater is considered to be obese.

Insulin resistance
In a person with normal metabolism, insulin is released from the beta (β) cells of the Islets of Langerhans located in the pancreas after eating (“postprandial”), and it signals insulin-sensitive tissues in the body (e.g., muscle, adipose) to absorb glucose to lower blood glucose to a normal level (approximately 5 mmol/L (mM), or 90 mg/dL). In an insulin-resistant person, normal levels of insulin do not trigger the signal for glucose absorption by muscle and adipose cells. To compensate for this, the pancreas in an insulin-resistant individual releases much more insulin such that the cells are adequately triggered to absorb glucose. On occasion, this can lead to a steep drop in blood sugar and a hypoglycemic reaction several hours after the meal.

Article discussed:
JAMA. 2008 Jan 9;299(2):185-93.
Lifestyle intervention and metformin for treatment of antipsychotic-induced
weight gain: a randomized controlled trial.
Wu RR, Zhao JP, Jin H, Shao P, Fang MS, Guo XF, He YQ, Liu YJ, Chen JD, Li LH.
PMID: 18182600
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