Evidence-Based Reviews

UPDATE ON ATYPICALS: Preemptive tactics to reduce weight gain

Current Psychiatry. 2003 March;2(3):58-62

References

1. Rockwell WJ, Ellinwood EH, Trader DW. Psychotropic drugs promoting weight gain: health risk and treatment implications. South Med J. 1983;76:1407-12.

2. Walsh AE, Smith KA, Oldman AD, et al. m-Chlorophenylpiperazine decreases food intake in a test meal. Psychopharmacology (Berl). 1994;116:120-2.

3. Garattini S, Mennini T, Samain R. Reduction of food intake by manipulation of central serotonin: current experimental results. Br J Psychiatry. 1989;155(suppl 8):41-51.

4. Tecott LH, Sun LM, Akana SF, et al. Eating disorder and epilepsy in mice lacking 5-HT2C receptors. Nature. 1995;374:542-6.

5. Howarth PH, Emanuel MB, Holgate ST. Astemizole, a potent histamine H1 receptor antagonist: effect on allergic rhinoconjunctivitis, on antigen and histamine-induced skin response and relationship to serum levels. Br J Clin Pharmacol. 1984;18:1-8.

6. Wirshing DA, Wirshing WC, Kysar L, et al. Novel antipsychotics: a comparison of weight gain liabilities. J Clin Psychiatry. 1999;60:358-63.

7. Casey DE, Zorn S. The pharmacology of weight gain with antipsychotics. J Clin Psychiatry. 2001;62 (suppl 7):4-10.

8. Allison DB, Mentore JL, Heo M, et al. Antipsychotic-induced weight gain: a comprehensive research synthesis. Am J Psychiatry. 1999;156:1686-96.

9. Leibowitz SF. Neurochemical system of the hypothalamus control of eating and drinking and behavior and water-electrolyte excretion. In: Morgan P, Panksepp J (eds). Handbook of the hypothalamus (vol, 3). New York: Marcel Dekker, Inc., 1980;299-438.

10. Basson BR, Kinon BJ, Taylor CC, et al. Factors influencing acute weight change in patients with schizophrenia treated with olanzapine, haloperidol, or risperidone. J Clin Psychiatry. 2001;62(4):231-8.

11. O’Keefe C, et al. Reversal of weight gain associated with antipsychotic treatment (paper presentation). New Orleans: American Psychiatric Association annual meeting, 2001.

12. Ball MP, Coons VB, Buchanan RW. A program for treating olanzapine-related weight gain. Psychiatr Serv. 2001;52(7):967-9.

13. Knox JM. A study of weight reducing diets in psychiatric in-patients. Br J Psychiatry. 1980;136:287-9.

14. Cohen S, Glazewski R, Khan S, Khan A. Weight gain with risperidone among patients with mental retardation: effect of calorie restriction. J Clin Psychiatry. 2001;62(2):114-16.

15. Littrell KH, et al. Educational interventions for the management of antipsychotic-related weight gain (paper presentation). New Orleans: American Psychiatric Association annual meeting, 2001.

16. Nguyen CT, Ortiz T, Franklin D, Yu B, Maguire GA. Nutritional education in minimizing weight gain associated with antipsychotic therapy. New Orleans: American Psychiatric Association annual meeting, 2001.

17. Kinon BJ, Basson BR, Gilmore JA, Tollefson GD. Long-term olanzapine treatment: weight change and weight-related health factors in schizophrenia. J Clin Psychiatry. 2001;62(2):92-100.

18. Ketter TA, et al. Int J Neuropsychopharmacol. 2000;3(suppl l):S344.-

19. Floris M, Lejeune J, Deberdt W. Effect of amantadine on weight gain during olanzapine treatment. Eur Neuropsychopharmacol. 2001;11(2):181-2.

The effectiveness of weight management programs associated with antipsychotics may depend on the target population. In a retrospective chart review, Cohen et al found that calorie restriction did not lead to weight loss among 50 adult inpatients with mental retardation who were being treated with risperidone.¹⁴

Timing is important. During olanzapine treatment, mean weight gain has been reported to plateau after approximately 39 weeks, with the most rapid gains in the first 12 weeks.⁶ Thus, early weight control efforts likely would be most effective. Two small, prospective studies suggest that starting behavioral interventions before you start olanzapine therapy may be the most effective strategy to minimize weight gain.

In the first study—a randomized trial of 12 patients with schizophrenia—those who received an educational intervention prior to starting olanzapine treatment gained a mean 1 lb in 4 weeks, compared with 6.4 lbs in a standard-care group.¹⁵ The behavioral intervention included a weekly 1-hour class using educational materials on nutrition and exercise.

In the second study, our group offered 22 psychiatric outpatients a nutrition course before starting olanzapine treatment.¹⁶ We included 17 patients with psychotic disorders and 5 with nonpsychotic diagnoses—including major depressive disorder, bipolar disorder, and stuttering—to compare antipsychotic-related weight gain between psychotic and nonpsychotic populations.

We began by talking with each patient for 5 minutes about the following nutritional concepts:

Weight gain is associated with increased appetite.
The more you eat, the more weight you gain.
To reduce hunger, it is better to snack on fruits, carrots, broccoli, or low-fat crackers than on high-calorie “junk food” such as potato chips, ice cream, candy, and cake.
Drink water or diet sodas instead of sugary soft drinks.

At follow-up visits, we spent 2 minutes reinforcing the educational messages by:

asking if patients’ appetite had increased
re-emphasizing that they should eat low-fat snacks to reduce hunger and drink water or diet sodas instead of sugary soft drinks.

After about 7 months, the mean weight gain from olanzapine therapy was 5.27 lbs, which is 40 to 60% less than that seen in studies of olanzapine without structured interventions.^6,8,17 Mean weight gain was 5 lbs for the psychotic patients and 6.2 lbs for the nonpsychotic group, which suggested that patients with schizophrenia or schizoaffective disorders may benefit from nutritional education.

Table 2

STRATEGY FOR MANAGING WEIGHT IN PATIENTS TAKING ANTIPSYCHOTICS

Begin nutritional and exercise education before starting antipsychotic treatment. Monitor weight weekly in the first 4 to 6 weeks of antipsychotic therapy, when the risk for weight gain is highest. Ask if the patient’s appetite has increased. If a patient gains >10 lbs during the first 4 to 6 weeks, consider adding nizatidine, 300 mg bid; topiramate, 100 to 200 mg/d; or amantadine, 100 mg bid, to the antipsychotic regimen. Continue adjunctive therapy until appetite has decreased and weight gain has stabilized, then taper off the medication and continue to monitor weight. Emphasize the importance of proper food choices. Review the patient’s diet at every visit. Provide very specific nutritional education. Discourage eating “junk food” such as chocolate, potato chips, cake, cookies, and soft drinks, and encourage drinking water and eating fruits and vegetables.

Begin nutritional and exercise education before starting antipsychotic treatment.
Monitor weight weekly in the first 4 to 6 weeks of antipsychotic therapy, when the risk for weight gain is highest. Ask if the patient’s appetite has increased.
If a patient gains >10 lbs during the first 4 to 6 weeks, consider adding nizatidine, 300 mg bid; topiramate, 100 to 200 mg/d; or amantadine, 100 mg bid, to the antipsychotic regimen.
Continue adjunctive therapy until appetite has decreased and weight gain has stabilized, then taper off the medication and continue to monitor weight. Emphasize the importance of proper food choices.
Review the patient’s diet at every visit. Provide very specific nutritional education. Discourage eating “junk food” such as chocolate, potato chips, cake, cookies, and soft drinks, and encourage drinking water and eating fruits and vegetables.

Medications for weight control

Three medications—nizatidine, topiramate, and amantadine—have shown some effect in controlling weight gain when taken concomitantly with atypical antipsychotics. These medications affect different receptors, and how they affect weight gain is not entirely understood.

Nizatidine—a selective histamine (H2) receptor antagonist—was shown to be significantly more effective than placebo in reducing olanzapine-related weight gain when given to 132 patients at 300 mg bid.¹⁸

Topiramate is believed to stimulate 5-HT2C receptors, thus suppressing the increased appetite caused by 5-HT2C antagonism. Among 13 bipolar patients with significant weight gain associated with olanzapine treatment, 73% lost weight with topiramate at 90.4 +/- 48.4 mg/d.¹⁸

Amantadine has also been shown to minimize weight gain without worsening psychotic symptoms. A case series reported a weight gain of 15.8 lbs in patients taking olanzapine alone, compared with 7.7 lbs in patients taking olanzapine plus amantadine.¹⁹

Related resources

Wirshing DA, Wirshing WC, Ksyar L, et al. Novel antipsychotics: a comparison of weight gain liabilities. J Clin Psychiatry 1999;60:358-63.
Casey DE, Zorn S. The pharmacology of weight gain with antipsychotics. J Clin Psychiatry 2001;62 (suppl 7):4-10.

Drug brand names

Amantadine • Symmetrel
Aripiprazole • Abilify
Clozapine • Clozaril
Nizatidine • Axid
Olanzapine • Zyprexa
Quetiapine • Seroquel
Risperidone • Risperdal
Topiramate • Topamax
Ziprasidone • Geodon

Disclosure

Dr. Nguyen is a speaker for Eli Lilly and Co. and GlaxoSmithKline; receives research support from Eli Lilly and Co., GlaxoSmithKline, and Forest Laboratories; and is a consultant to Eli Lilly and Co., Organon, and GlaxoSmithKline.