Treatment of Weight Gain

Most approaches to the problem of weight gain are based on a number called the Body Mass Index. This number is calculated from your height and your weight. There are several websites that have calculators to make it easy to figure out. We like the one from the National Institute of Health .

BMI Categories:

  • Underweight = <18.5
  • Normal weight = 18.5-24.9
  • Overweight = 25-29.9
  • Obesity = BMI of 30 or greater

American College of Physicians Guidelines

In 2003, the U.S. Preventive Services Task Force recommended that clinicians screen all adults for obesity (Defined as a Body Mass Index greater than 30) and offer intensive behavioral counseling to those with a BMI greater than 30. The American College of Physicians recently published guidelines on the management of obesity . They recommend the following:

  • Assess for the presence of illnesses that often are associated with obesity (e.g., hypertension, diabetes).
  • Determine the patients’ goals and time frames for achieving them. Goals might be focused on weight loss or on health related goals such as blood pressure and blood glucose control.
  • Provide counseling on weight loss, diet , and physical activity .
  • Discuss the use of medications ( see below ) with patients who are not meeting their goals through diet and exercise alone. Note the modest benefits typically achieved with such drugs (<5 kg loss at 1 year), known risks, lack of long-term safety data, and the fact that the weight loss is only maintained as long as the medication is taken. But also note the well known health risks of obesity.
  • Consider surgery for patients with BMI’s greater than 40 in whom adequate exercise and diet programs are failing and who have obesity-related comorbidity. Review with them the possible adverse effects of surgery (e.g., gall bladder disease, malabsorption, the possible need for a repeat operation), as well as the lack of outcome data on these procedures, for instance, no single procedure has been proven to be better than another. Refer patients who choose surgery to experienced surgeons at high-volume centers.

Herbs and Supplements

Many herbs and supplements have been marketed for the treatment of obesity.

Significant media attention has been given to the appetite-suppressing effects of Hoodia gordonii, a cactus-like plant which grows richly in the Kalahari Desert in South Africa. The active component of this “succulent” has been identified and named P57. The compound has been isolated from the Hoodia gordonii and shown to mimic the effects of glucose on nerve cells, thereby sending a message to the hypothalamus that we are full.

To the Kalahari Bushmen, who have been using Hoodia gordonii for thousands of years, its efficacy is unquestionable. When food and water are scarce, this naturally-occurring plant is used to “fight off the pain of hunger and thirst” making long treks through the desert tolerable. Despite the subjective claims of Hoodia’s use as an appetite suppressant, there is no solid evidence to date that shows Hoodia in fact works.

There are only two studies at all related to the topic. One unpublished study paid for by Phytopharm, a pharmaceutical company hoping to patent P57 into a drug found that the 9 volunteers who received P57 ate on average 1,000 fewer calories each day compared to those who received placebo. And one study in rats found that directly injecting the drug into the brains of the rats affected a chemical relevant to weight gain.

If you think that this is weak support for this supplement consider the fact that Pfizer bought the rights to market the drug and then abandoned the project after investing considerable money in assessing the usefulness of the compound.

At this time, Hoodia gordonii is available in health food stores across the country. The supplement, is marketed without any government oversight or regulation. Furthermore, the long term side effects of its use and potential interactions with other drugs are not known at this time.

Pharmacological Interventions

The use of anorectic agents for the treatment of obesity are generally recommended as an adjunct to behavioral modifications and only in those patients with a BMI of 30 or greater or a BMI of 27 or greater combined with medical co-morbidities. The currently available agents work through interactions with central serotonin or norepinephrine receptors to decrease food intake (e.g. mazindol, phentermine, sibutramine), increase satiety (fenfluramine, fluoxetine), stimulate metabolic rate (sibutramine), or inhibit absorption of dietary fat in the gastrointestinal tract (orlistat). Additionally, as the physiologic causes of primary obesity are further understood (e.g. leptin, cholecystokinin, and beta 3 adrenergic receptors), novel pharmacologic interventions are being developed and tested.

Likewise, as the mechanism(s) behind weight gain associated with antipsychotic use is further elucidated, novel pharmacologic interventions are being studied in preclinical and clinical trials. However, to date, there have been no published, well-controlled studies examining the effects of concomitant medications in reducing weight gain associated with atypical antipsychotic agents. Below is a summary of published case reports describing pharmacologic interventions that have been used to treat weight gain associated with antipsychotic therapy.

Anorectic Medications

All currently available agents that affect appetite work by increasing noradrenergic, dopaminergic, and/or serotonergic activity in the central nervous system. There is limited information on the use of these agents in a psychiatric population. Goodall and colleagues conducted a double-blind, placebo controlled trial to investigate the effects of d-fenfluramine on 29 overweight patients diagnosed with schizophrenia who were receiving depot antipsychotic injections. In the 16 patients who completed the 12-week trial there was a significantly greater rate of weight loss in those patients taking d-fenfluramine (mean weight loss of 5.4 kg for d-fenfluramine vs 2.8 kg for placebo). However, the occurrence of valvular heart disease has subsequently led to the removal of d-fenfluramine from the market.

Orlistat and Sibutramine

Both orlistat and sibutramine have been approved for the long-term treatment of obesity, however have not been studied in a psychiatric patient population to date. Orlistat, a locally acting pancreatic and gastric lipase inhibitor has demonstrated positive effects on lipid levels and glucose and insulin concentrations. The use of orlistat (120mg three times a day) in a multicenter trial produced a weight loss of 10.2% of patients’ starting weight versus a 6.1% loss in patients taking placebo. Sibutramine inhibits norepinephnne, serotonin, and dopamine reuptake. In multiple clinical trials, a dose-dependent significant weight loss was seen in patients treated with sibutramine (5-20mg) compared to patients treated with placebo. The manufacturer advises caution if sibutramine is administered concurrently with other psychotropic agents. There has been one preclinical study to evaluate the effects of sibutramine on olanzapine-induced weight gain in rats. This study found that in rats given a moderate carbohydrate, low fat diet and were treated concomitantly with Zyprexa and sibutramine, there was a significant reduction in weight gain compared to rats treated with Zyprexa alone.


An open-label study by Correa et al described 10 patients with schizophrenia treated with traditional antipsychotic therapy who experienced a weight loss of 3 to 13 pounds when treated concomitantly with amantadine (200 to 300 mg/day) for 3 weeks. The weight loss was regained after discontinuation of amantadine. A recent case series by Floris and colleagues have also shown an effective reversal of Zyprexa-related weight gain in 12 patients treated with amantadine (100 to 300 mg/day). All patients reported weight stabilization and 11 of the 12 experienced an average weight loss of 3.5 kg over a mean of 21 weeks[45]. In both of these reports, there were no cases of psychotic symptom exacerbation.

The potential role of amantadine for the treatment of Zyprexa-associated weight gain has been evaluated in an observational case series. Forty-three patients with schizophrenia and related psychoses treated with Zyprexa were given amantadine 100 to 300 mg /day for 12 weeks. Weight was measured at baseline and subsequent 4-week intervals. Weight loss was seen as early as 4 weeks after starting amantadine. At week 12, patients had lost an average of 2.2 kg. Patients with BMI>27 had the greatest weight loss (-2.6±3.3 kg). Patients treated with Zyprexa for _1 year lost more weight than those treated for < 1 year. Amantadine coadminstration was associated with weight loss when administered to patients who had gained weight during Zyprexa treatment. This case series confirms previous findings that amantadine may be an effective adjunctive therapy for treatment of Zyprexa associated weight gain.


Topiramate, an anticonvulsant, has been associated with weight loss. Three reports in the literature describe its application to manage psychotropic drug-induced weight gain. In the first case, a patient with chronic paranoid schizophrenia had topiramate (125 mg/day) added to control weight gain associated with clozapine therapy resulting in a 21 kg weight loss over 5 months. The second report was of two cases in which topiramate (200 mg and 300 mg) was substituted for valproate and resulted in a 25 pound weight loss over 3 months and a 15 pound weight loss over 2 months. In the third report, a patient with schizoaffective disorder had topiramate added to aid in mood stabilization and weight normalization. Topiramate was initiated at 25 mg/day and titrated to 150 mg/day over a 2-week period. At 32 weeks, her weight loss reached a plateau of 30.9 kg.

Chengappa and colleagues report data from three cases in which patients were given topiramate in combination with antipsychotics (quetiapine or clozapine) and valproate or carbamazepine. All three patients were obese and diagnosed with DSM-IV bipolar I disorder and type 2 diabetes. An initial topiramate dose (25 mg to 50 mg/day), titrated to a target dose (300 mg or 350 mg) was added to ongoing therapeutic regimens primarily to treat a manic episode. All patients reported weight loss (20 kg to 33 kg), and improvement in glycemic control in addition to mood stabilization.

Further systematic clinical investigations of the utility of topiramate to manage obesity have recently been suspended by the manufacturer, Johnson and Johnson, due to the appearance of unacceptable side effects.