Waiting for Antidepressants That Don’t Cause Weight Gain

When Prozac entered the market as the first serotonin reuptake blocker to treat depression, it was anticipated that in addition to reducing or eradicating the symptoms of depression, it might also prevent the weight gain seen with antidepressants being used at that time. The drug was approved by the FDA in December 1987 and launched the next month. Indeed, it seemed so promising in its ability to prevent weight gain that it was tested to see if it would be effective as a weight drug. And it worked, for about half a year; however, continued treatment after the mid-point in the year-long study resulted in the subjects who had lost weight gaining back all the weight they lost.

The hoped-for weight-neutral side effect of Prozac was not realized. And unfortunately, most antidepressants that entered the market subsequently also had weight gain as a potential side effect although one, bupropion, (Wellbutrin) seems to cause less weight gain than other SSRI medications. One antidepressant currently being prescribed, Mirtazapine (Remeron) has been associated with rapid and significant weight gain.

Some weight gained during treatment may be due to recovery from depression itself. Loss of appetite often accompanies depression and when normal eating is resumed, weight may return to pre-depression levels. However, weight gain as a side effect of the medication is unfortunately also common and may add unwelcome and unwanted pounds that alter body shape, energy levels, and satisfaction with one’s appearance. Social and work consequences may follow. A 10-pound weight gain is noticeable and may make a patient uncomfortable physically and emotionally. Does one tell family at a yearly gathering that the reason their clothes don’t fit very well is that the individual has been depressed, anxious, and on medication? Does one mention to co-workers who wonder about the increasing size of the patient that he or she has a mental illness and the treatment is causing weight gain? Or does the patient stand up at a Weight Watchers meeting and explain that her inability to lose weight is due to the medication she is taking for depression? Understandably, this information is probably generally not shared, but it leaves the patient with no way of explaining the unexpected addition of 5-20 or more pounds.

We established a weight-loss center at a university-affiliated psychiatric hospital more than 20 years ago to help patients from the hospital and community to lose weight they had gained or were gaining on their psychotropic medications. Few if any of the people coming to our clinic had been overweight or obese before being treated with antidepressants. Indeed, many did not know how to diet since they never had the need. Moreover, they enjoyed exercise and were upset because their increased weight made it hard for them to do so. And they all claimed that their weight gain was due to a new, unexpected craving for carbohydrate snacks and an absence of satiety after meals. These changes in their appetite made us suspect that the antidepressant medications might be interfering with serotoninergic activity, as one of serotonin’s functions is to produce a feeling of satisfaction after eating. A drug-free way of increasing serotonin levels and function; i.e. consuming a small amount of carbohydrates on an empty stomach, seemed a workable approach to helping our clients control their food intake. Perhaps we could make them feel slightly full and satiated before they started a meal by increasing serotonin.

Our approach seemed to work. The consumption of a carbohydrate-containing beverage about 90 minutes before eating lunch and dinner, and in tandem with an exercise regimen we developed for them, was effective in achieving significant weight loss. Presumably, the subsequent increase in serotonin diminished their appetite and increased their satiety, so they were content with diet-size meal portions.

Our results suggested a method for supporting weight-loss efforts even while patients are on medications that lead to weight gain. Eventually, we tried introducing our intervention as soon as individuals noticed changes in appetite and satiety. Coupled with an exercise program compatible with their level of fitness and energy, it seemed an effective approach to minimizing the amount of weight gained.

Unfortunately, there is evidence—admittedly, mostly anecdotal—of patients unable to lose weight even after discontinuing antidepressants, going on a calorie-restricted diet, and exercising. Very little data are available about whether certain antidepressants are more likely to cause resistance to weight loss than others. The difficulty people have in attaining their pre-medication weight status should not be explained as the difficulty many obese people have in losing weight, since many who have trouble returning to their pre-treatment weight were thin before starting on their medication.

All this could be avoided if antidepressants were available that did not have the potential to cause weight gain. The first antidepressants were discovered in the 1950s: iproniazid, a drug that had been used to treat tuberculosis, and imipramine, the first in a group of drugs known as the tricyclic antidepressant family. It has been a long wait.