Dear DOCTOR Owen:

My doctor just started me on an antidepressant for sleep called amitryptiline (brand names include Elavil and Pamelor). I have gained 20 pounds in three months. He said that the weight gain might be a side effect. He also thought it was because I am feeling better and more rested and, therefore, feel more like eating. I don’t think this is correct. Do you have any information on this problem?

Amy Tryp

Dear “Amy”:

An excellent review of the weight gain/loss potential for all psychiatric drugs appeared in Primary Psychiatry, Vol. 7, No. 5. The entire month’s issue was devoted to a review of this subject. This review is the most comprehensive to date on the subject. Yours is a common question. I suggest that you read all of the columns in this chapter, as they cover all of the most commonly used antidepressants.

Your doctor has prescribed amitryptiline, an antidepressant called a tricyclic. This variety has been in use for decades and has many purposes, including treatment of insomnia, chronic pain syndromes, migraine headache, PMS (pre-menstrual syndrome), and psychiatric conditions. These medications are used less for depression than in years past because of the emergence of the newer antidepressants called SSRIs (selective serotonin reuptake inhibitors), which have fewer side effects. Common brand names of SSRIs include Prozac, Zoloft®, Effexor, Paxil®, etc.

Tricyclic antidepressants are used less often now because of their side effects. In addition to dry mouth, constipation, blurry vision, and drowsiness (á la sleep), they are notorious for causing weight gain. The average person gains 5.5% of his or her body weight on any of these agents. For the average 150-pound person this would be 7–10 pounds in six months. Weight gains of large amounts have been reported, which I seen in my practice as well.

Health risks in taking the medication, including weight gain, must be evaluated against side effects. Before they take the medication, I believe that patients should be informed about—and consent to—the weight gain. Not only can the weight gain be socially and emotionally distressing, but it also can be medically detrimental. For example, a person with a body mass index (BMI) of 25 or below is at low risk for chronic diseases such as high blood pressure, diabetes, elevated cholesterol, and heart disease. If he or she gains as little as 10–30 pounds, the risk of those medical conditions rises considerably. The latest report from the National Institutes of Health (NIH) reveals that someone with a BMI above 27 has a 72% chance of having one of those conditions.

Other tricyclic medications include imipramine (Tofranil), desipramine (Norpramine), nortryptiline (Vivactyl), protyptiline, and trimipramine. More data exist on the most commonly used medications: amitryptiline and imipramine. For example, weight gain can be measured in short time periods, but there are few long-term studies of their weight-gain potential over longer time periods.

One problem in evaluating weight gain is the many confounding variables at play. Your doctor’s explanation, while not based on data, is logical. Sleep deprivation and depression may contribute to weight loss or gain. While a tricyclic may cause serious weight gain in one person, it may have has no effect on someone else. This is due to variations in brain chemistry, the environment (conditioned responses), and different pre-disposing conditions such as diabetes or pre-diabetes.

Here are a few reasons for weight gain, as per several studies and animal research:

• Marked increase in one’s preference for sweets.
• Excessive appetite—probably caused by a blockade of the histamine receptors.
• Changes in how body fat is stored—caused by changing brain chemicals in the hypothalamus (of the brain).
• Decreased calorie expenditure (moving more slowly).
• Improvement in the condition that was keeping the weight down (depression). Depression can cause weight loss in a small percentage of cases.

In my opinion, weight issues have not been a topic of focus for several reasons:

1. The medical profession and the culture as a whole still want to believe that controlling weight is simple: “Just quit eating.”
2. Serious weight gain as a public health issue would discourage sale of the drugs.
3. A side effect such as weight gain is hard to measure against the immediate effects of the medication that is treating the actual condition: For example, “You are sleeping better (and engaging in less physical activity). Is that worth your 20-pound weight gain?”