People suffering from depression or anxiety disorders generally are prescribed selective serotonin reuptake inhibitors (SSRIs) for treatment, which also cause weight gain in the users as an after effect. It may one of the reasons that people discontinue these beneficial medications for fear of gaining extra-ordinary gain in weight. People do not want to further add to their depression feeling by becoming obese, which again may become another cause for worry and more depression.

There may be many reasons for gaining weight. Depression medications will lift users from low feelings and elevate them to a feeling of well-being. This may result in an increase in appetite, which may get translated into obesity and weight gain. These serotonin specific drugs cause longing for sweet stuffs and carbohydrate based preparations, thereby increasing the desire for more food intake. Obviously, this will cause havoc with regulated diet. Body metabolic rates may also be affected by these SSRI drugs. Increased food intake and reduced metabolic activity will result in accumulation of excess fat in the body. Simple carbohydrates are converted into glucose and fat by the action of insulin.

If effects of SSRIs are to be considered, both short-term (3 to 6 months) and long-term (more than 6 months) effects are to be taken into account. SSRI induced weight gain is less likely in short-term. About 7% increase in weight during medication period is considered significant and pertinent. These things will help in prescribing proper SSRI medications that cause minimal effect on weight in a person.

SSRIs and Weight Gain

There is a hormone called leptin (Greek leptos, meaning thin) which plays an important role in controlling body weight, appetite and metabolic rate, besides reproductive function. Leptin is also released in small quantities by epithelium cells in the stomach and in the placenta. The brain contains clusters of leptin and there may be a possible link to a person’s depression.

Researchers say that during the periods of chronic or long-term stress, hormone cortisol (an adrenal secretion) is released, which is directly associated with depression. Depressed people are found with higher levels of cortisol, which is linked with obesity and increased fat accumulation in the body.

Long-term stress also lowers serotonin levels in the brain. Serotonin elevates the effectiveness of leptin in the hypothalamus. Stress induced lower serotonin levels adversely affect leptin function resulting in lower satiety and decreased metabolic rates. Lower satiety increases appetite for food. This appetite, coupled with lower metabolic rates result in weight gain.

Serotonin affects POMC cells (Pro-opiomelanocortin, a precursor polypeptide) to enhance the leptin influence. When SSRI medications are taken for the first time, they increase serotonin levels by inhibiting their re-intake. This increased serotonin makes leptin more effective, thereby decreasing the appetite and accelerating the sluggish metabolic rate. So, in the initial stages of the SSRI medication, people actually lose weight. But over time, say after 3 to 4 months, the serotonin receptors on the POMC cells start to have a decreasing control. This, in turn, will have an adverse impact on leptin and its effectiveness will come down. This is the period when lowering of satiety and metabolic sluggishness occurs. In such a situation, a person’s appetite will increase and eventually weight gain happens. This is what happens with SSRIs. First they cause weight loss and then they work in ways that result in weight gain.

If SSRI medication gets a positive effect on depression and when the medication is discontinued, then there is about a 70% possibility of a relapse happening in a person. In such situations, long-term drug administration may become inevitable. So, mere discontinuation will not be a good idea. It is better to replace SSRI medication with non-SSRIs for a few weeks, say 4 - 6 weeks. During this time, serotonin receptors on the POMS cells would get activated again. When SSRIs make a come back as medications, the higher serotonin levels make leptin effective in increasing the satiety and accelerating the metabolism, resulting in weight loss.

Taking an additional medication that inhibits CB1 (Cannabinoid receptor 1, which is associated with food intake) would be beneficial as it would offset the effect of serotonin on the POMC sell in the initial period of SSRI medication. This knowledge of SSRI behavior on appetite will help in organizing medication treatment options so as to keep the weight gain possibility to the minimum.