Letters

I have been a member of ASCP for several years and have found The Consultant Pharmacist to be a useful reference in both my practice and research. However, I must take exception with one statement in Jeannette Wick's recent article on drug-induced weight gain (Consult Pharm 1998; 13:1337-48). The article states that "selective serotonin re-uptake inhibitors (SSRIs) do not cause weight gain." However, recent data support the notion that, over the long term, SSRIs are, indeed, associated with weight gain in a substantial percentage of patients.¹

Histamine and serotonin are both thought to be associated with appetite control. A review of the literature indicates that histamine, acting at the H1 receptor, suppresses appetite.² The tricyclic antidepressants are potent histamine antagonists and therefore stimulate appetite, leading to weight gain.^3,4 Histamine antagonism is not thought to explain long-term weight gain associated with use of SSRIs since these agents are weak antagonists of the H1 receptor.

Research indicates that the 5-HT2C receptor is involved with appetite control. Mice that lack the 5-HT2C receptor rapidly gain weight,⁵ while patients given a compound that activates this receptor exhibit decreased appetite and lose weight.⁶ It is thought that chronic exposure to high levels of serotonin due to reuptake blockade causes 5-HT2C receptors to become less responsive through down-regulation and desensitization. Thus, in the long term, drugs that bind to the serotonin transporter with high affinity may exhibit a tendency to cause weight gain.

Although in vitro data suggest that the propensity to cause weight gain may be directly related to 5-HT receptor affinity,^1,7 these are contradicted by the results of postmarketing surveillance.⁸ Further research is needed to determine whether the frequency and amount of weight gain differ between the various SSRIs.

Increased appetite and weight gain were defined as frequent occurrences (i.e., occurring in > 1% of patients) during clinical trials of fluoxetine, paroxetine, and sertraline.^9-11 It is ironic that these data were referred to in advertisements appearing in the same issue of The Consultant Pharmacist as the article in question.

Overall, I found Ms. Wick's article to be both accurate and informative. Reviews such as hers provide valuable information for practitioners and researchers alike.

I thank Dr. Shaw for his comments. Clearly, the effects of the SSRIs on weight are still being defined. In general, however, psychiatry practitioners have noted that when compared with other types of antidepressants, the SSRIs cause considerably less weight gain.

In addition to the role of HT2C, two other factors contribute to weight gain in patients with depression. First, simply treating the depression often stimulates appetite as depression lifts; conversely, anorexia and weight loss are common signs of depression. Second, most people gain weight as they age. For those patients who are sensitive to tricyclic antidepressant-induced weight gain or have concerns about weight gain, SSRIs remain the drugs of first choice. With any patient, the possibility that medication may be causing weight changes should be considered when those changes occur after a new drug is started.