Dr. Andersohn Replies

To the Editor: We thank Dr. Jindal for his thought-provoking remarks and agree that, in addition to weight gain, other pharmacological mechanisms, such as the M ₃ muscarinic receptor affinity, might influence the risk of diabetes associated with certain antidepressants. However, one should note that a rather immediate receptor-mediated effect on the blood glucose homeostasis is not in accordance with the finding of an increased risk of diabetes only after >24 months of therapy. In addition, paroxetine not only has a higher M ₃ receptor affinity than the other SSRIs under study but also differs in other important aspects. For example, it is the most potent inhibitor of serotonin re-uptake among the currently available SSRIs (2) and it is associated with a significantly higher weight gain than fluoxetine or sertraline (1) . Since the tricyclic antidepressant dothiepin, which has a higher M ₃ affinity than paroxetine (3), was not associated with an increased risk of diabetes in our study, the impact of M ₃ receptor affinity remains unclear.

We agree with Dr. Jindal that drugs classified according to their most important pharmacological method of action can vary quite substantially in the frequency of certain side effects. In the discussion section of our article, we emphasized that individual SSRIs might differ with respect to their diabetogenic potential. However, there was no statistically significant difference in the risk of diabetes between paroxetine and fluvoxamine on the one hand and citalopram, fluoxetine, and sertraline on the other. Thus, highlighting differences within the class of SSRIs as one major finding of our study does not seem reasonable to us.