A Different Mechanism to Understand Activation/Sedation Side Effects of Ziprasidone

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Sir: The supplement article by Stahl and Shayegan1 on the psychopharmacology of ziprasidone was a nice review and is still the standard, but I would like to make exception to one well-accepted mechanism. As I review my clinical experience, I see that patients who were started on 40 mg b.i.d. of ziprasidone and then went on to receive 60 mg b.i.d., as suggested by Pfizer on the basis of the article by Stahl and Shayegan, often complained of restlessness and stopped the drug. This is contrary to the explanation of the article indicating that getting to D2 blockade balances out the putative serotonin-2C (5-HT2C) effect, which is the basis of the side effect.​

J Clin Psychiatry 2007;68(6):974-974