To the Editor: Pisa syndrome, or tonic flexion of the trunk, long considered a side effect of prolonged exposure to conventional antipsychotics, has recently been reported as occurring with atypical antipsychotics (1). It occurs mostly after changes in antipsychotic therapy. We report this syndrome appearing after the discontinuation of aripiprazole and the addition of clozapine.

A rechallenge with clozapine was associated with the reemergence of Pisa syndrome and thus can be implicated in this side effect. A PubMed search revealed only three previous reports of clozapine-associated Pisa syndrome (2–4). In most of these cases, the patients were elderly women exposed to typical antipsychotics and having an underlying disorder of the CNS, including brain atrophy on neuroimaging. However, to our knowledge, this is the first report of Pisa syndrome reemerging after reinitiation of clozapine. Risk factors for this syndrome include combined pharmacological treatment, old age, female gender, and the presence of an organic brain disorder (4), all of which were present in this patient. Aripiprazole, although discontinued about 11 days before Ms. A developed Pisa syndrome, cannot be ruled out as a potential cause of this side effect because of its long half-life of 60 hours. Moreover, Pisa syndrome has been described with antipsychotic discontinuation, which may be due to dopaminergic-cholinergic imbalance, the most accepted hypothesis for this syndrome (1, 5). Thus, caution is advised when changing atypical antipsychotic regimens in patients with risk factors for Pisa syndrome. As indicated by this and previous reports, reduction in dose or discontinuation of the antipsychotic drug remains the first-line treatment for Pisa syndrome. Besides this, about 40% of the patients with Pisa syndrome also show a therapeutic response to anticholinergics (1).