A very low dose of rivastigmine-induced Pisa syndrome in a clozapine-treated patient

Pisa syndrome (PS) is a movement disorder characterized by persistent dystonia with head lateralization and flexion of the back to one side. It is a rare axial symptom and is usually observed in patients with neurodegenerative diseases. Here, we present a patient with chronic schizophrenia who received clozapine to control her symptoms for years and subsequently developed acute PS after adding very low-dose rivastigmine.

A 67-year-old woman with chronic schizophrenia had been treated with clozapine at 150 mg/day for many years. She was diagnosed with Alzheimer’s disease (Mini–Mental State Examination score is 20 points) and was prescribed a low dose of the cholinesterase inhibitor rivastigmine 1.5 mg orally once a day. On the fifth day, she presented with acute and sustained lateral flexion of the body and head rotation to her right side. She could walk without assistance but showed a marked axial rotation of the trunk and contractures of the back muscles (Figure 1(A)). The patient was diagnosed with PS based on the marked lateral flexion on the coronal plane. After rivastigmine was tapered, her PS resolved fully within 7 days (Figure 1(B)). During the course, the patient’s positive, negative syndrome scale (PANSS = 47) score and dosage of clozapine did not change, and there were no symptoms of catatonia, such as catalepsy, waxy flexibility or posturing.

Figure 1.

(A) The patient presented right axial deviation and segmental truncal dystonia without head realignment after treatment with rivastigmine at 1.5 mg/day and (B) the symptoms resolved after discontinuing rivastigmine.

PS is a rare involuntary movement disorder in which patients exhibit postural disturbances with lateralization of the trunk and head to one side. According to the US Food and Drug Administration Adverse Event Reporting System in the United States, 52 cases of PS were reported from 1997 to 2011 (Zannas et al., 2014). Doherty et al. (2011) proposed the criterion of lateral flexion of more than 10° that can be resolved completely by passive movement or when lying supine. The initiation of neuroleptics induced or stopped the syndrome, which also supports the idea that an imbalance of dopaminergic neurons in the basal ganglia may contribute to PS. Clozapine has lower D2 antagonist action, with a dissociation constant (Ki) value of approximately 75 nm. PS after discontinuing antipsychotics with anticholinergic effects was reported before, and the physician should be aware of the risks of cholinergic rebound hypersensitivity after long-term inhibition (Yeh et al., 2009). In the presence of antagonism, the syndrome may also be explained by receptor upregulation and functional expression. Rivastigmine may induce higher levels of acetylcholine in the brain that competitively bind to receptors and cause dopamine–acetylcholine imbalance. The mechanism of PS proposed here suggests that any medication interfering with the equilibrium of cholinergic activity should be noted before initiation. Patient’s consent was obtained for the publication of this case presentation.