Pisa syndrome is an unusual movement side effect of traditional antipsychotics Reference Villarejo, Camacho and Garcia-Ramos(1). It is characterised by persistent dystonia to the cervical musculature of the trunk and tonic lateral flexion with slight rotation of the trunk Reference Villarejo, Camacho and Garcia-Ramos(1). Recent reports showed that this rare type of truncal dystonia is also related to the use of atypical antipsychotics including clozapine Reference Hung, Lee, Chang, Chong and Lin(2), risperidone Reference Harada, Sasaki, Ikeda, Nakano, Ozawa and Saito(3), olanazapine Reference Stubner, Padberg and Grohmann(4), ziprasidone Reference Duggal(5) and aripiprazole Reference Rota, Bergesio, Dettoni and Demicheli(6). We here report a case of a schizophrenic patient who developed acute Pisa syndrome after receiving 800 mg/day of amisulpride, another atypical antipsychotic. This movement side effect was in remission right after he received anticholinergic medications and his antipsychotic medication was switched.
A 29-year-old unemployed single male was diagnosed as having schizophrenia, paranoid type during his enlisting screening in 2000. Since then he had not received regular psychiatric treatment except that he was admitted to a psychiatric hospital for 3 weeks to treat his schizophrenia in 2006. The patient had a history of febrile seizure when he was 1-year old. There is no past history of head trauma or surgical illness. He has no past history of alcohol or substance abuse. There is no family history of psychiatric illnesses. The patient was brought to our psychiatry outpatient clinic in February of 2009 by his families because of exaggerated psychotic symptoms including persistent persecutory delusions, auditory hallucinations, violent behaviour and long-term social isolation. Based on the statement of his family, he did not take any medication for at least 2 years prior to this outpatient visit. His physical, neurological and laboratory examinations including magnetic resonance imaging of the brain and electroencephalogram did not reveal any remarkable finding. In addition, we evaluated his level of intelligence by using the Wechsler Adult Intelligence Scale-III, Chinese Version. The results showed that his full intelligence quotient (IQ) was 51, Verbal IQ 52, and Performance IQ 51. His mental status examination showed poor intelligence in addition to his psychosis. In our outpatient clinic, he was started with amisulpride 800 mg/day and trihexyphenidyl 2 mg/day for 1 week. Unexpectedly, on the third day, the patient developed the symptoms of leaning to right side about 45° and being unable to straighten up. When the patient returned to our clinic for follow-up on the 8th day, he showed tonic flexion of his trunk to right accompanied by slight backward axial rotation. Therefore, he was admitted to our acute ward for further management. After admission, the patient was given intramuscular injection of biperidin 5 mg for relieving his persistent dystonia. Furthermore, we changed his amisulpride 800 mg/day to quetiapine 800 mg/day and increased the dose of trihexyphenidyl up to 8 mg/day. With all these treatments, the patient's body posture returned to a normal position right on the day of his admission. However, his psychosis remained unresponsive. Because his persecutory delusions and auditory hallucinations did not respond to quetiapine in the following 2 weeks and even got worse, we put him on clozapine and the dose was gradually titrated up to 250 mg/day. His anticholinergic medications were all discontinued. The patient's psychosis finally responded to 250 mg/day of clozapine 2 weeks later and he was discharged under a stable mental condition without recurrence of any movement side effect.
Our case of amisulpride-associated acute Pisa syndrome suggests that this novel atypical antipsychotic, like most other atypical antipsychotics, can lead to the rare movement side effect, although atypical antipsychotics have generally been considered to be less likely to cause drug-induced movement side effects than traditional antipsychotics Reference Harada, Sasaki, Ikeda, Nakano, Ozawa and Saito(3,Reference Mlahi and Pantelis7).
Our case developed acute Pisa syndrome right after he received 800 mg/day of amisulpride for only 2 days. Regarding this, Duggal Reference Duggal(5) indicated several risk factors for developing acute antipsychotic-induced dystonia. These included young age, male gender and rapid escalation of antipsychotic dose Reference Duggal(5). Our case had other potential risk factors for developing this rare type of truncal dystonia: (a) an early history of febrile convulsion, (b) low intelligence and (c) a relatively high dose of amisulpride (i.e. 800 mg/day). These might explain why certain vulnerable individuals would develop acute Pisa syndrome.
The mechanisms underlying the antipsychotic-induced Pisa syndrome are not clear. But most studies suggested the dopamine-cholinergic imbalances to play a vital role in the development of this rare movement side effect Reference Villarejo, Camacho and Garcia-Ramos(1,Reference Lee, Shiah, Chen, Lin and Shen8). In our case, his good response to the anticholinergic medications supports this hypothesis. Further evidence in support of this came from the basic studies showing that amisulpride selectively blocked presynaptic dopamine D2 and D3 receptor at low doses thus enhancing dopamine release and synthesis mainly in limbic structures but at higher doses acting as a traditional antipsychotic with the blockage of postsynaptic dopamine D2 and D3 receptors Reference Sevincok, Balci and Akyildiz(9). Future studies are warranted to determine if there are other biological etiologies involved in the underlying mechanisms of amisulpride-associated acute Pisa syndrome.
