Carbon monoxide poisoning from burning charcoal has become a popular way of attempting suicide in East Asia. The delayed sequelae of carbon monoxide intoxication (COI) include dementia, amnestic syndrome, psychotic symptoms, aphasia, apraxia and parkinsonism (Reference Ernst and Zibrak1–Reference Choi3). To our knowledge, no report has examined the use of paliperidone to treat the sequelae of COI, although there were two reports of atypical antipsychotics, such as ziprasidone and aripiprazole (Reference Hu, Shiah, Yeh, Chen and Chen4,Reference Pae, Kim, Lee and Paik5). We report a patient with performance and memory dysfunction and psychotic symptoms as a result of persistent, delayed sequelae of COI that were treated successfully with paliperidone after a trial of quetiapine.

A 28-year-old male was exposed to COI with two others who met through the internet to commit suicide. On arrival at the Emergency Department, the patient had a carboxyhaemoglobin level of 35.7%, which dropped to 0.7% after receiving hyperbaric oxygen. Five days later, he was admitted to the Department of Psychiatry with an abrupt cognitive decline, performance dysfunction, auditory hallucinations and persecutory delusions affecting his overall personal and social functioning despite conservative treatment including O₂. The patient's family and medical histories did not include neurological, psychotic or medical disorders. There was no evidence of substance abuse.

On admission, the patient completed a full battery of neuropsychological tests, including the Korean Wechsler Adult Intelligence Scale (K-WAIS), Ray Kim Memory Test, Kims Executive Test, Mini-Mental State Examination (MMSE) and Positive and Negative Syndrome Scale (PANSS). The laboratory findings were normal, with the exception of his magnetic resonance imaging findings, which revealed abnormalities in the globus pallidus, hippocampus, temporal cortex and periventricular white matter.

We prescribed quetiapine titrated to 100 mg/day on admission for 2 weeks. After 2 weeks of quetiapine treatment, the patient showed improvement in his sleep problems, but the hallucinations and delusions had not changed on the Clinical Global Impression (CGI) and the sedation, dizziness and ataxia had become worse. The quetiapine was reduced to 25 mg/day without further improvement in the psychotic symptoms. Therefore, we slowly switched the quetiapine to paliperidone 6 mg/day, which we continued for 2 weeks and then increased to 9 mg. After 2 weeks of paliperidone treatment, the auditory hallucinations, persecutory delusions, performance dysfunction and memory dysfunction declined significantly on the CGI, while his sedation, dizziness and ataxia improved, enabling him to walk. His cognitive ability improved considerably, especially frontal executive function, performance intellectual function and psychotic symptoms. He was discharged 12 weeks after admission on paliperidone 9 mg. The patient did not show any side effects of paliperidone.

The cognitive and psychotic symptoms improved gradually, including the results of the K-WAIS, Ray Kim Memory Quotient, Kims Executive IQ, MMSE and PANSS. The improvements were significant. For example the K-WAIS (full scale/verbal IQ/performance IQ) scores increased from 88/96/78 at baseline to 93/100/85 at 12 weeks and 100/102/99 at 24 weeks. The Ray Kim Memory Quotient and Kims Executive IQ increased from 44/60 at baseline to 47/77 at 12 weeks and 50/93 at 24 weeks. The MMSE score increased from 14 at baseline to 25 at 12 weeks and 26 at 24 weeks. The PANSS changed significantly from 78 at baseline to 67 at 12 weeks and 53 at 24 weeks.

Paliperidone, or 9-hydroxy-risperidone, is the major active metabolite of risperidone (Reference Leysen, Janssen, Megens and Schotte6). It binds to both D2 and serotonin 2A(5-HT2_2a) receptors, and antagonism at these receptors is thought to account for its therapeutic activity in schizophrenia (Reference Richelson and Souder7). The favourable outcome of paliperidone in this patient was likely attributable to the role of paliperidone in enhancing dopaminergic neurotransmission coupled with reduced dopaminergic activity (Reference Nasrallah8). Given that paliperidone is the active metabolite of risperidone, it seems unlikely that paliperidone extended-release (ER) would be more efficacious than risperidone in a population with treatment-resistant schizophrenia (Reference Fowler, Bettinger and Argo9). Although it is difficult to explain the mechanism of the effects of paliperidone, atypical antipsychotics, such as risperidone and ziprasidone, have neuroprotective properties that might be relevant to their clinical efficacy (Reference Yulug, Yildiz, Guzel, Kilic, Schabitz and Kilic10). In the treatment of schizophrenia and schizoaffective disorder, second-generation antipsychotics may provide better negative symptom control, less dysphoria, less impairment of cognition and a lower risk of TD than first-generation antipsychotics (Reference Correll, Leucht and Kane11,Reference Tandon and Jibson12). The effects of antipsychotics on cognition are still a matter of debate (Reference Woodward, Purdon, Meltzer and Zald13). Few studies have evaluated the effects of second-generation antipsychotics on cognitive dysfunction in the early stages of schizophrenia. Keefe et al. (Reference Keefe, Bilder and Davis14) recorded significant improvement following treatment with olanzapine, quetiapine and risperidone. Two recent papers report on a comprehensive research programme in which the effects of two antipsychotics, olanzapine and ziprasidone, are investigated in patients with recent-onset schizophrenia (Reference Grootens, Van Veelen and Peuskens15,Reference Van Veelen, Grootens and Peuskens16). We assumed that the blocks serotonin 2A receptors of paliperidone might be causing enhancement of dopamine release in certain brain regions and thus reducing motor side effects and possibly improving cognitive and affective symptoms (Reference Nasrallah8,Reference Nussbaum and Stroup17) This is a case but not a placebo trial. So this case suggests that paliperidone have the potential effect as monotherapy in the treatment of psychotic symptoms and movement disorders associated with toxic brain injuries such as COI.

Seong-Beom Oh ¹ , Myung-Ho Lim ² , Ho-Jang Kwon ³ , Dong-Soo Yoo ⁴ , Chang-Min Lee ⁵