Pharmacological Treatment of Schizophrenia: Japanese Expert Consensus.

INTRODUCTION: Conventional treatment guidelines of schizophrenia do not necessarily provide solutions on clinically important issues. METHODS: A total of 141 certified psychiatrists of the Japanese Society of Clinical Neuropsychopharmacology evaluated treatment options regarding 19 clinically relevant situations in the treatment of schizophrenia with a 9-point scale (1="disagree" and 9="agree"). RESULTS: First-line antipsychotics varied depending on predominant symptoms: risperidone (mean±standard deviation score, 7.9±1.4), olanzapine (7.5±1.6), and aripiprazole (6.9±1.9) were more likely selected for positive symptoms; aripiprazole (7.6±1.6) for negative symptoms; aripiprazole (7.3±1.9), olanzapine (7.2±1.9), and quetiapine (6.9±1.9) for depression and anxiety; and olanzapine (7.9±1.5) and risperidone (7.5±1.5) for excitement and aggression. While only aripiprazole was categorized as a first-line treatment for relapse prevention (7.6±1.0) in patients without noticeable symptoms, aripiprazole (8.0±1.6) and brexpiprazole (6.9±2.3) were categorized as such for social integration. First-line treatments in patients who are vulnerable to extrapyramidal symptoms include quetiapine (7.5±2.0) and aripiprazole (6.9±2.1). DISCUSSION: These clinical recommendations represent the expert consensus on the use of a particular antipsychotic medication for a particular situation, filling a current gap in the literature.

Relationship between Clozapine-Induced Electroencephalogram Abnormalities and Serum Concentration of Clozapine in Japanese Patients with Treatment-Resistant Schizophrenia.

OBJECTIVE: The objective of this study was to investigate the relationship between the serum concentration of clozapine (C-CLZ), Ndesmethylclozapine (N-CLZ) and the daily dose of CLZ (D-CLZ), and the relationships among CLZ and electroencephalogram (EEG) abnormalities. METHODS: Twenty-eight patients were recruited to this study, but 8 patients were excluded because clozapine was discontinued before the post-treatment measurement of EEG or C-CLZ. Ultimately, 20 patients (6 men, 14 women) with an average age of 36 years were enrolled. The subjects were divided into EEG normal and abnormal groups. C-CLZ and N-CLZ were measured at 4, 12, 26, and 52 weeks after initiating CLZ administration. RESULTS: All patients had normal baseline EEG signals, and 8 patients showed EEG abnormalities later. There were significant correlations between C-CLZ and D-CLZ, and between N-CLZ and D-CLZ. The C-CLZ/D-CLZ, N-CLZ/D-CLZ, and C-CLZ/N-CLZ ratio were not significantly different between the EEG normal and EEG abnormal groups. The EEG abnormal group had significant higher proportion of patients with high intra-individual variability in their C-CLZ/D-CLZ ratio. CONCLUSION: There is no relationship between C-CLZ and EEG abnormalities. However, patients with high intra-individual variability in their C-CLZ/D-CLZ ratio had greater possibility of exhibiting EEG abnormalities.

Clozapine-induced seizures, electroencephalography abnormalities, and clinical responses in Japanese patients with schizophrenia.

PURPOSE: We describe electroencephalography (EEG) abnormalities and seizures associated with clozapine treatment in Japanese patients with schizophrenia and retrospectively compare EEG results and total Positive and Negative Syndrome Scale (PANSS [T]) scores before and after treatment. METHODS: Twenty-six patients with treatment-resistant schizophrenia were enrolled in this study. EEG measurements were obtained prior to clozapine treatment and every 4 weeks thereafter. EEG measurements were also obtained at the time of seizure. After seizures or EEG abnormalities were noted, additional EEGs were performed every 2 weeks. PANSS (T) scores were used to determine clozapine treatment outcome. RESULTS: All 26 patients had normal baseline EEG measurements, and ten patients (38.5%) later manifested EEG abnormalities. The mean age was significantly lower than in the abnormal EEG group. Six patients (23.1%) experienced seizures. The mean dose of clozapine at the first occurrence of seizure was 383.3 mg/day. Five of six patients who experienced seizures in this study were successfully treated with valproate or lamotrigine without discontinuation of clozapine. The one patient who continued to experience seizures was successfully treated without antiepileptic drugs. The mean baseline PANSS (T) scores were not significantly different between the normal and abnormal EEG groups, but the mean score in the abnormal EEG group was significantly lower than that in the normal EEG group at the final follow-up (P=0.02). CONCLUSION: EEG abnormalities may appear in younger patients, and our findings indicate that there is no need to discontinue clozapine when seizures occur. EEG abnormalities that appeared after clozapine treatment were associated with a good clinical response.