Ramelteon for Delayed Sleep-wake Phase Disorder: A Case Report

Recently developed melatonin receptor agonists are expected to be effective for delayed sleep-wake phase disorder (DSWPD). To date, however, no study has described the effect of melatonin receptor agonists on DSWPD. We report the case of a 15-year-old girl with DSWPD who was successfully treated with ramelteon 4 mg at 7 PM. DSWPD symptoms were resolved; her sleep-wake and biological rhythms were normalized.

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), N-desmethylclozapine (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.

Successful Management of Clozapine-induced Akathisia with Gabapentin Enacarbil: A Case Report

The management of clozapine (CLZ)-induced adverse events affects patient prognoses. Akathisia is a relatively rare adverse event related to CLZ administration and thus the management of this syndrome is not well established. Here, we report a case of treatment-resistant schizophrenia wherein CLZ-induced akathisia was successfully managed with gabapentin enacarbil (GE). The patient was a 39-year-old woman who had been treated with atypical antipsychotics other than CLZ for three years with poor tolerability. Initiation of CLZ (400 mg/day) attenuated her psychotic symptoms, but was followed by moderate akathisia. Neither benzodiazepines nor biperiden improved the akathisia; however, akathisia was finally diminished with co-administration of GE. GE facilitated a dosage increase in CLZ (450 mg/day) for the improved management of pyschotic symptoms, and thus indirectly contributed to treatment of the patient’s schizophrenia. We suggest that GE is a useful candidate for the management of CLZ-induced akathisia. The improved management of treatment-induced akathisia and other adverse events can extend the potential application of CLZ for treatment-resistant schizophrenia.