Polypharmacy for schizophrenia treatment is not justified by the available clinical evidence. We evaluated a treatment reduction approach that reduces the dose and number of antipsychotic medications simultaneously prescribed to patients. In a randomized open study of the Safe Correction of Antipsychotic Polypharmacy and High-Dose Prescriptions program funded by the Japanese Ministry of Health, Labour, and Welfare, we evaluated a drug reduction method consisting of a dose reduction intervention performed on 163 patients with schizophrenia for twelve or 24 weeks. One antipsychotic medication was removed each week from each patient's treatment regimen by reducing the dose by 0 to 50 chlorpromazine equivalents. Data on health-related indices of quality of life, clinical symptoms, and risk of side effects were analyzed using a two-way repeated-measures mixed linear model. Despite a 23% reduction in antipsychotic dose, no differences in outcomes were observed between the dose reduction and observation groups (effect size = 0.001 – 0.085, P = .24–.97), despite high statistical power (1-β = 0.48–0.97). The findings are limited by the nonuniformity of the participants' treatment history, duration, and dose reduction amount. Dose reduction protocol patients exhibited no difference in psychotic symptoms or adverse events compared with the observation group. Importantly, the low dropout rate in our study (6.9% of participants withdrew because of patient factors and 23.8% for all secondary reasons) indicates that our "slowly" method is well tolerated. We hope that this approach will result in therapeutic improvements.
To examine antidepressant prescription patterns in Japanese children and adolescents. We conducted a cross-sectional survey during October 2013 on outpatients, aged 19 or less, in 34 private mental clinics. Patients who were prescribed at least one antidepressant were analyzed in this report. Data on gender, age, principal psychiatric diagnosis (based on ICD-10), and types and doses of psychotropic drugs were extracted. The samples consisted of 137 males and 170 females. The average age (standard deviation) was 16.2 years (2.5). The mean length of psychiatric treatment was 23.6 months (23.3). The most frequent diagnostic category was neurotic disorders (F4; n=113), followed by mood disorders (F3; n=73), disorders of psychological development (F8; n=67), behavioral and emotional disorders (F9; n=22), schizophrenic spectrum disorders (F2; n=18), and other diagnoses (n=14). Among the 19 antidepressants available in Japan, the prescription rate of fluvoxamine (42.3%; n=130) was the highest, followed by sertraline (17.6%), duloxetine (10.4%), escitalopram (9.8%), trazodone (6.5%), and paroxetine (5.5%). Tricyclic or tetracyclic antidepressants (TCAs) were prescribed in 35 patients (11.4%). Two or more antidepressants were prescribed concurrently in 27 (8.8%) of the 307 patients. Anxiolytics/hypnotics were concurrently prescribed in 126 (41.0%). Mood stabilizers were co-prescribed in 35 (11.4%). Antipsychotics were concurrently prescribed in 134 (43.6%), with a median dose of 100mg/d chlorpromazine equivalent. In Japan, although augmentation of antidepressant treatment seemed relatively popular with antipsychotics in adolescent patients, antipsychotic doses might be relatively low.
To investigate the possible effect of polymorphism at the BalI site of the dopamine D3 receptor gene (DRD3) on the phenotype in human subjects, allele and genotype frequencies for this polymorphic site were examined in 113 schizophrenic patients, including six subgroups, and 48 normal controls. The schizophrenic subgroups included patients with early onset, those with a family history, and those who suffered from one of the following psychiatric symptoms at their first episode: (1) delusion and hallucination; (2) disorganization; (3) bizarre behavior; and (4) negative symptoms. No significant differences were observed in genotype, allele and homozygosity frequencies between the whole group or any subgroup of schizophrenic patients and the controls. The present results indicate that polymorphism at the BalI site of the DRD3 is unlikely to be a major contributor to any of the psychiatric parameters examined in the present population of schizophrenic subjects.
Surface cells of the mammalian distal colon are shown to molecularly express the amiloride-sensitive epithelial Na+ channel composed of three homologous subunits (alpha-, beta-, and gamma-ENaC). However, because basic electrophysiological properties of amiloride-sensitive Na+ channels expressed in these cells are largely unknown at the cellular level, functional evidence for the involvement of the subunits in the native channels is incomplete. Using electrophysiological techniques, we have now characterized functional properties of native ENaC in surface cells of rectal colon (RC) of rats fed a normal Na+ diet. Ussing chamber experiments showed that apical amiloride inhibited a basal short-circuit current in mucosal preparation of RC with an apparent half-inhibition constant (Ki) value of 0.20 microM. RT-PCR analysis confirmed the presence of transcripts of alpha-, beta-, and gamma-rENaC in rectal mucosa. Whole cell patch-clamp experiments in surface cells of intact crypts acutely isolated from rectal mucosa identified an inward cationic current, which was inhibited by amiloride with a Ki value of 0.12 microM at a membrane potential of -64 mV, the inhibition being weakly voltage dependent. Conductance ratios of the currents were Li+ (1.8) > Na+ (1) >> K+ ( approximately 0), respectively. Amiloride-sensitive current amplitude was almost the same at 15 or 150 mM extracellular Na+, suggesting a high Na+ affinity for current activation. These results are consistent with the hypothesis that a heterooligomer composed of alpha-, beta-, and gamma-ENaC may be the molecular basis of the native channels, which are responsible for amiloride-sensitive electrogenic Na+ absorption in rat rectal colon.
The percutaneous penetration of R-(+)- and S-(-)-propranolol (PL) through rat excised skin was investigated in vitro. The flux of S-(-)-PL after application to normal skin was high compared with that of R-(+)-PL. On the other hand, in damaged rat skin, the flux of R-(+)-PL was almost equivalent to that of S-(-)-PL. It is suggested that there is an enantiomeric difference between S-(-)- and R(+)-PL in terms of penetration through rat stratum corneum.
