Kensuke Nomura

Revising polypharmacy to a single antipsychotic regimen for patients with chronic schizophrenia

Antipsychotic polypharmacy has been empirically used and a recent trend in favour of that mode of therapy has been suggested for the treatment of schizophrenia. The clinical efficacy, however, still remains to be clarified. In order to critically evaluate the usefulness of such kind of psychopharmacotherapy, antipsychotic combination regimen (polypharmacy) was switched to a treatment with the single main antipsychotic (monotherapy) in cross-tapered fashion, while approximately maintaining the total amount, for patients with chronic schizophrenia. Patients had been treated with an average of three antipsychotics and maintained with the same antipsychotic polypharmacy regimen for more than 6 months before the entry. They were followed up with an antipsychotic monopharmacy and evaluated at 24 wk after completion of switching. Forty-seven patients were recruited for this study. Of 44 patients for whom evaluation was possible, 24 (54.5%) remained stable, while 10 (22.7%) showed improvement and the same number of patients ended in a deleterious status. Twenty-two patients were converted to antipsychotic monotherapy, while another 12 needed minimal dosing of low-potency agents. Overall, social functioning, evaluated by the Global Assessment of Functioning and the Clinical Global Impression, remained unchanged. Eighteen of 34 successful patients showed adverse effects of the main antipsychotic medication, which necessitated a significant dose reduction. Nine out of 10 deteriorating patients had been treated with a combination of low- and high-potency antipsychotics. It is suggested that many instances of antipsychotic polypharmacy is avoidable. The result is compatible with the current treatment recommendations, which dictate the use of a single antipsychotic agent.

Effectiveness of antipsychotic polypharmacy for patients with treatment refractory schizophrenia: an open-label trial of olanzapine plus risperidone for those who failed to respond to a sequential treatment with olanzapine, quetiapine and risperidone.

To evaluate the effectiveness of antipsychotic polypharmacy in a methodologically sound manner.

Augmentation of atypical antipsychotics with valproic acid. An open-label study for most difficult patients with schizophrenia

Most difficult inpatients with schizophrenia are in serious needs but obviously underrepresented in clinical trials.

Reducing the dose of antipsychotic medications for those who had been treated with high-dose antipsychotic polypharmacy: an open study of dose reduction for chronic schizophrenia.

Antipsychotic medications are often used at higher than the recommended dose and sometimes in a combination regimen to treat schizophrenia. However, in general, high-dose therapies have been abandoned in recent clinical studies. In this study, dose reduction of antipsychotic medication was implemented for patients with chronic schizophrenia, most of whom (81%) had been treated with an antipsychotic high-dose polypharmacy regimen consisting of more than 1000 mg/day in total amount. The results show that merely reducing the amount of antipsychotic led to favourable outcome in 23 out of 41 cases (56%), with another 13 cases (32%) showing no change. Dose reduction ended in failure in only five subjects (12%). Overall, the amount as well as the number of antipsychotic medications was significantly reduced from 1984 mg to 812 mg per day (reductions of 59% and from 3.6 to 2.2, respectively; both P<0.0001). The Global Assessment of Functioning scale improved from 30.6 to 37.2, which reached significance (P<0.001). Accordingly, the Severity of Illness improved from 4.7 to 4.2, and was also significant (P<0.01). Dose reduction is an encouraging strategy to consider for those patients with schizophrenia who have chronically been treated with high-dose antipsychotic polypharmacy, even if judged unavoidable in the past.

Novel rating scales for schizophrenia — Targeted Inventory on Problems in Schizophrenia (TIP-Sz) and Functional Assessment for Comprehensive Treatment of Schizophrenia (FACT-Sz)

OBJECTIVE Many rating scales have been in use to evaluate various symptomatic domains, and eventually there are too many scales to be selected and widely utilized in busy real-world settings. Relevant, quick, and user-friendly assessment scales are needed to facilitate measurement-based treatment of schizophrenia. METHODS The authors created unique convenient assessment scales: Targeted Inventory on Problems in Schizophrenia (TIP-Sz), and Functional Assessment for Comprehensive Treatment of Schizophrenia (FACT-Sz). The TIP-Sz consists of 10 items (behavioral dyscontrol/disorganization, hostility/agitation/violence, indifference/affective withdrawal/motor retardation, symptoms on mood/anxiety/obsession/compulsion, insight/reality testing, social competence/independence, adherence to treatment, therapeutic alliance/comfort of therapists on the situation, overall prognostic impression, and subjective well-being/satisfaction with therapy). They are all common and frequently problematic, and each item is rated from 0-10. The FACT-Sz evaluates psychosocial functioning of patients with a score of 0-100, and is judged entirely on an objective basis. Their correlations with the frequently utilized Positive and Negative Syndrome Scale (PANSS), Global Assessment of Functioning (GAF), and Clinical Global Impression-Severity subscale were determined. RESULTS Data on 36 patients, assessed separately by four experienced psychiatrists, were analyzed. Under an excellent interrater reliability among raters (Intraclass correlation coefficients: 0.822-0.966), correlations among the scales were very high (Spearmans rho: 0.825-0.909), and other indicators of the scale were generally good. Specifically, the TIP-Sz and FACT-Sz could be rated at 1/3-1/4 of time to complete the PANSS and GAF. CONCLUSION The TIP-Sz and FACT-Sz proved to be reliable and valid, which would be of value in daily clinical practice as a minimum standardized assessment set.

Combined treatment with sulpiride and paroxetine for accelerated response in patients with major depressive disorder.

Abstract: Although serotonin reuptake inhibitors are recommended as first-line agents for major depressive disorder, delayed onset of action is problematic, and faster effective treatment is needed. Sulpiride, a dopamine-mediated agent, has been reported to show faster antidepressant efficacy, and we examined the efficacy of adjunctive sulpiride in combination with paroxetine (PAX), compared with PAX alone, to clarify whether the combined treatment exerts faster effect. Forty-one major depressive disorder patients were enrolled in this 12-week open-label trial and were randomly assigned to a PAX (10-40 mg/d) or a PAX (10-40 mg/d) plus sulpiride (100 mg/d) group. Assessments included the Montgomery-Asberg Depression Rating Scale, the 17-item Hamilton Rating Scale for Depression, and the Zung Self-rating Depression Scale on an intent-to-treat basis, and safety was also monitored. Thirty-three patients completed the study. Both PAX + sulpiride and PAX treatments showed a mean reduction in the total Montgomery-Asberg Depression Rating Scale score of 34.4 to 5.6 and 32.2 to 10.4, respectively (P < 0.001). The combined treatment group had a significantly superior outcome in terms of the change in the total Montgomery-Asberg Depression Rating Scale, Hamilton Rating Scale for Depression, and Zung Self-rating Depression Scale scores between week 1 and the study end point (P < 0.05). Median times to response among responders alone for the combined treatment and monotherapy were 2 and 6 weeks, respectively. Both treatments were well tolerated, with no clinically significant differences in safety measures except for an elevation of prolactin in the combined treatment group. The combination treatment may be a safe and effective strategy for accelerating antidepressant response.

Survey of benzodiazepine and antidepressant use in outpatients with mood disorders in Japan

Data on benzodiazepine use in mood disorders are still limited, especially among seniors. A cross‐sectional review of psychotropic prescriptions in 948 outpatients with mood disorders (405 male; mean ± SD age, 52 ± 17 years; age range, 16– 91 years) was conducted in Japan. The use of benzodiazepine‐derivative anxiolytics was approximately 60% in all decades, including older patients, without a group difference. The frequent use of benzodiazepines is a cause for concern because they are not preferred treatment, given their well‐known adverse effects especially in the elderly.

Magnitude of rater differences in assessment scales for schizophrenia.

The magnitude of rater differences, instead of interrater reliability, in the assessment scales of schizophrenia has rarely been investigated and was therefore addressed in this study. Thirty-six patients with schizophrenia were independently assessed by 4 expert physicians, using clinical rating scales including the Positive and Negative Syndrome Scale (PANSS). The scores obtained by the physician in charge (PIC), who had a long close contact with the patients, served as the referent answer for the purpose of this study. The scores rated by the other 3 non-PIC psychiatrists, who had a first formal examination with them, were evaluated for percentage deviance from the referent answer. The results showed that the PIC raters endorsed the numerically highest score in 20 (56%) of the 36 patients, whereas they rated the lowest in only 2 (6%) in the PANSS total score. The non-PIC assessors on the average underrated the PANSS total score by 10%, and such a tendency of underestimating the severity was noted across other clinical scales. Furthermore, the PANSS total score by one of the non-PIC physicians was deviant from the referent answer by at least 20% in 15 (42%) of 36 instances. Importantly, this magnitude of deviance was noted in the context of an intraclass correlation coefficient of 0.92. This unique investigation disclosed clinically pertinent differences among raters, even under an excellent interrater reliability. The magnitude of differences described herein seems to be an underestimation, and the baseline scores by the independent new raters might need to be corrected for those by the PICs.

Impacts of switching antidepressants after successful electroconvulsive therapy on the maintenance of clinical remission in patients with treatment-resistant depression: A chart review

Introduction: There is no consensus regarding whether a previously prescribed, that is, failed, antidepressant should be continued or switched after a successful electroconvulsive therapy (ECT) for the maintenance of clinical remission in patients with treatment-resistant depression (TRD). In this study, we conducted a chart review to examine impacts of the antidepressant switch after the successful ECT on 1-year outcome in patients with TRD. Materials and Methods: This retrospective chart review included inpatients with TRD (ie, those who failed to respond to adequate trials of 2 distinctly different classes of antidepressants) who showed clinical remission after ECT. Readmission rate and social functioning 6 months and 1 year after the successful ECT were compared between patients who experienced an antidepressant switch and those who continued prior regimen. Results: Twenty-eight patients (mean age, 59 years; 9 men) were followed-up for 1 year. The patients who changed antidepressants after ECT (n = 7) experienced a readmission significantly less frequent than the others (n = 21) in 1 year (0% vs 43%, P = 0.043). In addition, the former showed significantly better social contacts at 6 months (P = 0.022) and 1 year (P = 0.015). There were no significant differences in baseline characteristics between the 2 groups. Conclusions: The patients who experienced an antidepressant switch after ECT required a readmission less frequently in 1 year than those who were maintained with the same antidepressant. The findings of this preliminary study suggest that a switch to another antidepressant after successful ECT may be encouraged for the maintenance of clinical remission in patients with TRD.