Single Versus Multiple Daily Dosing Regimens of Psychotropic Drugs for Psychiatric Disorders

Kikuchi, Yuhei; Shimomura, Yutaro; Suzuki, Takefumi; Uchida, Hiroyuki; Mimura, Masaru; Takeuchi, Hiroyoshi

doi:10.4088/jcp.20r13503

Cited by 8 publications

(9 citation statements)

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“…Indeed, a meta-analysis found no significant difference in psychopathology between single and multiple daily dosing regimens of antipsychotics, including those with a shorter half-life, in patients with schizophrenia. 11 Furthermore, a double-blind RCT found no significant difference in psychopathology between every other day and daily antipsychotic administration in patients with stable schizophrenia. 12 Second, our findings suggest that an antipsychotic can be abruptly discontinued when switching to another antipsychotic.…”

Section: Discussionmentioning

confidence: 99%

“…First, the finding that the antipsychotic effect persisting several days after discontinuation may support the feasibility of extending the interval between antipsychotic administrations. Indeed, a meta‐analysis found no significant difference in psychopathology between single and multiple daily dosing regimens of antipsychotics, including those with a shorter half‐life, in patients with schizophrenia 11 . Furthermore, a double‐blind RCT found no significant difference in psychopathology between every other day and daily antipsychotic administration in patients with stable schizophrenia 12 .…”

Section: Discussionmentioning

confidence: 99%

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Does short‐term antipsychotic discontinuation of up to 3 weeks worsen symptoms in acute schizophrenia? A pooled analysis of placebo washout data

Takeuchi

Watabe

2023

Psychiatry Clin Neurosci

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This study aimed to examine symptom changes during short-term discontinuation of antipsychotics up to 3 weeks including the placebo washout phase in acute schizophrenia. Methods:The data from three double-blind, randomized, controlled trials comparing lurasidone versus placebo in patients with acute exacerbation of schizophrenia were analyzed. Symptom severity was assessed using the Positive and Negative Syndrome Scale (PANSS) total and the Clinical Global Impression-Severity scale (CGI-S) scores. The scores before and after the antipsychotic discontinuation phase were compared, and factors associated with score changes were explored.Results: Among 2154 patients participating in the trials, 600 who received antipsychotic monotherapy and completed the antipsychotic discontinuation phase were included in the analysis. No patients received clozapine. The mean duration of the discontinuation phase was 5.9 AE 2.5 days. The PANSS total and CGI-S scores significantly changed from 94.0 AE 9.5 to 95.4 AE 10.5 (P < 0.001) and from 4.9 AE 0.6 to 4.9 AE 0.7 (P = 0.041), respectively, during this phase; however, the absolute difference was minimal. The score changes were not associated with the type or dose of prior antipsychotics, or the duration or strategy (abrupt vs gradual) of antipsychotic discontinuation.Conclusions: Symptoms may not worsen to a clinically meaningful degree after short-term discontinuation of nonclozapine antipsychotics up to 3 weeks in patients with acute exacerbation of schizophrenia, suggesting that antipsychotic efficacy persists at least several days after discontinuation. This finding supports once-daily dosing regimen of antipsychotics and abrupt antipsychotic discontinuation when switching to another antipsychotic.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Does short‐term antipsychotic discontinuation of up to 3 weeks worsen symptoms in acute schizophrenia? A pooled analysis of placebo washout data

Takeuchi

Watabe

2023

Psychiatry Clin Neurosci

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“…Prescribing antipsychotics once-daily may be convenient for patients and eagerly adopted by clinicians [1][2][3]. Specifically, a recent meta-analysis comparing once-vs. multiple-daily dosing regimens for various psychotropic agents reported a better safety profile while preserving comparable efficacy in patients prescribed antipsychotics once-daily [4].…”

Section: Introductionmentioning

confidence: 99%

Clozapine once- versus multiple-daily dosing: a two-center cross-sectional study, systematic review and meta-analysis

Kuzo

Haen

et al. 2022

Eur Arch Psychiatry Clin Neurosci

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Evidence regarding effectiveness and safety of clozapine once- vs. multiple-daily dosing is limited. We compared demographic and clinical parameters between patients with once- vs. multiple-daily dosing in the Department of Psychiatry and Psychotherapy, University of Regensburg, Germany (AGATE dataset), and the Department of Psychiatry, Lausanne University Hospital, Switzerland, using non-parametric tests. Effectiveness and safety outcomes were available in the AGATE dataset. We performed a systematic review in PubMed/Embase until February 2022, meta-analyzing studies comparing clozapine once- vs. multiple-daily-dosing. We estimated a pooled odds ratio for adverse drug-induced reactions (ADRs) and meta-analyzed differences regarding clinical symptom severity, age, percentage males, smokers, clozapine dose, and co-medications between patients receiving once- vs. multiple-daily dosing. Study quality was assessed using the Newcastle–Ottawa-Scale. Of 1494 and 174 patients included in AGATE and Lausanne datasets, clozapine was prescribed multiple-daily in 74.8% and 67.8%, respectively. In the AGATE cohort, no differences were reported for the clinical symptoms severity or ADR rate (p > 0.05). Meta-analyzing eight cohorts with a total of 2810 clozapine-treated individuals, we found more severe clinical symptoms (p = 0.036), increased ADR risk (p = 0.01), higher clozapine doses (p < 0.001), more frequent co-medication with other antipsychotics (p < 0.001), benzodiazepines (p < 0.001), anticholinergics (p = 0.039), and laxatives (p < 0.001) in patients on multiple- vs. once-daily dosing. Of six studies, five were rated as good, and one as poor quality. Patients responding less well to clozapine may be prescribed higher doses multiple-daily, also treated with polypharmacy, potentially underlying worse safety outcomes. Patient preferences and adherence should be considered during regimen selection.

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“…single-daily regimen administration of antipsychotics proved to be equivalent to multiple-daily regimen in terms of efficacy and safety, indicating that prolonging the administration interval of antipsychotics could not affect their clinical effects ( 33 ).…”

Section: Introductionmentioning

confidence: 99%

Case Report: Long-Acting Oral Cariprazine

Dyrmishi

Pieri

Ferrari³

et al. 2022

Front. Psychiatry

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IntroductionCariprazine is a third-generation antipsychotic, approved for the treatment of schizophrenia and bipolar disorder and used off-label for schizoaffective disorder and treatment-resistant depression. Cariprazine is a partial agonist at dopamine receptors D2 and D3 and serotonin receptor 5HT1A and an antagonist at serotonin receptors 5HT2B and 5HT2A. It is metabolized by CYP3A4 in desmetyl-cariprazine and didesmethyl-cariprazine, both active metabolites with a half-life of 1–2 days and 2–3 weeks, respectively.Case ReportHere we show the cases of 3 outpatients diagnosed with bipolar I disorder (two patients) and schizoaffective disorder (one patients) and characterized by low adherence to treatment, satisfactory cognitive and personal functioning and average disease severity to whom we administered cariprazine as a monotherapy, on a two-times a week schedule (i.e., every 72–96 h). We evaluated response to treatment and disease remission according to conventional definitions, using rating scales BPRS, PANSS and BDI-II. Two-times a week treatment was set either after a disease relapse (one patient), after a sustained remission obtained with daily administration of cariprazine (one patient) or since our first evaluation (one patient). After 4 weeks of treatment all three patients satisfied criteria for response to treatment and remission, a result that was sustained for 8 (in one patients) and 12 months (in other two patients) and still ongoing.DiscussionReported results support our hypothesis that long half-lives of cariprazine and its metabolites provide an adequate therapeutic response with a two-times a week administration. In selected patients, cariprazine administered as a “oral long-acting” seems effective in treating acute episodes of illness and in sustaining remission, combining advantages of oral and long-acting injectable antipsychotics concerning therapeutic alliance.

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Single Versus Multiple Daily Dosing Regimens of Psychotropic Drugs for Psychiatric Disorders

Cited by 8 publications

References 0 publications

Does short‐term antipsychotic discontinuation of up to 3 weeks worsen symptoms in acute schizophrenia? A pooled analysis of placebo washout data

Does short‐term antipsychotic discontinuation of up to 3 weeks worsen symptoms in acute schizophrenia? A pooled analysis of placebo washout data

Clozapine once- versus multiple-daily dosing: a two-center cross-sectional study, systematic review and meta-analysis

Case Report: Long-Acting Oral Cariprazine

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