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Randomized Controlled Trial
. 2025 Apr 23;26(9):4003.
doi: 10.3390/ijms26094003.

Halved Dose of Antipsychotics Versus High-Dose Antipsychotic Therapy for Relapse in Patients with Schizophrenia Receiving High-Dose Antipsychotic Therapy: A Randomized Single-Blind Trial

Ryota Ataniya  1   2 , Takeshi Koike  2 , Atsuko Inamoto  1
Affiliations
Randomized Controlled Trial

Halved Dose of Antipsychotics Versus High-Dose Antipsychotic Therapy for Relapse in Patients with Schizophrenia Receiving High-Dose Antipsychotic Therapy: A Randomized Single-Blind Trial

Ryota Ataniya et al. Int J Mol Sci. .

Abstract

Both a shortage and an excess of dopamine (DA) in the prefrontal cortex and striatum result in their decreased functions, and the relationship between the DA levels and their functions exhibits an inverted-U shape. Increased DA transmission via dose reduction in the currently used antipsychotics may improve the activation of DA-related symptoms in schizophrenia; these include delusions and auditory hallucinations caused by increased DA release. In this case, reducing the dose of the antipsychotic may be a treatment option for relapse in patients with schizophrenia who are already on high doses of antipsychotics and find it difficult to further increase the dose. A total of 54 inpatients with schizophrenia receiving high-dose antipsychotic therapy were randomly assigned to either the halved-dose group or the high-dose group (symptomatic treatment). The study compared the time from relapse to improvement between the two groups. In the halved-dose group, the period until relapse improvement ranged from 1 to 3 weeks, while the high-dose group experienced improvement in 4 to 9 weeks, and a significant difference was observed between the two groups using Kaplan-Meier survival analysis (p < 0.001).

Keywords: dopamine D2 receptor; high-dose antipsychotic therapy; inverted U-shaped dose response; relapse; schizophrenia.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Changes in dopamine stimulation and function at remission and relapse in patients with schizophrenia.
Figure 2
Figure 2
Halving the antipsychotic dose at relapse reduces DA-related function and positive symptoms in patients with schizophrenia.
Figure 3
Figure 3
CONSORT flow diagram.
Figure 4
Figure 4
The non-improvement rate in the halved-dose group and high-dose group after relapse.
See this image and copyright information in PMC

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