Guided Dose Reduction May Help Decrease Medication Dose in Schizophrenia

Over one-third of participants successfully tapered antipsychotic doses according to the algorithm, decreasing approximately 60% of the baseline doses.

Many patients with remitted psychosis are able to successfully taper their medication using a guided dose reduction (GDR) approach, according to study findings published in Psychological Medicine.

Patients (N=96) with schizophrenia-spectrum disorders receiving a fixed-dose antipsychotic treatment were recruited at the National Taiwan University Hospital. Willing participants were randomly assigned in a 2:1 ratio to receive GDR (n=51) or to continue maintenance therapy (MT1; n=24). Another group of unwilling patients were included in a naturalistic comparator maintenance therapy group (MT2; n=21).

The outcomes of interest were changes to Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression of Severity (CGI-S), Personal and Social Performance scale (PSP), and EuroQoL-5D visual analog scale (EQ-5D-VAS) for quality-of-life scores. Relapse was defined as having 1 of the PANSS positive symptoms and 2 general symptom scores greater than 3.

The GDR protocol started at a reduction of no more than 25% with monitoring occurring every 4 weeks. The next attempt at dose reduction occurred at week 24 using a hyperbolic dose reduction protocol. A total of 4 consecutive reductions were planned.

Moreover, our proposed algorithm can instill hope to patients that they can maintain stable remission under a slow and cautious tapering process.

Participants had a mean age of 36.3 (SD, 10.2) years, of whom 44.8% were men with a mean body mass index of 25.6 (SD, 4.5) kg/m2, and had an illness duration of 11.3 (SD, 8.4) years. A total of 67.7% of participants had a history of relapse and 56.3% had a history of hospitalization. Participants were also receiving a chlorpromazine equivalent dose (CPZE) of 200.6 (SD, 129.3) mg per day. Treatment groups were well-balanced at baseline.

The relapse rate during follow-up was 14.6% overall, 11.8% among the GDR, 16.7% among the MT1, and 19% among the MT2 cohorts. Compared with the maintenance therapy cohorts, relapse was not more likely among the GDR group compared with the randomly assigned (hazard ratio [HR], 0.659; 95% CI, 0.186-2.337; P =.526) or naturalistic (HR, 0.577; 95% CI, 0.163-2.046; P =.406) maintenance cohorts.

At the end of the 2-year follow-up, 35.3% of participants were able to complete all 4 GDRs, for an average dose reduction of 40% from baseline. The remaining GDR participants achieved 1 reduction (39.2%), reverted to their baseline dose (13.7%), or relapsed (11.8%).

Among all participants who did not relapse (74.5%), they maintained an average dose reduction of 39% of baseline. In addition, those in the MT1 group who desired to reduce their dose did so by 11% of baseline by the end of the 2-year follow-up.

Compared with baseline, participants in all 3 groups had significant improvements to PANSS total scores (mean difference [MD] range, -1.67 to -2.44; all P ≤.029),those in the the GDR and MT1 groups had improvements to PSP scores (MD range, 0.89-2.78; both P ≤.019), and those in the GDR cohort had improved CGI-S (MD, 0.24; P =.006) and EQ-5D-VAS (MD, 6.07; P =.009) outcomes.

Limitations of the study include the reliance on patient report to assess adherence to dosing.

Study authors conclude, “[O]ur findings suggest how to optimize the risk-to-benefit ratio of using antipsychotics in the protracted course of psychosis. Moreover, our proposed algorithm can instill hope to patients that they can maintain stable remission under a slow and cautious tapering process.”


Liu C-C, Hsieh MH, Chien Y-L, et al. Guided antipsychotic reduction to reach minimum effective dose (GARMED) in patients with remitted psychosis: a 2-year randomized controlled trial with a naturalistic cohort. Psychol Med. 2023;1-9. doi:10.1017/S0033291723000429