Medical Channel Guide
This new study shows that for the maintenance treatment of schizophrenia, most antipsychotics are recommended to use 0.9- <1.1 times the WHO-defined daily doses (DDDs), high doses (≥1.6 DDDs) or low doses (<0.6 DDDs) were often significantly associated with an increased risk of recurrent readmission, see text for details.
The current WHO standard dose is too high for perphenazine and slightly higher for risperidone. In addition, the antipsychotic long-acting injection (LAI) is more effective in preventing relapse than all other oral antipsychotics except clozapine.
Based on DDDs calculation, some commonly used oral second-generation antipsychoticsin population The optimal dose range for the maintenance period at the level is as follows: olanzapine, 9-<11mg/d; risperidone, 3-<4.5mg/d; quetiapine, 360-<440mg/d d; Aripiprazole, 13.5-<16.5 mg/d; Clozapine, 270-<330 mg/d.
<600">Most schizophrenia Patients respond well to treatment in the acute phase, but the real challenge lies in the prevention of relapse and readmission in the maintenance phase. In this context, it is important to explore the optimal dose of antipsychotics for maintenance therapy.
Previous evidence suggests that maintenance doses of antipsychotics above the WHO-defined daily dose (DDD) do not result in additional efficacy gains. doses below this level are associated with an increased risk of recurrence. Therefore, the use of 0.9-1.1 times the DDD seems to be the best choice for maintenance treatment, but it remains to be further confirmed, such as whether the above principles are applicable to all mainstream antipsychotics.
Research Brief
On May 7, 2022, Heidi Taipale and collaborators at the University of Eastern Finland in Schizophr Bull. (impact factor 9.306) published a cohort study online to explore the optimal doses of 15 commonly used antipsychotics for maintenance treatment of schizophrenia.
Nordic-based highlights of the study include: Nationally complete registry data, including all individuals admitted to hospital for schizophrenia from 1972 to 2014 in Finland and still alive on January 1, 1996, a total of 61 889 people; 2. Patient data were collected prospectively rather than retrospectively; 3. Intra-individual analysis was used to use patients themselves as controls (specific doses of antipsychotics vs. no use) to remove selection bias; 4. Antipsychotic doses were subdivided into <0.6 DDDs, 0.6-<0.9 DDDs, Six ranges of 0.9-<1.1 DDDs (standard dose, as a reference), 1.1-<1.4 DDDs, 1.4-<1.6 DDDs, and ≥1.6 DDDs are intended to obtain a more precise dose-response relationship.
The 15 antipsychotics involved in this study include first-generation antipsychotics haloperidol, perphenazine, fluphenazine and the second-generation antipsychotics aripiprazole, clozapine, olanzapine, quetiapine, risperidone, etc.; some drugs include oral and long-acting injection (LAI) dosage forms. The primary outcome of the study was schizophrenia relapse leading to readmission. For details of the study design and statistical analysis methods, please refer to the original text.
Results
The mean age of the cohort at the start of follow-up was 46.7 years (SD 16.0), the mean disease duration was 8.8 (SD 9.0) years, and 50.3% were male The most commonly used antipsychotics include olanzapine, risperidone, clozapine, and quetiapine.
Overall, 13 of the 15 antipsychotics showed a U- or J-shaped dose-response curve, suggesting a maintenance dose of 0.6 -1.1 DDDs had the lowest risk of recurrent readmission. The only two exceptions were oral perphenazine, which had the lowest risk of recurrent readmission (aHR=0.72) at doses <0.6 DDDs; and olanzapine LAI, which had the lowest risk of recurrent readmission at doses of 1.4-<1.6 DDDs lowest (aHR=0.17).
All antipsychotics were significantly higher than 0.9-<1.1 DDDs at doses ≥1.6 DDDs. It is particularly noteworthy that perphenazine, the risk of recurrence and readmission of 1.1-<1.4 DDDs, 1.4-<1.6 DDDs, and ≥1.6 DDDs was significantly higher than that of no medication, and the risk of ≥1.6 DDDs was 3.35 times that of no medication. prompt current DDD is too high.
Specific to the commonly used oral second-generation antipsychotics (all monotherapy):
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olanzapine
Figure 1 Risk of recurrence and readmission with different doses of oral olanzapine compared with no medication (Taipale H, et al. 2022)
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The DDD of oral olanzapine is 10mg/d.
Olanzapine doses were 0.9-<1.1 DDDs (9-<11 mg/ d) When , patients had the largest reduction in the risk of relapse and readmission (aHR 0.40, 95%CI=0.38-0.43), which was significantly better than the other four dose ranges except 1.4-<1.6 DDDs.
risperidone
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Figure 2 Risk of recurrence and readmission at different doses of oral risperidone compared to no medication (Taipale H, et al. 222)
The DDD of oral risperidone is 5mg/d.
The dose of risperidone was 0.6-<0.9 DDDs (3-<4.5 mg compared to no drug) /d) When , the reduction in the risk of recurrence and readmission was the largest (aHR 0.54, 95%CI=0.51-0.58), which was significantly better than all other 5 dose ranges, and the risk was 0.9-0.9- <1.1 DDDs (4.5-<5.5mg/d) were 21% lower.
Similar to perphenazine, when the dose of risperidone is ≥1.6DDDs (≥8mg/d), the risk of recurrence and readmission is significantly higher compared with no medication (aHR=1.34, 95%CI=1.22-1.47). The common point of these two drugs is that they have strong affinity for D2 receptors.
quetiapine
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Figure 3 Risk of relapse and readmission at different doses of oral quetiapine compared to no medication (Taipale H, et 202)
The DDD of oral quetiapine was 400 mg/d.
Quetiapine doses were 0.9-<1.1 DDDs (360-<440 mg/ d) When , patients had the largest reduction in the risk of relapse and readmission (aHR 0.71, 95%CI=0.64-0.79), which was significantly better than ≥1.6 DDDs, and was not significantly different from the other four dose ranges.
aripiprazole
Figure 4 Risk of recurrent readmission with different doses of oral aripiprazole compared with no medication (Taipale H, et al. 2022) span>
The DDD of oral aripiprazole is 15mg/d.
The aripiprazole dose was 0.9-<1.1 DDDs (13.5-<16.5 DDDs) compared to no drug mg/d), the reduction in the risk of recurrence and readmission was the largest (aHR 0.51, 95%CI=0.44-0.60), which was significantly better than 1.1-<1.4 DDDs and ≥1.6 DDDs, compared with other There were no significant differences among the three dose ranges.
Clozapine
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Figure 5 Risk of recurrent readmission with different doses of oral clozapine compared to no medication (Taipale H, et al. 2022 )
The DDD of oral clozapine is 300 mg/d.
Aripiprazole at a dose of 0.9-<1.1 DDDs (270-<330mg/d) was associated with a risk of relapse and readmission compared with no medication DDDs had the largest decrease (aHR 0.37, 95%CI=0.36-0.39), which was not significantly different from 1.1-<1.4 DDDs, and was significantly better than the other four dose ranges.
The results of the sensitivity analysis based on dimensions such as age are highly consistent with the main analysis.
span>Conclusion
This study may be the first A study comparing multiple doses of antipsychotics for the prevention of relapse in schizophrenia using real-world data. Overall, for most antipsychotics, the findings support the use of standard doses (0.9-<1.1 DDDs) for maintenance Treatment, doses that were too high (≥1.6 DDDs) or too low (<0.6 DDDs) were often significantly associated with an increased risk of recurrent readmission.
< span>There are certain limitations in this study, including the extrapolation of the results. However, based on the available results, the current WHO standard dose is too high for perphenazine and slightly higher for risperidone. In addition, LAI is more effective in preventing relapse than other oral antipsychotics except clozapine. For example, olanzapine has very good efficacy at all doses with LAI ≥ 0.9 DDDs, reducing the risk of relapse readmission by 75% Above (all aHR < 0.25).
Bibliography: Taipale H, Tanskanen A, Luykx JJ, Solmi M, Leucht S, Correll CU, Tiihonen J. Optimal Doses of Specific Antipsychotics for Relapse Prevention in a Nationwide Cohort of Patients with Schizophrenia. Schizophr Bull. 2022 May 7:sbac039. doi: 10.1093/schbul/sbac039. Epub ahead of print. PMID: 35524479.
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