Antipsychotics become less effective for relapse prevention after the second relapse: Lancet

A new study published in The Lancet Psychiatry shows that after the second relapse, antipsychotics' relapse prevention efficacy significantly dropped.

The most effective antipsychotic doses for relapse prevention in people with first-episode schizophrenia remain uncertain. In order to track the evolution of antipsychotic dose and the risk of serious relapse indicated by mental rehospitalization related with antipsychotic usage and particular dose categories, Heidi Taipale and colleagues undertook this study.

In Finland, this register-based cohort research covered the whole country. Patients 45 years of age or younger who were diagnosed with first episode schizophrenia as inpatients were followed up for 5 years of illness or until a fifth relapse episode. Rehospitalization for psychosis, which was utilized as a sign of recurrence and was characterized as inpatient hospital care with an ICD-10 code of F20-F29 diagnosis documented as the major discharge diagnostic, was the main outcome measure.

A minimum of 30 days has to pass between relapses in order for it to be deemed a new relapse. The use of antipsychotics was based on the prescription database. The dosage from all concurrent antipsychotics was added. Utilizing within-individual analyses to remove selection bias and stratifying time to before and after the second relapse, the effectiveness of antipsychotics for reducing rehospitalization was examined.

The key highlights of this study:

1. 5367 patients made up the entire study population, with 3444 (64%) males and 1923 (35%) women, and 3058 (57%) needed hospitalization.

2. Before the fifth relapse in these individuals, the mean dosage had grown from 1.22 defined daily doses per day (before the first relapse) to 1.56 defined daily doses per day (1.48-1.64) during the course of the previous relapses.

3. The adjusted hazard ratio (aHR) for rehospitalization with antipsychotic use versus non-use rose from 0.42 before the second relapse to 0.78 (0.62-0.99) following the second relapse, demonstrating significantly reduced efficacy.

4. When particular dose categories were analyzed, a U-shaped curve emerged, indicating that the standard dose was used before the second relapse but not subsequently, when the risk of rehospitalization was lowest.

5. Because all doses were less effective after the second relapse, low dosage was not linked with a significantly increased risk of rehospitalization compared to normal dose after the second relapse.

In conclusion, all patients should get adequate antipsychotic dosage and increased relapse prevention measures following their first relapse since preventing the second relapse is crucial.

Reference: 

Taipale, H., Tanskanen, A., Correll, C. U., & Tiihonen, J. (2022). Real-world effectiveness of antipsychotic doses for relapse prevention in patients with first-episode schizophrenia in Finland: a nationwide, register-based cohort study. In The Lancet Psychiatry (Vol. 9, Issue 4, pp. 271–279). Elsevier BV. https://doi.org/10.1016/s2215-0366(22)00015-3