Better long-term outcomes for those who stop taking antipsychotics

Stopping antipsychotic drugs is associated with better outcomes for people diagnosed with schizophrenia, according to a new study. In the long run, those who stopped taking antipsychotics had better social functioning and quality of life and were more likely to be employed than those who stayed on the drugs. The study was a meta-analysis of short-, medium- and long-term trials.

The study contradicts widely held beliefs that people with schizophrenia must take antipsychotics for life and that it is dangerous for people to go off their medication.

Short-term follow-up (less than two years) also showed no difference in outcomes between those who continued to take antipsychotics and those who stopped, which should call into question the need to continue taking these medicines.

Our results showed that while short-term follow-ups (<2 years) on social functioning did not produce significant differences between maintenance and discontinuation, mid- and long-term follow-ups significantly favored discontinuation, write the researchers

According to the researchers, a high risk of bias in the included trials reduces the quality of their results, and they advise that more high-quality research be conducted to ensure that this finding is accurate. Still, this study reflects the best available evidence on how to proceed in the long term.

The research was conducted by Bjrn Schlier, Laura Buck, Matthias Pillny and others at the University of Hamburg, Germany. It was published in Lancet magazine Clinical eMedicine.

The meta-analysis included 35 international studies and 5,924 participants. Studies had to include social functioning or quality of life scores as outcomes. All participants had schizophrenia spectrum diagnoses and were treated with antipsychotics at baseline.

Of these studies, 26 were RCTs and 9 were NRS (non-randomized studies [naturalistic/observational]). Twenty-six studies had short-term follow-up (less than two years), seven had medium-term follow-up (between two and five years), and two had long-term follow-up (more than five years). . years).

Four of the 26 short-term studies were NRS, four of the seven medium-term studies were NRS, and both long-term studies were NRS.

The researchers followed the gold standard meta-analysis protocol, PRISMA, and included the gold standard GRADE risk of bias to assess the credibility of their results.

Overall, their results showed that even in the short term (less than two years), there was no benefit to continuing antipsychotic drugs. Continuers and dropouts had similar outcomes.

In the medium- and long-term studies, those who stopped using had better results than those who continued to take the drugs in terms of social functioning, quality of life and employment.

Regarding relapse, in the main analysis, there was no difference between those who continued and those who stopped taking antipsychotics. However, in a subgroup analysis, RCTs found an increased risk of relapse after discontinuation, whereas naturalistic studies did not.

The study focused on comparing maintenance treatment with discontinuation, especially in the medium and long term. Therefore, it does not provide new data on the issue of whether drugs may be useful for short-term symptom stabilization/reduction.

The study also focused on real-life outcomes that matter to patients, social functioning, quality of life and employment rather than symptom reduction on a rating scale. Studies that focused on psychotic symptoms may find a different result than studies that measure patient-centered outcomes like this one.

Although short-term studies overall found no advantage to continuing antipsychotic drugs, RCTs specifically tended to find that antipsychotic maintenance was better than discontinuation, whereas observational studies tended to finding that disruption was better than maintenance.

The included RCTs have their own biases, which may explain this finding, according to the researchers. The RCTs were primarily funded by the pharmaceutical industry and involved abrupt discontinuation of the antipsychotic drug which causes withdrawal effects that could be confounded with poor outcomes after discontinuation. Only 8% of RCTs were classified as low risk of bias.

In fact, researchers found that studies with abrupt withdrawal favored maintenance, while studies using an individualized, progressive withdrawal program found that discontinuation led to better outcomes.

Significant moderating effects were found for timing of discontinuation (abrupt vs gradual) and degree of dose reduction (complete vs partial vs mixed). Subgroup analyzes revealed that abrupt discontinuation showed effect sizes that favored maintenance treatment and that a mixed approach including guided tapering strategies or targeted medications favored tapering, the researchers write.
Studies with individualized dose reduction schemes favor discontinuation, and studies with standardized dose reduction favor maintenance, they add.

Speaking of the strength of their findings, the researchers did an analysis of how risk of bias might have affected their results. The analysis confirmed that their results were robust and reliable, despite biases inherent in the design of the included trials.


Schlier, B., Buck, L., Mller, R., Lincoln, TM, Bott, A., & Pillny, M. (2023). Time-dependent effect of antipsychotic discontinuation and dose reduction on social functioning and subjective quality of life: a multilevel meta-analysis. eclinical medicine, 65, 102291. (Link)

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