Taper or maintain antipsychotics in schizophrenia?

Treatment with antipsychotic medications has been shown to reduce the risk of relapse after remission at least in the short-term, hence guidelines advocate their use as maintenance therapies.¹ But it is still not known precisely who can forego their antipsychotic medication altogether without relapsing and, until recently, long-term studies were lacking.

Meta-analyses – antipsychotics in relapse prevention

Two meta-analyses of RCTs compared use of antipsychotic medication and placebo in relapse prevention. ^1,2 These both support the premise that antipsychotics reduce the risk of relapse compared to placebo. ¹

Antipsychotics have been shown to reduce the risk of relapse compared to placebo

However, use of any medication including antipsychotics comes with the risk of side-effects. ¹ Because 50-60% of people with first-episode psychosis (FEP) were in remission at 10-year follow-up, and because almost half of those in remission had stopped taking their antipsychotic medication, investigators began looking into dose-tapering rather than maintenance therapy as an alternative strategy. ^3,4

TAILOR trial

In 2017, the TAILOR trial was begun to compare antipsychotic maintenance treatment with closely monitored tapering/discontinuation of antipsychotic medication in 250 Danish patients, who were newly-diagnosed with schizophrenia or persistent delusional disorder. A 1-year randomly assigned intervention period will be followed by assessments of remission of psychotic symptoms at 1 year at baseline, 1-, 2- and 5-years follow-up. ⁵

Reduce trial

In a similar Australian endeavor, the ‘reduce trial’, investigators are seeking to determine whether antipsychotic dose reduction can lead to better functional recovery in 180 young people with FEP compared with maintenance therapy. ⁶

RADAR trial

In the UK, the RADAR trial (Research into Antipsychotic Discontinuation and Reduction) randomized controlled trial (RCT) is underway. Its aim is to compare social functioning after 24 months follow-up in patients with schizophrenia and related disorders who have had one or more psychotic episode.

Study subjects will be assigned either maintenance or dose-reduction/discontinuation of antipsychotic medication; this study is expected to report in 2022. ⁷

HAMLETT study

More recently, Dutch investigators have announced the HAMLETT study. This is a multi-center, single-blind RCT investigating the effects of continued versus dose-reduction/discontinuation of antipsychotic medication up until 1 year after remission of FEP on personal and social functioning, psychotic symptom severity and HR-QoL.

This study of 512 anticipated recruits should report in 2026. ⁸

Worldwide, the results of these four studies are awaited with keen anticipation.

The outcomes of four clinical studies comparing antipsychotic medication maintenance with tapering/dose reduction in those in remission following a psychotic episode are keenly awaited

Further reading

Progress in Mind

The effects of antipsychotic dose reduction/discontinuation on long-term outcome in FEP patients