Does relapse cause illness progression in first-episode psychosis? A review

It is widely believed that relapse in first-episode psychosis (FEP) causes illness progression, with previous reviews suggesting that treatment non-response develops in one in six patients who relapse. This belief contributes to the primary treatment goal in FEP being relapse-prevention, often in favor of other recovery-oriented goals. However, previous reviews primarily reported on naturalistic studies in chronic schizophrenia and predated multiple major studies with higher-quality designs.

We conducted a narrative review of studies of any design that examine the impact of relapse on medication response and other symptomatic and functional outcomes in FEP.

We identified eight relevant studies, five of these published since the last major review on this topic. Observational studies show a clear association between relapses and worse response to medication, but poorly control for confounding. Three higher-quality studies (two randomized) generally do not find worse symptomatic or functional outcomes among medication reduction/discontinuation arms compared to maintenance controls, despite significantly higher initial rates of relapse.

While the social and psychological consequences of a relapse should not be dismissed, clinicians should demand high-quality evidence about the risks of relapse on long-term outcomes. The conventional notion that relapse leads to treatment non-response or worse long-term outcomes is generally not supported by the highest quality studies. These findings can help clinicians and patients weigh the risks and benefits of competing treatment strategies in FEP.