In the JournalsPerspective

Early medication discontinuation may worsen outcomes in first-episode psychosis

Research published in The Lancet Psychiatry indicated that patients with first-episode schizophrenia who continued their antipsychotic treatment for at least 3 years after initiation were less likely to relapse and develop poor long-term health outcomes than those who discontinued treatment.

“National clinical practice guidelines broadly agree that antipsychotic medication is indicated for the acute treatment and initial maintenance of first-episode psychosis,” Christy L. M. Hui, PhD, department of psychiatry, University of Hong Kong, and colleagues wrote. “On the one hand, naturalistic studies raise concerns about the long-term side-effects of maintenance medication. On the other hand, a small number of [randomized controlled trials] suggest that dose reduction or medication discontinuation results in an increase in relapse. However, the relation between relapse and long-term outcome is not well studied.”

To determine the long-term effects of discontinuing antipsychotic medication after successfully treating first-episode psychosis, researchers examined the link between early maintenance therapy choices and the clinical outcome 10 years later.

In this randomized, double-blind follow-up study conducted in Hong Kong from Sept. 5, 2003, to Dec. 30, 2014, 178 patients with first-episode psychosis who had full positive symptom resolution after 12 months of antipsychotic medication received maintenance treatment or discontinued treatment early for 1 year. The cohort received 3 years of treatment prior to the follow-up phase. Researchers then calculated the proportion of patients in each group with good or poor long-term clinical outcomes; poor long-term outcome was defined as persistent psychotic symptoms, requirement for clozapine or suicide.

Participants in the early medication discontinuation group had more relapses during the randomized controlled trial. Overall, poor long-term clinical outcome occurred in 39% of first-episode psychosis patients assigned to the discontinuation group compared with 21% of patients in the maintenance group (RR = 1.84; 95% CI, 1.15-2.96; P = .012). Suicide was the only serious adverse event during the follow-up period: 4% of patients who discontinued treatment early committed suicide compared with 2% who maintained treatment.

In a post-hoc analysis, researchers compared patients with at least 1 month of mild positive symptoms or who had already relapsed with the maintenance and discontinuation groups. Patients who discontinued treatment early and those with less favorable initial treatment response had similar high prevalence of poor outcomes after 10 years (39% and 49%; RR = 0.8; 95% CI, 0.56–1.14; P = .21), but the maintenance group had fewer long-term poor outcomes (21%; RR = 0.43; 95% CI, 0.27–0·69; P < .0001).

Another post-hoc analysis that examined the link between poor long-term outcomes and measures of symptomatic and functional outcome demonstrated that patients with bad outcomes had more severe overall symptom scores than those with good outcomes (P < .0001), more months with psychosis present (P = .003), a lower independent living score (P = .034) and lower mental health component scores that measured health-related quality of life (P = .003).

“Our data are relevant to patients who have symptomatic resolution following 1 year’s treatment of first-episode psychosis (predominantly schizophrenia) and wish to consider medication discontinuation after a period of maintenance,” Hui and colleagues wrote. “The data suggest that an awareness of the increased risk for poor long-term outcome, in addition to the risk for relapse in the short-term, must be taken into consideration in this decision.” – by Savannah Demko

Disclosures: The authors report no relevant financial disclosures.

Research published in The Lancet Psychiatry indicated that patients with first-episode schizophrenia who continued their antipsychotic treatment for at least 3 years after initiation were less likely to relapse and develop poor long-term health outcomes than those who discontinued treatment.

“National clinical practice guidelines broadly agree that antipsychotic medication is indicated for the acute treatment and initial maintenance of first-episode psychosis,” Christy L. M. Hui, PhD, department of psychiatry, University of Hong Kong, and colleagues wrote. “On the one hand, naturalistic studies raise concerns about the long-term side-effects of maintenance medication. On the other hand, a small number of [randomized controlled trials] suggest that dose reduction or medication discontinuation results in an increase in relapse. However, the relation between relapse and long-term outcome is not well studied.”

To determine the long-term effects of discontinuing antipsychotic medication after successfully treating first-episode psychosis, researchers examined the link between early maintenance therapy choices and the clinical outcome 10 years later.

In this randomized, double-blind follow-up study conducted in Hong Kong from Sept. 5, 2003, to Dec. 30, 2014, 178 patients with first-episode psychosis who had full positive symptom resolution after 12 months of antipsychotic medication received maintenance treatment or discontinued treatment early for 1 year. The cohort received 3 years of treatment prior to the follow-up phase. Researchers then calculated the proportion of patients in each group with good or poor long-term clinical outcomes; poor long-term outcome was defined as persistent psychotic symptoms, requirement for clozapine or suicide.

Participants in the early medication discontinuation group had more relapses during the randomized controlled trial. Overall, poor long-term clinical outcome occurred in 39% of first-episode psychosis patients assigned to the discontinuation group compared with 21% of patients in the maintenance group (RR = 1.84; 95% CI, 1.15-2.96; P = .012). Suicide was the only serious adverse event during the follow-up period: 4% of patients who discontinued treatment early committed suicide compared with 2% who maintained treatment.

In a post-hoc analysis, researchers compared patients with at least 1 month of mild positive symptoms or who had already relapsed with the maintenance and discontinuation groups. Patients who discontinued treatment early and those with less favorable initial treatment response had similar high prevalence of poor outcomes after 10 years (39% and 49%; RR = 0.8; 95% CI, 0.56–1.14; P = .21), but the maintenance group had fewer long-term poor outcomes (21%; RR = 0.43; 95% CI, 0.27–0·69; P < .0001).

Another post-hoc analysis that examined the link between poor long-term outcomes and measures of symptomatic and functional outcome demonstrated that patients with bad outcomes had more severe overall symptom scores than those with good outcomes (P < .0001), more months with psychosis present (P = .003), a lower independent living score (P = .034) and lower mental health component scores that measured health-related quality of life (P = .003).

“Our data are relevant to patients who have symptomatic resolution following 1 year’s treatment of first-episode psychosis (predominantly schizophrenia) and wish to consider medication discontinuation after a period of maintenance,” Hui and colleagues wrote. “The data suggest that an awareness of the increased risk for poor long-term outcome, in addition to the risk for relapse in the short-term, must be taken into consideration in this decision.” – by Savannah Demko

Disclosures: The authors report no relevant financial disclosures.

    Perspective
    Jeffrey A. Lieberman

    Jeffrey A. Lieberman

    The study reported in Lancet Psychiatry describing the beneficial effects of medication on long-term outcome is welcome and timely. The advent of antipsychotic medications was a therapeutic breakthrough, comparable in significance to that of other therapeutic milestones like the discovery of insulin, antibiotics and L-dopa, and changed the course of psychiatry. This study extends the evidence for their therapeutic effects showing that, in addition to psychotic symptom suppression and relapse prevention, receiving antipsychotic treatment in the initial years of illness improves long-term outcome (ie, is disease-modifying). The study design is not without limitations, so the results are not definitive but provide additional useful information as to the value of effective pharmacotherapy in the treatment of schizophrenia and related psychotic disorders.

    • Jeffrey A. Lieberman, MD
    • Lawrence C. Kolb Professor and Chairman of Psychiatry Columbia University, Vagelos College of Physicians and Surgeons Director, New York State Psychiatric Institute Psychiatrist-in-Chief New York Presbyterian Hospital-Columbia University Medical Center Healio Psychiatry Peer Perspective Board member

    Disclosures: Lieberman reports no relevant financial disclosures.