Early Identification and Treatment for Schizophrenia Is Crucial, Expert Says

By Gina Shaw
A person’s first episode of schizophrenia offers the greatest opportunity for effective treatment, an expert on the condition noted during a presentation at the 2023 Psych Congress.

“Early identification and intervention is crucial, as data show that patients have the greatest chance to improve if treated continuously from their first episode of schizophrenia,” said Christoph Correll, MD, a professor of psychiatry at the Donald and Barbara Zucker School of Medicine at Hofstra/Northwell Health, in Hempstead, N.Y., and psychiatrist at The Zucker Hillside Hospital, in Glen Oaks, N.Y. “The first remission is the best remission; everything else after the next relapse is generally not as good. Relapses can lead to chronicity and even secondary treatment resistance.”

Dr. Correll noted that to prevent relapse, managing nonadherence is critical. Multiple studies have shown that discontinuation of maintenance antipsychotic medications after a first episode strongly increases the risk for relapse (Psychol Med 2019;49[5]:772-779; Lancet Psychiatry 2021;8[5]:387-404).

A 20-year nationwide follow-up study on discontinuation of schizophrenia treatment also found that the lowest risk for death in people with schizophrenia was among those who received antipsychotic treatment continuously, with the risk being 174% to 214% higher among nonusers and patients with early discontinuation of antipsychotics compared with those who received antipsychotic treatment continuously (Am J Psychiatry 2018;175[8]:765-773; World Psychiatry 2022;21[2]:248-271).

Patients at highest risk for nonadherence to antipsychotic medications include those who are female, younger patients and substance users, Dr. Correll said (Schizophr Bull 2021;47[6]:1611-1620). “Patients who receive long-acting injectable medications have significantly better adherence and lower rates of relapse than those taking oral drugs, even than oral olanzapine, which patients often stay on somewhat longer than other oral antipsychotic drugs,” he said.

About 20% of patients with schizophrenia have primary resistance to current dopamine therapies, Dr. Correll said (Br J Psychiatry 2022;220[3]:115-120[GS5] ). “That resistance rate doubles to about 40% when patients have relapses. We can prevent that secondary treatment resistance by preventing relapses” (Braz J Psychiatry 2023; in press)

Pipeline Agents

For patients who are initially resistant to antidopaminergic therapies, there is potential hope in the pipeline, particularly with two investigational agents: the M1/M4 muscarinic agonist xanomeline-trospium (KarXT, Karuna Therapeutics) and the selective M4 receptor-positive allosteric modulator emraclidine (Cerevel Therapeutics).

“The three EMERGENT trials of KarXT were positive, and Karuna is expected to submit their data to the FDA this month,” Dr. Correll said. “It appears to be efficacious and safe, and if KarXT is approved, we will have a novel class of medications entering the field after seven decades of just dopamine receptor blocking agents. Hopefully these new agents will offer new treatment options for those who have been suboptimally treated with currently available treatments.”

Dr. Correll reported that he has served as a consultant to and/or advisor for, or has received honoraria from: AbbVie, Acadia, Adock Ingram, Alkermes, Allergan, Angelini, Aristo, Biogen, Boehringer Ingelheim, Cardio Diagnostics, Cerevel, CNX Therapeutics, Compass Pathways, CSL Seqirus, Darnitsa, Denovo, Gedeon Richter, Hikma, Holmusk, Intra-Cellular Therapies, Jamjoom Pharma, Janssen/Johnson & Johnson, Karuna, LB Pharmaceuticals, Lundbeck, MedAvante-ProPhase, MedInCell, Merck, Mindpax, Mitsubishi Tanabe Pharma, Mylan, Neurelis, Neurocrine, Newron, Noven, Novo Nordisk, Otsuka, Pharmabrain, PPD Biotech, Recordati, Relmada, Reviva, Rovi, Sage, SK Life Science, Sumitomo Pharma America, Sunovion, Sun Pharma, Supernus, Takeda, Teva, Tolmar, Vertex and Viatris.