MDLinx writer Marilynn Larkin reports that most patients in the early stages of schizophrenia can achieve symptom remission with sequential administration of amisulpride and clozapine, and the latter should be given after patients fail a single antipsychotic trial, researchers say.
The study is practice-changing, and clinical guidelines should be changed as a result, Dr. Rene Kahn of Icahn School of Medicine in New York told Reuters Health in an email.
Dr. Kahn and colleagues conducted a three-phase study in 27 centers in Europe and Israel from 2011 to 2016. Patients ages 18 to 40 (mean age, about 26) who met DSM-IV criteria for schizophrenia, schizophreniform disorder, or schizoaffective disorder were included. About 75% were men and most were white.
As reported online August 13 in The Lancet Psychiatry, 371 of 446 patients (83%) who initiated treatment completed the open-label phase 1, which consisted of up to 800 mg oral amisulpride daily for 4 weeks; 56% achieved remission.
Seventy-seven percent of those not in remission after phase 1 went on to double-blind phase 2 and were randomly assigned to continue amisulpride or switch to up to 20 mg olanzapine daily for 6 weeks. Forty-five percent of those on amisulpride achieved remission vs 44% on olanzapine.
Of those not in remission at 10 weeks, 70% went on to open-label phase 3, and were given up to 900 mg per day clozapine for an additional 12 weeks. Sixty-four percent completed this phase of treatment, of whom 28% achieved remission.
The number of serious adverse events was similar between treatment arms in phase 2: one patient on olanzapine was hospitalized for an epileptic seizure and one patient on amisulpride was hospitalized twice because of psychotic symptoms exacerbations. Two serious suicide attempts were reported over the course of the study.
“For most patients in the early stages of schizophrenia, symptomatic remission can be achieved using a simple treatment algorithm comprising the sequential administration of amisulpride and clozapine,” the authors state. “Since switching to olanzapine did not improve outcome, clozapine should be used after patients fail a single antipsychotic trial—not until two antipsychotics have been tried, as is the current recommendation.”
Dr. Kahn noted that the study also tried to determine whether it’s possible to know in advance who might respond to amisulpride or olanzapine (findings to be published later). “It appears that patients who do not respond to amisulpride do NOT have dopaminergic abnormalities, but changes in another brain system: glutamate.”
“Also, we found some evidence that immune markers may predict response,” he said. “However, all this works needs to be replicated before we can use it on an individual basis.”
“We are also looking at genetic markers,” he added.
Regarding non-drug therapies, Dr. Kahn said, “possibly in very refractory and severe cases, deep brain stimulation may do the trick. We will be studying that [as well].”
Dr. Ragy Girgis, Director, Center of Prevention and Evaluation and associate professor of psychiatry at Columbia University Medical Center in New York City, commented, “The study is important and well done, and adds to the current literature about the equivalent efficacy of antipsychotic medications.”
“While non-medication therapies, such as cognitive behavioral therapy for psychosis and family psychoeducation, can be very important components of treatment plans for individuals with early psychosis, the mainstay of treatment remains antipsychotic medications,” he said in an email to Reuters Health.
“The authors’ suggestion to use clozapine earlier in the treatment of schizophrenia has a lot of support and requires further controlled studies to confirm that this would be a useful treatment paradigm,” Dr. Girgis concluded.
Icahn School of Medicine in New York
Dr. Rene Kahn