Several augmentation strategies such as glycine, non-invasive stimulation, and psychotherapy may benefit patients with treatment-resistant schizophrenia, according to a
review published in
Molecular Psychiatry. However, none of the interventions had enough evidence to be routinely recommended as an alternative to clozapine.
Clozapine is the gold-standard therapy for treatment-resistant schizophrenia, and starting the medication early can significantly improve outcomes, wrote Richard Carr, Ph.D., of King’s College London, and colleagues. The researchers continued: “Some patients, however, are unable to tolerate or otherwise unwilling to consider treatment with clozapine due to its side effect burden and monitoring requirements, while it is contraindicated in others.”
Carr and colleagues conducted a meta-analysis of 68 randomized controlled trials that involved 3,241 patients (average age 41 years, 63% male) with treatment-resistant schizophrenia or schizoaffective disorder who were taking an antipsychotic other than clozapine. The trials involved augmenting the participants’ existing treatments, either by boosting their antipsychotic dose or adding another treatment. The studies assessed participants’ positive, negative, and total symptoms at baseline and at the end of the trials.
Some augmentation strategies improved one or more symptom domains:
- Augmenting antipsychotics with drugs that target the glycine modulatory site of the NMDA receptor (glycine, d-serine, or d-cycloserine) significantly improved positive, negative, and total symptoms.
- Non-invasive stimulation (electrical or magnetic) improved positive symptoms.
- Psychotherapy (cognitive behavioral therapy and acceptance and commitment therapy) moderately improved positive symptoms.
- Augmentation with antidepressant medications (mianserin, sertraline, and escitalopram) improved negative and total symptoms.
However, giving patients higher doses of antipsychotics compared with the standard dose did not improve any of the assessed symptoms, nor did augmenting antipsychotics with mood stabilizers.
The authors emphasized that their meta-analysis was limited by small sample sizes and publication bias. “As such, while results are not conclusive, they do point towards some promising avenues for future larger, well-designed trials of interventions in [treatment-resistant schizophrenia], in particular [glycine modulatory site] agonists,” they wrote.
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