Richard Carr and colleagues from King's College London conducted a systematic review and meta-analysis that demonstrated that glycine, neurostimulation, psychotherapy, and antidepressants, in addition to antipsychotics, are effective in treating drug-resistant schizophrenia in patients who are not candidates for the atypical antipsychotic of last resort, clozapine. The researchers conducted a systematic search of the PsycInfo, PubMed, and EMBASE databases and included 78 studies, 68 of which, involving a total of 3,241 patients, were included in the meta-analysis. The data were summarized using random-effects models, and the risk of bias was assessed according to the Cochrane guidelines. The article was published in the journal Molecular Psychiatry.
A meta-analysis showed that increasing antipsychotic doses to high doses does not lead to improvement in any symptom domain. Adding NMDA receptor allosteric glycine-binding site agonists—high doses of glycine and d-serine—significantly improved positive (Hedges' g -0.56), negative (g -1.18), and general (g -1.17) symptoms to therapy. Adding noninvasive neurostimulation or psychotherapy led to moderate improvements in positive symptoms (g -0.42 and -0.56, respectively), while antidepressants improved negative (g -0.74) and general (g -0.69) symptoms. However, sample sizes were small, the GRADE rating was low, and studies on neurostimulation were at high risk of bias.
