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Add-on N-acetyl-cysteine, Polyunsaturated Fatty Acids May Benefit Patients With Schizophrenia
Adjunctive N-acetyl-cysteine and polyunsaturated fatty acids can be provisionally recommended for improving negative symptoms, general psychopathology, and possibly cognition in patients with schizophrenia, according to a systematic umbrella review published in BMJ Mental Health.
“These drugs should potentially be prescribed for patients for whom antipsychotics have proven ineffective in addressing negative symptoms and/or general psychopathology and/or cognitive function,” wrote corresponding author Guillaume Fond, MD, PhD, of Fondation FondaMental, in Marseille, France, and study coauthors. “Furthermore, if these drugs are found to be ineffective, they should be discontinued. The term ‘provisional’ has been used to underscore this point.”
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The systematic umbrella review of selected adjunctive therapies to antipsychotics for patients with schizophrenia included 63 randomized controlled trials, spanning a total 4219 participants, and 29 meta-analyses.
Based on their findings, researchers tentatively recommended 2 molecules: N-acetyl-cysteine and polyunsaturated fatty acids. N-acetyl-cysteine at a dose of 1200 to 3600 mg daily for more than 12 consecutive weeks showed evidence for improving negative symptoms and general psychopathology per the Positive and Negative Syndrome Scale general psychopathology factor subscale. The most robust findings were found in longer trials, according to the review.
Polyunsaturated fatty acids, particularly 3000 mg of daily eicosapentaenoic acid for more than 12 weeks, also showed evidence for improving general psychopathology, researchers reported.
Weaker, preliminary evidence was found for sarcosine and minocycline for improving negative symptoms in chronic, but not early, schizophrenia, as well as for N-acetyl-cysteine for improving positive symptoms and cognition.
“Transdermal estradiol, used for short-term, can also be provisionally recommended in women of childbearing age to improve positive symptoms,” the authors wrote. “Other adjunctive agents, such as sarcosine, minocycline, oestrogens or SERMs [selective estrogen receptor modulators], may also be effective in certain clinical scenarios, but additional low-risk randomized controlled trials are needed.”
Researchers called for large-scale studies to investigate specific types of patients most likely to benefit from specific adjunctive therapies.
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