The efficacy of nutritional supplements for the adjunctive treatment of schizophrenia in adults: A systematic review and network meta-analysis

Xu, Xianrong; Shao, Ge; Zhang, Xu; Hu, Yan; Huang, Jia; Su, Yousong; Zhang, Min; Cai, Yao; Zhou, Huiping

doi:10.1016/j.psychres.2022.114500

Cited by 9 publications

(3 citation statements)

References 74 publications

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“…This NMA concurrently appraised 22 nutraceutical and phytoceutical interventions for adjunctive treatment of schizophrenia and related conditions, expanding the series of compounds already appraised by previous work (although a handful of compounds could nonetheless not be included in the present report due to the stringent inclusion/exclusion criteria) 14 , 16 . Specifically, the present NMA also included N-Methyl-D-Aspartate receptor (NMDAR) modulators, such as D-alanine, D-serine, D-cycloserine, glycine, sarcosine (N-substituted glycine), and plant-derived compounds such as curcumin, in addition to vitamins (e.g.…”

Section: Discussionmentioning

confidence: 99%

“…Existing meta-analytic evidence 14 , 15 and the most current World Federation of Societies of Biological Psychiatry (WFSBP) and Canadian Network for Mood and Anxiety Treatments (CANMAT) clinical guidelines 11 inform about the efficacy, safety, and tolerability of different nutraceuticals and phytoceuticals in the treatment of schizophrenia. However, no network meta-analysis (NMA) has been conducted to assess these compounds’ efficacy, acceptability, and tolerability in schizophrenia directly, except for a recent Bayesian NMA appraising selected compounds 16 .…”

Section: Introductionmentioning

confidence: 99%

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Nutraceuticals and phytoceuticals in the treatment of schizophrenia: a systematic review and network meta-analysis

Fornaro,

Caiazza,

Billeci

et al. 2024

Preprint

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Background: Sub-optimal response in schizophrenia is frequent, warranting augmentation strategies over treatment-as-usual (TAU). Methods: We assessed nutraceuticals/phytoceutical augmentation strategies via network meta-analysis. Randomized controlled trials in schizophrenia/schizoaffective disorder were identified via the following databases: PubMed, MEDLINE, EMBASE, Scopus, PsycINFO, CENTRAL, and ClinicalTrials.gov. Change (Standardized Mean Difference=SMD) in total symptomatology and acceptability (Risk Ratio=RR) were co-primary outcomes. Secondary outcomes were positive, negative, cognitive, and depressive symptom changes, general psychopathology, tolerability, and response rates. We conducted subset analyses by disease phase and sensitivity analyses by risk of bias and assessed global/local inconsistency, publication bias, risk of bias, and confidence in the evidence. Results: The systematic review included 49 records documenting 50 studies (n=2,384) documenting 22 interventions. Citicoline (SMD=-1.05,95%CI=-1.85; -.24), L-lysine (SMD=-1.04,95%CI=-1.84;-.25), N-acetylcysteine (SMD=-.87,95%CI=-1.27;-.47) and sarcosine (SMD=-.5,95%CI=-.87-.13) outperformed placebo for total symptomatology. High heterogeneity (tau2=.10, I2=55.9%) and global inconsistency (Q=40.79, df=18, p=.002) emerged without publication bias (Egger’s test, p=.42). Sarcosine improved negative symptoms (SMD=-.65, 95%CI=-1.10; -.19). N-acetylcysteine improved negative symptoms (SMD=-.90, 95%CI=-1.42; -.39)/general psychopathology (SMD=-.76, 95%CI=-1.39; -.13). No compound improved total symptomatology within acute phase studies (k=7, n=422). Sarcosine (SMD=-1.26,95%CI=-1.91; -.60), citicoline (SMD=-1.05,95%CI=-1.65;-.44), and N-acetylcysteine (SMD=-.55,95%CI=-.92,-.19) outperformed placebo augmentation in clinically stable participants. Sensitivity analyses removing high-risk-of-bias studies confirmed overall findings in all phases and clinically stable samples. In contrast, the acute phase analysis restricted to low risk-of-bias studies showed a superior effect vs. placebo for N-acetylcysteine (SMD=-1.10,95%CI=-1.75,-.45), L-lysine (SMD=-1.05,95%CI=-1.55,-.19), omega-3 fatty acids (SMD=-.83,95%CI=-1.31,-.34) and withania somnifera (SMD=-.71,95%CI=-1.21,-.22). Citicoline (SMD=-1.05,95%CI=-1.86,-.23), L-lysine (SMD=-1.04,95%CI=-1.84,-.24), N-acetylcysteine (SMD=-.89,95%CI=-1.35,-.43) and sarcosine (SMD=-.61,95%CI=-1.02,-.21) outperformed placebo augmentation of TAU (“any phase”). Drop-out due to any cause or adverse events did not differ between nutraceutical/phytoceutical vs. placebo+TAU. Conclusions: Sarcosine, citicoline, and N-acetylcysteine are promising augmentation interventions in stable patients with schizophrenia, yet the quality of evidence is low to very low. Further high-quality trials in acute phases/specific outcomes/difficult-to-treat schizophrenia are warranted.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Nutraceuticals and phytoceuticals in the treatment of schizophrenia: a systematic review and network meta-analysis

Fornaro,

Caiazza,

Billeci

et al. 2024

Preprint

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“…Notable adjunctive therapies for schizophrenia include omega-3 fatty acids, minocycline, aspirin, and N-acetylcysteine (NAC). Several meta-analyses examining these drug types have reported reductions in the overall severity of symptoms in patients with schizophrenia, suggesting their potential utility as augmentation therapies alongside antipsychotics 68 – 72 . Recent meta-analyses have provided compelling quantitative evidence, demonstrating significant improvements in cognitive domains like executive function, visual learning, and attention following augmentation with minocycline or pregnenolone 73 , 74 While the investigation of anti-inflammatory drugs as a novel treatment for schizophrenia is ongoing, it’s important to note that the existing data are limited in terms of both quality and quantity.…”

Section: Discussionmentioning

confidence: 99%

Inflammatory markers of symptomatic remission at 6 months in patients with first-episode schizophrenia

Kim,

Baek,

Kim

et al. 2023

Schizophr

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Neuroinflammation contributes to the pathophysiology of various mental illnesses including schizophrenia. We investigated peripheral inflammatory cytokines as a biomarker for predicting symptomatic remission in patients with first-episode schizophrenia. The study included 224 patients aged 15–60 years who fulfilled the criteria for schizophrenia spectrum disorder with a treatment duration ≤6 months. Serum levels of tumor necrosis factor (TNF) -α, interferon-γ, interleukin (IL)-1α, IL-1β, IL-6, IL-8, IL-10, and IL-12 were measured. Psychotic symptoms, depressive symptoms, and general functioning were assessed using the Positive and Negative Syndrome Scale, Beck Depression Inventory (BDI), Calgary Depression Scale for Schizophrenia, and Personal and Social Performance scale, respectively. Duration of untreated psychosis (DUP) was also recorded. We investigated the factors associated with remission for each sex in logistic regression analysis. In total, 174 patients achieved remission at the 6-month follow-up (females, 83.5%; males, 70.9%). Remission was associated with older age and lower BDI scores in male patients and with lower TNF-α levels and shorter DUP in female patients. Our findings suggest that peripheral inflammatory cytokines may impede early symptomatic remission in female patients with schizophrenia. In addition, depressive symptoms in males and long DUP in females may be poor prognostic factors for early remission in patients with first-episode psychosis.

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Diet and Psychosis

Ghanem,

Almarshedi,

Adam

et al. 2024

Nutritional Neurosciences

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The efficacy of nutritional supplements for the adjunctive treatment of schizophrenia in adults: A systematic review and network meta-analysis

Cited by 9 publications

References 74 publications

Nutraceuticals and phytoceuticals in the treatment of schizophrenia: a systematic review and network meta-analysis

Nutraceuticals and phytoceuticals in the treatment of schizophrenia: a systematic review and network meta-analysis

Inflammatory markers of symptomatic remission at 6 months in patients with first-episode schizophrenia

Diet and Psychosis

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