Efficacy of Zinc Sulfate as an Add-on Therapy to Risperidone Versus Risperidone Alone in Patients With Schizophrenia: A Double-Blind Randomized Placebo-Controlled Trial

Abstract

Background:Zinc can modulate fast-excitatory transmission, facilitate the release of amino butyric acid and potentiate nicotinic acetylcholine receptors. There are also emerging evidences discussing the implication of these neurotransmitters in pathophysiology of schizophrenia.Objectives:The purpose of this study was to evaluate the efficacy of Zn sulfate as an add-on therapy in the treatment of schizophrenia in a 6-week, double-blind and placebo-controlled trial.Patients and Methods:Eligible participants were 30 inpatients with schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria. Patients were randomly allocated into two equal groups; one group of patients received risperidone 6 mg/day plus capsules of Zn sulfate (each containing 50 mg elemental Zn) three times a day and another group received risperidone 6 mg/day plus placebo. The Positive and Negative Syndrome Scale (PANSS) was applied to assess the psychotic symptoms and aggression risk at baseline, week 2, 4, and 6 of the study.Results:The results of this study showed that both protocols significantly decreased the scores on all subscales of the PANSS and supplemental aggression risk subscale as well as PANSS total score over the study. However, this improvement was significantly higher in Zn sulfate receiving group compared to the placebo group. No major clinical side-effects were detected.Conclusions:It may be concluded that Zn is an effective adjuvant agent in the management of patients with schizophrenia.

The effects of vitamin and mineral supplementation on symptoms of schizophrenia: a systematic review and meta-analysis

“…Random-effects meta-analyses found no overall effect ( N = 2, n = 129, g = 0.324, 95% CI −0.48 to 1.30, p = 0.430), although there was significant heterogeneity between studies ( Q = 3.81, p = 0.05, I 2 = 73.8%). Specifically, 150 mg zinc per day significantly reduced total PANSS scores after 6 weeks in comparison to placebo treatment ( n = 29, p = 0.003), with significant benefits also evident in individual domains of positive ( p = 0.04) and negative ( p = 0.02) symptom subscales, but not for general symptoms (Mortazavi et al 2015). Conversely, there were no significant differences across 100 patients with schizophrenia after 12 weeks of receiving either 400 µ g chromium daily or placebo supplements in PANSS total scores ( p = 0.88), or positive and negative symptoms (Hockney et al 2006).…”

“…Two studies investigated the effects of mineral supplements (zinc and chromium) on psychiatric symptoms (Hockney et al 2006; Mortazavi et al 2015). Random-effects meta-analyses found no overall effect ( N = 2, n = 129, g = 0.324, 95% CI −0.48 to 1.30, p = 0.430), although there was significant heterogeneity between studies ( Q = 3.81, p = 0.05, I 2 = 73.8%).…”

“…Future trials should aim to establish which vitamins and minerals interventions (if any) can be used to treat specific symptoms of schizophrenia. For instance, individual trials to date have shown significant reductions in residual positive symptoms from a combination vitamin B supplement (Levine et al 2006) and zinc (Mortazavi et al 2015), whereas folic acid has been found to be effective in reducing negative symptoms among patients with genetic variations which Vitamin and mineral supplementation in schizophrenia 9 https:/www.cambridge.org/core/terms. https://doi.org/10.1017/S0033291717000022 inhibit folate absorption (Hill et al 2011;Roffman et al 2013b).…”

“…Random-effects meta-analyses found no overall effect (N = 2, n = 129, g = 0.324, 95% CI −0.48 to 1.30, p = 0.430), although there was significant heterogeneity between studies (Q = 3.81, p = 0.05, I 2 = 73.8%). Specifically, 150 mg zinc per day significantly reduced total PANSS scores after 6 weeks in comparison to placebo treatment (n = 29, p = 0.003), with significant benefits also evident in individual domains of positive (p = 0.04) and negative (p = 0.02) symptom subscales, but not for general symptoms (Mortazavi et al 2015).…”

Schizophrenia Aetiology and Drug Therapy: A Tale of Progressive Demystification and Strides in Management

“…Zn is one of the trace elements whose abnormal homeostasis had been implicated in the expression of symptoms of schizophrenia [309]. Trial of Zn add-on therapy (to risperidone) has proven the efficacy of Zn as an adjuvant in the management of schizophrenia [310]. Also in an animal study, Zn proved beneficial (either as monotherapy or as adjunct to haloperidol or olanzapine) in the attenuation of behavioural deviations or brain antioxidant changes in mice that were given repeated ketamine injection [122]; although more research is needed to ascertain its role in schizophrenia management.…”