Antioxidant treatments for schizophrenia

Abstract

BackgroundThere is accumulating evidence that progressive changes in brain structure and function take place as schizophrenia unfolds. Among many possible candidates, oxidative stress may be one of the mediators of neuroprogression, grey matter loss and subsequent cognitive and functional impairment. Antioxidants are exogenous or endogenous molecules that mitigate any form of oxidative stress or its consequences. They may act from directly scavenging free radicals to increasing anti-oxidative defences. There is evidence that current treatments impact oxidative pathways and may to some extent reverse pro-oxidative states in schizophrenia. The existing literature, however, indicates that these treatments do not fully restore the deficits in antioxidant levels or restore levels of oxidants in schizophrenia. As such, there has been interest in developing interventions aimed at restoring this oxidative balance beyond the benefits of antipsychotics in this direction. If antioxidants are to have a place in the treatment of this serious condition, the relevant and up-to-date information should be available to clinicians and investigators. ObjectivesTo evaluate the effect of antioxidants as add-on treatments to standard antipsychotic medication for improving acute psychotic episodes and core symptoms, and preventing relapse in people with schizophrenia. Search methodsWe searched the Cochrane Schizophrenia Group's Study-Based Register of Trials which is based on regular searches of CINAHL, BIOSIS, AMED, Embase, PubMed, MEDLINE, PsycINFO, and registries of clinical trials. There are no language, time, document type, or publication status limitations for inclusion of records in the register. We ran this search in November 2010, and again on 8 January 2015. We also inspected references of all identified studies for further trials and contacted authors of trials for additional information. Selection criteriaWe included reports if they were randomised controlled trials (RCTs) involving people with schizophrenia who had been allocated to either a substance with antioxidant potential or to a placebo as an adjunct to standard antipsychotic treatment. Data collection and analysisWe independently extracted data from these trials and we estimated risk ratios (RR) or mean differences (MD), with 95% confidence intervals (CI). We assessed risk of bias for included studies and created a 'Summary of findings' table using GRADE.

Effect of Adjuvant Vitamin C on Brain-Derived Neurotrophic Factor Levels and Improvement of Negative Symptoms in Schizophrenic Patients

“…Table 3 demonstrates that there were changes in Vitamin C blood levels in the treatment group from the initial to week 8 which indicated that there was an increase in ascorbic acid levels in the treatment group. This is in line with the previous studies which reported that schizophrenic patients experience a deficiency of ascorbic acid levels in the blood [16], [17]. Meanwhile, increased levels of Vitamin C in the blood inhibit brain damage due to oxidative stress and increase NMDA levels, which resultantly elevate serum BDNF levels in the brain, especially the prefrontal cortex [18].…”

Effect of Adjuvant Vitamin C on Brain-Derived Neurotrophic Factor Levels and Improvement of Negative Symptoms in Schizophrenic Patients

“…Table 3 demonstrates that there were changes in Vitamin C blood levels in the treatment group from the initial to week 8 which indicated that there was an increase in ascorbic acid levels in the treatment group. This is in line with the previous studies which reported that schizophrenic patients experience a deficiency of ascorbic acid levels in the blood [16], [17]. Meanwhile, increased levels of Vitamin C in the blood inhibit brain damage due to oxidative stress and increase NMDA levels, which resultantly elevate serum BDNF levels in the brain, especially the prefrontal cortex [18].…”

Effect of Cuscuta epithymum Acquainted with Risperidone on the Improvement of Clinical Symptoms and Cognitive Impairment in Patients with Schizophrenia: A Triple-Blind Randomized Placebo-Controlled Trial

“…Meanwhile, CE with its rich flavonoid and alkaloid content [ 10 ], is influential in reducing oxidative stress and protecting the CNS. On the other hand, the result of the studies showed that treatment with antioxidant agents significantly improved the symptoms of the disease with respect to the reduction of PANSS scale scores, which is consistent with the results of the present study [ 26 ]. Therefore, it can be concluded that one of the other mechanisms of CE has an additional effect on improving symptoms of the patients, most likely being its antioxidant and neuroprotective traits.…”

The effect of Withania somnifera (Ashwagandha) on mental health symptoms in individuals with mental disorders: systematic review and meta-analysis

“…However, these individual studies reported a reduction in schizophrenia symptoms for Withania somnifera used as an add-on to antipsychotics, whereas no significant effects were observed for mania or OCD symptoms. Similar results were obtained for other add-on treatments for schizophrenia, such as sarcosine and antioxidants, 60 , 61 which share some similarities with Withania somnifera , warranting further investigations on Withania somnifera as a potential treatment option with a good tolerability.…”

Effect of Adjuvant Vitamin C on Brain-Derived Neurotrophic Factor Levels and Improvement of Negative Symptoms in Schizophrenic Patients

“…Table 3 demonstrates that there were changes in Vitamin C blood levels in the treatment group from the initial to week 8 which indicated that there was an increase in ascorbic acid levels in the treatment group. This is in line with the previous studies which reported that schizophrenic patients experience a deficiency of ascorbic acid levels in the blood [16], [17]. Meanwhile, increased levels of Vitamin C in the blood inhibit brain damage due to oxidative stress and increase NMDA levels, which resultantly elevate serum BDNF levels in the brain, especially the prefrontal cortex [18].…”

Effect of Cuscuta epithymum Acquainted with Risperidone on the Improvement of Clinical Symptoms and Cognitive Impairment in Patients with Schizophrenia: A Triple-Blind Randomized Placebo-Controlled Trial

“…Meanwhile, CE with its rich flavonoid and alkaloid content [ 10 ], is influential in reducing oxidative stress and protecting the CNS. On the other hand, the result of the studies showed that treatment with antioxidant agents significantly improved the symptoms of the disease with respect to the reduction of PANSS scale scores, which is consistent with the results of the present study [ 26 ]. Therefore, it can be concluded that one of the other mechanisms of CE has an additional effect on improving symptoms of the patients, most likely being its antioxidant and neuroprotective traits.…”

The effect of Withania somnifera (Ashwagandha) on mental health symptoms in individuals with mental disorders: systematic review and meta-analysis

“…However, these individual studies reported a reduction in schizophrenia symptoms for Withania somnifera used as an add-on to antipsychotics, whereas no significant effects were observed for mania or OCD symptoms. Similar results were obtained for other add-on treatments for schizophrenia, such as sarcosine and antioxidants, 60 , 61 which share some similarities with Withania somnifera , warranting further investigations on Withania somnifera as a potential treatment option with a good tolerability.…”

Effect of Adjuvant Vitamin C on Brain-Derived Neurotrophic Factor Levels and Improvement of Negative Symptoms in Schizophrenic Patients

“…Table 3 demonstrates that there were changes in Vitamin C blood levels in the treatment group from the initial to week 8 which indicated that there was an increase in ascorbic acid levels in the treatment group. This is in line with the previous studies which reported that schizophrenic patients experience a deficiency of ascorbic acid levels in the blood [16], [17]. Meanwhile, increased levels of Vitamin C in the blood inhibit brain damage due to oxidative stress and increase NMDA levels, which resultantly elevate serum BDNF levels in the brain, especially the prefrontal cortex [18].…”

Effect of Cuscuta epithymum Acquainted with Risperidone on the Improvement of Clinical Symptoms and Cognitive Impairment in Patients with Schizophrenia: A Triple-Blind Randomized Placebo-Controlled Trial

“…Meanwhile, CE with its rich flavonoid and alkaloid content [ 10 ], is influential in reducing oxidative stress and protecting the CNS. On the other hand, the result of the studies showed that treatment with antioxidant agents significantly improved the symptoms of the disease with respect to the reduction of PANSS scale scores, which is consistent with the results of the present study [ 26 ]. Therefore, it can be concluded that one of the other mechanisms of CE has an additional effect on improving symptoms of the patients, most likely being its antioxidant and neuroprotective traits.…”

The effect of Withania somnifera (Ashwagandha) on mental health symptoms in individuals with mental disorders: systematic review and meta-analysis

“…However, these individual studies reported a reduction in schizophrenia symptoms for Withania somnifera used as an add-on to antipsychotics, whereas no significant effects were observed for mania or OCD symptoms. Similar results were obtained for other add-on treatments for schizophrenia, such as sarcosine and antioxidants, 60 , 61 which share some similarities with Withania somnifera , warranting further investigations on Withania somnifera as a potential treatment option with a good tolerability.…”