Laupu, Wendy Kay (2014) The efficacy of Garcinia mangostana L. (mangosteen) pericarp as an adjunctive to second-generation antipsychotics for the treatment of schizophrenia: a double blind, randomised, placebo-controlled trial. PhD thesis, James Cook University.

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Abstract

Background: Current treatments for schizophrenia, while effective, often lead to partial functional recovery for affected individuals. The neurobiology of schizophrenia consists of a complex array of factors whose interplay is not well understood. As a consequence, schizophrenia remains sub-optimally treated by existing therapeutic options. With a paucity of available novel therapies for schizophrenia and a lack of biologically driven targets being explored by pharmaceutical companies, there is a need for investigator-initiated trials examining novel pathways for the reduction of core symptoms and improved functionality. A review of the literature identifies the presence of mitochondrial dysfunction, oxidative stress and impaired redox defenses such as reduced glutathione levels and impaired antioxidant enzymes (glutathione S-transferase) in the primary disorder. Secondary metabolites in mangosteen pericarp are hypothesised to protect against oxidative stress by evoking an intrinsic pathway including mitochondria. It is unclear whether mangosteen pericarp may affect the severity of negative and positive symptoms and cognitive and social functioning in schizophrenia. These symptom domains are known to persist despite wide use of existing treatment options. The current study aims to assess whether adjunctive treatment with mangosteen pericarp influences these residual symptom domains in individuals with schizophrenia.

Methods: A randomised, placebo-controlled adjunctive trial was conducted. Structured interviews using the Mini International Neuropsychiatric Interview (MINI-plus) were conducted to establish the diagnosis of schizophrenia or schizoaffective disorder. The efficacy of the intervention on symptom domains was assessed using established outcome measures, consisting of structured interviews at baseline, 90 days, 150 days and 180 days. The primary outcome measure was the Positive and Negative Syndrome Scale (PANSS) total score, with secondary measures including the PANSS subscales (positive, negative and general), the Montgomery Asberg Depression Rating Scale (MADRS), the Clinical Global Impression Improvement (CGI-I) and Severity scales (CGI-S), the Abnormal Involuntary Movement Scale (AIMS), the Self-Rated Life Satisfaction Scale (SRLS), the Liverpool University Neuroleptic Side Effect Rating Scale (LUNSERS) and the Global Assessment of Functioning (GAF). It was hypothesised that adjunctive mangosteen pericarp would reduce symptoms of schizophrenia indexed by PANSS total scores compared to placebo. The study followed Good Clinical Practice and National Health and Medical Research Council guidelines for clinical trials. Participants were randomly allocated to either 1000mg/day of encapsulated Garcinia mangostana L. (mangosteen) pericarp powder or a matching placebo for a period of 180 days, in addition to treatment as usual. xii

Results: The primary and secondary measures were assessed at each interview. The placebo and experimental group had statistically significant differences between groups on the primary and secondary outcomes at the 180-day endpoint. The efficacy of mangosteen pericarp was supported by a high level of compliance and significant difference of the primary indicator, PANSS total (p < 0.01), with a large effect size (1.41) between groups at endpoint. Secondary measures demonstrated significant between-group differences across all measures of dimensional outcome: PANSS positive (p < 0.01), PANSS negative (p < 0.01), PANSS general (p < 0.01), MADRS (p = 0.01) and CGI-S (p = 0.03). Functioning and well-being measures were significantly different between groups for SRLS (p < 0.01) and GAF (p = 0.03). The effect of treatment over time was different between groups, as measured by CGI-I (p < 0.01). Side-effect rating across LUNSERS scores indicated significant between-group differences (p < 0.01), with greater reduction in the mangosteen pericarp group. There were non-significant differences between groups of tardive dyskinesia (p = 0.16) measured by AIMS scores. Tobacco and alcohol use did not differ between groups at 180 days. Mangosteen pericarp was well tolerated. Conclusions: Our data supports a causal relationship between mangosteen pericarp and a reduction of symptom domains associated with schizophrenia. Our results support the efficacy of 1000mg/day encapsulated mangosteen pericarp compared to the placebo for the treatment of schizophrenia and schizoaffective disorder.

Item ID:	40097
Item Type:	Thesis (PhD)
Keywords:	adjunctive treatment; adjuvant treatment; antioxidant defences; antioxidants; antipsychotic drugs; antipsychotics; clinical management; Garcinia mangostana L.; mangosteen pericarp; mangosteen; mitochondrial pathology; placebo-controlled trial; schizoaffective disorder; schizophrenia; treatment
Additional Information:	Australian and New Zealand Clinical Trial Registration number: ACTRN12611000910909.
Funders:	Far North Queensland Hospital Foundation (FNQHF), Mangosteen Dietary Supplements (MDS)
Projects and Grants:	Far North Queensland Hospital Foundation Research Award
Date Deposited:	27 Aug 2015 04:39
FoR Codes:	11 MEDICAL AND HEALTH SCIENCES > 1103 Clinical Sciences > 110319 Psychiatry (incl Psychotherapy) @ 10% 11 MEDICAL AND HEALTH SCIENCES > 1110 Nursing > 111005 Mental Health Nursing @ 25% 11 MEDICAL AND HEALTH SCIENCES > 1111 Nutrition and Dietetics > 111104 Public Nutrition Intervention @ 65%
SEO Codes:	92 HEALTH > 9202 Health and Support Services > 920209 Mental Health Services @ 10% 92 HEALTH > 9202 Health and Support Services > 920210 Nursing @ 90%
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