Reviewed: Brondino N, De Silvestri A, Re S, et al. A systematic review and meta-analysis of Ginkgo biloba in neuropsychiatric disorders: from ancient tradition to modern-day medicine. Evid Based Complement Alternat Med. 2013;2013:1-11. doi: 10.1155/2013/915691.

Ginkgo (Ginkgo biloba, Ginkgoaceae) extract is one of the most popular phytomedicines; however, according to the authors, there has been no systematic review on its effect on neuropsychiatric disorders other than dementia. Hence, the purpose of this report was to conduct a systematic review of ginkgo clinical trials for such disorders.

The authors searched MEDLINE^®, Embase™, PsycINFO^®, and the Cochrane Database of Systematic Reviews from inception through April 2012. The search terms were gingko biloba, ginkgo, ginko, gingko, bilobalid* [asterisk commands search to locate all terms that start with the preceding word], egb 761, dementia, cognitive impairment, Alzheimer, autism, autistic spectrum disorder, schizophrenia, psychosis, psychotic disorder, delusion, depression, major depression, depressive symptom, anxiety, generalized anxiety disorder, anxious, attention deficit disorder, ADHD, attention deficit, hyperactivity, and addiction. According to the article, “All search terms were searched individually in each database and combined together. The search strategy had no time restriction but was limited to articles in English, Italian, French, Spanish, and German. Additionally, all recovered papers were reviewed for further relevant references.” Study inclusion criteria were randomized, controlled clinical trials; a minimum of 10 patients per group; and treatment for less than six weeks. When possible, the data were pooled for a meta-analysis.

A total of 1,109 studies were identified. Of these, 113 were obtained for additional evaluation, and 18 met the inclusion criteria and were incorporated in this review. There was one randomized, double-blind study of patients with attention deficit hyperactivity disorder, which included 50 children treated with 80 mg/day (for participants weighing < 30 kg) or 120 mg/day ginkgo compared with methylphenidate for six weeks. Methylphenidate — a psychostimulant marketed under several trade names, including Ritalin® — was much more effective than ginkgo, though the latter had significantly fewer adverse side effects.

There was one randomized, placebo-controlled study of patients with autism, which included 47 children who were treated with the antipsychotic drug risperidone (on the market as Risperdal® and generic) in addition to either 80 mg/day (if < 30 kg) or 120 mg/day ginkgo extract or placebo for 10 weeks. There was no significant difference between groups, which means that no added effect for risperidone could be shown for ginkgo extract.

There was one randomized, double-blind, placebo-controlled study in patients with cocaine addiction, which included 44 patients who received either 240 mg/day ginkgo extract, the nootropic piracetam, or placebo for 10 weeks. There was no significant difference among the three groups.

There was one randomized, placebo-controlled study in patients with generalized anxiety disorder (GAD) or adjustment disorder with anxious mood in which participants were treated with 240 mg/day ginkgo, 480 mg/day ginkgo, or placebo for four weeks. There was a significant dose-response improvement in the ginkgo-treated patients compared with placebo-treated patients.

There was one randomized, placebo-controlled study of medicated patients with chronic schizophrenia and tardive dyskinesia who were treated with 240 mg/day ginkgo extract or placebo for 12 weeks. The ginkgo group had a significant improvement in the Abnormal Involuntary Movement Scale but not on secondary outcomes — namely the psychopathological scales — as the placebo group also showed improvements over time.

There were three other randomized, controlled studies in patients with chronic schizophrenia treated with ginkgo extract and either clozapine, haloperidol, or olanzapine (antipsychotic drugs), and these data were pooled for meta-analysis. The studies with clozapine and haloperidol were double-blind and placebo-controlled (n=42 and n=109, respectively), and the third study was olanzapine-controlled (n=29). The pooled analysis favored ginkgo; however, the results had substantial heterogeneity (i.e., when looking at the individual outcome measures, not all outcomes favored ginkgo treatment).

There were 10 studies of dementia; eight placebo-controlled and two donepezil-controlled. (Donepezil [sold as Aricept® and DONEP] is an acetylcholinesterase inhibitor.) Only the eight placebo-controlled studies (which utilized 120 or 240 mg/day ginkgo for 12-52 weeks) could be included in a meta-analysis. All trials used the standardized extract EGb 761® (Dr. Willmar Schwabe GmbH & Co. KG; Karlsruhe, Germany). The methodological quality of the eight studies was judged to be “adequate.” The pooled data showed that the Alzheimer’s Disease Assessment Scale-cognitive subscale and Syndrom-Kurz test outcome measures favored ginkgo treatment. There was also a significant difference in activities of daily living (ADL) standardized change scores between treatment groups when combining different scales: the Alzheimer’s Disease Activities-of-Daily-Living International Scale, Geriatric Evaluation by Relatives Rating Instrument, Gottfries-Bråne-Steen-Activities of Daily Living scale, Nürnberger Alters-Alltagsaktivitäten-Skala, and Nürnberger Alters-Beobachtungsskala. The two studies comparing donepezil and ginkgo showed no significant differences between treatments.

The authors conclude that the general lack of evidence prevents them from drawing conclusions for most neuropsychiatric conditions. However, the meta-analysis of dementia studies shows that ginkgo provides benefits for cognition and ADL. The authors state that the benefits for dementia and schizophrenia were modest and that some studies showed statistical improvements that were not necessarily clinically meaningful. Nonetheless, the authors conclude that despite heterogeneous results, the evidence supports the use of the proprietary standardized ginkgo extract in patients with dementia and as an adjunct therapy for patients with schizophrenia.

—Heather S. Oliff, PhD