Efficacy and tolerability of Ginkgo biloba extract EGb 761® in dementia: a systematic review and meta-analysis of randomized placebo-controlled trials

Abstract

The objective of this systematic review was to evaluate current evidence for the efficacy of Ginkgo biloba extract EGb 761(®) in dementia. Seven of 15 randomized, placebo-controlled trials in patients with dementia identified by database searches met all our selection criteria and were included in the meta-analysis. In these trials, patients were treated with 120 mg or 240 mg per day of the defined extract EGb 761 or placebo. Efficacy was assessed using validated tests and rating scales for the cognitive domain, the functional domain (activities of daily living), and global assessment. Tolerability was evaluated by risk differences based on incidences of adverse events and premature discontinuation rates. Of 2,684 outpatients randomized to receive treatment for 22-26 weeks, 2,625 represented the full analysis sets (1,396 for EGb 761 and 1,229 for placebo). Standardized mean differences for change in cognition (-0.52; 95% confidence interval [CI] -0.98, -0.05; P=0.03), activities of daily living (-0.44; 95% CI -0.68, -0.19; P<0.001), and global rating (-0.52; 95% CI -0.92, -0.12; P=0.01) significantly favored EGb 761 compared with placebo. Statistically significant superiority of EGb 761 over placebo was confirmed by responder analyses as well as for patients suffering from dementia with neuropsychiatric symptoms. Treatment-associated risks in terms of relative risks of adverse events and premature withdrawal rates did not differ noticeably between the two treatment groups. In conclusion, meta-analyses confirmed the efficacy and good tolerability of Ginkgo biloba extract EGb 761 in patients with dementia.

Keywords: Alzheimer’s disease; efficacy; mixed dementia; safety; vascular dementia.

Figure 1

Change in scores for cognition (SKT, ADAS-cog). Notes: (A) All trials, (B) trials using the SKT, (C) daily dose of EGb 761 120 mg, (D) daily dose of EGb 761 240 mg, and (E) studies in patients with NPS. Abbreviations: ADAS-cog, cognitive subscale of the Alzheimer’s Disease Assessment Scale; EGb, EGb 761^®; SKT, Short Cognitive Performance Test (Syndrom-Kurztest); NPS, neuropsychiatric symptoms; CI, confidence interval; SD, standard deviation; SMD, standardized mean difference; IV, inverse variance method.

Figure 2

Change in scores for activities of daily living (NAB, GERRI, GBS-ADL, ADL-IS). Notes: (A) All trials, (B) daily dose of EGb 761 120 mg, (C) daily dose of EGb 761 240 mg, and (D) studies in patients with NPS. Abbreviations: EGb, EGb 761^®; NAB, Nuremberg Gerontopsychological Observation Scale; GERRI, Geriatric Evaluation by Relatives Rating Instrument; GBS-ADL, Gottfries-Bråne-Steen Activities of Daily Living Scale; ADL-IS, Alzheimer’s Disease Activities of Daily Living International Scale; CI, confidence interval; SD, standard deviation; SMD, standardized mean difference; IV, inverse variance method.

Figure 3

Clinical global impression of change from baseline (CGIC, ADCS-CGIC, GBS). Notes: (A) All trials, (B) daily dose of EGb 761 120 mg, (C) daily dose of EGb 761 240 mg, and (D) studies in patients with NPS. Abbreviations: EGb, EGb 761^®; CI, confidence interval; SD, standard deviation; NPS, neuropsychiatric symptoms; SMD, standardized mean difference; IV, inverse variance method; GBS, Gottfries-Bråne-Steen scale; CGIC, Clinical Global Impression of Change; ADCS-CGIC, Alzheimer’s Disease Cooperative Study Clinical Global Impression of Change.

Figure 4

Clinically relevant response. Notes: (A) Odds ratios for improvement in cognition (at least 3 points in the SKT or at least 4 points on the ADAS-cog). (B) Odds ratios for improvement in CGIC and ADCS-CGIC. Abbreviations: EGb, EGb 761^®; CGIC, Clinical Global Impression of Change; ADAS-cog, cognitive subscale of the Alzheimer’s Disease Assessment Scale; ADCS-CGIC, Alzheimer’s Disease Cooperative Study Clinical Global Impression of Change; CI, confidence interval; M-H, Mantel-Haenszel test; SKT, Short Cognitive Performance Test (Syndrom-Kurztest).

Figure 5

Safety analyses. Notes: (A) Patients reporting at least one adverse event, (B) patients reporting at least one serious adverse event, and (C) patients who terminated the study prematurely due to an adverse event. Abbreviations: CI, confidence interval; IV, inverse variance method; EGb, EGb 761^®.