Ginkgo has been used to treat cerebral insufficiency and dementia of the Alzheimer type. The term cerebral insufficiency, however, includes a variety of manifestations ranging from poor concentration and confusion to anxiety and depression as well as physical complaints such as hearing loss and headache. For this reason, studies evaluating cerebral insufficiency tend to be more inclusive and difficult to assess than trials evaluating dementia. A meta-analysis of ginkgo for cognitive impairment or dementia was performed by the Cochrane Collaboration. They reviewed 36 randomized, double-blind, placebo-controlled trials ranging in length from 3 to 52 weeks. Significant improvements in cognition and activities of daily living were observed at 12 but not 24 weeks. Significant improvements in clinical global assessment however, were observed at 24 but not 12 weeks. The authors concluded that the effects of ginkgo in the treatment of cognitive impairment and dementia were unpredictable and unlikely to be clinically relevant. However, recent meta-analyses of randomized controlled trials, 22–26 weeks in duration, using EGb761 that limited inclusion criteria to patients with dementia of the Alzheimer type (in eight studies), vascular or mixed dementia type (in six studies), or dementia with neuropsychiatric features (in four studies) showed favorable results. Significant improvements in cognition and activities of daily living were observed for ginkgo compared to placebo. Clinical global assessment of improvement also was significantly improved when EGb761 doses of 240 mg/d were used, but not doses of 120 mg/d. Because of the stricter inclusion criteria used, the overall methodologic quality of the studies was higher than that of the Cochrane review, when determining a benefit in patients with dementia. This suggests that patients with a diagnosis of dementia are more likely to benefit than patients with more mild cognitive impairment. In the GEM and GuidAge studies that included persons with normal or mild cognitive impairment, the effects of ginkgo as a prophylactic agent to prevent progression to dementia were assessed. No benefit was observed with 5–6 years of ginkgo treatment.
4. Miscellaneous effects—Ginkgo has been studied for its effects in schizophrenia, tardive dyskinesia, allergic and asthmatic bronchoconstriction, short-term memory in healthy, nondemented adults, erectile dysfunction, tinnitus and hearing loss, and macular degeneration. Preliminary data from eight randomized, double-blind, placebo-controlled trials suggest that EGb761 can significantly reduce the symptoms of chronic schizophrenia when used in combination with standard treatment (eg, clozapine, haloperidol, olanzapine). These trials were conducted in China, so firm conclusions about benefit in a broader population are lacking. There is insufficient evidence to warrant clinical use for the other conditions listed.
Adverse effects of ginkgo have been reported with a frequency comparable to that of placebo. These include nausea, headache, stomach upset, diarrhea, allergy, anxiety, and insomnia. A few case reports noted bleeding complications in patients using ginkgo. In some of these cases, the patients were also using either aspirin or warfarin.
Ginkgo may have antiplatelet properties and should not be used in combination with antiplatelet or anticoagulant medications. Other single case reports noted virologic failure when ginkgo was combined with efavirenz, sedation when combined with trazodone, priapism when combined with risperidone, and seizure when combined with valproic acid and phenytoin; all warrant further pharmacokinetic studies before firm conclusions can be drawn. Seizures have been reported as a toxic effect of ginkgo, most likely related to seed contamination in the leaf formulations. Uncooked ginkgo seeds are epileptogenic due to the presence of ginkgotoxin. Ginkgo formulations should be avoided in individuals with preexisting seizure disorders.