Polysomnographic Effects of Adjuvant Ginkgo Biloba Therapy in Patients with Major Depression Medicated with Trimipramine1

Abstract

Sleep disturbance and cognitive impairment are frequent complaints of depressed patients under standard antidepressant medication. Therefore, additional therapies are required which specifically focus on the improvement of these deficits without exerting major side effects. Ginkgo biloba extract (EGb) has been shown to improve cognitive abilities in elderly subjects and in patients with disorders of the dementia spectrum. Animal studies surmise that EGb may reduce CRH activity, which is substantially related to depressive mood and behavior, predominantly cognition and sleep. An open non-randomized pilot study has been conducted to investigate the effects of ginkgo biloba extract (EGb Li 1370) on cognitive performance and sleep regulation in depressed inpatients. 16 patients were treated with a trimipramine (T)-monotherapy (200 mg) for six weeks. In eight of the 16 patients, an adjunct EGb therapy (240 mg/d) was applied for four weeks after a baseline week, the other eight patients remained on trimipramine monotherapy (200 mg) during the entire study. Polysomnography, cognitive psychomotor performance and psychopathology were assessed at baseline, after short-term and long-term adjunct EGb treatment, and after one week of ginkgo discontinuation (at the respective evaluation times in the eight patients on T-monotherapy). This report focuses on the results of EGb on sleep EEG pattern. EGb significantly improved sleep pattern by an increase of sleep efficiency and a reduction of awakenings. In addition, sleep stage 1 and REM-density were reduced, while stage 2 was increased. Non-REM sleep, predominantly slow wave sleep in the first sleep cycle, was significantly enhanced compared to trimipramine monotherapy. Discontinuation of EGb reversed most of these effects. Based on the animal data, these results suggest that EGb may improve sleep continuity and enhance Non-REM sleep due to a weakening of tonic CRH-activity. The compensation of the deficient Non-REM component in depression by the EGb application may provide a new additional treatment strategy, especially in the treatment of the depressive syndrome with sleep disturbance.

Oxidative stress in psychiatric disorders: evidence base and therapeutic implications

“…A small (n=16), open-label study of adjunctive EGb in the treatment of patients with major depressive has been published, reporting positive outcomes in terms of improved sleep efficiency and awakenings, but depressive outcomes were not reported (Hemmeter et al, 2001). The beneficial effects of NAC on mood in a non-clinically depressed population have been reported from a double-blind, placebo-controlled study of NAC in patients with mild chronic bronchitis.…”

Induction of Propranolol Metabolism by Ginkgo biloba Extract EGb 761 in Rats

“…The commonly recognized therapeutic benefits for this drug in central nervous system diseases have been demonstrated in Alzheimer's disease, chronic refractory schizophrenia and in sleep disturbance of depressed patients [32,33]. Most clinical studies on efficacy and safety of ginkgo have been conducted with a standardized aqueous acetone extract, EGb 761 that is in a solid form.…”

Anti-depressant natural flavonols modulate BDNF and beta amyloid in neurons and hippocampus of double TgAD mice

“…In animal studies, EGb 761 improves cognitive function in an age-related memory impairment model (Stoll et al, 1996; Cohen-Salmon et al, 1997), and in a transgenic mouse model of AD (Stackman et al, 2003). It was revealed recently that EGb 761 displays anti-depressive and anti-stress actions in animal behavioral models (Naik et al, 2006; Sakakibara et al, 2006; Kalkunte et al, 2007), and in human volunteers (Hemmeter et al, 2001; Trick et al, 2004). These observations prompted us to test the hypothesis that modulation of depression-related neuroplastic pathways by active constituents of ginkgo extract may explain its anti-depressant action and provide therapeutic impact to depressive disorders in AD.…”