Rhodiola SHR-5 extract and the treatment of depression

Rhodiola (Rhodiola rosea) is a medicinal plant exhibiting significant adaptogenic properties that have been extensively studied and exploited in Scandinavia and Russia with particular reference to increasing mental performance against a background of fatigue and asthenia. In a randomised, double-blind, placebo-controlled phase III clinical trial, the effects of standardised extract SHR-5 of Rhodiola rhizome on mild to moderate depression were examined. Medication with SHR-5 was administered in the form of 400mg tablets each of which contained 170mg of Rhodiola extract that had been quantified by HPLC with respect to triandrin, rhodioloside, tyrosol and rosavin content. Male and female participants, aged between 18–70 years, were selected according to DSM-IV diagnostic criteria for depression, the severity of which was determined by scores gained in Beck Depression Inventory and Hamilton Rating Scale for Depression (HAMD) questionnaires. Patients with initial HAMD scores between 21 and 31 were randomised into three groups, one of which (group A: n=30) received two tablets daily of SHR-5 (340mg/day), a second (group B: n=29) received two tablets twice-per-day of SHR-5 (680mg/day), whilst a third (group C: n=29) received two placebo tablets daily. The efficacy of the extract with respect to the reduction of depressive condition was assessed from the total and specific subgroup HAMD scores obtained on days 0 and 42 of the study period. For individuals in groups A and B, overall depression together with insomnia, emotional instability and somatisation, but not self-esteem, improved significantly following medication, whilst the placebo group showed no such improvements. No serious side effects were recorded in any of the study groups, and we were able to show that in animal systems SHR-5 does not interact with other drugs sensitive to CYP1A2, CYP2C9 and CYP3A4 enzymes. Results from a series of experiments involving rabbits have demonstrated that SHR-5 inhibits the over-activation of p-SAPK/p-JNK induced by emotional stress. The SAPK/JNK pathway is known to be involved in the pathogenesis of glucocorticoid resistance (GR), found in subgroups of patients with major depression, and the activation of SAPK/JNK has been reported to inhibit GR function. Hence it can be hypothesised that the antidepressant effects of SHR-5 are associated with the inhibition of stress activated protein kinases. This study constitutes the first report that Rhodiola extracts exhibit anti-depressive potency in patients with mild to moderate depression.