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Ashwagandha for anxiety disorders

In their extensive review and treatment guideline, Bandelow et al. (2008) described various pharmacological interventions for the management of anxiety disorders. They listed Ginkgo biloba and kava kava among the herbal preparations that have been studied. However, they did not refer to an important herb, Ashwagandha (ASW), which has for long been used in traditional medicine to treat disorders related to stress (Handa 1995; Satyavati 1995). ASW is obtained from the root of the plant Withania somnifera. The plant grows wild but is also cultivated for medicinal use in many parts of India as well as in other Asian countries. Preclinical studies suggest that ASW contains an ingredient with GABA-mimetic activity (Mehta et al. 1991; Kulkarni et al. 1993; Cott et al. 1994). ASW also downregulates 5-HT1 and upregulates 5-HT2 receptors in the rat brain; these changes are accompanied by a decrease in behavioural indices of anxiety and depression (Tripathi et al. 1998). In animal models, ASW glycowithanolides have an anxiolytic effect comparable to that of lorazepam (Bhattacharya et al. 2000). At least three studies have examined the efficacy of ASW in anxiety disorders. In a preliminary investigation, the safety and efficacy of an ethanolic extract of ASW were examined in 50 patients with anxiety disorders. By the end of the first month of treatment, 36 patients showed moderate to excellent improvement at a dose of 1 g/day; in about half of these cases, these statistically significant benefits developed within the first 2 weeks, itself. These 36 patients were continued on ASW for up to 18 months, after which the medication was uneventfully withdrawn. ASW remained effective and was very well tolerated (data available from the author on request). In a double-blind, placebo-controlled clinical trial, we (Andrade et al. 2000) randomized 40 patients with ICD-10 anxiety disorders to receive either flexibly-dosed ethanolic extract of ASW (1.0 2.5 g/ day) or placebo for 6 weeks. About two-thirds of the sample was diagnosed with generalized anxiety disorder. By the end of the second week of treatment, 12 of 17 ASW patients but only six of 16 placebo patients met criteria for response. At the end of the study, 15 of 17 ASW patients versus only eight of 16 placebo patients had responded (PB0.05). Mean Hamilton Anxiety Scale scores dropped from about 18.0 in the two groups at baseline to 8.5 with ASW versus 12.2 with placebo at the 6-week treatment endpoint. ASW was well tolerated and had a placebo level of adverse effects. At the end of the study, abrupt withdrawal of ASW did not precipitate withdrawal phenomena. Thus, ASW appeared to have several of the advantages but none of the disadvantages of conventional anxiolytic drugs such as antidepressants and the benzodiazepines. Auddy et al. (2008) described a 2-month, doubleblind, randomized controlled study which examined benefits with a standardized extract of ASW in 130 subjects who received a descriptive diagnosis of chronic stress in an Ayurvedic hospital. ASW was dosed at 125, 250, or 500 mg/day; a fourth group of patients received placebo. All doses of ASW attenuated modified HAM-A scores significantly more than did placebo at the 1-month follow-up; there was