The Journal of ECT
16(2):144-156 0 2000

Summary: During the last decade the use of herbal medicinal substances in the attenuation of anterograde and retrograde amnesia induced by electroconvulsive shock (ECS) has been studied using animal research. We will discuss the background of herbal medicine in India, review the research findings on herbal medicines for ECS-induced amnestic deficits, and examine the applications and limitations of animal models in this context. We will focus on our own research and insights, with particular emphasis on practical issues.

Electroconvulsive therapy (ECT) is associated with anterograde and retrograde amnestic deficits that can, in certain cases, be severe, persistent, or both (Abrams, 1997). Several pharmacological treatments have been suggested to reduce such deficits, but in general the results have been disappointing (Andrade, 1990; Krueger et al., 1992; Nobler and Sackeim, 1993). In recent years, studies have explored the antiamnestic efficacy of herbal medicines in the context of animal models of ECT (Andrade, 1995). This paper will briefly introduce the practice of herbal medicine in India, summarize the studies that have examined herbal attenuation of amnestic deficits induced by electroconvulsive shocks (ECS), and discuss the application and limitations of animal models in the context of such research.

Herbal Medicine and Its Practice in India

Systems of herbal medicine are practiced in traditional societies in many parts of the world; allopathic science may gain much from the study of such systems. Several important allopathic drugs, such as digitalis, quinine, and atropine, originated from plant sources; psychiatrists need no reminding that over half a century ago, the (Indian) herbal pharmacopoeia contributed reserpine to modern medicine. The need to study the psychotropic properties of herbal drugs is recognized even in developed societies; for example, clinical research on St. John's Wort was recently reviewed in the British Medical Journal (Linde et al., 1996), and a multicenter study on the efficacy of an extract of Gingko biloba in patients with dementia was recently published in the Journal of the American Medical Association (JAMA) (Le Bars et al., 1997). During November 1998, an entire issue of JAMA was devoted to articles on alternative systems of medicine, including herbal treatments.

American laboratories are already screening individual herbs for psychotropic potential; the United States' efforts in this regard have been summarized by Cott (1995). By way of example, Cott et al. (1994) reported that extracts from Withania somnifera show high affinity for GABA receptors, and that extracts from Centella asiatica show affinity for CCK receptors. Withania somnifera and Centella asiatica are known as Ashwagandha and Mandookaparni (respectively) in Ayurveda, which is a traditional system of medicine in India. Since GABA agonism and CCK antagonism have been linked to anxiolysis, these findings support the recommendation in Ayurveda that Ashwagandha and Mandookaparni be used as sedatives (Handa, 1995).

The discipline of Ayurveda has existed in India for millennia. One of the practices of Ayurveda is to treat poor health with medicines obtained from herbs. These medicines are prepared from the leaves, roots, or other parts of certain plants. The medicines are most commonly dispensed in the form of a powder or as a water-based extract that is prepared as a decoction, much as tea is brewed. Indian herbal substances with psychotropic properties have been described by Iyengar (1981), Satyavati (1995), Dhawan (1995), and Handa (1995).

Ayurvedic medicine is widely practiced in India to this day. Students receive their training in Ayurvedic medical colleges, and are subsequently licensed by the state to practice their art. Their training and licensing is independent of and parallel to the training and licensing of allopathic practitioners.

The Indian government as a policy encourages Ayurvedic and other forms of indigenous medicine (such as Unani and Sidda). One of the forms of encouragement is to permit the marketing and prescribing of herbal medicinal substances with no prior requirement that these substances be demonstrated to be effective and safe. All that the Drug Controller of India requires, in fact, is evidence that the substances in question have been recorded to have medicinal properties in the ancient Indian literature. In contrast, allopathic drugs introduced into the country must pass through clinical trials before their marketing is permitted; this requirement is not relaxed even if the drug has been approved of for marketing in the developed world.

Ayurvedic clinicians classify and diagnose illness in a manner that is radically different from that followed in allopathy; concepts in the field of mental health have been described by Ramachandra (1990). Furthermore, Ayurvedic clinicians do not have adequate training in the design, conduct, and analysis of clinical trials. As a result, they do not engage themselves in research that is of a nature that allopathic medical journals will find acceptable. In consequence of this, and in consequence of the policy of the Drug Controller of India, a very large number of herbal medicines and formulations thereof are commercially marketed and prescribed in the country without evidence of efficacy and safety. In general, however, experience suggests that adverse effects are not an issue because patients hardly ever experience ill effects when receiving herbal medicines; what remains in question is whether these medicines are effective at all.

The study of the Indian herbal pharmacopoeia through clinical trials is an expensive, laborious, and time-consuming option. The logistics of conducting clinical trials on herbal medicines are further complicated by two factors: most herbal pharmaceutical companies are too small to be able to afford to commission clinical trials, and the larger companies are not interested in clinical trials because their products have already been licensed for sale. Interested scientists are therefore compelled to resort to animal models for the efficacy screening.

Efficacy Screening

Where Should One Begin?

Our interest in the herbal attenuation of ECT-induced cognitive impairment arose in the early 1990s. We were faced with a wide choice of individual substances, all of which were described in Ayurveda to enhance central nervous system functioning; these substances included Shankapushpi, Brahmi, Ashwagandha, Mandookaparni, and others (for review, see Iyengar, 1981; Dhawan, 1995; Handa, 1995; Satyavati, 1995). We were also faced with a wide choice of commercial formulations comprising combinations of various substances in various proportions; these formulations were marketed with the assertion that individual ingredients complement each other in efficacy and cancel out each other in adverse effects (this assertion is a common philosophy underlying Ayurvedic medical practice).