List of essential psychotherapeutic medicines 2019 of India: When science was left behind.

INTRODUCTION

The Ministry of Health and Family Welfare, Government of India, has recently come up with the “list of psychotherapeutic drugs/medicines” on August 16, 2019, which was notified as per letter F. No. V. 15012/04/2019-PH-I dated August 16, 2019.[1] A comprehensive list of essential drugs has been provided in accordance with subsection 18 of section 10 of the Mental Health Care Act (MHCA), 2017 in the said list. The MHCA, 2017 has been an improvised version of the previous Mental Health Act, 1987, that has put forward a more rights-based approach for persons with mental illness (PMI), with more focus on autonomy in the hands of the PMI and their nominated representatives.[23] This list of psychotherapeutic drugs/medicines has enlisted many Ayurveda, Yoga, Unani, Siddha, Homeopathy, or Naturopathy (AYUSH) systems’ medicines [Figure 1] as “essential drugs” along with those of modern medicines, and they are notified to be “also be made available free of cost to all persons with mental illness.” The notification further mentions that these medicines for various mental health conditions have been approved to be made available at all times at health establishments run or funded by the appropriate government starting from community health centers and upward. The list spells out psychotherapeutic agents for various psychiatric disorders and also includes medicines for extrapyramidal symptoms which may arise as an adverse effect of few psychotropics. We hereby discuss some of the issues with the list.

Figure 1

List of essential medicines of Ayurveda, Yoga, Unani, Siddha, Homeopathy, or Naturopathy specialties for mental health problems as per notification (letter F. No. V. 15012/04/2019-PH-I dated August 16, 2019).[1]

ESSENTIAL MEDICINES: WHAT DOES IT MEAN?

Before discussing our concerns, it is important to know what the term “essential medicine” (EM) means. Although neither the notification in question nor the MHCA act defines what essential psychotherapeutic medicines/drugs mean, the National List of EMs (NLEMs), most recently revised in 2015, laid down necessary criteria for determining the essential drugs.[4] Any medicine that fulfills certain basic requirements would make into the NLEM of India. These include medicines for certain diseases concerned which must be a public health problem in this country and the medicine must be essential in a sense that once included in the list, it must be able to contribute to a reduction in the overall burden of the disease. The medicine should have proven efficacy, safety, and cost-effectiveness based on valid scientific evidence. The drug should be a single medicine and not a fixed-drug combination (unless the combination is rational and advantageous). Furthermore, the medicine should be approved and licensed for use in India, should be stable under the storage conditions in this country and should align with the current treatment guidelines. Finally, the criteria also state that if there are more than one medicine available from the same therapeutic class, preferably one best-suited prototype medicine of the class after due evaluation of their relative safety, efficacy, and cost-effectiveness, is to be included in the list.[4] These are the laid down criteria for any medicines as formulated by the government of a country (here India) and thus should also hold good when choosing psychotherapeutic medicines for managing mental illnesses which forms one of the most important components of the noncommunicable diseases in India, having an overall weighted lifetime and current prevalence of 13.7% and 10.6%, respectively.[5]

ISSUES WITH THE CURRENT LIST OF PSYCHOTHERAPEUTIC DRUGS/MEDICINE

Inclusion of Ayurveda, Yoga, Unani, Siddha, Homeopathy, or Naturopathy medicines

This has been the first time when a separate list psychotherapeutic EM list has been prepared and circulated and also the first time for the inclusion of AYUSH psychotherapeutic drugs/medicines in line with those of modern medicine. This list of AYUSH EMs (psychotherapeutics) has intrigued us into a plethora of questions when we are trying to find a justification of their inclusion as per the laid down criteria for NLEM (if the same rules of EMs have been applied to the psychotherapeutics). Has there been enough evidence base (like that of “allopathy” psychotropics) for AYUSH medicines mentioned in the list in managing mental disorders to find their place in this “essential medicine list?” A recent review in “The Lancet Psychiatry” mentioned “Scientifically rigorous clinical trials assessing the efficacy of traditional, complementary, and alternative medicine practices for the treatment of mental illnesses are scarce” and “no firm conclusion can be drawn about the effectiveness of any category of traditional, complementary, and alternative medicine for the treatment of any specific mental illness,” which they concluded after systematically reviewing 94 systematic reviews and meta-analysis in English and 19 in Chinese.[6] This points to the fact that the evidence on the effectiveness of AYUSH medicines in general (and possibly to those in the list) is lacking, with limited/no data on their cost-effectiveness, safety, and ability to reduce the disorder’s public health burden.

Second, in the list of “allopathy” medicines, each mental disorder has separate and distinct psychotropics listed as EMs. As of now, we do not have medicines from “allopathy” that are effective and safe for both psychotic and neurotic groups of psychiatric disorders. On the other hand, in the AYUSH list, we see many medicines (e.g., kalyanaka Ghritha and Kushmanda Ghritha) which are EMs for both psychotic and neurotic disorders. Does this mean that these medicines are fulfilling the required criteria of essentiality for the entire gamut of psychotic as well as neurotic disorders from the current classificatory systems? Or, they are just empirically used in these conditions which in turn question the evidence base for them and thus their inclusion in the EM list.

Third, Ayurvedic formulations often include toxic metals and other elements as part of the Rasa Shastra practice.[789] They are reported to contain toxic metals such as lead, mercury, and/or arsenic which have been estimated in over 20% of their formulations manufactured and distributed by the United States and Indian companies.[710] These can pose potential health risks. Since safety profile is a point criterion for inclusion of medicine in NLEM, the authors are intrigued to know if the efficacy of these formulations significantly outweighs the risks to find their place in the NLEM list.

Fourth, many of these medicines are churnas, which contain many alkaloids and other phytochemical constituents. Do these churnas meet the requirements for rational fixed-drug combinations as per the NLEM or different norms and rules apply to them?

Finally, if these medicines make a mention under any guidelines of the indicated conditions as is a prerequisite for being an EM is also an important issue.

Inclusion of alien mental disorders

Another issue is the use of nonspecific terms to describe the indications for which the medications are essential. In the Siddha medicine list, “mental disorders” and “multiple mental disturbances” are mentioned, for which few drugs are EM. This further adds to the confusion about whether they are the panacea for all “mental disorders” or the Siddha system of medicine has not come up with robust evidence for these medicines for specific disorders, which again questions their position in the list. Furthermore, the term “panic depression” has been mentioned in the “indications” list of the Siddha system of medicine for which two drugs (Muthuchippi Parpam and Gandhaga Parpam) are listed. The notification letter says these AYUSH indications as “Equivalent terms of indications in modern medicine.” However, there is no diagnosis named “panic depression” in psychiatric nosology from a modern medicine perspective.

On the other hand, some of these medicines are indicated, as per this list, for not just psychiatric conditions but even for conditions such as epilepsy, syncope, and essential hypertension. The NLEM was prepared using a complex process consisting of the number of consultations with experts and stakeholders from different fields. Whether the same thorough process was followed or not for selecting this psychotherapeutics list is not very clear.

Other issues with Ayurveda, Yoga, Unani, Siddha, Homeopathy, or Naturopathy medicines are included in the list

There are some neurodevelopmental disorders (mental retardation and learning disability) mentioned in the “indications” list for which few essential Ayurvedic drugs (e.g., Sarawatharishta, Brahmi Churna, Vacha Churna, and Saraswata Churna) are listed. Currently, there are no psychopharmacological agents approved to manage/treat these neurodevelopmental disorders. If these medications are indeed effective (which is probably not the case), psychiatrists and other mental health professionals should be made aware of this to get the maximum benefits. Publishing the robust original data about their safety, efficacy, and other relevant clinical aspects, which currently is lacking, would go a long way in justifying the inclusion of these medicines in the list.

Exclusion of modern evidence-based medicines used for substance use disorders

Apart from the overinclusion of AYUSH medicines, there are some notable exclusions from modern evidence-based medicine. Substance use disorders (SUDs) fall under the diagnostic scope of psychiatry, with a 22.4% of prevalence in India.[5] SUDs come under the ambit of MHCA as well. Tobacco, alcohol, and opioid use disorders are important public health concerns in India and they have effective psychopharmacological options available for their treatment. Medicines such as bupropion, nicotine replacement therapy, and varenicline for tobacco use disorders, disulfiram, naltrexone, and acamprosate for alcohol use disorders, as well as naltrexone, methadone, and buprenorphine/buprenorphine + naloxone for opioid use disorders, are safe, efficacious, and cost-effective for long-term management of these conditions. Similarly, medicines such as long-acting benzodiazepines are effective, safe, and cost-effective for the short-term withdrawal management of alcohol use disorders. These medications feature into all the major treatment guidelines of SUDs including the clinical practice guidelines of the Indian Psychiatric Society.[11] There have been recent calls to include medications used for SUDs in India’s NLEM and the EML of the World Health Organization.[12] This could have been a prudent decision considering AYUSH drugs with questionable evidence base are finding their names in the list. Keeping this in mind, the exclusion of these medicines is unjustifiable.

Other notable exclusions

In the modern medicine essential psychotherapeutic list, apart from SUD medications, other psychotropics of considerable usage and robust indications could have been introduced in this list. Clozapine is considered the gold standard for treatment-resistant schizophrenia. Considering that treatment-resistant schizophrenia is a prevalent entity (with rates of 10%–60% in patients with schizophrenia), the inclusion of clozapine should have been considered.[13] This might also give a little boost to the prescribing of clozapine, a drug underused in India, for treatment-resistant schizophrenia.[14]

Dementia is also fast becoming a public health concern in India. As per the recent estimates, the estimated number of elderly with dementia in India is 3.7 million.[15] As per the Dementia India Report 2010, two-fold increase in the prevalence of dementia is estimated by 2030, making it one of the important public health issues.[16] The prevalence of dementia among the elderly in India ranges from 0.9% to 4.86% in urban areas and 0.8% to 5.55% in rural areas.[15] Keeping this in mind, tablet donepezil was also added in the revised NLEM 2015 of India.[4] Dementia as a neurodegenerative disorder is a widely studied and managed clinical condition in psychiatry practice. The Ayurvedic formulation, Brahmi Churna, has found its position in the 2019 essential psychotherapeutic medicines list for “dementia, mental retardation, and cognitive disorders” while a not so old meta-analysis concluded that it (Bacopa monnieri) “may be beneficial in improving cognitive function in the attention domain, especially speed of attention. Nevertheless, there is a clear and urgent need for large scale independent clinical trials on well-characterized patient cohorts, using rigorously applied design criteria and well-established endpoints.”[17] Donepezil, a acetylcholinesterase inhibitor, has robust evidence in dementia[18] but still it could not find a place in the said list. It can thus be argued that while Brahmi Churna finds its position, donepezil could have surely made it to the 2019 essential psychotherapeutic medicines list.

CONCLUSION

To conclude, although the development of essential psychotherapeutic medicines is a laudable step, the selection criteria for drugs in the list is questionable. The overarching inclusion of AYUSH medications and omission of medicines such as clozapine and those for treatment of SUDs is an important contentious issue. Fortifying this list keeping in mind the scientific evidence base and not just the belief in ancient systems would go a long way in treating PMI effectively. The inclusion of drugs in the essential list may have a game-changing impact (e.g., HIV and HCV treatments) on the disease concerned.[19] Thus, a more science-based approach to public mental health is required to fortify the list that may strengthen the treatment options in its management.

Disclaimer

Views expressed in the article are personal opinion of the authors and does not reflect the official stand of the Indian Journal of Psychiatry.