Montelukast, developed by Merck and Co.in 1990, was approved by the FDA in 1998 and marketed under the brand name ‘Singulair’.
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In February 2018, Harry Miller, a 14-year-old British teenager, died by suicide after struggling to cope with mental health issues for two years. Miller, who had been suffering from asthma, had been prescribed montelukast on an ongoing basis for those two years. A couple of years after this incident, the U.S. Food and Drug Administration (FDA) added a ‘black box warning’ to montelukast and the Medicines and Healthcare Products Regulatory Agency, U.K. issued a health warning saying the drug could cause serious neuropsychiatric adverse effects. Several patient advocacy groups across the world have been lobbying for the restricted use of this drug. While caution is being exercised everywhere, the sale of this drug in India is unregulated, largely irrational, and seems to be increasing exponentially.
Montelukast, developed by Merck and Co., was approved by the FDA in 1998 and marketed under the brand name ‘Singulair’. The oral medication was approved to be prescribed daily for long-term use as a “preventer” or “controller” of asthma and allergic rhinitis. There is universal consensus, based on multiple comparative studies, that as a treatment for asthma, the drug is inferior to inhaled corticosteroids, which are considered first-line therapy for the control of the disease. For allergic rhinitis, most guidelines across the world recommend intranasal corticosteroids and/or antihistamines; montelukast is not recommended first-line therapy.
Unrestricted use in India
Yet, it is widely prescribed in India. There are multiple reasons for this. Patients prefer short-term oral medication over long-term inhalers and topical nasal sprays. Inhalers are often thought to have an addictive potential and are considered unsafe. There is also stigma associated with the use of inhalers, and patients do not want to be seen by their family and peers as needing inhalers to breathe. In the treatment of children, parents are often concerned about the effect of inhaled corticosteroids on growth, and montelukast has been considered to be safe in comparison. This is despite the fact that poorly controlled asthma can have far more deleterious effects on growth and development than those caused by inhalers. There also appears to be widespread ignorance of the adverse effects of the drug in India, resulting in rampant over-the-counter use. Even among physicians, the adverse effects of the drug do not appear to be widely known, as evidenced by the cavalier prescribing practices. Most prescriptions even for the common cold appear to have the drug in combinations for short-term use.
With antihistamines
What is especially worrying is the unrestricted use of the drug in combination with antihistamines. This is unscientific, as the drug is approved for use as a controller, and not as a short-term reliever medication, as is being widely marketed. A prescription of montelukast for 10 days is unscientific. Patients possibly benefit with time-tested antihistamines, such as levocetirizine, loratadine or fexofenadine, in combinations, while being exposed to the adverse effects of montelukast. Such combinations appear to be driven by profits — combining antihistamines with montelukast often triples the price of the drug. This is true, despite the patent on the drug expiring in 2012. Industry sources inform us that over 193 registered brands offer such combination treatment in India. The annual sales of montelukast were more than ₹2,400 crore during the April 2023-24 period. Less than 3% of these sales are potentially guideline-based, i.e. the sales of the drug alone; the rest are in irrational and unindicated combinations with antihistamines, oral bronchodilators, and mucolytics.
Concerns related to the drug are not a recent phenomenon. They were investigated as early as 2009, when an FDA review reported serious post-marketing concerns regarding the neuropsychiatric adverse effects. There is growing recognition that the drug can cause aggression, nightmares, depression, and cognitive impairment. It has been associated with deaths by suicide. A study from the University of Oxford, published in JAMA in 2022, concluded a much higher risk of anxiety and insomnia, among other neuropsychiatric adverse effects, from this drug. Large studies in Denmark, the U.S., Korea, and the U.K. have suggested a strong association between the use of the drug and serious mental health issues.
As pulmonologists, we notice a trend of aggressive marketing of montelukast in combinations by the pharmaceutical industry. Every major pharmaceutical company markets the drug in combination with an assortment of quick-acting, reliever medications. Our ENT colleagues have experienced a similar trend. This possibly explains the 25% growth in sales over the past year (industry sources).
Time for regulators to step in
Regulators need to step in to ensure that the abuse of this drug stops, and that these health concerns are amplified among both physicians and patients. Not only will this protect citizens from a harmful drug, but it will also ensure that patients are prescribed inexpensive and time-tested options for short-term use, and better ones for long-term use. In a country where post-marketing surveillance tends to be limited, and mental health issues are largely under-reported and stigmatised, we need to raise awareness and prevent an epidemic of neuropsychiatric adverse effects, especially in young children.
Lancelot Pinto is a consultant pulmonologist and an epidemiologist at P.D. Hinduja National Hospital, Mumbai; Sanjitha Muneeswaran is a postgraduate student in the Department of Respiratory Medicine at P.D. Hinduja National Hospital, Mumbai. Views are personal
Published – September 11, 2024 01:38 am IST
