Comments on: “The Utility of Betahistine Dihydrochloride,a Structural Analog of Histamine,in Clozapine-Associated Daytime Sedation: A Case Series”

Dear Editor,

In psychiatry clinics, we frequently encounter patients of hypersomnia: drug-related or even otherwise. Many of these patients do not respond well to the available management strategies, leading to the early ceiling of dosing and compromised efficacy. Moreover, available pharmacological strategies for primary hypersomnia syndromes remain insufficient, especially in India. Agarwal et al., ¹ on the use of betahistine in clozapine-related sedation, provided a new perspective in this regard, and therefore, we read it with great interest.

We certainly agree with the authors on the utility of betahistine in mitigating hypersomnia associated with clozapine while not compromising on its exceptional antipsychotic effects, especially in treatment-resistant cases. We also suggest betahistine’s utility in improving the metabolic parameters in patients treated with clozapine due to its complementary weight loss effect. Clozapine, by blocking the H1 receptor, leads to an increase in appetite, which often results in substantial weight gain among patients. ² Betahistine, through its agonistic action at H1 receptors, enhances histaminergic neurotransmission, which can lead to appetite suppression. ³ Therefore, betahistine might have a dual role in clozapine-treated patients. Perhaps its utility may expand to patients who are treated on other psychotropics, such as olanzapine, quetiapine, and mirtazapine, which cause sedation and weight gain due to their action on histaminergic receptors.

A more important insight we gain from this case series is the potential utility of betahistine in the management of hypersomnia syndromes, especially idiopathic hypersomnia, and narcolepsy. In India, the first-line drugs used for these disorders are stimulants: modafinil and armodafinil. Perhaps, in most cases, they are not just first-line drugs but also only available drugs. Sodium oxybates (low-sodium oxybate (LXB) and high sodium oxybate (SXB))^4,5 are scarcely available, and even if available, they pose a significant financial challenge. The newly approved drugs, pitolisant and solriamfetol,^4,5 are yet to reach the Indian market. Most other agents are still only in the pipeline.^4,5 Moreover, although low, there is a risk of misuse with stimulants. ⁶ In this background, betahistine might be an excellent option given its availability, low cost, and favorable side-effect profile.

There is a need for well-controlled studies to leverage the potential that betahistine can provide and to use it for drug-related hypersomnia as well as primary hypersomnia syndromes, both in terms of long-term efficacy and safety.