[Anticholinergic scales: Use in psychiatry and update of the anticholinergic impregnation scale]

Anticholinergic properties are well known to prescribers, notably in mental health, as a therapeutic strategy for i.e. extrapyramidal syndrome but also as a source of numerous adverse side effects. Herein, we propose a narrative literature review describing: (i) cholinergic pharmacology and anticholinergic properties; (ii) the importance of anticholinergic therapeutic properties in psychiatry; (iii) the existing anticholinergic drug scales and their usage limitations in Psychiatry and; last (iv) an update to the anticholinergic drug impregnation scale, designed for the French psychiatry practice. The anticholinergic side effects can appear both in the peripheral level (dry mouth, constipation, etc.) and in the central level (especially as cognitive deficits). Many of the so called « anticholinergic » drugs are in fact entirely or mostly antimuscarinic and act essentially as parasympathetic system antagonists. Overall, anticholinergic/antimuscarinic side effects are usually attributed to psychotropic medications: to certain antipsychotics, notably classical neuroleptics such as phenothiazine and also to tricyclic antidepressants. In practice, the impact of anticholinergic toxicity treatments is often highlighted due to their excessively prolonged use in patients on antipsychotics. Interestingly, these antipsychotic treatments are better known for their anticholinergic side effects, especially cognitive ones, with an early onset specially in elder patients and/or in the case of polymedication. In order to evaluate anticholinergic side effects, metrics known as anticholinergic burden scales were created in the last few decades. Nowadays, 13 different scales are documented and accepted by the international academic community, but only three of them are commonly used: the Anticholinergic Drug Scale (ADS), the Anticholinergic Risk Scale (ARS) and the Anticholinergic Burden Scale (ACB). All of them are based on a similar principle, consisting of grading treatments individually, and they are normally scored from 0 - no presence of side effects - to 3 - anticholinergic effects considered to be strong or very strong. Using these scales enables the calculation of the so-called "anticholinergic burden", which corresponds to the cumulative effect of using multiple medications with anticholinergic properties simultaneously. The application of anticholinergic scales to patients with psychiatric disorders has revealed that schizophrenic patients seem to be especially sensitive to anticholinergic cognitive side effects, while elder and depressed patients were more likely to show symptoms of dementia when exposed to higher anticholinergic burden. Unfortunately, these tools appear to have a low parallel reliability, and so they might induce large differences when assessing side effects predictability. In addition, the capacity of these scales to predict central adverse effects is limited due to the fact they poorly or do not differentiate, the ability of treatments to cross the blood-brain barrier. Finally, one last limitation on the validity of these scales is prescription posology is not accounted for side effects considered to be dose dependent. Recently, the MARANTE (Muscarinic Acetylcholine Receptor ANTagonist Exposure) scale has incorporated an anticholinergic burden weighting by posology. Nevertheless, this new model can be criticized, due to the limited number of medications included and due to testing a limited number of potency ranges and dosages for each treatment. Herein, we propose an update to the Anticholinergic Impregnation Scale, developed specifically for the French Psychiatry practice. The scale validation was based on an evaluation of the prescriptions correcting anticholinergic peripheral side effects (constipation, xerostomia and xeropthalmia). This indirect evaluation allowed us to show patients with an anticholinergic impregnation score higher than 5 received significantly more treatments for constipation and xerostomia. This strategy bypasses the bias of a cognitive evaluation in patients with severe mental health disorders. Moreover, the relevance of a tool developed specifically for French psychiatry is justified by the fact that some highly prescribed treatments for mental illness in France (cyamemazine and tropatemine) are strong anticholinergics, and also by the fact they are rarely included in the existing anticholinergic scales. This update of the original scale, published in 2017, includes information whether prescribed drugs cross the blood-brain barrier and thus makes possible a more accurate assessment when evaluating anticholinergic central side effects. Finally, the anticholinergic impregnation scale will soon be integrated into a prescription help software, which is currently being developed to take into consideration dose dependent adverse effects.