1 Introduction

Anticholinergic drugs are prescribed for a wide range of conditions such as overactive bladder, chronic obstructive pulmonary disease, nausea and vomiting, depression and psychosis [1]. Anticholinergics are drugs that block the action of acetylcholine and can cause a variety of peripheral side effects, such as dry mouth caused by a reduction in the flow of saliva, and central side effects, such as cognitive impairment or worsening of tardive dyskinesia [2]. Harmful cumulative effects from anticholinergic drugs might have already impacted people with one clinical condition [3]. Furthermore, anticholinergic adverse effects increase with increasing the dose, and multiple low-level anticholinergic drugs can add up to the same anticholinergic burden (or more) than a single high-level anticholinergic drug [4, 5]. This potential for harm increases with frailty and age [6], and the anticholinergic drug use is closely related to serious negative outcomes for people using these drugs [7]. As far as we know, various anticholinergic burdens or risk scales have been devised, but no single standard anticholinergic burden scale stands out [8, 9, 10, 11, 12, 13, 14, 15].

Antipsychotic drugs represent the mainstay for the pharmacologic treatment of people suffering from schizophrenia. All antipsychotics are dopamine D2 receptor antagonists and induce blockage of dopaminergic neurotransmission in subcortical areas either acutely or during chronic treatment and they can also block other receptors such as histamine-1, muscarinic-1 and alpha-1 [16, 17]. The extrapyramidal side effect of treatment is more pronounced with the first-generation antipsychotics (FGA), such as haloperidol or chlorpromazine, than with the second-generation antipsychotics (SGA), such as aripiprazole or olanzapine [16, 17]. However, the blockage of D2 receptors is also a way to treat positive symptoms of schizophrenia.

Schizophrenia is a severe mental disorder characterized by delusions, hallucinations, and other cognitive difficulties [18]. Furthermore, people with schizophrenia (PWS) often neglect their self-care and suffer often from conditions such as dry mouth. Dry mouth can be attributed to the medications used to manage schizophrenia and to somatic disorders like type 2 diabetes [19, 20]. Smoking can also be an attributing factor for dry mouth. Furthermore, psychiatric patients are known to smoke more often than general population [21].

People in the general population who suffer from dry mouth clearly express difficulty speaking, eating and swallowing. Some patients complain of halitosis, chronic burning sensation, altered taste and intolerance to spicy food [22]. In general terms, the oral health-related quality of life (OHrQoL) of patients with dry mouth could be affected [23, 24]. However, PWS often fail to recognize their health needs and delay seeking advice or treatment [25]. We frequently observe wider variations between a patient’s perception and an objective evaluation of the patient’s dental status among PWS [26]. In this situation, it is difficult for caregivers to fully manage oral health needs.

In a previous study, we found that the Global Oral Health Assessment Index (GOHAI) exhibited excellent psychometric characteristics among PWS and could be used to assess the OHrQoL of these patients [27].

In this case, the role of dry mouth on the OHrQoL and how PWS perceive the side effects of these drugs need to be clarified before preventive recommendations and support for managing the oral side effects of psychotropics could be initiated.

The aim of this study was to explore, in a sample population of PWS in France, the role of anticholinergic burden drugs on the perception of the OHrQoL of these patients.

2 Material and methods

3 Results

4 Discussion

In our study, we highlighted that anticholinergic drugs take part in the OHrQOl of PWS like the dental condition, age and the xerostomia perception. But we can’t precise the impact of anticholinergic drugs in OHrQoL of PWS. The impact of anticholinergic drugs on oral health-related quality of life is a well-known matter, particularly among older people, but the impact of these drugs on the OHrQoL and dental diseases is often overlooked among people who suffer from severe mental illness, such as schizophrenia. We observed that the PWS sex ratio of our sample was in accord with the incidence of schizophrenia, which is significantly higher in males than in females [36]. The DMFT score was higher than in countries with the same income levels as France. For example, in Spain with persons suffering from schizophrenia, DMFT was 13.5±7.2 with a mean age of 40±11.2 vs. 16.5±8.7 [37] and was higher than the general population in France [38]. Many drugs prescribed for PWS show anticholinergic activity, and relationships seem to be emerging between a poor OHrQoL, the DMFT score, the XI score and anticholinergic drugs, but it was difficult to distinguish them from each other.

The OHrQol that includes dry mouth as evaluated by the XI scale is a complex and subjective multidimensional concept. The OHrQoL concept integrates several dimensions, such as functional limitation, physical pain, psychological discomfort, and physical, psychological and social disability or handicap related to the presence of oral disorders. But, side effects of antipsychotics are not directly evaluated by the GOHAI [27]. In other words, oral health is defined differently by each person according to his/her understanding of what a healthy mouth is, the type of symptoms previously experienced, cultural values, past experience with the health care system (regular visit at the dentist or not), general health, psychosocial wellbeing, impact of severe mental illness, age or gender [39]. Furthermore, schizophrenia leads to disturbances in the progression of thought, errors in contextual analysis and errors of logic. Often PWS do not recognize their health needs and delay seeking advice or treatment [40]. The neglect of self-care by PWS appears to be influenced predominantly by negative symptoms of schizophrenia, such as lack of initiation, a lack of concern for personal health, social withdrawal and a lack of motivation [41]. Studying the social construction of the illness, the characteristics related to quality of life and the description of the determinants of health inequalities in individuals suffering from this disease is important [42]. Nevertheless, qualitative research on this topic is scarce. Specific tools to assess the OHrQoL for PWS, including the side effects of antipsychotics, should be useful for a better understanding and management the oral side effects of medications used to treat mental illness [43].

Evidence is accumulating in relation to a range of adverse outcomes associated with using multiple drugs with anticholinergic properties for PWS in term of their OHrQol [2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 19, 20, 21, 22, 23]. To the best of our knowledge, no other studies have been conducted using a method to quantify the cumulative effect of taking multiple drugs with anticholinergic properties that addressed the perception of dry mouth or side effects of these drugs in the OHrQol of PWS.

In the literature, a wide range of anticholinergic burden scales have been devised for the older population to aid in medication reviews so that certain drugs can either be stopped, or the medication regimen altered [4447]. In this study, we chose the AIS because this is a scale that considers drugs used in France and is based on an assessment of the drugs used together with the peripheral anticholinergic side effects. However, there is no single standard anticholinergic burden scale to aid in conducting medication reviews. Furthermore, most scales are constructed using expert opinion panels and do not take into account the perception of the OHrQoL of concerned people. However, the limitations include also differences in exposure to medicines, dosing, route of administration and false positives [44, 45, 46, 47].

In mental health, prescribers can use both FGA and SGA compounds at doses that result in levels between the domains on the dose–response curves for beneficial and anticholinergic effects. This dose-dependent therapeutic domain differs not only between drugs but also between patients. The effect of a certain dose of a certain drug on an individual is difficult to predict, as it depends on several and very different parameters, such as the magnitude of the compensatory response, the level of tolerance, the subject’s state of health and the history of the drug administration [48].

5 Limitations

First, properties of anticholinergic drugs may cause peripheral or central side effects that hard to distinguish from illness-related symptoms [3]. The GOHAI identify more oral functional than psychosocial impact and these measures are mainly assessing the consequences of dental conditions rather than the PWS’s perception and understanding of the chronicity of their underlying oral disease [27]. In other words, it is difficult to determine whether it is the condition (schizophrenia) or the medication that affects the oral health-related quality of life.

Second, the AIS scale was specifically designed to evaluate the anticholinergic burden in a French setting. Typically, French drugs, such as cyamemazine are evaluated with AIS scale [35]. But for example, this molecule is not marketed in the United States. There is a lot of scales to measure anticholinergic burden but not all the lists include the same drugs, and the points given for certain drugs differ among them [8, 9, 10, 11, 12, 13, 14, 15]. Furthermore, when-needed drugs are problematic when added into these scales due to their possible irregular usage and effects. Thus, they might cause falsely high anticholinergic burden, if their use is not regular. Finally, they are no agreement between scales to measure the anticholinergic burden. It is likely that our results should be different if we have used another scale to measure the anticholinergic burden.

In this study, the hypersalivation paradoxical side effect of clozapine [50] is not specifically highlighted by the AIS scale and no item of the GOHAI investigate discomfort induced by hypersalivation and it’s impact in OHrQoL.

Finally, in view of our small sample, we could not discriminate any different results between PWS suffer from positive or negative symptoms.

6 Conclusion

This pilot study highlighted the potential role of anticholinergic drugs on the OHrQoL of PWS. However, in order to help clinicians take into account the side effect profiles when choosing an agent, a study with a validated specific OHrQoL scale and a standard anticholinergic burden scale should be conducted to clarify the impact of anticholinergic drugs on the OHrQoL for PWS.