Deprescribing is the process of reducing or discontinuing medicines that are unnecessary or deemed to be harmful [1][2]. The goal of deprescribing is to reduce medication burden and harm, while maintaining or improving qualify of life [3]. Many guidelines describe the indications for treatment initiating, but only some of them give recommendation to stop therapy. The aim of the study was to present up-to-date information on deprescribing, its fields of application, and the experience of other countries.

Deprescribing is a proposed antidote to the harms of polypharmacy and is associated with numerous health benefits including improvement in cognition, a reduction in falls, a decrease in fractures, better medication adherence and improvement in qualify of life [1].

Deprescribing is an inherent component of good prescribing practice, but is rarely implemented in routine clinical care, and physician practice or views on deprescribing vary greatly [4][5][6]. It is important to recognize that deprescribing involves more than just identifying inappropriate medicine use [7]. It involves reviewing of all medical appointments, identifying un-necessary and potentially harmful drugs, deciding which of them can be stopped and setting the order of cancellation or change of dose, form of drug, with adequate monitoring for this. A deprescribing medication management plan is a final step of this process and should include discussion of changes with the patient and getting patient's consent.

Accordingly, the concept of deprescribing first arose in geriatric medicine. Recently, it has been mentioned that deprescribing is also associated with other medical specialties, including cardiology and psychiatry. The increase in potentially inadequate polypharmacy in child psychiatry (observed in many countries) without a clear improvement in functioning is just one reason to focus and stimulate the practice of a thoughtful withdrawal process [8][9].

The term deprescribing was used in the English language health literature in 2003 in an Australian hospital pharmacy journal in an article titled, «De-prescribing: achieving better health outcomes for older people through reducing medications» [10].

The literature from January 1, 2003 to March 30, 2020, was searched to identify published systematic reviews and meta­analyses that were relevant to the project. Search terms included Deprescribing, polypharmacy, suboptimal drug therapy, Deprescribing in psychiatry. Terms were searched alone and in combination. Search limits included human subjects, English language. Data sources for the initial search included PubMed, and references lists of selected articles that the panel.

The initial search identified 50 citations, of which 30 were selected for preliminary review. 20 were excluded for not meeting the study purpose or not containing primary data. An additional research was conducted with the supplementary terms such as antipsychotics and, geriatrics, and elderly prescribing. Previous searches were used to develop additional terms to be included in subsequent searches, such as a list of authors whose work was relevant to the goals of the project. When evidence was sparse on older medications, searches were conducted on drug class and individual medication names and included older search dates for these drugs. Additional articles were found in a manual search of the identified articles reference lists and the panelist's files, book chapter, and recent articles review.

Deprescribing is necessary in connection with the develop­ing polypharmacy of the medical community, which is associ­ated with the multimorbidity of patients, affecting more than 50% of people in primary care [11]. As a result, patients are often prescribed several drugs. In addition, old age and weakness con­tribute to a decrease in life expectancy [12]. Therefore, physicians often must balance a variety of factors, including the disease (s) the patient may have, the benefit-risk profile of the prescribed drugs, the personal views of the patients, and the opinions of oth­er prescribers. Patients who visit four or more doctors experience problems, like a conflicting medical advice, because of which the number of drugs taken does not decrease [13].

Due to the stigma associated with mental illness, which is often heightened by news media coverage, and an initial treatment focus on remission, a patient's first impression of the psychiatrist may be that of a «pill pusher». Alternatively, a patient may desire to please the prescriber through continued adherence, which might also generate conflict regarding treat­ment [14]. Medicaid claims data have shown that psychotropic polypharmacy has risen consistently over the past two decades in various states [15][16]. Although certain combinations of psychotropics have been shown to be beneficial in «treatment resistant» psychiatric disorders, the stability of the treatment- resistant label over time is unknown. In fact, Stahl and Grady found in their review that most practitioners do not try to dis­continue one of the drugs after a combination proves beneficial, even if cancellation is necessary [17].

Biological, psychological, and social factors must align to produce a favorable risk-benefit ratio such that a medication regimen becomes established for a patient. Over time, this risk- benefit ratio can change, providing an indication for deprescrib­ing: certain adverse effects may develop only after longer-term use (for example, tardive dyskinesia with antipsychotics and renal impairment with lithium); normal aging alters both the pharmacodynamics and the kinetics of medications, increasing vulnerability to side effects; pregnancy; development of general medical comorbidities; new medication interactions; substance abuse raise. Psychological factors, such as patients' choice, their understanding of illness and medication, and their coping strat­egies, may evolve over time, shifting their individual risk-bene­fit ratio. Social factors, such as geographical relocation, changes in financial and insurance status, and changes in religion, may prompt a reappraisal. The growth of the recovery movement and patient-centered care in psychiatry, including in pharma­cological management, further necessitates the development of deprescribing skills [14].

The imperfection of psychiatric classifications leads to the fact that in psychiatry (as in geriatrics) often several diagnoses can coexist in one patient. The practice of prescribing treatment «syndromically» is quite common, although international rec­ommendations advise sticking to monotherapy. There are not so many combinations effectiveness of which would be con­firmed by high-level studies. In the same way, the point of rec­ommendations on the use of the lowest possible doses is not always followed: often the patient continues the therapy that was needed during the exacerbation, in spite of the fact that smaller doses are sufficient for maintenance therapy. Firstly, it is obvious, deprescribing is not suitable for all patients. This op­portunity should be considered if: the patient is determined to participate in resolving issues about his treatment; the majority of the disorder symptom is currently absent; for this patient, unlikely behavior associated with a danger to themselves and others (auto- and hetero-aggressiveness), at the moment and for a long time there were no facts of drugs abuse; the social environment can support the patient, track changes in his con­dition; it is possible to turn to psychological therapy [18].

Secondly, to cancel drugs is the same science as to prescribe. There are only few studies that would specifically explore the cancellation process. A review of deprescribing processes in medical practice identified five key components: preparing a comprehensive medication history, identifying potentially inappropriate medications, determining whether a potentially inappropriate medication can be ceased, planning the withdrawal regimen (e.g. tapering where necessary), and provision of monitoring, support and documentation [19]. For use in psychiatry, this five-step process has been expanded to include appropriate timing, inclusion of the patient's family, friends and mental health team in the deprescribing process, and development of a plan for relapse identification, prevention and management (Table 1) [9][14][18].

Table 1

Steps of deprescribing in psychiatry

Step Purpose Implementation Assess the timing of the intervention To avoid initiating deprescribing at a time when the individual may be particularly vulnerable to a relapse, e.g. a period of psychosocial instability and/or heavy substance use, recent hospital admission Assess housing, employment, financial status, social relationships, impending changes in these, and substance use Review psychiatric and medication history To minimise chances of relapse or clinical risk during deprescribing Review psychiatric records, obtain history from the patient and available collateral sources Assess any previous trials of deprescribing/ attempts at reduction or discontinuation Contact other physicians involved in the patient's care and compile a complete medication list Document the dose, route, duration, indication, perceived benefit and side-effects for each medication Initiate the discussion about deprescribing To assess the patient's thoughts and feelings about deprescribing If appropriate (e.g. in antipsychotic polypharmacy) a hierarchy of medications with highest to lowest risk/ benefit ratio could be generated Assess the patient's learning style and check for understanding Explore preferences and values Explore current knowledge Explain risks and benefits Examine choices Involve the team and so­cial supports If the patient agrees, to acknowledge and support them in their decision, help them maintain wellness, monitor for early signs of relapse and notify the care team if signs are noticed. With the patient's consent, all providers involved in care should be aware of the initiation of deprescribing, including visiting nurse services, therapists, case managers and primary care Consider a meeting with family, friends and other significant individuals Establish reliable means of contact, such as telephone or secure email Invite participation and contact from friends and family as desired by the patient Develop and initiate psy­chosocial interventions To help define, detect, and address any increase in symptoms To add supports to help the patient cope with anxiety, threats and challenges related to deprescribing Develop a relapse prevention plan such as WRAP Consider additional support through psychotherapy, potentially targeting specific symptoms Consider self-help and mutual support groups Develop and initiate the antipsychotic taper To reduce the dose in a controlled and conservative way, to minimize negative impact Decide which antipsychotic to taper Decide the rate of taper Adjust concomitant medications such as anticholinergics accordingly Monitor and adjust taper according to response To prevent, as much as possible, relapse or life disruptions due to the taper Monitor for early signs of relapse Monitor functioning Monitor metabolic and neurological side-effects Slow the rate of taper if needed Reverse the taper if needed

Deprescribing hinges on effective relapse prevention. A biopsychosocial perspective on relapse prevention, for example, in schizophrenia highlights the significance of psychosocial stressors such as loss of employment or housing, bereavement or disruption of relationships. As well stressors of a biological nature such as substance misuse and, perhaps, precipitous, or ill- timed discontinuation of antipsychotics. They root deprescribing in psychiatry in recovery-oriented practices (Table 2), including shared decision-making, a person-centered approach and the nurturing of empowerment and hope [9][20][21][22][23].

Table 2

Recovery-oriented practices in mental healthcare and their application to deprescribing

Practice Description Application to deprescribing Shared decision-making A process of collaboration to arrive at a mutually acceptable treatment plan. It involves two experts: one who knows the scientific literature and has clinical experience, and one who knows their own preferences and subjective experiences Collaboration and solicitation of the patient's preferences and values at every step are essential components of deprescribing Person-centered care Designed to promote service engagement by increasing patient self-deter­mination during treatment. It is defined as a highly individual comprehensive approach to assessment and services and is more focused on developing customized plans for achieving life goals rather than on symptom relief Deprescribing aims to increase patient en­gagement and participation in treatment. Person-centered care offers a framework in which individualized antipsychotic taper­ing plans as well as psychosocial supports are nested Hope Hope is the belief that recovery is possible. It involves the recognition and acceptance of the problem and a commitment to change With its emphasis on individual goals and preferences, deprescribing is based on hope and, by its nature, instils hope Empowerment Empowerment may be viewed as a corrective for the helplessness and lack of control that an individual may face in the mental health system. It includes autonomy, courage and re­sponsibility Deprescribing empowers the individual by encouraging them to take charge of their treatment and providing the space for them to take risks, should they choose to do so

Consider the clinical situations in psychiatry in which deprescription can be used. Maintenance Phase of Treatment of Chronic Psychotic Disorders or Bipolar Disorder - the dose of antipsychotic drugs needed to prevent relapse (maintenance therapy) can be reduced. Medications prescribed for certain side effects. Anticholinergics used to treat extrapyramidal symptoms may not be needed after a certain period due to the development of tolerance to the parkinsonian effects of antipsychotic drugs. Medications Prescribed for Off-Label Uses. Highly sedating antipsychotic medications such as quetiapine are often prescribed for management of insomnia in patients with psychiatric disorders. Similarly, antipsychotic medications are often prescribed for aggression and other behavioral problems not necessarily caused by psychosis or for the control of transient psychotic symptoms in post-traumatic stress disorder. These off-label uses put the patient at risk for serious side effects when other less risky medications or behavioral interventions such as cognitive behavioral therapy for insomnia may be equally or more effective [18][24].

Another example is Alzheimer's disease (AD) incidence. AD represents a significant challenge for the aging health of our over the world. Because of medical advances, the life expectancy of our residents is increasing. By the year 2030, it is estimated that more than 20% of the United States residents will be older than 65 yr [25]. Advancing age is related to an increased risk of dementia. AD is the most common cause of dementia, accounting for an estimated 60% to 80% of cases [26]. Review Renn examined published practice recommendations for discontinuation of cholinesterase inhibitors (ChEI) in AD. ChEI are widely used and typically employed as first-line pharmacotherapy for symptomatic treatment of major neurocognitive disorder caused by AD; however, treatment often continues through advanced disease stages [27]. A recent Cochrane Review found that ChEI treatment effects are small and of uncertain clinical importance [28]. The trials reviewed did not elucidate the relationship between duration of treatment and response. Because cognitive and behavioral impairments change during the progressive disease course, the effects of medications may be unpredictable, especially over long durations of treatment. Persons with advanced dementia may receive overly aggressive care that does not align with person-centered care goals, and polypharmacy from medications that are minimally beneficial may place patients at unnecessary risk [29][30][31]. However, ChEI treatment may contribute to meaningful improvements in noncognitive domains, such as reduction in neuropsychiatric symptoms and behavioral disturbance [32].

Twenty years ago antipsychotic polypharmacy (APP) was criticized as being more expensive, having unproven efficacy, and causing more side effects. However, in recent years, anti­psychotic polypharmacy has become acceptable in the views of clinical practitioners and academic researchers. In an early 1970s survey of 4 states of the United States, the results re­vealed that New York psychiatrists most frequently prescribed a combination of 2 drugs, and some even prescribed 6 drugs at a time. Currently, no consensus regarding the definition of APP is available; however, most of the research papers have referred to it as the simultaneous use of 2 or more types of antipsychotic medication [33][34].

Interesting that Currently, APP has become more accept­able than in previous decades, and more evidence-based studies have proved its benefit. As there is no consensus on the ideal rate of APP and the combined use of other psychotropic drugs, the conception of a Health Care Quality Indicator Project can be utilized [35][36]. In this project, a set of indicators is devel­oped by comparing data from different resources, and then the exact positions of these indicators can be learned by clinicians and health administrators to obtain consistent results. Thus, according to the 2 compatible results from Asia and Europe and previous reports of APP, they suggest the following ap­proximated ideal rates of maintenance treatments in patients with schizophrenia: APP, 30%; combined mood stabilizer, 15%; combined antidepressant, 10%; combined anxiolytics, 30%; and combined hypnotic, 10%. A large discrepancy in the use of an­ticholinergics exists between Asia and Europe (45,1% vs 16%). This difference might be because Asian patients have been more susceptible to extrapyramidal side effects [37][38][39][40][41]. Thus, the doctor should constantly review the drugs that are prescribed to the patient, especially at the stage of maintenance therapy.

Other scientists-researchers from the Bruyere Research Institute and the Ontario Pharmacy Research Collaboration developed evidence-based guidelines for deprescribing. Each guideline is summarized in an easy-to-use algorithm and information brochure [42]. Algorithm of this guideline is shown in Figure 1. These recommendations apply to adult patients who have been prescribed antipsychotics for insomnia or behavioral and psychological symptoms in dementia (BPSD), provided the symptoms of the latter are controlled or the patient is unresponsive to a reasonable trial of therapy.