Shortages of medicines in a psychiatric hospital in Cyprus

What is already known on this subject

Cyprus has a small and unattractive pharmaceutical market

What this study adds

This is the first study to explore the perceptions of health professionals regarding shortages

Mental health comprises an integral part of a person’s overall health [1]. Mental illness refers to disorders that affect the ability to think, feel and/or behave. Moreover, the spectrum of mental illness includes distress and problems functioning in the context of a social network. Mental illnesses affect almost one out of four individuals; their burden can be substantial unless the proper treatment is administered to the patient [2]. Apart from the social perspective, percolating mental health needs can undermine health budgets, if they are not addressed on time. Our society is an intellectual capital–based one; therefore, mental health, besides being a social determinant, permeates the economic context, constituting an economic factor as well.

Current literature is rather bereft of data on drug-related deficiencies pertaining to mental health and, in particular, medicines shortages. A study by Sunkel & Viljoen [3], who assessed the effects of drug shortages on patients with various mental disorders in South Africa, reported that 30% of patients experienced a complete relapse and an additional 30% needed to be treated with minor symptoms. 17% said they had difficulty sleeping while 23% experienced increased stress levels. Overall, a marked deterioration in their quality of life due to drug shortages occurred. Omorodion et al. (2017) showed that 15% of total medicines shortages referred to neurology products and the median shortage period was 7.4 months [4]. Al Ruthia et al. highlighted, as one of the shortages’ root causes, their low profit margin [5].

A remedy for shortages is the prescribing of alternative treatment modalities, primarily generic substitution or generic-to-generic substitution. Nevertheless, the use of generics in psychiatry has been embroiled in controversy and conflicting data have been published. The use of generic clozapine led to re-emergence of psychotic symptoms and worsening of Clinical Global Impression (CGI) and Brief Psychiatric Rating Scale (BPRS) [6–7].

The generic substitution of lamotrigine was associated with increased seizures and side effects, while depressive symptoms and vague suicidal ideations were reported following a switch from original valproic acid to its generic formulation. In many cases, this occurs unbeknownst to the prescribing physician. Another source of worry is the elusive practice of generic-generic substitution, for which scarce data are available. An array of adverse events have occurred:

anticonvulsant hypersensitivity syndrome after generic substitution

Following this direction, the scope of this study is to highlight the attitudes and perceptions of healthcare professionals regarding the shortages of neuroleptic products in a specialised mental hospital in Cyprus. Cyprus is a small EU country. Mental care is provided to all citizens for free, regardless of beneficiary status, by the public health care sector [8]. Previous authors reported that Cyprus’s pharmaceutical market is an unattractive and small one, and as such, prone to shortages [9]. Its location also may exacerbate supply issues. This study aims to elucidate the framework of medicines shortages, assess the breadth and scope of the problem, and enable the formulation of targeted strategies to efficiently address this multifaceted topic. The adequate provision of neuroleptic products is vital nowadays since the pandemic of Covid-19 and the consequent lockdown, take their toll on the public, alongside existing mental health issues.

This is a cross-sectional study that utilised a structured questionnaire. The study was conducted in the Athalassa Psychiatric Hospital, which is the single mental health tertiary institution in Cyprus, and it operates on the basis of the asylum model. Patients are admitted compulsorily or optionally in accordance with the provisions of the Law on Psychiatric Care (Amending) Law 2003, 2007. Hospitalisation can be short or chronic, depending on the needs of each patient. The study was conducted from November 2019 to January 2020.

The sample of the present study consisted of mental health professionals (psychiatrists, trainees, psychologists, neurologists) working at the Athalassa Psychiatric Hospital (n=100). Participants were extensively informed to ensure their anonymity and the confidentiality of their responses, while those who did not wish to participate had the right not to.

We used a structured questionnaire developed by the European Association of Hospital Pharmacists (EAHP) and Al Ruthia et al. (2017) [10–11]. The questionnaire was translated forward and backward in order to ensure its credibility. The questionnaire consists of two parts. The first part concerns the collection of demographic characteristics of the sample under study, such as gender, age, level of education, type of employment, occupation and years of service. The second part concerns the recording of the attitude and opinions of mental health professionals about drug shortages. In particular, the frequency and type of deficiencies were recorded, as were strategies for minimising the impact of drug shortages on patients, and proposed solutions to the problem.

Participants were initially informed that both their confidentiality and anonymity would be fully guaranteed. The information and delivery of the questionnaire was done by personal meeting. A reasonable amount of time was given to complete the questionnaire. In case the participants wanted to send the questionnaires by post, they were given stamped envelopes ready for the mail, as provided by the current legislation, in order to safeguard the protection of their personal data. The collected data were processed through statistical analysis using SPSS 25 (Statistical Package for the Social Science) software. The Cronbach’s alpha coefficient was used to assess the reliability of the questionnaire. Descriptive and inductive analysis was then performed. To compare the different groups that emerged, t-test, chi-square test, or Fisher’s exact test were applied, as appropriate. The statistical significance level was set to 0.05.

The identity of the participants remained confidential throughout the collection, data analysis, and manuscript draft. A protocol was submitted for approval to the National Bioethics Committee, the Office of the Commissioner for Personal Data Protection and the Commission for the Promotion of Research of the Ministry of Health.

50 mental care professionals completed the questionnaire. 44.0% of the sample were men and 56.0% were women. 2.0% were higher institute graduates and 98.0% were university graduates. 52.0% said they did not have additional academic qualifications, while 48.0% said they had a master’s degree. All participants were civil servants. The majority of the sample (84%) were psychiatric nurses. (TABLE 1)

The age of the participants ranked from 28 to 56 years, with an average value of 36.8 (sd 7.60). The work experience fluctuated from 2 to 34 years, with an average value of 10.96 (sd 8.73).

96% of the responders brought to the forepoint that shortages do impair the provided health care quality. (figure 1)

Figure 1

46% of the responders corroborated that shortages occur on a monthly basis, and 36% encounter shortages every week. Daily shortages were claimed by 14%. On the contrary, only 4% contended that shortages take place occasionally.

Most of the responders evinced that the average duration of shortages lasted between one and three months. Only 8% claimed duration which spanned 3 to 6 months, while no shortages in excess of 6 months in duration were affirmed (figure 2).

Figure 2

Branded products were more frequently cited as under shortage, rather than generics (62 % vs. 38%) (figure 3).

Figure 3

50% of the responders postulated that an equivalent product can be administered without impairing therapeutic outcome in some cases. “Most of the time” 34% of the sample claimed that they can achieve it “Most of the time”. On the contrary, 12% and 4% of the sample rarely or never achieve substitution without deterioration in the patient’s condition (figure 4).

Figure 4

According to 44% of the responders, five hours per week are dedicated to medicines shortages 38% of the sample mentioned that they spent between 6–10 hours per week. More than 15 hours were allocated by 2%, while 16 reported less than one hour per week dealing with shortages (figure 5). Issues with branded products’ marketing authorisation holders (MAH) were raised by 46% of the sample, while 42% dealt with generic products’ MaH. Of intertest is that 36% of the responders could not distinguish between generic and branded products’ MaH. None of the responders indicated issues with MaH of innovative products, which are defined as products which produce significant clinical benefit.

Figure 5

The compromised therapeutic effect emerged as the most significant repercussion of shortages, as attested by 96% of the responders underlining it. The second most common side effect, as suggested by 72% of the responders, was re-admission, while delay in provision of health care was cited by 68% of the sample. Increased incidences of adverse events ranked fourth in the judgment of 26%. Medical errors were reported by 2%. (table 3)

Patient awareness about potential alternative treatment is the most commonly proposed policy (74%). Raising awareness of patients regarding shortages was ranked second. Engagement of management and all personnel in order to collectively tackle shortages was considered by 58% of the responders. Moreover, a search for other MaH or other supply chain pathways was proposed by 26%. In addition, a treatment switch was advocated by 20%, without providing info to the patients. Finally, budget adjustments were posited by 12%, in order to deal with additional incurred costs, while 4% would require additional human resources.

Investigation of root causes was the suggestion of 78% of the sample, while a corresponding 76% proposed elaboration of a common national database, which will be accessible by all health care institutions; 56% put forward an annual report by MOH and 22% assumed legal liability of MaH. (Table 4)

We observed a significant correlation between additional academic qualifications and the perception of encountering more adverse events following shortage-induced therapeutic substitutions in patients.

There is also a statistically significant difference between men and women pertinent to adverse events occurrence due to shortages, as more men (45.45% vs. 10.7%) endorsed this statement X²₁=7,728, p= ,005< ,05). This is probably confounded by academic qualifications since more men (63,6% vs. 35.7%) possess such degrees.

Drug shortages comprise a complicated and multipronged problem. While it has been thoroughly studied in certain countries, EU countries lag [12–13] and Cyprus illustrates this evidence gap.

To our knowledge this is the first study to explore the impact of medicines shortages in a specialised tertiary mental health hospital in Cyprus, while it adds to a small pool of studies on an EU level.

Our study is the first one to document attitudes and perceptions of medicine shortages by mental health professionals. It highlighted that drug shortages do occur in Cyprus and the ramifications of this are both important and diverse. Among the array of findings, time spent and deterioration of health conditions stand out.

Deterioration of health condition, along with increased incidence of adverse events, merit more research. It is widely accepted that even in cases where an alternative or a generic product is available, substitution may disrupt the continuity of treatment [2–3]. This position aligns with previous authors who proved that several mental health conditions are sensitive to products’ formulation and any substitutions should be carefully performed. The re-admission to hospital comprises a principal finding as well. As the average duration of hospital stay can exceed 2 months, such evolution exerts a detrimental effect on patients’ general health and welfare and augments rehabilitation failures.

Our data illustrate the multilevel effect of shortages across the entire supply chain as well. This calls for strict monitoring of shortages and implementation of pre-emptive measures which should embrace all stakeholders. Some policies tackling shortages were delineated in the survey, such as assuming legal liability of MaH, making a real-time database available to all health care professionals, obligatory stockpiling and formulation of a national strategic plan. Stockpiling has been put forward by many countries [14]; however, we cannot rule out a backfire stemming out of it [15]. Moreover, information about impending shortages should be sought, which will allow early mitigation. Additionally, identification of alternative sources should proceed. It is also crucial to track down all shortages, and if possible, to formulate guidelines to regulate substitution, based on best available evidence.

Time spent is an important aspect. The functional capacity of the Cyprus public health care sector has been stretched due to austerity measures, which included a recruitment freeze [16]. In this perspective, depleted resources have also to cope with shortages. Medicine shortages found a foothold in some seemingly unrelated developments such as Brexit. It is unknown whether Cyprus would have fared better if Brexit hadn’t occurred.

Moreover, the State should consider additional burden, in terms of costs and human resources and accordingly revise budget and staffing.

Our findings highlight the need for pre-emptive measures. Identification of alternative suppliers should be pursued, and a vigilant system of addressing to shortages should be enforced, in order to track down shortages in real time. MaH should also be legally bonded. This can be achieved either with the obligation to cover any costs incurred pertinent to emergency procurement of products from other sources, or mandatory stock, keeping sufficient to satisfy local needs for a specific timeframe, which usually is set at 3–6 months.

The investigation of the root causes of shortages was also raised. A small and unattractive market such as Cyprus displays additional causes, compared to EU continental counties. These include minimum order quantities, transportation issues, Brexit, serialisation, and in general economies of scale parameters. Once these are fully apprehended, then the government should proceed with the elaboration of a strategic plan that will address all emerging causes. Each one may require an individualised response, since an array of heterogeneous causes were already specified in our study. We hope that this study constitutes a building block for the formulation of a thorough action plan on shortages. Cyprus is currently navigating through an unprecedented reform, the introduction of its National Health System. It is possible that shortages may experience oscillation, since reimbursement is shifting from tendering to a more competitive, market-oriented open formulary. It will bring about several benefits; however, it may remove the safety net of the tender system, in terms of better forecasting and pre-ordering.