Physician Perspectives on Codeine Accessibility, Patterns of Use, Misuse, and Dependence in Saudi Arabia

The misuse and abuse of codeine-containing medications both prescribed and over the counter continues to represent a global public health and policy challenge (Bergin et al., 2015; Dada et al., 2015; Myers et al., 2003; Parry et al., 2015; Wells et al., 2018). Despite it being a weak opiate and used to treat mild to moderate pain in adults, misuse is broadly defined as “the use of a medicine, with or without a doctor’s prescription, clearly outside of accepted medical practice or guidelines, for recreational purposes or in the framework of self-medication, in greater dosages or for longer periods than were prescribed, in which the risks and problems associated with use outweigh the benefits” (Casati et al., 2012, p. 230). The maximum recommended dosage of codeine is 240 mg daily (Moore et al., 2001), often in combination with paracetamol, aspirin, or ibuprofen in codeine combination preparations (Foley et al., 2015). A range of related health harms are reported as consequence of prolonged use, high-dose use, and misuse of codeine combination productions, which include acute hemorrhagic necrotizing pancreatitis, hypokalemia, nephrotoxicity, gastrointestinal hemorrhage, dependence, and depression (Barreto et al., 2011; Chetty et al., 2003; Dutch, 2008; Ng et al., 2011; Nielsen et al., 2012; Romach et al., 1999). Substance use disorders are classified as a psychiatric disorder under the DSM-V diagnostic criteria (American Psychiatric Association 2013), with several studies exploring the unique codeine pathways toward iatrogenic dependence, generally commencing with a legitimate medical reason (Parry et al., 2017; Van Hout et al., 2017a, 2017b, 2018).

There is a growing literature base in many countries on consumer access routes and trajectories to codeine misuse and dependence via community pharmacy dispensing and diversion (Carney et al., 2016, 2018; Nielsen et al., 2012; Van Hout et al., 2017b; Wells et al., 2018;). There are increased efforts to develop medical and community practice-based innovations to detect, intervene, and support those affected(Norman et al. 2014; Van Hout, 2014; Van Hout & Norman, 2016), supported by assessments of medical and pharmacy practitioner perspectives on codeine use, pathways toward misuse and dependence, the detection of patient aberrance, and support interventions (Foley et al., 2016, 2017, 2018).

With most studies on codeine aberrance originating in the UK, Ireland, South Africa, and Australia (Van Hout et al., 2014), very little is known about prescribing patterns, patient use, and misuse of this drug in the Middle East. Research on pain management and patient care (particularly those with non-cancer musculoskeletal pain), prescribing rates of opioids, and consumption trends, are scarce in the Middle East (Cleary et al., 2013; Wilby & Wilbur, 2017). We report here from the Kingdom of Saudi Arabia (hereafter Saudi Arabia), a high income Islamic country, which has experienced rapid societal change with increased drug consumption patterns (including amphetamine type stimulants, cannabis, heroin, and cocaine) in recent years (Abomughaid et al., 2018; Abualola & Rahamathulla., 2017; Alhazmi et al., 2020; Kravitz & Nichols, 2016; Saquib et al., 2020; United Nations Office on Drugs and Crime 2020). Very little is known however regarding pain management, prescribing trends, and patient misuse of opioids (tramadol is most commonly prescribed) in Saudi Arabia (Alharbi et al., 2020; Al-Rowaili et al., 2009; AlRuthia et al., 2020). There are a few pain management clinics in Saudi Arabia, which operate under strict rules for opioid prescription by medical specialists and dispensing regulations by narcotic pharmacists (Alomi, 2017). These strict regulations (in addition to local drug enforcement laws) operate alongside the law that those found engaging in prescription drug diversions can be sentenced to death (Alomi, 2017; Cleary et al., 2013). Of note is that Saudi Arabia was responsible for the most confirmed drug-related executions globally in 2018; at least 59 (Girelli, 2019).

The Ministry of Health (MoH) publishes the Formulary Drug List (MoH 2014) which is publicly available through its website. The Saudi Food and Drug Authority (SFDA) continuously updates and maintains the drugs approved for marketing in Saudi Arabia and also provides the complete list of drugs in a spreadsheet format on its website (SFDA 2021). According to the MOH Formulary Drug List and the Saudi Food and Drug Authority (SFDA), all codeine products are listed as narcotic, controlled, and prescription-only. At the time of data collection, the SFDA website yielded four products currently approved for marketing in Saudi Arabia (see Table 1), all of which were to be dispensed only on a valid prescription from a licensed medical practitioner. The available MoH Formulary Drug List had four codeine items (paracetamol + codeine tablet, paracetamol + codeine + caffeine tablet, codeine phosphate tablet, and codeine phosphate syrup).

The Procedures and Controls for Narcotics and Psychotropic Substances published by the SFDA enlists the regulations pertaining to the acquisition, storage, and dispensing of codeine and the penalties in case of any violation. Despite the regulations, the non-compliance regarding the dispensing of prescription-only medications is a common malpractice in Saudi Arabia, resulting in both inappropriate dispensing and self-medication (Aljadhey et al., 2015; Al-Mohamadi et al., 2013; Sabry et al., 2014). It is common for individuals to access community pharmacies as first port of call prior to a medical practitioner, which has been observed to result in instances of inappropriate dispensing (Hussain et al., 2012; Sabry et al., 2014). Studies have assessed the compliance of community pharmacies with the regulations that prohibit the dispensing of prescription-only medications in the absence of a physician prescription in Saudi Arabia and have reported on concerning rates of non-compliance, including of codeine-containing medicines (Alshammari et al., 2017).

Mobrad et al. (2020) reported in 2020 that the majority of community pharmacists were trained in recognizing the signs of misuse, to provide warnings and counseling to patients. Despite this, there are increased reports of community pharmacy routes to access drugs with potential for misuse (opioids, gabapentinoids) in Saudi Arabia (Alibrahim et al., 2012; AlKhamees et al., 2018; Al-Mohamadi et al., 2013). Corporate chain community pharmacies also operate online pharmacies in Saudi Arabia and have dedicated apps for mobile phone users. These online pharmacies ask the patient to upload their prescription when they select the home delivery option. Possibly, a person sitting at home may upload a codeine prescription to more than one online pharmacy and get it delivered to his/her home from multiple sources. While residents of Saudi Arabia have access to online stores outside the country, these online stores generally restrict supply to only over the counter drugs.

There is a dearth of research in the Middle East and particularly in Saudi Arabia regarding the views and experiences of physician on the misuse of codeine-containing medicines (MENAHRA, 2021). Hence, this is the first study to date which examines their perceptions regarding codeine prescribing, availability, safety, risks, patient use, misuse, and dependence in Saudi Arabia.

To the authors’ knowledge, this is the first study of its kind in the Middle East and presents a unique illustration of physician perspectives on the prescribing of codeine, patient consumption patterns, and levels of awareness of risks and related harms of long-term/high-dose use and dependence in Saudi Arabia. Limitations of the study center on its small-scale cross-sectional nature. It is possible that those physicians with an interest in addictions or experience of codeine misuse in their practices were more likely to complete the survey. Equally it is likely that misuse and dependence may have different meanings to specific respondents. The study while small-scale is however indicative of medical professional and pharmacy practitioner concerns raised in other parts of the world where codeine is available in community pharmacies (Carney et al., 2016, 2018; Foley et al., 2016, 2017, 2018; Nielsen et al., 2012; Van Hout et al., 2017b; Wells et al., 2018). Countries elsewhere across Europe, Australia, Africa, and the USA have shifted to stronger regulatory controls on over the counter codeine or to only dispense with medical prescription (Tobin et al., 2013). Given that codeine is classed a narcotic, controlled and prescription-only drug in Saudi Arabia, and yet continues to be dispensed illegally via community pharmacy is a grave cause for concern; and indicative of a need for tightening of regulatory mechanisms and pharmacy sanctions to prevent such diversion. Tackling the malpractice of non-compliance regarding the dispensing of prescription-only medications is imperative, especially the case regarding habit-forming medications such as those containing codeine and anti-biotics (Alibrahim et al., 2012; Aljadhey et al., 2015; AlKhamees et al., 2018; Al-Mohamadi et al., 2013; Sabry et al., 2014).

Of note was the strong concern by physicians, largely Saudi nationals, around the routine prescription of codeine to patients with pain, where non-opioid analgesics were ineffective, but with an observable increase in patient requests for codeine-containing medications. There was strong agreement regarding low awareness of patients around risks and harms associated with high dose, long term use and dependence; and as reported elsewhere, concern around the use of codeine for its mood altering properties, and in order to alleviate medication overuse headaches (Katsarava & Jensen, 2007; Nielsen & Van Hout, 2015; Van Hout et al., 2017a, 2017b, 2018). As here, studies have highlighted patient lack of understanding around drug terminology, medicines compliance and adherence to recommended regimes, and awareness of side effects (Hurwitz et al., 2014; Salter, 2013).

A minority of these physicians reported confidence in identifying codeine dependence in patients. All medical students in Saudi Arabia have to successfully complete 1-year internship training in order to graduate from medical school. Specialized fields such as psychiatry are however usually offered as elective rotations. Therefore, all students may not get the desired training and experience to observe and identify drug misuse and dependence. This is in contrast to a study by Mobrad et al. (2020), which indicated that the majority of community pharmacists are trained in recognizing misuse, providing warnings, and counseling patients. Further adding to the complexity is that findings in our study indicate that patient sourcing of codeine is driven by circumnavigation of online pharmacies and illegal dispensing practices.

Despite both religious and legal prohibitions against possession and consumption of alcohol and narcotics, in response to the rise in substance use among its youth, including problem drug use, the government of Saudi Arabia has ramped up its community substance awareness raising and has shifted its drug policy from zero tolerance toward harm minimisation (Abualola & Rahamathulla, 2017; Bamofleh et al., 2017; Bassiony, 2013; MENAHRA, 2021; Siddiqui & Salim, 2016; Sweileh et al., 2014). To date however, Saudi Arabia does not implement harm reduction programs such as opioid agonist treatment, needle and syringe exchange, or naloxone for people who use drugs in the community or in prisons (MENAHRA 2021). We recommend that the Saudi authorities consider to include opiate- and opioid-based pharmaceutical medicines in their prevention, pharmacovigilance, and harm minimization strategies. There is growing national level recognition of the complexities of addressing drug dependence and related comorbidities (Al Harbi, 2017; Ibrahim et al., 2018; Katselou et al., 2016; Saquib et al., 2020). While opioid use is most prevalent in drug treatment patient populations (Alshomrani et al., 2017), we recommend that addiction treatment systems in Saudi Arabia now diversify to recognize and support individuals with codeine dependence and work hand in hand with pain management clinics.

Lastly, the study highlights the need for Saudi authorities to implement and develop medical and community pharmacy practice-based innovations to raise patient awareness, detect aberrance, intervene, and support those affected (Bergin et al., 2015; Norman et al., 2016; Van Hout & Norman, 2016; Van Hout, 2014). Further medical education is warranted both at university level, during internships, and during continuing professional development to raise awareness around patient safe use of codeine; the risk factors for misuse and dependence; how best to support pain patients with iatrogenic dependence; and how best to intervene at dispensing point of care. Future research directions could expand to focus on other drugs of misuse available via community pharmacies, for example, the gabapentinoid group.

This is the first study to date in Saudi Arabia which examines the perceptions of physicians regarding codeine use, misuse, and dependence in Saudi Arabia. It indicates the imperatives of the Saudi government to address Saudi pharmacy compliance with pharmaceutical regulatory controls and implement enhanced pharmacovigilance at prescriber and dispensing levels and a need to improve patient awareness around safe use of codeine-containing medications.