Survey of Pentazocine Addiction and Opioid Use in Adult Sickle Cell Anaemia Patients: The Perspective of Healthcare Providers

Introduction

Sickle cell anaemia is marked by acute exacerbations of bone pain secondary to vaso-occlusion and ischaemia [1, 2]. Analgesia and fluid therapy are key aspects of sickle bone pain crisis management [3]. Choice of analgesia usually includes opioids or non-steroidal anti- inflammatory drugs either alone or in combination [4]. The prolonged use of NSAIDs is discouraged due to their effect of inhibiting cyclo-oxygenase 2 (COX-2) and consequent vaso-constriction of the vasculature including the renal parenchyma [5]. With prolonged use this may cause chronic kidney disease in sickle cell anaemia coupled with the already existing background predisposition to develop nephropathy [5, 6]. In SCD, pentazocine is usually prescribed in the management of acute pain, chronic pain or a combination of both [3, 7]. The use of pentazocine in combinations containing an antihistamine (Tripelaminne) as a recreational drug was quite frequent due to its synergistic sedative action hence the choice of naloxone in most combinations available in Europe and America [8]. Pentazocine lactate, the intramuscular/intravenous injectable form is largely available in Nigeria and most African countries and is still widely used for pain control. Opioids act by binding to mainly kappa, mu and delta (α, µ & δ) receptors in the sensori-neural system and other tissues [8, 9]. Pentazocine is a syntheticopioid kappa receptor agonist of the benzomorphan family [10].

Other treatment modalities for chronic pain in SCD include nerve block, physiotherapy, orthopaedic intervention or surgery, and cognitive behaviour therapy [3, 11]. The doctor has an obligation to ensure effective pain relief and at the same time be mindful not to exceed the medical needs of the patients [3]. It is worthy of note that in the current world health organization (WHO) analgesic ladder and guidelines in pain control, pentazocine and pethidine were omitted due to their tendency to cause dependence as well as other notable adverse effects [12, 13, 14]. It is noteworthy that phenotypic and genotypic differences exist in among individuals with sickle and even occur over time in the same patient. This may present challenges over time with regards management of bone pain crisis.

Opioid addiction is defined as a psychological dependence on opioids with associated craving, loss control of drug use or compulsive drug use aimed at achieving psychic effects despite obvious harm [15]. This persistent abuse may lead to deleterious consequences associated with inordinate craving despite adequate dosing and pain control with other non-opioid drugs [16, 17]. The use of opioids as a sole agent in the treatment of chronic pain has been identified as a cause of addiction [18]. Pentazocine addiction may present as intense craving for the drug, excessive sweating, body (not bone) pains, signs of needle pricks on the body and poor academic performance [19, 20]. Some personality disorders resulting from opioid dependence reflective of dysfunction in the limbic system and higher centres are loss of productivity at work, truancy and criminal tendency ostensibly to raise funds for crave satisfaction. Ultimately, job loss, premature school attrition and other socio-economic are untoward effects of pentazocine abuse [20, 21]. It has also been associated with stealing [20, 21] and other corrupt practices (to raise money for its purchase) as well as loss of job following associated physical deformity [21].

Pentazocine addiction is underreported in Nigeria probably due to low index of suspicion especially in cases where the patients do not easily divulge information [22]. In Nigeria, despite regulation, pentazocine is still being purchased “over the counter” in many places [21]. Clinical experience has indicated a rising prevalence of addiction to pentazocine in the Nigerian population in people living with sickle cell disease [20, 21]. This study is designed to determine the extent of the problem, assess the prescription pattern of the attending physicians as well as evaluate the necessity for guidelines in the prescription of opioids.

Anazoeze Jude M, et al. Survey of Pentazocine Addiction and Opioid Use in Adult Sickle Cell Anaemia Patients: The Perspective of Healthcare Providers. Haematol Int J 2018, 2(2): 000133.

Materials and Methods

This was a descriptive study carried out among Physicians involved in sickle cell patients’ care in Nigeria who were in attendance at the annual general meeting of the Nigerian Society of Haematology and Blood Transfusion in October 2016. The participants were consenting consultants and resident doctors include resident doctors in different stages of residency of training. Physicians in attendance who did not manage sickle cell anaemia were excluded. The instrument of assessment was a 10-item self-administered questionnaire pre-validated by doctors working in the UNTH, Enugu Haematology unit. Information sought for included the name of institution of practice, number of registered adult sickle cell patients in those institutions, number of cases of pentazocine addiction recorded in the past 5 years, first choice and other types of analgesics prescribed, counselling practices, need for guidelines, personal view of the problem of addiction and availability of neuropsychiatric units in the different centers.

Results

Responses were obtained from 55 out of 76 doctors who correctly completed the questionnaire. These were doctors from 25, out of the 53 tertiary health institutions across Nigeria. The number of registered sickle cell patients in these institutions ranged from10 to 3000, with a median of 100. The number of pentazocine addiction cases seen in the past 5 years ranged from 0 to 50 with a median value of 4 patients per health institution. The total number of patients observed to have had pentazocine addiction in the past 5 years was 386 out of 13,314 registered sickle cell patients across these health institutions. This gives an estimated 5 year prevalence rate of 0.029 or 2.9%.

Table 1 shows the frequency of use of the various analgesic agents by the respondents. With regards to dihydrocodeine (DF118), majority of the physicians 48.1% used this drug very often, while an additional 28.8% used it often. Cocodamol, a combination of acetaminophen and codeine, was prescribed sparingly and once in a while by 35.1% and 29.7% of them. About 53.2% of the responding physicians sparingly prescribed oral morphine while 29.8% of them agreed to only prescribe it once in a while see Table 1. This implies that more than 80% of the Physicians managing sickle cell pain rarely used morphine.

Table 1: Prescription pattern of analgesics for sickle cell by Nigerian haematologists Routine counselling on dangers in opioid use was done always by majority (61.8%) of these doctors while 23.6% only counselled these patients sometimes. About 88.9% of the managing physicians believe guidelines need to be put in place to restrict or modify clinical use of opioid analgesics. 89.1% of them agree that pentazocine addiction is a major health challenge in the Nigerian sickle cell patient population. The responses to questions on opioid use and availability of neuropsychiatry teams and facilities in the centers are recorded in Table 2.

Anazoeze Jude M, et al. Survey of Pentazocine Addiction and Opioid Use in Adult Sickle Cell Anaemia Patients: The Perspective of Healthcare Providers. Haematol Int J 2018, 2(2): 000133.

Discussion

Regulation of opioid use aimed at averting addiction should be an important aspect of pain care in people living with sickle cell. Evaluation of the prescription pattern of analgesics as well as a definition of the extent of the problem was the focus of this survey. Fifty five out of 76 doctors who were in attendance were included in this survey. This represents an adequate proportion of haematologists in the country. These doctors predominantly worked in teaching hospitals, federal medical centers and general hospitals from across the country. However, all the respondents filled their questionnaires on-the-spot and this might account for some recollection bias. The significance of this bias is however difficult to estimate in this occasion as in any other on-the-spot questionnaire-based study where specific figures are needed. These facilities are tertiary health institutions and referral centers and may be involved in handling a different spectrum of patients at variance with those seen in the primary and secondary health facilities. The obvious consequence is that majority of the patients seen here may be those with complicated disease. However, experience has shown most patients choose to be attended to in these facilities due to paucity of manpower and facilities at other levels of healthcare. Therefore this study, albeit tertiary-based, still provides a true representation of the situation amongst doctors involved in handling this condition.

This study also found that the first choice analgesic in managing painful episodes in sickle cell disease patients is non-steroidal anti-inflammatory drugs (NSAIDs), followed by pentazocine, tramadol, paracetamol, dihydrocodeine and morphine in that order. Common use of NSAIDs in management of pain associated with sickle cell disease was also reported by Jimoh, et al. [25]. Non-steroidal anti- inflammatory drugs have been reported to be effective in relieving the inflammatory component of vaso-occlusive bone pain in addition to analgesic effect [3]. Its popularity may also be due to its availability in different preparations including the suppository form and the fact that it may be conveniently used in both in-patient and out-patient setting. However, nephropathy, gastritis and anti-platelet effect associated with its long term use is a limitation [1]. The most commonly used opioid among the Anazoeze Jude M, et al. Survey of Pentazocine Addiction and Opioid Use in Adult Sickle Cell Anaemia Patients: The Perspective of Healthcare Providers. Haematol Int J 2018, 2(2): 000133.

respondents was pentazocine. Previous studies have also reported that pentazocine is commonly used in the treatment of pain associated sickle cell disease [4, 21]. This may be due to its wide availability, easy accessibility and low cost [21]. There is also a possibility that it is used as the sole option for management of chronic pain disregarding other possible potent treatment options like nerve block, physiotherapy, orthopaedic intervention or surgery, and cognitive behaviour therapy [3].

Acetaminophen, though a relatively weak analgesic, can be effective for some pain episodes in sickle cell disease. It can be used either singly or in combination with other analgesics in management of mild to moderate pain. Apart from the dose-dependent hepatotoxicity, side effects of acetaminophen are less than those of the other NSAIDs [2]. Morphine was rarely used by respondents in this study for pain management in sickle cell disease. This may be due to the unavailability of a parenteral preparation of the drug in Nigeria [26] and its multi-organ toxicity including respiratory depression as reported by previous study.

There is dearth of data on pentazocine addiction as a major health challenge among people living with sickle cell in Nigeria [27]. Lack of guidelines of opioid use and ease of procurement of the drug in Nigeria could possibly contribute to pentazocine addiction as had been reported in other environments [23]. There is a great need to increase awareness on WHO guidelines on pain control and the use of the analgesic ladder in patient evaluation, analgesic prescription and monitoring. Morphine, which apart from Tramadol and dihydrocodeine is the predominant opioid on the guideline, should be made readily available for the management of severe pain. Counselling for dangers in opioid abuse is a very important aspect of patient care [28].

Management of addiction of any kind is usually specialized and requires trained and dedicated personnel. Adequate accommodation and security is also central in the success of treatment and optimal rehabilitation. This study also showed that majority of our institutions had neuropsychiatric units while a lower percentage accepted that these units in their center were well equipped to handle addiction cases. This pre-supposes that the respondents were aware of the demands of an addiction rehabilitation unit in terms of personnel and staff. Further studies will be needed to assess the capacity of the several neuropsychiatry units in most centers to handle addiction cases. A multi-disciplinary approach involving the psychiatrist, palliative and pain care specialists and anesthetists in-pain management of sickle cell disease in our institutions is critical and may help to reduced cases of addiction.

The limitations of this study include the survey of doctors who were in attendance at the annual meeting of haematologists as this did not offer them the opportunity to access their hospital data. Some of the responses therefore might not be precise thus affecting data quality and thus introducing some recall bias, the significance of which is difficult to estimate. The survey did not include the psychiatrists who may have a different experience as they also manage opioid addicts who do not live with sickle cell. New areas of study would involve investigating the views and opinions of people living with sickle cell who have pentazocine addiction with the aim of defining the factors, causes and challenges of this peculiar patient group.

Conclusion

Pentazocine addiction, with a prevalence rate of 2.9% is a major health challenge among people living with sickle cell in Nigeria. It was the most the most frequently used opioid in treatment of pain in SCA. Most of the respondents accepted that there is a need to provide guidelines for opioid use in these patients. Tertiary health institutions in the country were deemed fit to handle cases of opioid addiction.