The Prevalence and Correlates of Aberrant Opioid-Related Behaviours among Patients with Sickle Cell Disease in Oman: A cross-sectional study

Summary

Objectives:

This study aimed to assess the prevalence of aberrant opioid-related behaviours (AORB) among patients with sickle cell disease (SCD) in Oman and identify associated risk factors.

Methods:

This cross-sectional analytical study was conducted at Sultan Qaboos University Hospital, Muscat, Oman from June to December 2022. Patients with SCD aging 18–65 years old were included and clinically observed for more than 3 months. The Current Opioid Misuse Measure (COMM) was used to evaluate AORB with scores of ≥9 indicating high risk. Demographic and clinical data were collected. The association between AORB and clinical-demographic variables was examined using the Chi-square test.

Results:

A total of 144 SCD patients were included in this study; 58.3% of the participants were at high risk of AORB with a mean COMM score of 12.08. A significant relationship was found between perceived lack of family social support and AORB (P <0.001). No significant associations were observed between AORB risk and other studied factors.

Conclusion:

This study was the first to document a high prevalence of AORB among SCD patients in Oman. The findings underscore the critical role of family support in mitigating this risk of opioid misuse among this vulnerable population.

Advances in Knowledge

• The study revealed that 58.3% of patients with sickle cell disease in the study's cohort are at high risk for opioid misuse.

• The perceived lack of family social support was associated with the risk of aberrant opioid-related behaviours (AORB).

Application to Patient Care

• Multi-disciplinary care, regulation of opioid prescriptions and alternative pain management strategies are essential to prevent opioid misuse.

• Establishing family support systems is a priority to reduce the risk of developing AORB.

• Timely referral to psychiatric services is recommended to prevent the progression to opioid misuse.

1. Introduction

Sickle-cell disease (SCD) is a prevalent genetic disorder worldwide and poses a substantial public health challenge. In Oman, the prevalence of SCD is 3.8%, the second highest among Middle Eastern Arab countries within the Gulf Cooperation Council.¹ SCD is an autosomal recessive haematologic disorder caused by a mutation in the beta-globin gene, which leads to the production of abnormal cell shape.^2,3 The hallmark of SCD is the sickling of red blood cells, which obstructs microvascular blood flow and impairs oxygen delivery to tissues, causing damage to various organ systems. One of the most common and severe clinical manifestations of SCD is a vaso-occlusive episode, characterised by sudden and debilitating episodes of pain.¹

Pain management in SCD is primarily focused on symptomatic relief, with opioids being a central part of treatment during acute vaso-occlusive episodes.⁴ Commonly prescribed opioids, including morphine, fentanyl and enkephalin, provide significant relief for acute pain. However, concerns arise regarding their long-term efficacy and safety in managing chronic pain associated with SCD. Opioids, while effective in the short term, have been associated with increased pain intensity, opioid-induced hyperalgesia and mental health issues such as depression and anxiety.⁵

In recent years, the Food and Drug Administration (FDA) has approved several non-opioid drugs to help manage SCD, including hydroxyurea, crizanlizumab, glutamine and voxelotor.⁶ Nevertheless, opioids remain the cornerstone of acute pain management, despite growing concerns about their long-term impact on neurological pathways, particularly the mesolimbic dopamine pathway, which is linked to reward and addiction mechanisms.⁷

Aberrant opioid-related behaviours (AORB) represent a spectrum that ranges from minor deviations in prescription adherence to severe misuse indicative of opioid use disorder (OUD). The distinction between AORB, opioid misuse and OUD is crucial for understanding the spectrum of opioid-related issues. It mainly refers to behaviours that deviate from prescribed opioid use, which may include taking higher doses than prescribed or using opioids for non-medical reasons. These behaviours can be early indicators of potential misuse or disorder but do not necessarily meet the clinical criteria for OUD.⁸ Opioid misuse is a broader term that encompasses any use of opioids outside of prescribed guidelines, including using someone else's prescription or using opioids to achieve euphoria. It is a significant public health concern due to its potential to lead to OUD.⁹ OUD, on the other hand, is a chronic relapsing disorder characterised by compulsive opioid use, loss of control over use and continued use despite harmful consequences. It is diagnosed based on specific criteria outlined in the Diagnostic and Statistical Manual of Mental Illnesses-5, which includes a strong desire to use opioids, increased tolerance and withdrawal symptoms upon cessation.^8,10 OUD is associated with significant morbidity and mortality, and its treatment involves a combination of FDA-approved medications such as buprenorphine and methadone, as well as psychosocial interventions.¹¹ Understanding these distinctions is vital for clinicians to provide appropriate interventions and prevent the progression from misuse to disorder.

The literature reveals a significant gap in understanding and managing AORB among SCD patients, including those in Oman. Opioids are essential for managing severe vaso-occlusive episodes, yet their prolonged use can lead to tolerance and dependence, raising concerns about potential misuse.¹² Studies indicate that while SCD patients frequently require opioids, the prevalence of substance abuse, including opioids, appears low, suggesting that opioid use for pain management may not inherently lead to addiction.¹³ However, the subtlety of opioid use disorder in this population necessitates heightened awareness and monitoring.¹⁴ Furthermore, inconsistent terminology regarding opioid-related behaviours complicates the discourse, underscoring the need for standardised definitions to facilitate better management strategies.¹⁵ Thus, addressing these gaps is crucial for improving patient outcomes in SCD management. Therefore, this study aimed to answer the following questions: (1) what is the prevalence of AORB among patients with SCD in Oman and (2) what factors are associated with this prevalence? Based on existing literature and clinical observations, this study hypothesises that the prevalence of AORB among SCD patients is higher than that observed in the general chronic pain population. Additionally, it is hypothesised that psychological support, along with demographic and clinical factors, significantly influences the risk of AORB seen by higher scores in the Current Opioid Misuse Measure (COMM) in this population.

2. Methods

This cross-sectional analytical study was conducted from June to December 2022 at Sultan Qaboos University Hospital (SQUH), Muscat, Oman. Patients diagnosed with SCD, aged 18–65 years, who had been under clinical observation for more than 3 months were included. Patients with severe illness, illiteracy, a diagnosed opioid use disorder, or those who did not consent to participate were excluded.

A convenience sampling method was employed to recruit the participants. Based on existing literature indicating a 10% prevalence of AORB among SCD patients experiencing chronic pain,¹⁶ the sample size was calculated with 80% power at a 95% confidence level using the following formula:¹⁷

$$n=\left(4\hspace{0.17em}p\hspace{0.17em}q\right)\hspace{0.17em}/d^2$$

Where p = expected prevalence of aberrant opioid-related behaviour (0.10); q = 1 – p (0.90); d = desired absolute precision (0.05).

Data were collected using the COMM, a 17-item questionnaire designed to assess AORB among patients on chronic opioid therapy.¹⁸ Each item is rated on a 5-point Likert scale ranging from 0 (‘never’) to 4 (‘very often’), resulting in a total score between 0 and 68. A total score of 9 or higher suggests the presence of AORB, demonstrating 77% sensitivity and 66% specificity for diagnosing opioid use disorder.¹⁹ To ensure cultural and linguistic appropriateness, the COMM was translated into Arabic using a forward-backward translation process. First, a bilingual expert in pain management and addiction produced a forward translation of the original English version. Subsequently, a different bilingual professional with no prior exposure to the original COMM performed a back-translation. Both versions were reviewed by an expert panel consisting of psychiatrists, clinical psychologists and addiction specialists, ensuring semantic, idiomatic, and conceptual equivalence. The preliminary Arabic translation was then pilot-tested on chronic pain patients receiving opioid therapy; their feedback guided refinements to enhance clarity and cultural relevance. The final Arabic version demonstrated good internal consistency, with a Cronbach's alpha of 0.834. Based on the COMM tool, the patients were categorized into 2 AORB-risk groups: low risk (COMM <9) and high risk (COMM ≥9). In addition to the COMM, demographic and clinical data were gathered, including age, gender, marital status, educational level, employment status, nature of job, job satisfaction, family support, history of mental illness and smoking status.

All eligible patients were approached during their routine visits to the SCD clinic, and the study objectives were explained to them. Those who consented to participate completed the Arabic version of the COMM and the demographic/clinical questionnaire in a private setting, with the assistance of trained nursing staff when needed. The questionnaires were collected immediately after completion, ensuring privacy and minimizing the possibility of data contamination.

All data were analysed using the Statistical Package for the Social Sciences (SPSS), Version 28.0.1.1 (IBM Corp., Armonk, New York, USA). Descriptive statistics were utilised to summarise participant characteristics and frequencies or means were calculated as appropriate. Univariate analysis was conducted using Chi-square or Fisher's exact tests to identify potential risk factors for AORB. Statistical significance was determined at a P value of less than 0.05.

3. Results

A total of 144 patients with SCD were included in this study; the mean age was 30.02 ± 9.90 years and the cohort was predominantly of male (66%) compared to females (34%). Most patients were well-acquainted with their healthcare providers for having a history of opioid use for pain management. Some patients, recently referred to SQUH for opioid management, were monitored for over 4 months to allow physicians to assess their opioid use patterns and clinical history comprehensively. The mean COMM score was 12.08. A total of 58.3% (n = 84, 95% CI: 49.8–66.5) of participants were at high risk of opioid misuse according to the COMM, while 41.7% (n = 60, 95 % CI: 33.5–50.2%) were considered at low risk.

The analysis of demographic and clinical data revealed no significant differences between the AORB and non-AORB groups with respect to age (P = 0.57), sex (P = 0.88), marital status (P = 0.99), education level (P = 0.51), or employment status (P = 0.06). However, a significant correlation was found regarding psychological support (P <0.001).

Clinically, 47.9% of patients had a history of acute chest syndrome, with no significant difference seen between the AORB and non-AORB groups (P = 0.399). Tramadol was the most used opioid (36.4%), followed by co-codamol (16.1%), morphine (14.7%) and fentanyl (2.1%). No significant correlation was found between AORB status, and the type of opioid used (P = 0.289). In terms of non-opioid pain management, 3.5% used paracetamol, 53.8% used aspirin, ibuprofen or mefenamic acid, and 23.8% used multiple non-opioid medications. Another 18.9 % did not use any non-opioid pain medications in the previous 3 months [Table 1].

Table 1.

Association between demographic, clinical characteristics and Current Opioid Misuse Measure (N = 144).

	n (%)
Variable	Total (N = 144)*	COMM <9 (n = 60)	COMM ≥9 (n = 84)	P value
Mean age ± SD	30.02 ± 9.90	30.55 ± 9.47	29.64 ± 10.23
Sex
Male	95 (66)	39 (65)	56 (66.7)
Female	49 (34)	21 (35)	28 (33.3)
Marital status
Single	79 (54.9)	33 (55)	46 (54.8)
Married	65 (45.1)	27 (45)	38 (45.2)
Education level
Below secondary school	16 (11.1)	8 (13.3)	8 (9.5)
Finished secondary school	60 (41.7)	22 (36.7)	38 (45.2)
College and above	68 (47.2)	30 (50)	38 (45.2)
Employment status
Student	27 (18.8)	9 (15)	18 (21.4)
Job seeker	39 (27.1)	13 (21.7)	26 (31)
Employed	63 (43.8)	34 (56.7)	29 (34.5)
Retired/unable to work	15 (10.4)	4 (6.7)	11 (13.1)
Nature of the job (n = 66)
Office	27 (40.9)	13 (39.4)	14 (42.4)
Field	17 (25.8)	9 (27.3)	8 (24.2)
Both	22 (33.3)	11 (33.3)	11 (33.3)
Job place (n = 69)
Government	42 (60.9)	20 (57.1)	22 (64.7)
Private	27 (39.1)	15 (42.9)	12 (35.3)
Job satisfaction (n = 66)				0.339
Satisfied	54 (81.8)	29 (87.9)	25 (75.8)
Dissatisfied	12 (18.2)	4 (12.1)	8 (24.2)
Satisfaction with the financial situation				0.594
Satisfied	97 (67.4)	42 (70)	55 (65.5)
Dissatisfied	47 (32.6)	18 (30.0)	29 (34.5)
Psychological support from your family members?				<0.001
Get enough support	110 (76.4)	55 (91.7)	55 (65.5)
I need more support	24 (16.7)	2 (3.3)	22 (26.2)
No support	10 (6.9)	3 (5)	7 (8.3)
Do you suffer from any mental illness?				0.510
Yes	2 (1.4)	-	2 (2.4)
No	142 (98.6)	60 (100)	82 (97.6)
Smoking status				0.599
Non-smoker	136 (94.4)	58 (96.7)	78 (92.9)
Used to smoke	4 (2.8)	1 (1.7)	3 (3.6)
I currently smoke	4 (2.8)	1 (1.7)	3 (3.6)
Do you drink alcohol?				0.337
Yes	1 (0.7)	-	1 (1.2)
I used to drink in the past	1 (0.7)	-	1 (1.2)
Never	142 (98.6)	60 (100)	82 (97.6)
Acute chest syndrome				0.399
Yes	69 (47.9)	26 (43.3)	43 (51.2)
No	75 (52.1)	34 (56.7)	41 (48.8)
Pain regimen (n = 143)				0.249
Aspirin/ibuprofen/mefenamic acid	77 (53.8)	35 (58.3)	42 (50.6)
Paracetamol	5 (3.5)	3 (5)	2 (2.4)
Multiple	34 (23.8)	15 (25)	19 (22.9)
None	27 (18.9)	7 (11.7)	20 (24.1)
Opioid category (n = 143)				0.289
Co-codamol	23 (16.1)	13 (21.7)	10 (43.5)
Tramadol	52 (36.4)	17 (28.3)	35 (42.2)
Morphine	21 (14.7)	7 (11.7)	14 (16.9)
Fentanyl	3 (2.1)	1 (1.7)	2 (2.4)
Multiple	14 (9.8)	6 (10)	8 (9.6)
None	30 (21)	16 (26.7)	14 (16.9)
Medical condition (n = 143)				0.485
Yes	54 (37.8)	20 (33.9)	34 (40.5)
No	89 (62.2)	39 (66.1)	50 (59.5)
Surgical procedure				0.171
Yes	61 (42.4)	21 (35)	40 (47.6)
No	83 (57.6)	39 (65)	44 (52.4)

COMM = Current Opioid Misuse Measure; SD = standard deviation.

^* The total for some variables is <144 because the item was not applicable to every participant or the response was left blank.

4. Discussion

This study is the first to document the prevalence of AORBs among a Gulf population with chronic pain, specifically focusing on SCD patients. No prior studies address AORBs in SCD or provide a validated risk assessment tool tailored for this group. This study's findings reveal important insights into factors influencing AORB in this context.

Chronic opioid use is linked to increased risks of misuse and aberrant behaviours.^20,21,22 Numerous risk factors, including mental health issues, are known from non-malignant pain literature and are included in the COMM checklist.^23,24,25 The lack of a significant correlation between mental health history and AORB in the current study may be attributed to potential underreporting of mental health issues due to stigma. Stigma surrounding mental health can lead individuals to conceal or downplay their psychological struggles, resulting in incomplete or inaccurate data.²⁶ The study highlights a strong correlation between family support and problem-focused coping in managing chronic pain, with 22 out of 24 patients needing more psychological support from families being AORB patients. This finding underscores the need for strategies to enhance family support as part of comprehensive care.

The integration of family therapy into treatment models, emphasises the importance of family dynamics in recovery, highlighting how familial support can mitigate stressors associated with addiction.²⁷ Systemic family psychotherapy recognises that substance use issues often stem from and impact family systems, advocating for early identification of these dynamics to develop effective interventions.²⁸ Moreover, the Family Behaviour Therapy model provides structured guidance for clinicians, focusing on behavioural strategies that engage families in the treatment process, thereby enhancing adherence and outcomes for adolescents with substance use issues.²⁹

Sex did not significantly correlate with AORB, consistent with a study done in the USA.³⁰ However, contradictory evidence exists, with some studies suggesting higher prevalence among men and others indicating a risk in adolescent females.^31,32 Further research is needed to clarify these differences in haematology and oncology settings.

Several factors, including age, marital status, education, pain location, duration and opioid duration, were not predictive of AORB, aligning with previous studies.³³ Additionally, variables such as vaso-occlusive episodes frequency, intensive care unit admissions, emergency room visits, comorbidities and surgeries showed no significant association with AORB risk. Given the high prevalence of pain and opioid use in SCD, it is unsurprising that 79% of participants received opioid therapy. Exposure to multiple opioids showed no significant difference in AORB risk between single and multiple prescriptions, contrasting with a previous study that noted such a correlation, possibly due to ethnic variations.³⁰

Building on these findings, it is imperative to recognise the complex psychological and physiological factors that contribute to AORBs. Psychological responses such as negative emotions, stress and ineffective coping mechanisms can exacerbate both pain and opioid misuse, making psychological support essential in comprehensive care.⁵ In SCD patients, the chronic nature of pain may induce inflammatory and neuropathic changes, leading to heightened pain sensitivity and further complicating pain management.^34,35 Furthermore, opioids' effects on the dopamine reward pathway reinforce the potential for misuse, highlighting the need for careful monitoring of patients with prolonged opioid use.⁷

This study's cross-sectional design limits the ability to infer causal relationships between psychological factors and AORB. Additionally, reliance on self-reported data introduces potential biases, such as underreporting due to the stigma surrounding opioid misuse. Furthermore, the absence of a control group limits the ability to compare AORB prevalence and risk factors with populations not affected by SCD, reducing the generalisability of the results. The study also relies on the COMM scale, which has limited accuracy in diagnosing OUD, potentially affecting the validity of the findings. This study does not explore the potential impact or feasibility of alternative pain management modalities, which may serve as critical components in reducing opioid misuse. To address these limitations, future research with should prioritise longitudinal, multicentre studies to validate the findings, evaluate the role of alternative pain management approaches and better understand the dynamic nature of AORB in SCD patients.

5. Conclusion

This study highlights a high prevalence of AORB among SCD patients in Oman, emphasising the need for careful opioid prescribing and the integration of comprehensive pain management strategies. The observed associations between psychological support and AORB risk underscore the importance of incorporating psychosocial interventions, such as family support systems, into patient care. While the findings provide valuable insights for improving SCD management in Oman, their applicability may extend to other healthcare settings with similar challenges, particularly in resource-limited environments. Future research should focus on developing targeted interventions and assessing their scalability across diverse patient populations to enhance outcomes and reduce opioid misuse.

Authors' Contribution

Abdullah Al Abulsalam: Conceptualization, Methodology, Investigation, Writing – original draft. Khawla Al Kindi: Writing – review & editing. Abdullah Al Ghailani: Writing – final draft, Resources, Literature review. Salam Al Kindi: Clinical supervision, Review & editing. Sathiya P. Murthi: Statistical analysis, Software, Methodology, Visualization. Hamed Al Sinawi: Supervision, Review & editing. Naser Al Balushi: Investigation, Writing – review & editing. Amal Al Fahdi: Supervision, Review & editing. Mohammed Al Alawi: Supervision, Finalization of manuscript, Correspondence.

Acknowledgement

The authors gratefully acknowledge the sickle-cell clinic nursing team at Sultan Qaboos University Hospital for their assistance with participant recruitment and questionnaire administration, and thank all patients who generously contributed their time to this study.

Ethics Statement

Ethical approval was obtained from the Medical Research Ethics Committee of the College of Medicine and Health Sciences at Sultan Qaboos University (MREC: #2558). All participants signed a written statement outlining the aims of the study, confirming that their participation was voluntary and that the data collected would remain confidential. They were also informed that they could withdraw at any stage without any impact on their clinical care. Participants identified as having significant AORB, based on a COMM score of 9 or higher, were offered a specialist assessment for further care if needed.

Conflict of Interest

The authors declare no conflicts of interest.

Funding

No funding was received for this study.

Data Availability

Data is available upon reasonable request from the corresponding author.