The Association Between Opioid Abuse and Depression in Young Adults

The Association Between Opioid Abuse and Depression in Young Adults in Toronto: A Case-Control Study HLTC27: Community Health and Epidemiology Dr. David Schleuter Tutorial 0004 April 8, 2024 Background Information, Significance, and Research Question: 1 ​ The opioid epidemic is a relevant public health issue that is associated with a multitude of negative physiological and psychological health outcomes1. Opioids refer to a group of drugs that are frequently used (and abused) to reduce pain, including prescription medications (e.g., morphine, oxycodone), and illicit drugs (e.g., cocaine, heroin)1. In individuals seeking out treatment for opioid addiction, depression and anxiety are two of the most common issues reported, according to the American Medical Association2. This alludes to the concept of ‘concurrent disorders’, which refers to the presence of a substance abuse and mental health disorder in the same individual, simultaneously3. Individuals with concurrent disorders also experience more psychological distress and worse physical health outcomes compared to those with a single disorder3. These outcomes also mean that this group experiences longer hospital stays, higher healthcare costs, and greater rates of hospital readmission3. Mental health and opioid abuse disorders also contribute to the global disease burden significantly, and an increase in their impact over the years has been observed in both low-, middle-, and high-income countries4. ​ Existing literature provides various mechanisms pointing to the association between opioid abuse and mental health disorders, specifically depression. For example, the chemical structure of heroin mimics the structure of neurotransmitters in the body and can abnormally activate neurons by attaching to them in place of neurotransmitters5. This disrupts the normal functioning of the brain and the normal release of neurotransmitters like serotonin and dopamine5. Altered levels of these neurotransmitters in the brain can lead to depression, in part due to the altered functioning in the brain resulting from opioid abuse5. Despite the evidence-based association between opioid misuse and mental health outcomes, research on this area has only recently begun to accumulate and is still quite limited, especially within the Canadian context1. Although Statistics Canada collects data on the proportion of Canadians with mental health illnesses and substance abuse separately, 2 there is a lack of data looking at the proportion of Canadians who also have a history of substance abuse6. This points to the importance of conducting more studies and research that clearly highlights the prevalence of mental health issues (specifically depression) within those with a history of opioid abuse, in order to create targeted interventions and prevention programs for this specific population in Canada. Therefore, this paper proposes a case-control study design to be conducted over a period of 8 months in order to investigate whether young adults in Toronto aged 18-26 with a history of opioid abuse have an increased risk of developing depression compared to individuals of the same age without a history of opioid abuse. Case-Control Studies: Advantages and Disadvantages: ​ Case-control studies offer a useful epidemiological study design for determining the association between an exposure and a given health outcome. It involves categorizing a randomly selected and representative study population into two groups based on disease status: cases (individuals with the disease of interest – in this case, it is a diagnosis of depression), and controls (individuals who do not have the disease of interest). Case-control studies are helpful for studying rare diseases without requiring a large sample size because researchers are identifying existing cases of the disease and evaluating past exposure status of patients7. This study design is especially useful in the context of this study because there is not much existing data on the latency period between opioid abuse and the development of depression3. Case-control studies are also less expensive and time-consuming compared to other designs, such as prospective cohort studies7. ​ Like all epidemiological study designs, case-control studies are not without their limitations. For example, case-control studies are particularly subject to recall bias when researchers are ascertaining past exposure status of participants7. Another disadvantage is that since the process of selecting cases and controls is not random, prevalence rates cannot and 3 should not be calculated from case-control studies since these rates would not be generalizable to the population at large8. Main Elements of a Case-Control Study: Source Population: Cases will include men and women with depression, aged 18-26 who have been admitted to the Department of Psychiatry division of Mount Sinai Hospital in Toronto, Ontario. Controls will include men and women without depression, aged 18-26 living in Toronto, Ontario who are referred to us by the patients in the ‘case’ group as well as the hospital staff. Note that we will only recruit friends of the patients, not family members. ‘Case’ Definition: In order to be considered a case, the patient must have been professionally diagnosed with depression based on the Hamilton Rating Scale for Depression (HRSD)9, in addition to meeting the inclusion/exclusion criteria for this study, which will be mentioned later. For this study, although participants admitted to the hospital will have some sort of mental health disorder, participants will be required to complete the HRSD questionnaire to confirm a diagnosis of depression and to ascertain its severity. ‘Control’ Definition: In order to be considered a control, the individual must meet the inclusion/exclusion criteria mentioned later. Exposure Definition: The exposure (presence of opioid addiction) is defined as frequent, recent (within the last 6 months), and non-medicinal abuse of any or all of the following opioids: heroin, fentanyl, hydrocodone, and oxycodone10. Data Collection Procedures: Source Population: Identifying the source population from which to recruit cases for this study will be fairly straightforward, as participants aged 18-26 will be selected from the Department of Psychiatry division of Mount Sinai Hospital. To recruit potential participants for the control group, names and contact information of the patients’ friends will be obtained from the patients themselves as well as hospital staff. A survey will then be mailed to the 4 participants, including questions regarding the individual’s characteristics (age and sex), and information pertaining to their health status (including mental health and/or chronic or acute illness diagnoses). We hope to recruit a sample size of 50 cases and 50 controls. The inclusion criteria for ‘cases’ in the study is as follows: 1) be between the ages of 18-26; 2) be currently diagnosed with depression based on the HRSD questionnaire; and 3) be living in Toronto, Ontario. The inclusion criteria for ‘controls’ is as follows: 1) be between the ages of 18-26; and 2) be related to either a patient in the study or a hospital staff member. The exclusion criteria for the ‘cases’ group is as follows: 1) the individual has a chronic illness diagnosis besides depression; and 2) the individual developed an opioid addiction after being formally diagnosed with depression. The exclusion criteria for the ‘controls’ group is as follows: 1) the individual has a formal depression diagnosis; and 2) the individual has been diagnosed with any other chronic medical condition. ‘Case’ Group: The HRSD questionnaire will be used to confirm a depression diagnosis for the purposes of this study. This questionnaire, invented by Max Hamilton in 1960, includes 21 items that rate depression severity9. Scores ranging from 13-16 indicate mild depression, scores ranging from 17-19 indicate moderate depression, and a score of 20 or above indicates severe depression9. The questionnaire will be administered face-to-face in the presence of a psychologist and a psychiatrist. All researchers involved will be introduced to the participants and consent will be clearly obtained. ‘Control’ Group: In order to meeting the inclusion/exclusion criteria and completing the initial recruitment survey, individuals for the control group will also be required to complete the HRSD questionnaire to rule out a diagnosis of depression. The method of questionnaire administration and consent procurement will be identical to the ‘case’ group. Exposure: Both control and case groups will undergo a Drug Use Disorder Identification (DUDI) Test to ascertain the presence of and nature of drug abuse. This test contains 11 items 5 and a highest possible score of 442. A score of 6 or higher is indicative of a drug-related problem, and a score of 25 or higher means the individual is heavily drug-dependent2. Cases and controls will be further divided into ‘exposed’ and ‘unexposed’ groups based on if they have a history of opioid abuse based on the DUDI test. Potential Sources of Biases: Selection Bias: Since the controls in this study were recruited from the social networks of the cases and hospital staff, this could introduce selection bias if these individuals are not representative of the general population of individuals without depression in Toronto, Ontario. For example, if individuals connected to hospital staff have different health-seeking behaviours or access to healthcare compared to the general population. This would introduce a systematic difference in the characteristics of the controls compared to the cases, hence the introduction of selection bias into this study8. This can affect the external validity of the study by limiting the generalizability of the results of this study9. Measurement Bias: A source of measurement bias in this study could present in the form of self-reporting bias. Both cases and controls may overreport or underreport symptoms (such as suicidal tendencies) on the HRSD questionnaire due to social desirability bias (when individuals alter their answer to make themselves appear better) and/or fear of stigma10. This can result in the misclassification of cases and/or control and a distortion of the true association between opioid addiction and depression. Confounding Bias: Since this study includes both men and women, sex could be a potential confounder. It is associated with the exposure since opioid addiction rates can differ between men and women, with men being more likely to develop opioid addictions11. Sex is also associated with the depression prevalence, with women being more likely to be diagnosed than men12. Sex can also independently affect depression risk, with women being at a greater 6 risk than men due to hormone fluctuations, society-driven risk factors, and pregnancy13. This may effect the study by distorting the association between depression and opioid addiction. Impact Statement: This relationship is worth studying because the use of illicit drugs peaks within the age group of focus in this study (18-26)2. This study aims to confirm the relationship between depression and opioid addiction in order to create targeted intervention and prevention strategies for improving mental health outcomes and reducing burden on health systems for this specific group. The findings of this study will hopefully destigmatize conversations about substance abuse and mental health, resulting in better access to treatment for affected individuals in Toronto and further research on this subject. References 7 1.​ Rogers AH, Zvolensky MJ, Ditre JW, Buckner JD, Asmundson JG. Association of opioid misuse with anxiety and depression: A systematic review of the literature. Clinical Psychology Review. 2021 Mar;84:101978. 2.​ Mohamed II, Ahmed H, Hassaan S, Hassan SM. Assessment of anxiety and depression among substance use disorder patients: a case-control study. Middle East Current Psychiatry. 2020 June;27(22). 3.​ Saeeda K. Concurrent mental and substance use disorders in Canada. Statistics Canada: Health Reports. 2017 Aug;28(8):3-8. 4.​ Vispo-Martinez C, Martizen U, Lopez-Duran A, Rio EF, Becona E. Effects of behavioural activation on substance use and depression: a systematic review. Substance Abuse Treatment, Prevention, and Policy. 2018 Sept;13(36). 5.​ Office of the Surgeon General (US). Facing addiction in America: the Surgeon General’s report on Alcohol, Drugs, and Health. Neurobiology of Substance Use, Misuse, and Addiction. 2016 Nov;2. 6.​ Study: Mental disorders and access to mental health care. Statistics Canada. 2023 Sept. 7.​ Tenny S, Kerndt CC, Hoffman MR. Case control studies. StatPearls Publishing. 2023 Mar;28846237. 8.​ Schleuter D. Week seven: Bias and confounding in epidemiological studies [lecture notes]. HLTC27: Community health and epidemiology: University of Toronto Scarborough; lecture given 2023 Mar. 9.​ Carrozzino D, Patierno C, Fava GA, Gu J. The Hamilton rating scales for depression: a critical review of clinimetric properties of different versions. Psychotherapy and Psychosomatics. 2020 May;89(3):133-150. 8 10.​Canadian Alcohol and Drugs Survey (CADS): summary of results for 2019. Statistics Canada. 2023 June. 11.​Teh LW, Abdin E, P.V A, Kumar F, Roystonn K, Wang P, Shafie S, Chang S, Jeyagurunathan A, Vaingankar JA, Sum CF, Kee ES, Dam RM, Subramaniam M. Measuring social desirability bias in a multi-ethnic cohort sample: its relationship with self-reported physical activity, dietary habits, and factor structure. BMC Public Health. 2023 Mar;415:3326. 12.​Mazure CM, Fiellin DA. Women and opioids: something different is happening here. The Lancet. 2018 Jul; 392(10141):9-11. 13.​Zhao L, Han G, Zhao Y, Jin Y, Ge T, Yang W, Cui R, Xu S, Li B. Gender differences in depression: evidence from genetics. Frontiers Genetics. 2020 Oct;11:562316. 9