Table 3.
Summary of measures and findings for included studies
| Author (Year) | Measure of mental disorder | Opioids involved | Overdose characteristic (intent; type) | Measure of overdose | Main findingsa,b | Risk of bias |
|---|---|---|---|---|---|---|
| Bohnert et al. [28] | Any mental disorder | Prescription | Unintentional; fatal | ICD-10 codes for opioid poisoning deaths |
Mental disorders in individuals with chronic pain: AHR 1.87, 95%CI 1.48–2.38 Mental disorders in individuals with acute pain: AHR 1.77, 95% CI 1.19–2.65 Mental disorders in individuals with substance use disorder: AHR 1.73, 95% CI 1.10–2.72 No significant associations were found between mental disorders and overdose in individuals with cancer |
Fair |
| Burns et al. [39] | Hopelessness, any prior mental disorder, reported self-harm, depressive symptoms | Non-prescription | NR; non-fatal | Self-reported lifetime history of overdose |
Hopelessness: Wald’s statistic 6.12, p < 0.01 Antisocial behaviour: Wald’s statistic 8.21, p < 0.01 Prior mental illness: Wald’s statistic 4.15, p < 0.05 No significant associations were found between depression, reported self-harm and overdose |
Poor |
| Campbell et al. [51] | Mood/anxiety disorders | Prescription | NR; fatal and non-fatal | ICD-9 codes for non-fatal opioid poisonings and State death certificates | Mood/anxiety disorders: AHR 2.30, 95% CI 1.98–2.68 | Fair |
| Carrà et al. [40] | Suicidality | NR | NR; non-fatal | Self-reported lifetime history of non-fatal opioid overdose | No significant associations were found between suicide attempts and likelihood of overdose | Poor |
| Chahua et al. [41] | Depression | Prescription and non-prescription | NR; non-fatal | Self-reported past year history of non-fatal opioid overdose | Depression: AOR 2.2, 95% CI 1.01–4.74 | Poor |
| Cheng et al. [29] | Any mental disorder | Prescription and non-prescription | Unintentional; fatal | Post-mortem toxicology and autopsy reports for deaths with at least one opioid |
Mental disorder in opioid overdose decedents vs. poor mental disorder estimates for state-level population: 50.0% vs. 15.0%, p < 0.001 ‘‘Poor mental disorder’’ in the population defined as stress, depression and problems with emotions for more than 7 days in the past 30 days |
Fair |
| Chua et al. [52] | Mental disorder | Prescription | NR; fatal and non-fatal | ICD-9/10-CM code for opioid poisoning | Mental disorder: AOR 3.14, 95% CI 2.40–4.12 | Fair |
| Cochran et al. [53] |
Mood/anxiety disorders Adjustment disorders, Personality disorders, other mental disorders |
Prescription | NR; fatal and non-fatal | ICD-9 codes for opioid poisoning deaths and hospitalization and ED visits |
Anxiety disorder: ARR 1.26, 95% CI 1.07–1.48 Mood disorders: ARR 1.29, 95% CI 1.12–1.50 No significant associations were found between adjustment disorders, personality disorders, other mental disorder disorders and overdose |
Good |
| Connery et al. [42] | Any mental disorder, Anxiety, Suicidality | Prescription and non-prescription | Intentional and unintentional; non-fatal | Self-reported lifetime history of non-fatal opioid overdose |
Mental disorder in opioid overdose history vs. no opioid overdose history, 72.2% vs. 50.0% p-value = 0.013 History of suicide attempt, 50.0% vs. 17.2% p-value = 0.001 No significant associations were found between anxiety symptoms and overdose |
Poor |
| Darke et al. [15] |
Bipolar Disorder Anti-Social Personality Disorder |
Non-prescription | NR; non-fatal | Self-reported lifetime and past year history of non-fatal opioid overdose |
Bipolar Disorder: OR 3.37, 95% CI 1.44–7.88 Anti-Social Personality Disorder: OR 2.20, 95% CI 1.15–4.21 BPD and ASPD: OR 4.70, 95% CI 2.54–8.69 |
Poor |
| Dilokthornsakul et al. [61] | Any mental disorder | Prescription | NR; NR | ICD-9 codes for opioid hospitalizations and ED visits | History of mental illness: AOR 1.73, 95% CI 1.31–2.29 | Fair |
| Dunn et al. [54] | Depressive disorder | Prescription | Intentional and unintentional; fatal and non-fatal | ICD codes for opioid poisoning deaths and adverse events | Overdose rates (history of depression vs. no history of depression): 311/100,000 person-years, 95% CI 203–441 vs. 96/100,000 person-years, 95% CI 62–137 | Good |
| Fendrich et al. [43] |
Depression PTSD Psychosis Severe anxiety |
Prescription and non-prescription | Intentional and unintentional; non-fatal | Self-reported past 3 months history of non-fatal opioid overdose |
Severe depression: AOR 2.46, 95% CI 1.24–4.89 PTSD: AOR 2.77, 95% CI 1.37–5.60 Psychosis: AOR 2.39, 95% CI 1.10–5.15 No significant associations were found between severe anxiety and overdose |
Fair |
| Foley Schwab-Reese [30] | Depression | NR | Intentional and unintentional; fatal | ICD-10 codes for opioid poisoning deaths | Depression and fatal opioid overdose: AIRR 1.26, 95%CI 1.01–1.58; Depression and unintentional fatal opioid overdose: AIRR 1.31, 95%CI 1.03–1.68 | Fair |
| Follman et al. [55] |
Mood Anxiety PTSD |
NR | Intentional and unintentional; NR | ICD-10 codes for opioid poisoning and adverse events |
Anxiety: AOR 1.24, 95% CI 1.12–1.36, p < 0.001 No significant associations were found between mood, PTSD and overdose |
Fair |
| Gerhart et al. [21] | Depression | NR | Intentional and unintentional; fatal | Mortality data provided by from the Kaiser Family Foundation and CDC Wonder Databases | Depression prevalence was significantly associated with opioid overdose deaths: Adjusted Robust Mixed Model: b = 1.97, 95% CI 0.47, 3.47, p = 0.01 | Fair |
| Glanz et al. [56] | Mental disorder diagnosis | Prescription and non-prescription | Intentional and unintentional; fatal and non-fatal | ICD-9/10 codes for opioid poisoning and opioid poisoning deaths | Individuals with mental disorder diagnosis were more likely to have experienced an overdose in two models. Without adjustment for opioid dose in the 3 months before the index date: AOR 2.72, 95% CI 1.43–5.18; With adjustment for opioid dose in the 3 months before the index date: AOR 2.97, 95% CI 1.57–5.64 | Good |
| Groenewald et al. [62] |
Anxiety Mood disorders |
Prescription | NR; NR | ICD-9 codes for opioid poisoning and adverse events |
Anxiety: AHR 1.65, 95% CI 1.33–2.06, p-value < 0.0001 Mood disorders: AHR 2.77, 95% CI 2.26–3.34, p-value < 0.0001 |
Good |
| Hartung et al. [57] |
Depression Psychoses |
Prescription and non-prescription | Intentional and unintentional; fatal and non-fatal | ICD-9/10 codes for opioid poisoning and opioid poisoning deaths | Those with heroin-involved overdoses were more likely to have depression (28.0% vs. 10.9%, p < 0.001) and psychoses (31.4% vs. 6.3%, p < 0.001) compared to those who have never overdosed | Good |
| Hasegawa et al. [44] |
Psychoses Depressive disorder |
Prescription and non-prescription | Intentional and unintentional; non-fatal |
Opioid -related near-fatal events involving mechanical ventilation Opioid-related hospitalization |
Psychoses were significantly associated with opioid-related hospitalizations (for those who have an opioid-related ED visit): AOR 5.40, 95% CI 4.85–6.00, p < 0.001 and with frequency of ED visits: AOR 1.44, 95% CI 1.25–1.65, p < 0.001 Depression is significantly associated with opioid-related hospitalizations (for those with an opioid-related ED visit): AOR 2.71, 95% CI 2.46–2.97, p < 0.001 No significant associations were found between depression and frequent ED visits for overdose |
Poor |
| Karmali et al. [58] |
Anxiety Bipolar disorder Depression Panic disorder Schizophrenia Any mental disorder condition |
Prescription and non-prescription | NR; fatal and non-fatal | ICD-9/10 codes for opioid poisoning and opioid poisoning deaths |
Anxiety: Among adults with non-fatal opioid overdose from 2009 to 2016, those with a second overdose were more likely to have anxiety compared to those without a second overdose (47.0% vs. 39.5%, p = 0.013) Bipolar disorder: Among adults with non-fatal opioid overdose from 2009 to 2016, those with a second overdose were more likely to have bipolar disorder compared to those without a second overdose (22.3% vs. 14.8%, p < 0.001) No significant associations were found between depression, panic disorder, schizophrenia, any mental disorder and opioid overdose |
Good |
| Kline et al. [45] |
PTSD Suicidal ideation |
Prescription & non-prescription | Intentional and unintentional; non-fatal | Self-reported lifetime and past two years history of non-fatal opioid overdose |
Those with persistent overdoses were more likely to have a diagnosis of PTSD (AOR 3.84, 95% Cl l.41–10.46, p = 0.01) than those who have never overdosed No significant associations were found between suicidal ideation and opioid overdose |
Poor |
| Kuo et al. [32] |
Depression Anxiety Bipolar disorder PTSD Schizophrenia and other psychotic disorders ADHD Personality disorder |
Prescription and non-prescription | Intentional and unintentional; fatal | ICD-10 codes for opioid poisoning deaths |
Depression: AOR 1.29, 95% CI 1.09–1.53 Anxiety: AOR 1.65, 95% CI 1.37–1.97 Bipolar disorder: AOR 1.51, 95% CI 1.28–1.79 PTSD: AOR 0.73, 95% CI 0.58–0.92 Those who had fatal opioid overdose were more likely to have mental disorders (depression, 56.8% vs. 30.2%; anxiety, 63.4% vs. 30.9%; bipolar disorder, 35.6% vs. 14.0%; schizophrenia and other psychotic disorders, 18.8% vs. 11.5%; ADHD, 12.0% vs. 4.6%; personality disorders, 9.8% vs. 4.1%) |
Poor |
| Lagisetty et al. [46] |
Depression Serious mental illness PTSD Anxiety |
Prescription and non-prescription | NR; non-fatal | ICD-9 codes for opioid poisoning |
Opioid-overdose hospitalizations vs. Non-Opioid-related hospitalizations: Depression (56.4% vs 36.7%) p < 0.0001* Serious mental illness (24.2% vs 9.7%) p < 0.0001* PTSD (30.4% vs 19.0%) p < 0.0001* Anxiety (22.3% vs 15.1%) p < 0.05* The p values given here are for all opioid-related hospitalizations (including abuse, dependence and overdose) vs. non-opioid-related hospitalizations |
Fair |
| Leece et al. [33] |
Mood disorder Schizophrenia |
Prescription | NR; fatal | Opioid overdose deaths identified through coroners |
Mood disorder: AOR 1.80, 95% CI 1.00–3.24 No significant associations were found between schizophrenia and opioid overdose deaths |
Fair |
| Madadi et al. [37] |
Depressive Disorder Bipolar Disorder Schizophrenia |
Prescription and non-prescription | Intentional and unintentional; fatal | Opioid overdose deaths identified through coroners | Individuals who died of intentional overdose were significantly more likely to have mental disorders such as ADD, OCD, bipolar, schizophrenia [OR (95% CI) 2.1 (1.4–3.2)] and depression [OR (95% CI) 5.2 (3.8–7.1)] | Fair |
| Maloney et al. [47] |
Anxiety disorder Depressive episode Screening for Bipolar disorder |
Prescription and non-prescription | Intentional and unintentional; non-fatal | Self-reported lifetime history of non-fatal opioid overdose |
Those with history of both opioid overdose and suicide attempt were more likely to have anxiety disorder (AOR 1.48, 95% CI 1.04–2.12, p < 0.05), depressive episode (AOR 1.71, 95% CI 1.17–2.51, p < 0.05), and screening for bipolar disorder (AOR 2.29, 95% CI 1.55–3.34, p < 0.001) compared to those with history of neither behavior There was no significant difference between those with no overdose or suicide attempt and those with history of opioid overdose only (without suicide attempt) for anxiety disorder, depressive episode, and screening for bipolar disorder |
Fair |
| Mazereeuw et al. [38] | Self-harm Affective disorder Anxiety disorder Psychotic disorder Psychiatrist visits | Prescription | Intentional and unintentional; fatal | Opioid overdose deaths identified through coroners |
Case subjects were more likely to have had anxiety disorders (63.2% vs. 54.9%, SD = 0.13), affective disorders (11.2% vs. 5.6%, SD = 0.19), received psychiatric care (34.7% vs. 27.5%, SD = 0.16), and have a history of self-harm (8.5% vs. 2.5%, SD = 0.26) in the year preceding opioid-related suicide No significant associations were found between psychotic disorder and opioid-related suicide |
Fair |
| Nadpara et al. [48] |
Depressive Disorder Bipolar disorder Schizophrenia Anxiety disorder ADHD PTSD OCD |
Prescription | NR; non-fatal | Post-overdose reports for ODs with prescription opioids |
Depression in Commercial insured population (CIP): AOR (95% CI) 3.12 (2.84–3.42) Bipolar disorder in CIP: AOR (95% CI) 2.18 (1.83–2.60). Bipolar disorder in Veterans Health Administration (VHA): AOR (95% CI) 1.68 (1.17–2.43). Schizophrenia in CIP: AOR (95% CI) 2.06 (1.17–3.69). Anxiety disorder in CIP; AOR (95%CI) 1.64 (1.50–1.80). ADHD in VHA: AOR (95% CI) 0.33 (0.11–0.99) No significant association between PTSD/OCD and overdose in Commercial insured or VHA populations |
Fair |
| Peterson et al. [49] |
Depression Psychoses |
Prescription and non-prescription | Intentional and unintentional; non-fatal | ICD-10 codes for opioid poisoning | Psychoses: AOR 1.25, 95% CI 1.01–1.53 AOR for opioid overdose readmissions ≤ 90 days among patients with non-fatal index stays for opioid overdose. No significant associations were found between depression and opioid overdose readmissions | Poor |
| Pham et al. [34] |
Anxiety Mild depression Major depressive disorder Bipolar disorder Schizophrenia |
Prescription | Unintentional; fatal | Toxicology reports from medical examiner |
Bipolar disorder: AOR 1.78, 95% CI 1.20–2.65 Schizophrenia: AOR 1.15, 95% CI 1.04–1.27 Case subjects were also more likely to have anxiety (61.7% vs. 32.7%, p < 0.001), mild depression (38.0% vs. 23.7%, p < 0.001), and major depressive disorder (30.8% vs. 17.0%, p < 0.001). However, anxiety and depression were not significant in multivariable models |
Good |
| Ranapurwala et al. [35] | In-prison mental disorder treatment | Prescription and non-prescription | NR; fatal | ICD-10 codes for opioid poisoning deaths |
Those who received in-prison mental disorder treatment were more likely to experience opioid overdose death after release (AHR 1.9, 95% CI 1.7–2.2) and 1 year after release (AHR 2.2, 95% CI 1.7–2.9) No significant associations were found between in-prison mental disorder treatment and opioid overdose death 2 weeks after release |
Fair |
| Roxburgh et al. [36] | Mental health problems | Prescription and non-prescription | Intentional and unintentional; fatal | Post-mortem toxicology and autopsy reports |
Mental health problems in deaths where codeine toxicity was a contributory factor: Intentional vs. accidental OD: OR (95% CI) 2.1 (1.6–2.7) Mental health problems defined as any history of mental health problems recorded in the National Coronial Information System |
Poor |
| Schiff et al. [59] |
Anxiety Depression |
NR | NR; fatal and non-fatal | ICD-9 code for opioid poisoning, toxicology reports, ambulance incident report |
OUD diagnosis and overdose in the year before or after delivery vs. OUD diagnosis but no overdose in the year before or after delivery vs. no diagnosis of OUD in the year prior Anxiety: 82.1% vs. 60.2% vs. 18.29%, p < 0.001 Depression: 84.8% vs. 61.2% vs. 18.90%, p < 0.001 |
Fair |
| Smolina et al. [60] |
Major depressive disorder Anxiety disorder Adjustment disorder Bipolar disorder Schizophrenia Personality disorder ADHD |
Prescription and non-prescription | Intentional and unintentional; fatal and non-fatal | ICD-9/10 codes for opioid poisoning and opioid poisoning deaths, record of naloxone administration in ambulance incident report, or cases identified by coroners, ED physicians or the Drug and Poison Information Centre |
Prevalence of diagnosed mental disorders in the past year and in the past 5 years was significantly different between overdoses cases and controls Past year prevalence: Major depressive: Men (14% vs. 2.6, p < 0.01) Women (21% vs. 4.4%, p < 0.01) Anxiety: Men (13% vs. 2.2, p < 0.01) Women (20% vs. 3.7%, p < 0.01) Adjustment disorder: Men (6.2% vs. 0.67%, p < 0.01) Women (9.5% vs. 1.2%, p < 0.01) Bipolar disorder: Men (6.3% vs. 0.82%, p < 0.01) Women (11% vs. 1.0%, p < 0.01) Schizophrenia: Men (7.0% vs. 0.93%, p < 0.01) Women (7.3% vs. 0.38%, p < 0.01) Personality disorder: Men (3.3% vs. 0.16%, p < 0.01) Women (5.2% vs. 0.16%, p < 0.01) ADHD: Men (1.9% vs. 0.35%, p < 0.01) Women (1.2% vs. 0.30%, p < 0.01) Past 5-year prevalence: Major depressive: Men (34% vs. 7.9, p < 0.01) Women (52% vs. 13%, p < 0.01) Anxiety: Men (30% vs. 6.8, p < 0.01) Women (45% vs. 11%, p < 0.01) Adjustment disorder: Men (16% vs. 2.4%, p < 0.01) Women (25% vs. 4.7%, p < 0.01) Bipolar disorder: Men (14% vs. 2.2%, p < 0.01) Women (23% vs. 2.9%, p < 0.01) Schizophrenia: Men (12% vs. 1.6%, p < 0.01) Women (12% vs. 0.88%, p < 0.01) Personality disorder: Men (7.6% vs. 0.54%, p < 0.01) Women (11% vs. 0.66%, p < 0.01) ADHD: Men (4.9% vs. 1.1%, p < 0.01) Women (3.3% vs. 0.83%, p < 0.01) |
Fair |
| Suffoletto and Zeigler [63] |
Anxiety disorder Bipolar disorder Depression disorder Schizophrenia Stress disorder Any mental disorder |
Prescription and non-prescription | NR; fatal and non-fatal | ICD-9/10 codes for opioid poisoning and opioid poisoning deaths |
Anxiety disorder: AHR 1.41, 95% CI 1.13–1.77 Depression disorder: AHR 1.38, 95% CI 1.02–1.73 Any mental disorder: AHR 1.32, 95% CI 1.08–1.61 AHR for repeated overdose No significant associations were found between bipolar disorder, schizophrenia, stress disorder and repeated opioid overdose |
Good |
| Yoon et al. [50] |
Depressive Disorder Bipolar disorder Anxiety disorder |
Prescription and non-prescription | Unintentional; non-fatal | ICD-9 codes for opioid- poisoning |
Bipolar disorder: Poisoning by prescription opioids; Female: ARR (95% CI) 1.05 (1.01–1.10) Depressive disorder: Poisoning by illicit opioids; Female: ARR (95% CI) 1.06 (1.00–1.12) Poisoning by prescription opioids; Male: ARR (95%CI) 1.10 (1.05–1.15); Female: ARR (95% CI) 1.12 (1.08–1.15) No significant association between anxiety disorder and poisoning by illicit/prescription opioids |
Fair |
| Zedler et al. [64] |
ADHD Anxiety disorder Bipolar disorder Depression PTSD Schizophrenia |
Prescription and non-prescription | NR; fatal and non-fatal |
ICD-9 codes for opioid poisoning and adverse events CPT codes for mechanical ventilation or critical care |
ADHD: AOR 0.3, 95% CI 0.1–1.0, p = 0.048 Bipolar disorder: AOR 1.7, 95% CI 1.2–2.4, p = 0.005 Case subjects were also more likely to have anxiety disorder (22.0% vs. 8.3%, p < 0.001), depression (43.7% vs. 19.1%, p < 0.001), PTSD (27.1% vs. 13.7%, p < 0.001), and schizophrenia (4.4% vs. 1.4%, p < 0.001) |
Fair |
aStatistically significant results denoted in bold
bLanguage (e.g., mental health problems, mental illness, mental disorder, etc.) used in the findings column in accordance with descriptions used in the original study