Key Points
Question
Is there an association between parental use of prescription opioids and suicide attempts by their children?
Findings
This pharmacoepidemiologic study compared rates of suicide attempts in children of parents who used opioids (>1 year of filled prescriptions) with a matched set of families in which parents did not fill opioid prescriptions. A statistically significant doubling of the risk of suicide attempts among the children of parents who used opioids was found.
Meaning
Children of parents who use opioids may be at increased risk for suicide attempts, which may be a contributing factor to the time trend in adolescent suicidality.
Abstract
Importance
The rate of youth suicide has increased over the past 15 years in the United States as has the rate of death due to opioid overdose in adults of parental age.
Objective
To explore the possible connection between parental use of prescription opioids and the increasing rate of youth suicide.
Design, Setting, and Participants
A pharmacoepidemiologic study was conducted from January 1, 2010, to December 31, 2016, linking medical claims for parental opioid prescriptions with medical claims for suicide attempts by their children. The study used MarketScan medical claims data covering more than 150 million privately insured people in the United States. The study included 121 306 propensity score–matched 30- to 50-year-old parents who used opioids and parents who did not use opioids and their 10- to 19-year-old children (148 395 children of parents who did not use opioids and 184 142 children of parents who used opioids). Propensity score matching was used to identify relevant control families based on demographic features and concomitant use of psychotropic medication.
Exposures
Opioid use in a parent was defined as having prescription fills covering more than 365 days of an opioid between 2010 and 2016.
Main Outcomes and Measures
Suicide attempt rate in the children of parents who used opioids and those who did not use opioids.
Results
A total of 148 395 children (75 575 sons and 72 820 daughters; mean [SD] age, 11.5 [1.6] years at the start of follow-up) had parents who did not use opioids and 184 142 children (94 502 sons and 89 640 daughters; mean [SD] age, 11.8 [1.8] years at the start of follow-up) with parents who did use opioids. There were 100 899 children aged 10 to 14 years and 47 496 children aged 15 to 19 years with parents who did not use opioids and 96 975 children aged 10 to 14 years and 87 163 children aged 15 to 19 years with parents who did use opioids. Of the children with parents who did not use opioids, 212 (0.14%) attempted suicide; of the children with parents who did use opioids, 678 (0.37%) attempted suicide. Parental use of opioids was associated with a doubling of the risk of a suicide attempt by their offspring (odds ratio [OR], 1.99; 95% CI, 1.71-2.33). The association remained significant after adjusting for child age and sex (OR, 1.85; 95% CI, 1.58-2.17), addition of child and parental depression and diagnoses of substance use disorder (OR, 1.46; 95% CI, 1.24-1.72), and addition of parental history of suicide attempt (OR, 1.45; 95% CI, 1.23-1.71). Geographical variation in opioid use did not change the association (OR, 2.00; 95% CI, 1.71-2.34).
Conclusions and Relevance
Children of parents who use prescription opioids are at increased risk for suicide attempts, which could be a contributing factor to the time trend in adolescent suicidality. The care of families with a parent who uses opioids should include mental health screening of their children.
This pharmacoepidemiologic study explores the possible association between parental use of prescription opioids and the increasing rate of youth suicide.
Introduction
The suicide rate in children and adolescents has increased dramatically during the past 15 years after an equally long period of decline.1 Parallel increases in suicidal ideation and suicide attempts among youths have also been reported.2,3 To date, there is no empirically based explanation for this increase in the suicide rate among youths, to our knowledge.
This upward trend in suicide among youths first emerged around the same time as the US Food and Drug Administration’s black box warning about antidepressants contributing to an increased risk for suicidal events, defined as an increase in suicidal ideation or actual suicidal behavior.4 Subsequent to this warning, the use of antidepressants among adolescents decreased markedly, as did the rate of diagnosed depression.5 Some initial analyses found an association between the decrease in antidepressant use and the increase in adolescent suicide,6,7,8 and 1 study conducted in a large health system found that a decrease in the use of antidepressants was tied to an increased rate of overdoses of psychotropic medication.9 However, while there are strong and consistent data showing that the rates of antidepressant prescriptions and sales are inversely proportional to regional and national suicide rates,10,11 the subsequent rebound in the use of selective serotonergic reuptake inhibitors among adolescents has not been met with a parallel decrease in the suicide rate.12,13
A second hypothesis is that the increase in adolescent suicides is attributable to social media use because the increase in suicides (in most demographic age groups) has paralleled increased penetration and the use of social media and smartphones.14 Although there are some prospective studies linking increased social media use with decreased sleep and increased depression and suicidal ideation, there are other countervailing studies that find no such association.15 Although a link between the increased use of social media and the increase in youth suicides is plausible, the attribution of a national increase in suicides to an increased use of social media belies the fact that, while social media use has increased globally, the increase in suicides is relatively unique to the United States compared with many other wealthy developed countries.16,17
In this article, we focus on a third explanation, which is that the dramatic increase in opioid use and abuse among adults in the United States has also had an adverse effect on the children of these adults. The US mortality rate due to opioid overdose has increased dramatically among adults of parental age; this increased rate is in contrast to the decreasing rate of opioid overdoses in other comparable countries.16 Three lines of evidence link trends in opioid abuse and suicide. First, the increases in opioid deaths and suicides are greatest in the same demographic groups.16 Second, the geographic distributions of opioid deaths and suicides in the United States are similar.16,17 Finally, people who abuse opioids have an increased risk of suicide attempt and suicide completion.18 For example, for individuals who present with an opioid overdose, the standardized mortality ratio for suicide in the next year is elevated more than 25-fold.19
To date, there has been little focus on the association of parental opioid abuse with the risk of suicidal behavior by their offspring. Such a link is plausible because parental substance abuse is a well-known risk factor for offspring suicide attempts20,21,22 and because other parental conditions that also predispose their offspring to suicidal behavior, including depression and suicide attempt, are more common among adults who abuse opioids.23,24,25,26,27,28 In this article, we examine the risk of suicide attempt among the offspring of parents with prescription opioid use of at least 1 year compared with the offspring of matched controls with no history of prescription opioid use. We hypothesize that there will be an increased risk of suicide attempt among the offspring of parents who use opioids and that this association will persist after controlling for the contribution of concomitant comorbidity in parents.
Methods
Study Design
Data were obtained from the MarketScan Commercial Claims and Encounters databases.29 The MarketScan data are distributed through IBM Watson and include inpatient, outpatient, and prescription claims from more than 100 insurers in the United States (146 million unique enrollee observations since 2005). International Classification of Diseases, Ninth Revision codes for suicidal events (E950-E959) were used before October 1, 2015, and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes for suicidal events (X71-X82 and T1491) were used after October 1, 2015. Opioid prescription fills were based on the following medications: buprenorphine hydrochloride, butorphanol tartrate, codeine sulfate, dihydrocodeine bitartrate, fentanyl citrate, hydrocodone bitartrate, hydromorphone hydrochloride, levomethadyl acetate, levorphanol tartrate, meperidine hydrochloride, methadone hydrochloride, morphine sulfate, opium, oxycodone hydrochloride, oxymorphone hydrochloride, pentazocine hydrochloride, propoxyphene hydrochloride, tapentadol hydrochloride, and tramadol hydrochloride. Parents aged 30 to 50 years who received more than 365 days of opioid medications in 2010-2016 were included in the opioid group. Parents who received no opioid medications in 2010-2016 were included in the nonopioid group. There were 157 005 parents in the opioid group and 948 711 parents in the nonopioid group (chosen via random selection of 30% of 3 162 370 nonopioid patients). The opioid and nonopioid groups were matched on age, sex, prior medication history (Table 1), and opioid use index date using propensity score matching.30 The matching resulted in 121 306 parent pairs. Children of these parents were included if they were aged 10 to 15 years at the opioid index date of the parent using opioids in each matched pair. The matching strategy yielded 148 395 children in the nonopioid group and 184 142 children in the opioid group. Children were followed up from the parent’s index date or the first enrollment date at the age of 10 years or older in 2010-2016 to the first suicide event, the date on disenrollment, or end of the study observation period. This study was deemed exempt from review by the University of Chicago Institutional Review Board. Patient consent was waived as the data used are deidentified medical claims data commercially distributed by IBM Watson.
Table 1. Sample Characteristics Before and After Matching.
| Characteristic | Participants, No (%) | |||
|---|---|---|---|---|
| Before Matching | After Matching | |||
| Nonopioid Group (n = 948 711) | Opioid Group (n = 157 005) | Nonopioid Group (n = 121 306) | Opioid Group (n = 121 306) | |
| Age, mean (SD), y | 41.7 (5.4) | 38.8 (5.3) | 39.1 (5.4) | 39.1 (5.3) |
| Male sex | 361 428 (38.1) | 69 569 (44.3) | 58 509 (48.2) | 55 821 (46.0) |
| ADHD medication | 11 256 (1.2) | 5421 (3.5) | 2182 (1.8) | 2820 (2.3) |
| AED | 9060 (1.0) | 8112 (5.2) | 2931 (2.4) | 3279 (2.7) |
| Antianxiety medication | 5905 (0.6) | 4296 (2.7) | 1506 (1.2) | 1853 (1.5) |
| Antipsychotic medication | 3887 (0.4) | 4709 (3.0) | 1414 (1.2) | 1590 (1.3) |
| Duloxetine | 5180 (0.5) | 8134 (5.2) | 2535 (2.1) | 2602 (2.1) |
| Gabapentin | 3502 (0.4) | 16 161 (10.3) | 2545 (2.1) | 2899 (2.4) |
| SNRI | 10 659 (1.1) | 5837 (3.7) | 2459 (2.0) | 2796 (2.3) |
| SSRI | 67 772 (7.1) | 24 269 (15.5) | 13 095 (10.8) | 14 176 (11.7) |
| TCA | 3904 (0.4) | 6449 (4.1) | 1996 (1.7) | 2073 (1.7) |
| Z drug | 14 985 (1.6) | 17 973 (11.5) | 7201 (5.9) | 7474 (6.2) |
| Benzodiazepine | 32 484 (3.4) | 38 181 (24.3) | 18 325 (15.1) | 17 948 (14.8) |
Abbreviations: ADHD, attention-deficit/hyperactivity disorder; AED, antiepileptic drug; SNRI, serotonin-norepinephrine reuptake inhibitor; SSRI, selective serotonin reuptake inhibitor; TCA, tricyclic antidepressant; Z drug, nonbenzodiazepine medication used in the treatment of sleeping disorders.
Statistical Analysis
Propensity score matching was performed using a greedy matching algorithm with a caliper width set at 0.2 of the SD of the logit of the propensity score.31 Rates of child suicide attempts were compared between the opioid and nonopioid matched cohorts using generalized estimating equation models with logit link, family as the clustering unit, and the number of follow-up months as an offset.32 Sensitivity analyses were performed by adjusting for (1) parental depression and other substance use disorder (SUD), (2) child SUD and depression after the index date, (3) parent’s sex (if both parents were using opioids [3.7% of the opioid group], the sex of the parent with an earlier index date was used), (4) number of opioid-using parents in the family (0, 1, or 2), (5) prior 5-year history of parental suicide attempt, (6) geographical variation in opioid use (metropolitan statistical area), and (7) comparison with parents with sleep disorders who were taking insomnia medications (separate propensity score–matched sample). Stratified analyses were also performed based on child’s sex and age (younger, 10-14 years and older, 15-19 years). All analyses were conducted using SAS, version 9.4 (SAS Institute Inc). All P values were from 2-sided tests, and results were deemed statistically significant at P < .05.
Results
Propensity Score Matching
Table 1 presents summary statistics for the original opioid and nonopioid cohorts and for the propensity score–matched samples. Large group differences in concomitant use of psychotropic medications were largely eliminated in the propensity score–matched sample.
Characteristics of the Children
In the matched sample, 50.9% of children were male in the nonopioid group and 51.5% were male in the opioid group. The mean (SD) age at the start of follow-up was 11.5 (1.6) years in the nonopioid group and 11.8 (1.8) years in the opioid group. The mean (SD) follow-up was 2.44 (1.80) years for the nonopioid group and 3.15 (1.89) years for the opioid group. The number of person-years of follow-up was 361 467 for the nonopioid group and 580 482 for the opioid group; these differences were incorporated into all analyses.
Rates of Suicide Attempts Among the Children
During 2010-2016, a child of parents who used opioids had a risk of 3.68 per 1000 children of attempting suicide. The children of parents in the opioid group showed an increased rate of suicide attempts compared with the children of matched controls (odds ratio [OR], 1.99; 95% CI, 1.71-2.33) with rates of 11.68 vs 5.87 per 10 000 person-years. Of the children with parents who did not use opioids, 212 (0.14%) attempted suicide; of the children with parents who did use opioids, 678 (0.37%) attempted suicide. This finding was true for both sons (6.44 vs 3.04 per 10 000 person-years) and daughters (17.22 vs 8.80 per 10 000 person-years) and for younger children (aged 10-14 years, 7.28 vs 3.41 per 10 000 person-years) and older children (aged 15-19 years, 14.10 vs 8.34 per 10 000 person-years) (Table 2). The difference between suicide attempt rates among children in families who used opioids and those who did not use opioids during this period of time was 2.25 per 1000 children. Adjusting for child sex and age yielded an OR of 1.85 (95% CI, 1.58-2.17). There was no interaction of parental opioid use with either offspring sex or age with regard to its association with suicide attempts among offspring.
Table 2. Suicide Attempt Rates by Age and Sex.
| Stratum, Group | Children, No. | Suicide Attempts, Children, No. (%) | Person-Years | Rate per 10 000 Person-Years |
|---|---|---|---|---|
| Son | ||||
| Nonopioid | 75 575 | 56 (0.07) | 184 102 | 3.04 |
| Opioid | 94 502 | 192 (0.20) | 298 190 | 6.44 |
| Daughter | ||||
| Nonopioid | 72 820 | 156 (0.21) | 177 365 | 8.80 |
| Opioid | 89 640 | 486 (0.54) | 282 292 | 17.22 |
| Aged 10-14 y | ||||
| Nonopioid | 100 899 | 62 (0.06) | 181 581 | 3.41 |
| Opioid | 96 975 | 150 (0.15) | 205 912 | 7.28 |
| Aged ≥15 y | ||||
| Nonopioid | 47 496 | 150 (0.32) | 179 887 | 8.34 |
| Opioid | 87 163 | 528 (0.61) | 374 571 | 14.10 |
Parent and Child Depression and Substance Use Disorders
Table 3 shows that, among parents with more than 1 year of filled opioid prescriptions, the rate of SUD was 16.9% and the rate of opioid use disorder (OUD) was 10.3%. Among the children, rates of SUD and OUD were higher for the children of parents who used opioids (SUD, 2.3% vs 0.8%; P < .001; OUD, 0.4% vs 0.1%; P < .001). Rates of depression were also higher for both parents who used opioids (25.9% vs 9.5%; P < .001) and their children (7.3% vs 3.3%; P < .001). The association between parental opioid use and suicide attempt by child was still significant after adjusting for parent SUD and depression as well as child age, sex, depression, OUD, and SUD (OR, 1.46; 95% CI, 1.24-1.72). Only 4.4% of the parents who used opioids were treated with buprenorphine, a medication used for the treatment of OUD. Among parents with a diagnosis of OUD, only 2.7% were taking buprenorphine.
Table 3. Depression, SUD, and OUD Among Parents and Children by Parental Opioid Use Groups.
| Stratum, Group | Patients, No. | Patients, No. (%)a | ||
|---|---|---|---|---|
| Pre | Post | New Post | ||
| Parents with depression | ||||
| Nonopioid group | 121 306 | 6745 (5.6) | 15 918 (13.1) | 11 474 (9.5) |
| Opioid group | 121 306 | 8225 (6.8) | 37 578 (31.0) | 31 415 (25.9) |
| Parents with SUD | ||||
| Nonopioid group | 121 306 | 589 (0.5) | 2565 (2.1) | 2187 (1.8) |
| Opioid group | 121 306 | 1425 (1.2) | 21 468 (17.7) | 20 486 (16.9) |
| Parents with OUD | ||||
| Nonopioid group | 121 306 | 149 (0.1) | 466 (0.4) | 334 (0.3) |
| Opioid group | 121 306 | 590 (0.5) | 12 944 (10.7) | 12 538 (10.3) |
| Children with depression | ||||
| Parental nonopioid group | 148 395 | 889 (0.6) | 5453 (3.7) | 4928 (3.3) |
| Parental opioid group | 184 142 | 1953 (1.1) | 14 747 (8.0) | 13 445 (7.3) |
| Children with SUD | ||||
| Parental nonopioid group | 148 395 | 46 (0.03) | 1267 (0.9) | 1247 (0.8) |
| Parental opioid group | 184 142 | 147 (0.1) | 4292 (2.3) | 4219 (2.3) |
| Children with OUD | ||||
| Parental nonopioid group | 148 395 | 3 (0.002) | 102 (0.1) | 102 (0.1) |
| Parental opioid group | 184 142 | 11 (0.01) | 653 (0.4) | 648 (0.4) |
Abbreviations: OUD, opioid use disorder; SUD, substance use disorder.
Pre indicates within 1 year prior to index date; Post indicates after index date; and New Post indicates after index date without counting preexisting condition.
Association With 2 vs 1 Parents Who Used Opioids
Stratifying by number of parents who used opioids and adjusting for the covariates yielded an OR of 1.44 (95% CI, 1.24-1.71) for no parents vs 1 parent and an OR of 1.51 (95% CI, 1.124-2.04) for no parents vs 2 parents. There was a nonsignificant difference between 2 parents and 1 parent who used opioids (OR, 1.05; 95% CI, 0.80-1.37).
Association With a Parental History of Suicide Attempt
Parental suicide attempt is associated with an increased risk of offspring suicide attempt, both in the literature and in this sample.33 Even after adjusting for a parental history of suicide attempts, child age, child sex, child SUD, child depression, parental SUD, and parental depression, there was still a significant association between parental use of opioids and child suicide attempt (OR, 1.45; 95% CI, 1.23-1.71). In this analysis, parental history of suicide attempts was not a significant contributor to offspring risk of suicide attempt after taking into account the association of parental opioid use.
Access to Opioids as a Method of Suicide Attempt
An alternative explanation for the increase in suicide attempts by the children of opioid users is that the children have increased access to a means of attempting suicide (ie, opioids in the home). When we excluded all child suicide attempts by overdose of any medication, the association between parental opioid use and child suicide attempt remained significantly elevated (OR, 2.02; 95% CI, 1.64-2.46).
Comparison With Parents With Sleep Disorders Taking Insomnia Medications
Using the same propensity score–matching algorithm, we were able to match 40 643 parents who used insomnia medication with parents who used opioids (insomnia medication, 63 747 children; opioids, 59 758 children). Rates of suicide attempts were 10.87 per 10 000 person-years for children whose parents used insomnia medication and 14.03 per 10 000 person-years for children whose parents used opioids (unadjusted OR, 1.30; 95% CI, 1.08-1.56; adjusted OR, 1.26; 95% CI, 1.05-1.51 for child sex and age). None of the individuals who used insomnia medication were in the opioid user group; however, 11.9% of the parents who used opioids also used insomnia mediations. Across the entire period, suicide attempt rates were 0.4% in the opioid-only group and 0.6% in the opioid and insomnia medication group (P = .009, determined by use of the Fisher exact test).
Geographical Variability in Opioid Use
To adjust for geographical variability in opioid use, we added the proportion of parents using opioids within each family’s metropolitan statistical area as a covariate in the model. The association between parental opioid use and child suicide attempt was virtually identical to that in the original analysis (unadjusted OR, 2.00; 95% CI, 1.71-2.34; adjusted OR, 1.86; 95% CI, 1.58-2.17 for child sex and age).
Discussion
In this study, we demonstrated that parental opioid use is a risk factor for suicide attempts by their offspring with an associated doubling of the risk. This finding was robust to the sex and age of the youths and was robust after controlling for both parental and child comorbidity. A single parent using opioids exhibited a similar association with child suicide attempt as 2 parents using opioids. Parental history of suicide attempts, which was more common among parents with OUD vs those without OUD, did not explain the association between parental opioid use and offspring suicide attempt. A second finding was that the actual diagnosis of OUD among parents was rare even among those who had more than 1 year of opioid use. Only 4.4% of the parents using opioids were treated with buprenorphine. Among parents with a diagnosis of OUD, only 2.7% were taking buprenorphine, so buprenorphine treatment does not explain the low rate of OUD among patients filling 1 year or more of opioid prescriptions.
We found an association between parental opioid use and child suicide attempt that was not fully explained by parental SUD, depression, or suicide attempt or by child SUD or depression despite the fact that all of these conditions were associated with child suicide attempt and were also associated with parental opioid use. We also explored the possibility that the association between parental opioid use and child suicidal behavior was produced by geographical factors associated with both opioid use and child suicidality. Adjustment for metropolitan statistical area–level opioid use produced virtually identical results to the unadjusted findings.
As an additional control, we repeated the propensity score matching in a sample of parents with sleep disorders who were taking insomnia medications. Although the magnitude of the difference in child suicide attempts was reduced, the association with parents using opioids remained significant (a 30% increase in likelihood of a child suicide attempt). This finding further supports the specificity for the role of parental opioid use in the increases seen in suicide attempts among their children. A total of 11.9% of the parents who used opioids also took insomnia medications. The suicide attempt rates among their children were significantly higher in families in which the parents used both opioids and insomnia medications relative to families in which 1 or both parents used only opioids.
Strengths and Limitations
The strengths of this study include access to a large database that includes opioid use, psychiatric disorders, psychotropic medication use, and the ability to link parent and child data. Nevertheless, there are several limitations of this study as well. The definition of opioid use is quite conservative, and there may be a lower threshold of parental opioid use that is also associated with adverse child outcomes. Furthermore, we cannot detect nonprescription use of opioids via this database. Aside from being able to determine if the coparent also used opioids, it was not possible to adjust for other characteristics of the coparent that may have contributed to suicidal risk. For example, information on socioeconomic status was not available, and lower socioeconomic status could be associated with both parental opioid use and child suicide rates. However, all claims were for families with private health insurance, which places a lower bound on socioeconomic status. Surveys of opioid misuse find that the rates of opioid misuse in the past year among those with medical assistance, Children’s Health Insurance Program, or with no insurance are more than double the rates among those who have private insurance.34 Also, geographical variability in opioid use that may be associated with socioeconomic status did not reduce the magnitude of the association. Finally, while we did not show a link between parental opioid use and youth suicide (because the claims data are not linked to the national death index), suicidal behavior is the single strongest factor associated with eventual youth suicide.35,36
To put the magnitude of these associations in context, we found that during 2010-2016, a child of parents who used opioids had a risk of 3.68 per 1000 children of attempting suicide. The rate over a similar period of time for nonfatal bicycle injuries among children younger than 19 years was 3.94 per 1000 children.37 The difference between child suicide attempt rates in families who used opioids and those who did not use opioids during this period of time was 2.25 per 1000 children. Suicide attempts occur at a rate that is of major public health significance, and the increase in the rate in families that use opioids is substantial as well. The deeper question is determing the significance of the increased rates of child suicide attempts and completion in families that use opioids in terms of explaining the recent increases in the overall child and adolescent suicide rates. Such an analysis is beyond the scope of this article because we do not have data on suicide deaths and our data are restricted to families with private health insurance. Nevertheless, we can draw some inferences from the data that we do have. Over the entire period of 2010-2016, we identified 157 005 families with a parent who used opioids and 3 162 370 families that did not use opioids that fit our age specifications, which represents a rate of 4.7%. With a relative risk of approximately 2.0, the population attributable risk is 4.5%. The 2016 National Survey of Drug Use and Health found that the overall rate of opioid misuse is 4.4%,34 resulting in a very similar population attributable risk.
Conclusions
Helping the families of parents with OUD depends on identifying OUD in the parents. The low rate of diagnosis of OUD in our study among parents who had been using opioids continuously for at least 1 year suggests the need for improved surveillance, recognition, and treatment of this potentially fatal condition. Furthermore, when estimating the costs and treatment needs of families affected by opioid abuse, these results support the importance of incorporating the clinical needs and attendant costs of the assessment and care of children of affected parents. Recognition and treatment of parents with OUD, attendance to comorbid conditions in affected parents, and screening and appropriate referral of their children may help, at least in part, to reverse the current upward trend in mortality due to the twin epidemics of suicide and opioid overdose.
References
- 1.Curtin SC, Tejada-Vera B, Warmer M. Drug overdose deaths among adolescents aged 15-19 in the United States: 1999-2015. NCHS Data Brief. 2017;(282):1-8. [PubMed] [Google Scholar]
- 2.Mercado MC, Holland K, Leemis RW, Stone DM, Wang J. Trends in emergency department visits for nonfatal self-inflicted injuries among youth aged 10 to 24 years in the United States, 2001-2015. JAMA. 2017;318(19):1931-1933. doi: 10.1001/jama.2017.13317 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Lowry R, Crosby AE, Brener ND, Kann L. Suicidal thoughts and attempts among US high school students: trends and associated health-risk behaviors, 1991-2011. J Adolesc Health. 2014;54(1):100-108. doi: 10.1016/j.jadohealth.2013.07.024 [DOI] [PubMed] [Google Scholar]
- 4.Stone M, Laughren T, Jones ML, et al. . Risk of suicidality in clinical trials of antidepressants in adults: analysis of proprietary data submitted to US Food and Drug Administration. BMJ. 2009;339:b2880. doi: 10.1136/bmj.b2880 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Libby AM, Orton HD, Valuck RJ. Persisting decline in depression treatment after FDA warnings. Arch Gen Psychiatry. 2009;66(6):633-639. doi: 10.1001/archgenpsychiatry.2009.46 [DOI] [PubMed] [Google Scholar]
- 6.Gibbons RD, Hur K, Bhaumik DK, Mann JJ. The relationship between antidepressant prescription rates and rate of early adolescent suicide. Am J Psychiatry. 2006;163(11):1898-1904. doi: 10.1176/ajp.2006.163.11.1898 [DOI] [PubMed] [Google Scholar]
- 7.Gibbons RD, Brown CH, Hur K, et al. . Early evidence on the effects of regulators’ suicidality warnings on SSRI prescriptions and suicide in children and adolescents. Am J Psychiatry. 2007;164(9):1356-1363. doi: 10.1176/appi.ajp.2007.07030454 [DOI] [PubMed] [Google Scholar]
- 8.Katz LY, Kozyrskyj AL, Prior HJ, Enns MW, Cox BJ, Sareen J. Effect of regulatory warnings on antidepressant prescription rates, use of health services and outcomes among children, adolescents and young adults. CMAJ. 2008;178(8):1005-1011. doi: 10.1503/cmaj.071265 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Lu CY, Zhang F, Lakoma MD, et al. . Changes in antidepressant use by young people and suicidal behavior after FDA warnings and media coverage: quasi-experimental study. BMJ. 2014;348:g3596. doi: 10.1136/bmj.g3596 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Grunebaum MF, Ellis SP, Li S, Oquendo MA, Mann JJ. Antidepressants and suicide risk in the United States, 1985-1999. J Clin Psychiatry. 2004;65(11):1456-1462. doi: 10.4088/JCP.v65n1103 [DOI] [PubMed] [Google Scholar]
- 11.Gibbons RD, Hur K, Bhaumik DK, Mann JJ. The relationship between antidepressant medication use and rate of suicide. Arch Gen Psychiatry. 2005;62(2):165-172. doi: 10.1001/archpsyc.62.2.165 [DOI] [PubMed] [Google Scholar]
- 12.Mittal M, Harrison DL, Miller MJ, Brahm NC. National antidepressant prescribing in children and adolescents with mental health disorders after an FDA boxed warning. Res Social Adm Pharm. 2014;10(5):781-790. doi: 10.1016/j.sapharm.2013.11.001 [DOI] [PubMed] [Google Scholar]
- 13.Rhodes AE, Skinner R, McFaull S, Katz LY. Canada-wide effect of regulatory warnings on antidepressant prescribing and suicide rates in boys and girls. Can J Psychiatry. 2013;58(11):640-645. doi: 10.1177/070674371305801110 [DOI] [PubMed] [Google Scholar]
- 14.Pew Research Center. Social media use in 2018. http://www.pewinternet.org/2018/03/01/social-media-use-in-2018/. Published March 1, 2018. Accessed March 18, 2019.
- 15.Hökby S, Hadlaczky G, Westerlund J, et al. . Are mental health effects of internet use attributable to the web-based content or perceived consequences of usage? a longitudinal study of European adolescents. JMIR Ment Health. 2016;3(3):e31. doi: 10.2196/mental.5925 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Case A, Deaton A. Rising morbidity and mortality in midlife among white non-Hispanic Americans in the 21st century. Proc Natl Acad Sci U S A. 2015;112(49):15078-15083. doi: 10.1073/pnas.1518393112 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Mack K, Clapperton A, Macpherson A, et al. . Trends in the leading causes of injury mortality, Australia, Canada, and the United States, 2000-2014. Can J Public Health. 2017;108(2):e185-e191. doi: 10.17269/CJPH.108.5695 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18.Roy A. Risk factors for attempting suicide in heroin addicts. Suicide Life Threat Behav. 2010;40(4):416-420. doi: 10.1521/suli.2010.40.4.416 [DOI] [PubMed] [Google Scholar]
- 19.Olfson M, Wall M, Wang S, et al. . Suicide after deliberate self-harm in adolescents and young adults. Pediatrics. 2018;141(4):e20173517. doi: 10.1542/peds.2017-3517 [DOI] [PubMed] [Google Scholar]
- 20.Borges G, Borges R, Medina Mora ME, Benjet C, Nock MK. Parental psychopathology and offspring suicidality in Mexico. Arch Suicide Res. 2013;17(2):123-135. doi: 10.1080/13811118.2013.776449 [DOI] [PubMed] [Google Scholar]
- 21.Gureje O, Oladeji B, Hwang I, et al. . Parental psychopathology and the risk of suicidal behavior in their offspring: results from the World Mental Health surveys. Mol Psychiatry. 2011;16(12):1221-1233. doi: 10.1038/mp.2010.111 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22.Rossow I, Moan IS. Parental intoxication and adolescent suicidal behavior. Arch Suicide Res. 2012;16(1):73-84. doi: 10.1080/13811118.2012.640576 [DOI] [PubMed] [Google Scholar]
- 23.Weissman MM, McAvay G, Goldstein RB, Nunes EV, Verdeli H, Wickramaratne PJ. Risk/protective factors among addicted mothers’ offspring: a replication study. Am J Drug Alcohol Abuse. 1999;25(4):661-679. doi: 10.1081/ADA-100101885 [DOI] [PubMed] [Google Scholar]
- 24.Rende R, Weissman MMJ. Sibling aggregation for psychopathology in offspring of opiate addicts: effects of parental comorbidity. J Clin Child Psychol. 1999;28(3):342-348. doi: 10.1207/S15374424jccp280306 [DOI] [PubMed] [Google Scholar]
- 25.Luthar SS, Merikangas KR, Rounsaville BJ. Parental psychopathology and disorders in offspring: a study of relatives of drug abusers. J Nerv Ment Dis. 1993;181(6):351-357. doi: 10.1097/00005053-199306000-00003 [DOI] [PubMed] [Google Scholar]
- 26.Lee CT, Chen VC, Tan HK, et al. . Suicide and other-cause mortality among heroin users in Taiwan: a prospective study. Addict Behav. 2013;38(10):2619-2623. doi: 10.1016/j.addbeh.2013.03.003 [DOI] [PubMed] [Google Scholar]
- 27.Degenhardt L, Larney S, Randall D, Burns L, Hall W. Causes of death in a cohort treated for opioid dependence between 1985 and 2005. Addiction. 2014;109(1):90-99. doi: 10.1111/add.12337 [DOI] [PubMed] [Google Scholar]
- 28.Pan CH, Jhong JR, Tsai SY, Lin SK, Chen CC, Kuo CJ. Excessive suicide mortality and risk factors for suicide among patients with heroin dependence. Drug Alcohol Depend. 2014;145:224-230. doi: 10.1016/j.drugalcdep.2014.10.021 [DOI] [PubMed] [Google Scholar]
- 29.Hansen L. MarketScan white paper: the MarketScan Databases for Life Sciences Researchers. Ann Arbor, MI: Truven Health Analytics; 2016.
- 30.Rosenbaum PR, Rubin DB. The central role of the propensity score in observational studies for causal effects. Biometrika. 1983;70(1):41-45. doi: 10.1093/biomet/70.1.41 [DOI] [Google Scholar]
- 31.Austin PC. An introduction to propensity score methods for reducing the effects of confounding in observational studies. Multivariate Behav Res. 2011;46(3):399-424. doi: 10.1080/00273171.2011.568786 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 32.Zeger SL, Liang KY. Longitudinal data analysis for discrete and continuous outcomes. Biometrics. 1986;42(1):121-130. doi: 10.2307/2531248 [DOI] [PubMed] [Google Scholar]
- 33.Brent DA, Melhem NM, Oquendo M, et al. . Familial pathways to early-onset suicide attempt: a 5.6-year prospective study. JAMA Psychiatry. 2015;72(2):160-168. doi: 10.1001/jamapsychiatry.2014.2141 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 34.Substance Abuse and Mental Health Services Administration. Results from the 2016 National Survey on Drug Use and Health: detailed tables. https://www.samhsa.gov/data/sites/default/files/NSDUH-DetTabs-2016/NSDUH-DetTabs-2016.pdf. Published September 7, 2017. Accessed March 18, 2019.
- 35.Shaffer D, Gould MS, Fisher P, et al. . Psychiatric diagnosis in child and adolescent suicide. Arch Gen Psychiatry. 1996;53(4):339-348. doi: 10.1001/archpsyc.1996.01830040075012 [DOI] [PubMed] [Google Scholar]
- 36.Brent DA, Baugher M, Bridge J, Chen T, Chiappetta L. Age- and sex-related risk factors for adolescent suicide. J Am Acad Child Adolesc Psychiatry. 1999;38(12):1497-1505. doi: 10.1097/00004583-199912000-00010 [DOI] [PubMed] [Google Scholar]
- 37.Borse N, Sleet DA. CDC childhood injury report: patterns of unintentional injuries among 0- to 19-year olds in the United States 2000-2006. Fam Community Health. 2009;32(2):189. doi: 10.1097/01.FCH.0000347986.44810.59 [DOI] [PubMed] [Google Scholar]