Association of Risk of Suicide Attempts With Methylphenidate Treatment

Association between methylphenidate treatment and risk of seizure: a population-based, self-controlled case-series study

BackgroundChildren and adolescents with attention deficit hyperactivity disorder (ADHD) are at higher risk of all-cause poisoning by drugs and chemicals (intentional or accidental). Currently, there is limited data on whether medication treatment for ADHD can reduce the risk of all-cause poisoning.MethodsPatients aged 5–18 years with a methylphenidate (MPH) prescription and an incident poisoning diagnosis between January 2001 and June 2020 were identified from the Hong Kong Clinical Data Analysis and Reporting System. A self-controlled case series study design was used to compare the incidence rate ratios (IRRs) of all-cause poisoning during different risk windows (30 days before the first MPH prescription, exposure periods within 30 days of the first prescription, and periods of subsequent exposure) compared with the reference window (other non-exposure periods).Results42,203 patients were prescribed ADHD medication in Hong Kong during the study period. Of these, 417 patients who had both an MPH prescription and poisoning incident recorded were included in the main analysis. Compared with other non-exposed periods, a higher risk of poisoning was found in the 30 days before the first prescription (IRR 2.64, 95% confidence interval [CI] 1.33–5.22) and exposure periods within 30 days of the first prescription (IRR 2.18, 95% CI 1.06–4.48), but not during prolonged exposure. However, compared with 30 days before the first prescription as well as exposure periods within 30 days of the first prescription, there was a lower risk during the subsequent exposure (IRRs 0.49 and 0.60, respectively). Similar results to the main analysis were also found in the subgroup analysis of intentional poisoning and females, but not in that of accidental poisoning and males.ConclusionsThe risk of all-cause poisoning was higher shortly before and after the first MPH prescription and became lower during the subsequent prescription period. Our results do not support an association between the use of MPH and an increased risk of all-cause poisoning in children and adolescents and, in fact, suggest that longer-term use of MPH may be associated with a lower risk of all-cause poisoning, although this latter finding requires further study.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40263-021-00824-x.

Previous studies have suggested that risk of psychotic events may be increased in children exposed to methylphenidate (MPH). However, this risk has not been fully examined, and the possibility of confounding factors has not been excluded. Patients aged 6–19 years who received at least one MPH prescription were identified using Hong Kong population-based electronic medical records on the Clinical Data Analysis and Reporting System (2001–2014). Using the self-controlled case series design, relative incidence of psychotic events was calculated comparing periods when patients were exposed to MPH with non-exposed periods. Of 20,586 patients prescribed MPH, 103 had an incident psychotic event; 72 (69.9%) were male and 31 (30.1%) female. The mean age at commencement of observation was 6.95 years and the mean follow-up per participant was 10.16 years. On average, each participant was exposed to MPH for 2.17 years. The overall incidence of psychotic events during the MPH exposure period was 6.14 per 10,000 patient-years. No increased risk was found during MPH-exposed compared with non-exposed periods (incidence rate ratio (IRR) 1.02 (0.53–1.97)). However, an increased risk was found during the pre-exposure period (IRR 4.64 (2.17–9.92)). Results were consistent across all sensitivity analyses. This study does not support the hypothesis that MPH increases risk of incident psychotic events. It does indicate an increased risk of psychotic events before the first prescription of MPH, which may be because of an association between psychotic events and the behavioural and attentional symptoms that led to psychiatric assessment and initiation of MPH treatment.

The association between first abortion and first-time non-fatal suicide attempt: a longitudinal cohort study of Danish population registries

The European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA) have raised concerns about a potential link between glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and suicide or suicide attempts. We conducted two new-user, active comparator cohort studies. The GLP1-RAs vs sodium-glucose cotransporter-2 (SGLT-2) inhibitors cohort included new users of GLP-1 RAs (n = 83,464) or SGLT-2 inhibitors (n = 78,366), and the GLP1-RAs vs dipeptidyl peptidase-4 (DPP-4) inhibitors cohort included new users of GLP-1 RAs (n = 108,322) or DPP-4 inhibitors (n = 55,411). We also employed a self-controlled case series design to compare suicide, or suicide attempts before and after GLP-1 RA treatment initiation across three time periods. In the cohort analyses patients who initiated GLP-1 RAs did not differ in the hazard ratio (HR) for suicide or suicide attempts from SGLT-2 inhibitor users (HR: 0.93; 95% CI: 0.57-1.52), and GLP-1 RA users had a lower risk of suicide or suicide attempts compared with DPP-4 inhibitor users (HR: 0.58; 95% CI: 0.37-0.91). In the self-controlled case series design, use of GLP-1 RAs was associated with a lower incidence rate ratio (IRR) of suicide or suicide attempts one year after treatment initiation (IRR: 0.45; 95% CI: 0.10-0.50) and 13-24 months after treatment initiation compared with pretreatment. This study showed that use of GLP-1 RAs was not associated with increased incidence of suicide or suicide attempts in either the active comparator new-user design or in the self-controlled case series design.

Abortion and suicide attempt

Back to table of contents Next article Clinical & Research NewsFull AccessSuicide Attempts Decline With Psychotherapy or AntidepressantsJoan Arehart-TreichelJoan Arehart-TreichelPublished Online:3 Aug 2007https://doi.org/10.1176/pn.42.15.0001aResults from two studies reported in the July American Journal of Psychiatry bolster the position that antidepressants prevent suicides, not cause them.In the first study, two researchers at the Center for Health Studies of the Group Health Cooperative in Seattle—Gregory Simon, M.D., and James Savarino, Ph.D.—studied suicide-attempt patterns among 109,256 individuals in the Group Health Cooperative who were starting treatment for depression. The Group Health Cooperative is a prepaid health plan serving about 500,000 members in Washington state and northern Idaho. The individuals fell into three groups—those receiving antidepressants from a primary care doctor, those receiving antidepressants from a psychiatrist, and those receiving psychotherapy.More notable, the researchers found the same time pattern of suicidal attempts in all three groups. The incidence was highest in the month before the start of treatment and declined steadily over a six-month period after treatment began.The investigators then restricted their analyses to patients less than 25 years old, since concern about antidepressants possibly triggering suicides has focused primarily on that age group. Across all three groups, the overall incidence of suicide attempts was about twice as high as in the full subject sample. Nonetheless, adolescents and younger adults showed the same time pattern of suicidal attempts in all three groups as the full subject sample did.The overall incidence of suicide attempts during the study period was highest among patients receiving antidepressant treatment from a psychiatrist; slightly lower among patients starting psychotherapy, and much lower among patients starting antidepressant treatment in primary care. "We do not interpret this difference as evidence that psychiatric care increases the risk of suicide," Simon and Savarino wrote. "Instead, we would conclude that...patients at higher risk for suicide attempts are more often referred for psychiatric care."In the second study, Robert Gibbons, Ph.D., of the University of Illinois at Chicago, and coworkers studied 226,866 veterans diagnosed with depression during 2003 and 2004. They found not only a decrease in suicidal attempts among the subjects once treatment began, but also a lower rate of suicidal attempts in depressed veterans who took antidepressants compared with those who did not (see Original article: VA Finds Antidepressants Reduce Suicide Risk)."The study by Simon and colleagues is very interesting and helpful," David Fassler, M.D., a clinical professor of psychiatry at the University of Vermont and an APA trustee-at-large, told Psychiatric News. "It confirms the general clinical consensus that treatment for depression, including treatment with medication, is associated with a significant reduction in suicide attempts. The take-home message is: if you think you're depressed, get help. Treatment works. The findings should be reassuring to physicians and patients."This study also highlights the growing concerns about the impact of the FDA's decision to add black-box warnings to all antidepressant medications. As a result of this action and the related media coverage, we've seen a precipitous decline in the use of these medications in the treatment of children and adolescents. Tragically, we've also seen the first increase in the actual adolescent suicide rate since the early 1990's.""These studies of treatment in actual clinical practice find a decrease in suicide attempts after treatment, regardless of whether the treatment is psychotherapy or drug therapy," AJP Editor in Chief Robert Freedman, M.D., observed. "Patients and their doctors are concerned because of the FDA's black-box warning that antidepressants can cause suicide attempts. The studies in this issue provide more evidence that this side effect is rare, compared to the overall decrease in suicide attempts that occurs when treatment is initiated. Furthermore, suicide attempts in the first month of treatment [can] occur regardless of whether the treatment is psychotherapy or drug therapy, which suggests that these attempts are part of the natural evolution of symptoms in depression itself."Even though both studies bolster the position that antidepressants protect against suicide, not cause it, they do not rule out the possibility that antidepressants may increase suicide risk in a vulnerable subgroup of patients, Simon and Savarino stressed in their study report. The reason why, they explained, is that "randomized trials or large observational studies can only examine average effects." "Given this uncertainty," they concluded, "prescribers should certainly heed recommendations by the U.S. Food and Drug Administration to advise patients about their risk and to maintain close contact after patients start medication."The two studies were funded by the National Institute of Mental Health."Suicide Attempts Among Patients Starting Depression Treatment With Medications or Psychotherapy" and "Relationship Between Antidepressants and Suicide Attempts: An Analysis of the Veterans Health Administration Data Sets" are posted at<http://ajp.psychiatryonline.org> under the July issue. ▪ ISSUES NewArchived

Attention-deficit/hyperactivity disorder (ADHD) symptomatology in childhood is associated with a high risk of suicide attempt later in life. However, symptom presentation in ADHD is heterogeneous, and little is known about how suicide risk varies according to different profiles of ADHD symptoms and sex. The aim was to investigate the longitudinal associations between childhood profiles of ADHD symptoms (ie, hyperactivity-impulsivity and inattention) and youth suicide attempt in males and females, separately. This population-based cohort study used data from three longitudinal cohorts: the Quebec Longitudinal Study of Child Development (QLSCD), the Quebec Longitudinal Study of Kindergarten Children (QLSKC) and the Quebec Newborn Twin Study (QNTS) for a total of 4399 participants (1490 from the QLSCD, 2134 from the QLSKC and 775 from the QNTS; 50% females) followed up from ages 6-23 years. Symptoms of hyperactivity-impulsivity and inattention were assessed by teachers five times from ages 6-12 years. Suicide attempt in adolescence and young adulthood (by age 23) was self-reported. Multitrajectory modelling was used to identify profiles of ADHD symptoms, and regression analysis was used to test their association with suicide attempt, adjusting for childhood socioeconomic and clinical characteristics. We identified four ADHD symptom profiles with distinct associations with suicide attempt for males and females. Compared with those with persistently low symptoms, females with persistently high inattention and hyperactivity-impulsivity (OR: 2.54, CI 1.39 to 4.63) or high inattention and low hyperactivity-impulsivity (OR: 1.81, CI 1.21 to 2.70) were at higher risk of suicide attempt, while, among males, only those with decreasing hyperactivity-impulsivity and inattention over time (OR: 2.23, CI 1.20 to 4.13) were at higher risk of suicide attempt. Risk of suicide attempt in children with ADHD symptoms varies according to both symptom profile and sex, the highest risk being for females with high inattention symptoms (with or without hyperactivity), and males with decreasing symptoms. Taking into account differences in both sex and ADHD symptoms profile may be relevant to more accurately identify and manage suicide risk in individuals with high ADHD symptoms, though caution is needed when generalising our population-based findings to clinical populations.

Whether the risks of maternal and paternal suicide attempt during and after pregnancy differ remains unclear. Here, in this nationwide register-based study in Sweden (2,196,276 pregnancies), we defined the year before conception, pregnancy and the year after birth and estimated week-specific incidence rate ratios (IRRs). We identified 7,469 (1.39 per 1,000 person-years) suicide attempts among mothers and 8,338 (1.62 per 1,000 person-years) among fathers. Compared with the corresponding week in the preconception period, mothers had a lower risk of suicide attempt during and after pregnancy (with the lowest IRR of 0.14 (0.11-0.17) at first week postpartum); fathers' risk of suicide attempt remained largely stable before childbirth, but a lower risk was observed during the first 10 postpartum weeks (IRRs ranging from 0.69 (0.58-0.81) to 0.91 (0.84-0.99)), followed by a higher risk in the later postpartum period (IRRs ranging from 1.10 (1.01-1.21) to 1.72 (1.33-2.24)). Compared with fathers, mothers had a lower risk of suicide attempt during and after pregnancy (for example, IRR of 0.22 (0.18-0.28) at first week postpartum). Compared with the general population, the sex difference of suicide attempt is reversed during and after pregnancy, suggesting pregnancy or childbirth may have a more pronounced association with suicide attempt among mothers than fathers.

ObjectiveThere is clinical concern that the stimulant methylphenidate (MPH) might increase the risk of depression, particularly in children. This study aimed to investigate the association between MPH use and the risk of depression.MethodsA population-based electronic medical records database was used. We obtained claims data for prescription of ADHD medication, diagnosis of depression, and prescription of antidepressant medication between January 2007 and December 2016 for 43,259 individuals aged 6 to 19 who were diagnosed with ADHD between July 1, 2007 and December 31, 2007. The final analysis was based on 2,330 eligible participants. A self-controlled case series design was used to identify risk factors for major depressive disorder (MDD).ResultsAn elevated MDD risk was found during the 90 days before MPH exposure, with an incidence rate ratio (IRR) of 12.12 (95% confidence interval [95% CI] 10.06−14.61, p < 0.0001). During methylphenidate treatment, the IRR was 18.06 with a 95% CI of 16.67 to 19.56 (p < 0.0001), but it returned to baseline levels after day 31 of MPH treatment discontinuation. The IRR for patients aged 6 to 9 years was 13.11 (95% CI 9.58−17.95) during the 90 days before MPH exposure, and 17.7 (95% CI 15.6−20.08) during MPH treatment, but returned to baseline levels after discontinuation of MPH treatment.ConclusionWe confirmed the temporal relationship between depression and methylphenidate use in young people with ADHD. Though the absolute risk is low, the risk of depression should be carefully considered, particularly in the period directly following the start of methylphenidate treatment.

Differences in the incidence of suicide attempts during various phases of bipolar disorder (BD), or the relative importance of static versus time-varying risk factors for overall risk for suicide attempts, are unknown. We investigated the incidence of suicide attempts in different phases of BD as a part of the Jorvi Bipolar Study (JoBS), a naturalistic, prospective, 18-month study representing psychiatric in- and outpatients with DSM-IV BD in three Finnish cities. Life charts were used to classify time spent in follow-up in the different phases of illness among the 81 BD I and 95 BD II patients. Compared to the other phases of the illness, the incidence of suicide attempts was 37-fold higher [95% confidence interval (CI) for relative risk (RR): 11.8-120.3] during combined mixed and depressive mixed states, and 18-fold higher (95% CI: 6.5-50.8) during major depressive phases. In Cox's proportional hazards regression models, combined mixed (mixed or depressive mixed) or major depressive phases and prior suicide attempts independently predicted suicide attempts. No other factor significantly modified the risks related to these time-varying risk factors; their population-attributable fraction was 86%. The incidence of suicide attempts varies remarkably between illness phases, with mixed and depressive phases involving the highest risk by time. Time spent in high-risk illness phases is likely the major determinant of overall risk for suicide attempts among BD patients. Studies of suicidal behavior should investigate the role of both static and time-varying risk factors in overall risk; clinically, management of mixed and depressive phases may be crucial in reducing risk.

Maternal infections during pregnancy may impact offspring brain development and increase the risk of mental disorders, but their impact on suicidal behavior remains unclear. In this study, we investigated associations between maternal infections before, during, and after pregnancy and offspring suicide attempt later in life to understand the mechanisms explaining these associations. Furthermore, paternal infections during these same periods were examined to pinpoint the possible specific role of intra-uterine exposure vs. genetic and socioeconomic confounding factors. A cohort design was applied to individual-level register-based data including all persons aged 10+ years and living in Denmark in 1987-2021. Information on maternal infection (bacterial, viral, and other, as well as at different body sites) was obtained from the Medical Birth Register based of diagnoses received during hospital contacts. The main outcome was hospital presentations for suicide attempt in the offspring. Adjusted Incidence Rate Ratios (IRR) were estimated to quantify the association between exposure to maternal infections and offspring suicide attempt. Of 2,157,641 individuals (35,047,803 person-years), 38,840 (1.8%), 26,158 (1.2%), and 34,853 (1.6%), had been exposed to maternal infection during, before, and after pregnancy, respectively, while 32,275 attempted suicide. Rates among those exposed to maternal infection during pregnancy and those non-exposed were 141.2 and 90.0 per 100,000 person-years, respectively. After adjustment, individuals exposed to maternal infections during pregnancy had higher risk of suicide attempt when compared to non-exposed (IRR 1.46 [1.36-1.56]), particularly those exposed in the second and third trimesters. Elevated risks were also observed among individuals whose mothers with infections prior (incidence rate: 144.3 per 100,000; IRR 1.45 [1.33-1.57]) and after pregnancy (incidence rate: 128.3 per 100,000; IRR 1.31 [1.21-1.42]). However, no associations were found for paternal infections during, before, or after pregnancy and offspring suicide attempt. These findings show that maternal, but not paternal, infections were associated with later risk of suicide attempt in the offspring, pointing out to a possible role of the intra-uterine environment. The similar estimates obtained for exposure to maternal infections before and after pregnancy suggests that part of this risk may stem from an underlying susceptibility to infections or socioeconomic confounding factors, as well as to possible measurement errors in the onset of infections.

ADHD symptoms and suicide attempts in adults with mood disorders: An observational naturalistic study

Objective The overall rate of suicide between 1999 and 2017 increased by 33% in the United States. We sought to examine suicide attempts in the trauma patient population, hypothesizing that in adult trauma patients race and lack of insurance status would be predictors of suicide attempt. Method The Trauma Quality Improvement Program (2010–2016) was queried for trauma patients ≥18 years old. The primary outcome was suicide attempt. A multivariable logistic regression model was performed including covariates that influence risk of suicide attempt. Results From 1,403,466 adult trauma admissions, 16,263 (1.2%) patients attempted suicide. Death after suicide attempt occurred in 30.2% of patients. Independent predictors of suicide attempt were age < 40 years old (odds ratio [OR] = 1.46, 95% confidence interval [CI] [1.41, 1.51], p < .001) and no insurance (OR = 1.92, 95% CI [1.85, 2.00], p < .001). Black (vs. White) race was associated with decreased risk of suicide attempt (OR = 0.63, 95% CI [0.60, 0.67], p < .001). Hispanic (versus non-Hispanic) patients demonstrated lower associated risk of suicide attempt by gun (OR = 0.50, 95% CI [0.45, 0.54], p < .001), while Asian (vs. White) patients exhibited higher risk of suicide attempt overall (OR = 1.25, 95% CI [1.12, 1.39], p < .001) and more specifically by knife (OR = 2.55, 95% CI [2.16, 3.00], p < .001). Conclusions Age younger than 40 years and lack of insurance were associated with higher risk of suicide attempt in adult trauma patients. Asian race was associated with the highest risk of suicide, with >2.5 times increased risk of attempt by knife. Awareness of these demographic-specific risk factors for suicide attempt, and in particular violent mechanisms of suicide attempt, is critical to implementation of effective suicide prevention efforts. Highlights Age younger than 40 and no insurance were associated with risk of suicide attempt. Black (vs. White) race was associated with decreased risk of suicide attempt. Asian race was associated with an increased risk of suicide attempt with a knife.

Incidence and predictors of suicide attempts in bipolar I and II disorders: A five-year follow-up