77
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Changes in antidepressant use by young people and suicidal behavior after FDA warnings and media coverage: quasi-experimental study

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Objective To investigate if the widely publicized warnings in 2003 from the US Food and Drug Administration about a possible increased risk of suicidality with antidepressant use in young people were associated with changes in antidepressant use, suicide attempts, and completed suicides among young people.

          Design Quasi-experimental study assessing changes in outcomes after the warnings, controlling for pre-existing trends.

          Setting Automated healthcare claims data (2000-10) derived from the virtual data warehouse of 11 health plans in the US Mental Health Research Network.

          Participants Study cohorts included adolescents (around 1.1 million), young adults (around 1.4 million), and adults (around 5 million).

          Main outcome measures Rates of antidepressant dispensings, psychotropic drug poisonings (a validated proxy for suicide attempts), and completed suicides.

          Results Trends in antidepressant use and poisonings changed abruptly after the warnings. In the second year after the warnings, relative changes in antidepressant use were −31.0% (95% confidence interval −33.0% to −29.0%) among adolescents, −24.3% (−25.4% to −23.2%) among young adults, and −14.5% (−16.0% to −12.9%) among adults. These reflected absolute reductions of 696, 1216, and 1621 dispensings per 100 000 people among adolescents, young adults, and adults, respectively. Simultaneously, there were significant, relative increases in psychotropic drug poisonings in adolescents (21.7%, 95% confidence interval 4.9% to 38.5%) and young adults (33.7%, 26.9% to 40.4%) but not among adults (5.2%, −6.5% to 16.9%). These reflected absolute increases of 2 and 4 poisonings per 100 000 people among adolescents and young adults, respectively (approximately 77 additional poisonings in our cohort of 2.5 million young people). Completed suicides did not change for any age group.

          Conclusions Safety warnings about antidepressants and widespread media coverage decreased antidepressant use, and there were simultaneous increases in suicide attempts among young people. It is essential to monitor and reduce possible unintended consequences of FDA warnings and media reporting.

          Related collections

          Most cited references37

          • Record: found
          • Abstract: found
          • Article: not found

          Suicidality in pediatric patients treated with antidepressant drugs.

          There has been concern that widely used antidepressant agents might be associated with an increased risk of suicidal ideation and behavior (suicidality) in pediatric patients. To investigate the relationship between antidepressant drugs and suicidality in pediatric patients participating in randomized, placebo-controlled trials. Data were derived from 23 trials conducted in 9 drug company-supported programs evaluating the effectiveness of antidepressants in pediatric patients and 1 multicenter trial (the Treatment for Adolescents With Depression Study) that evaluated fluoxetine hydrochloride. All placebo-controlled trials submitted to the Food and Drug Administration were eligible for inclusion. Evaluable data were derived from 4582 patients in 24 trials. Sixteen trials studied patients with major depressive disorder, and the remaining 8 studied obsessive-compulsive disorder (n = 4), generalized anxiety disorder (n = 2), attention-deficit/hyperactivity disorder (n = 1), and social anxiety disorder (n = 1). Only 20 trials were included in the risk ratio analysis of suicidality because 4 trials had no events in the drug or placebo groups. Individual patient data were available for all the trials. A meta-analysis was conducted to obtain overall suicidality risk estimates for each drug individually, for selective serotonin reuptake inhibitors in depression trials as a group, and for all evaluable trials combined. There were no completed suicides in any of these trials. The multicenter trial was the only individual trial to show a statistically significant risk ratio (4.62; 95% confidence interval [CI], 1.02-20.92). The overall risk ratio for selective serotonin reuptake inhibitors in depression trials was 1.66 (95% CI, 1.02-2.68) and for all drugs across all indications was 1.95 (95% CI, 1.28-2.98). The overall risk difference for all drugs across all indications was 0.02 (95% CI, 0.01-0.03). Use of antidepressant drugs in pediatric patients is associated with a modestly increased risk of suicidality.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Antidepressants and the risk of suicidal behaviors.

            The relation between use of antidepressants, especially selective serotonin reuptake inhibitors (SSRIs), and suicidal ideation and behaviors has received considerable public attention recently. The use of such drugs among teenagers has been of particular concern. To estimate the relative risks (RRs) of nonfatal suicidal behavior in patients starting treatment with 1 of 3 antidepressant drugs compared with patients starting treatment with dothiepin. Matched case-control study of patients treated in UK general practices using the UK General Practice Research Database for 1993-1999. The base population included 159,810 users of the 4 antidepressant drugs. Participants could have used only 1 of these antidepressants and had to have received at least 1 prescription for the study antidepressant within 90 days before their index date (the date of suicidal behavior or ideation for cases and the same date for matched controls). Frequency of first-time exposure to amitriptyline, fluoxetine, paroxetine, and dothiepin of patients with a recorded diagnosis of first-time nonfatal suicidal behavior or suicide compared with comparable patients who did not exhibit suicidal behavior. After controlling for age, sex, calendar time, and time from first antidepressant prescription to the onset of suicidal behavior, the relative risks for newly diagnosed nonfatal suicidal behavior in 555 cases and 2062 controls were 0.83 (95% confidence interval, [CI] 0.61-1.13) for amitriptyline, 1.16 (95% CI, 0.90-1.50) for fluoxetine, and 1.29 (95% CI, 0.97-1.70) for paroxetine compared with those using dothiepin. The RR for suicidal behavior among patients first prescribed an antidepressant within 1 to 9 days before their index date was 4.07 (95% CI, 2.89-5.74) compared with patients who were first prescribed an antidepressant 90 days or more before their index date. Time since first antidepressant prescription was not, however, a confounder of the relation between specific antidepressants and suicidal behavior since its relation to suicidal behavior was not materially different among users of the 4 study drugs. Similarly for fatal suicide, the RR among patients who were first prescribed an antidepressant within 1 to 9 days before their index date was 38.0 (95% CI, 6.2-231) compared with those who were first prescribed an antidepressant 90 days or more before their index date. There were no significant associations between the use of a particular study antidepressant and the risk of suicide. The risk of suicidal behavior after starting antidepressant treatment is similar among users of amitriptyline, fluoxetine, and paroxetine compared with the risk among users of dothiepin. The risk of suicidal behavior is increased in the first month after starting antidepressants, especially during the first 1 to 9 days. A possible small increase in risk (bordering statistical significance) among those starting the newest antidepressant, paroxetine, is of a magnitude that could readily be due to uncontrolled confounding by severity of depression. Based on limited information, we also conclude that there is no substantial difference in effect of the 4 drugs on people aged 10 to 19 years.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Methods for estimating confidence intervals in interrupted time series analyses of health interventions.

              Interrupted time series (ITS) is a strong quasi-experimental research design, which is increasingly applied to estimate the effects of health services and policy interventions. We describe and illustrate two methods for estimating confidence intervals (CIs) around absolute and relative changes in outcomes calculated from segmented regression parameter estimates. We used multivariate delta and bootstrapping methods (BMs) to construct CIs around relative changes in level and trend, and around absolute changes in outcome based on segmented linear regression analyses of time series data corrected for autocorrelated errors. Using previously published time series data, we estimated CIs around the effect of prescription alerts for interacting medications with warfarin on the rate of prescriptions per 10,000 warfarin users per month. Both the multivariate delta method (MDM) and the BM produced similar results. BM is preferred for calculating CIs of relative changes in outcomes of time series studies, because it does not require large sample sizes when parameter estimates are obtained correctly from the model. Caution is needed when sample size is small.
                Bookmark

                Author and article information

                Contributors
                Role: instructor
                Role: assistant professor
                Role: analyst
                Role: instructor
                Role: program manager
                Role: assistant investigator; affiliate assistant professor
                Role: senior invstigator; lead investigator
                Role: assistant research scientist
                Role: senior investigator
                Role: senior research scientist
                Role: investigator
                Role: assistant investigator
                Role: senior investigator
                Role: geriatric psychiatrist
                Role: research scientist
                Role: associate director
                Role: professor
                Journal
                BMJ
                BMJ
                bmj
                BMJ : British Medical Journal
                BMJ Publishing Group Ltd.
                0959-8138
                1756-1833
                2014
                18 June 2014
                : 348
                : g3596
                Affiliations
                [1 ]Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA
                [2 ]Group Health Research Institute, Seattle, WA, USA
                [3 ]Department of Health Services Research, University of Washington, Seattle, WA, USA
                [4 ]Mental Health Research Network
                [5 ]Center for Health Policy and Health Services Research, Henry Ford Health System, Detroit, MI, USA
                [6 ]Kaiser Permanente Center for Health Research, Portland, OR, USA
                [7 ]The Division of Research, Kaiser Permanente Medical Care Program Northern California, Oakland, CA, USA
                [8 ]Kaiser Permanente Center for Health Research Hawaii, Honolulu, HI, USA
                [9 ]The Center for Health Research Southeast, Kaiser Permanente Georgia, Atlanta, GA, USA
                [10 ]Kaiser Permanente Colorado Institute for Health Research, Denver, CO, USA
                [11 ]HealthPartners Institute for Education and Research, Bloomington, MN, USA
                [12 ]Kaiser Permanente Southern California, Department of Research and Evaluation, Pasadena, CA, USA
                [13 ]Center for Applied Health Research, Central Texas Veterans Health Care System jointly with Scott & White Healthcare, Temple, TX, USA
                Author notes
                Correspondence to: C Y Lu 133 Brookline Avenue, 6th Floor, Boston, MA 02215, USA christine_lu@ 123456harvardpilgrim.org
                Article
                luc016618
                10.1136/bmj.g3596
                4062705
                24942789
                08d22ba4-b7ed-4eec-b324-9356e787afc1
                © Lu et al 2014

                This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 3.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/3.0/.

                History
                : 21 May 2014
                Categories
                Research
                1779

                Medicine
                Medicine

                Comments

                Comment on this article