Simultaneous Benzodiazepine and SSRI Initiation in Young People With Anxiety Disorders

Greta A. Bushnell, PhD^a,b ; Moira A. Rynn, MD^c ; Stephen Crystal, PhD^a ; Tobias Gerhard, PhD^a,d ; Mark Olfson, MD, MPH^e

J Clin Psychiatry 2021;82(6):20m13863

ABSTRACT

Objective: There are potential risks and benefits of combining benzodiazepine (BZD) and selective serotonin reuptake inhibitor (SSRI) therapy at anxiety disorder treatment onset. We investigated how often adolescents and young adults with anxiety disorders simultaneously initiate BZD treatment with SSRI treatment and examined whether SSRI treatment duration varies by simultaneous BZD initiation.

Methods: In a United States commercial claims database (January 2008–December 2016), we identified adolescents (10–17 years) and young adults (18–24 years) with ICD-9-CM/ICD-10–CM anxiety disorder diagnoses initiating SSRI treatment, without past-year SSRI and BZD treatment. We defined simultaneous initiation as filling a new BZD prescription on the date of SSRI initiation. We estimated time to SSRI treatment discontinuation and used stabilized inverse probability of treatment weighting for adjusted estimates.

Results: The study included 94,399 adolescents and 130,971 young adults initiating SSRI treatment with an anxiety disorder. Four percent of adolescents and 17% of young adults simultaneously initiated BZD treatment, varying by age, anxiety disorder, comorbidities, health care utilization, and provider type. Simultaneous BZD initiation among SSRI initiators declined from 2008 to 2016. SSRI treatment duration was similar in initiators of simultaneous therapy vs SSRI monotherapy: ≥ 6 months in adolescents (55% vs 56%, respectively) and in young adults (39% vs 40%). Nine percent of simultaneous initiators continued BZDs for ≥ 6 months.

Conclusions: Simultaneous initiation of BZD and SSRI treatment is relatively common in young adults with anxiety disorders and was not associated with longer SSRI persistence. Given risks of BZD treatment, potential benefits and risks of adding a BZD at SSRI treatment initiation must be carefully weighed.

Continue Reading...

Members enjoy unlimited free PDF downloads as part of their subscription! Subscribe today for instant access to this article and our entire library in your preferred format. Alternatively, you can purchase the PDF of this article individually.

Subscribe Now

Already a member? Login

Buy PDF for $40

Please sign in or purchase this PDF for $40.

References (38)

Stein MB, Goin MK, Pollack MH, et al. Practice Guideline for the Treatment of Patients with Panic Disorder. Washington, DC: American Psychiatric Association: 2009.
Clinical Practice Review for GAD. Anxiety and Depression Association of America. 2015. https://adaa.org/resources-professionals/practice-guidelines-gad
Stein MB, Craske MG. Treating anxiety in 2017: optimizing care to improve outcomes. JAMA. 2017;318(3):235–236. PubMed CrossRef
Generalised anxiety disorder and panic disorder in adults: management. National Institute for Health and Care Excellence. 2011. https://www.nice.org.uk/guidance/cg113
Connolly SD, Bernstein GA; Work Group on Quality Issues. Practice parameter for the assessment and treatment of children and adolescents with anxiety disorders. J Am Acad Child Adolesc Psychiatry. 2007;46(2):267–283. PubMed CrossRef
Walter HJ, Bukstein OG, Abright AR, et al. Clinical Practice Guideline for the Assessment and Treatment of Children and Adolescents With Anxiety Disorders. J Am Acad Child Adolesc Psychiatry. 2020;59(10):1107–1124. PubMed CrossRef
Dunlop BW, Davis PG. Combination treatment with benzodiazepines and SSRIs for comorbid anxiety and depression: a review. Prim Care Companion J Clin Psychiatry. 2008;10(3):222–228. PubMed CrossRef
Goddard AW, Brouette T, Almai A, et al. Early coadministration of clonazepam with sertraline for panic disorder. Arch Gen Psychiatry. 2001;58(7):681–686. PubMed CrossRef
Dobson ET, Bloch MH, Strawn JR. Efficacy and tolerability of pharmacotherapy for pediatric anxiety disorders: a network meta-analysis. J Clin Psychiatry. 2019;80(1):17r12064. PubMed CrossRef
Bushnell GA, Stürmer T, Gaynes BN, et al. Simultaneous antidepressant and benzodiazepine new use and subsequent long-term benzodiazepine use in adults with depression, United States, 2001–2014. JAMA Psychiatry. 2017;74(7):747–755. PubMed CrossRef
Furukawa TA, Streiner DL, Young LT. Antidepressant plus benzodiazepine for major depression. Cochrane Database Syst Rev. 2001;(2):CD001026. PubMed
Stein MB, Cantrell CR, Sokol MC, et al. Antidepressant adherence and medical resource use among managed care patients with anxiety disorders. Psychiatr Serv. 2006;57(5):673–680. PubMed CrossRef
Bushnell GA, Brookhart MA, Gaynes BN, et al. Examining parental medication adherence as a predictor of child medication adherence in pediatric anxiety disorders. Med Care. 2018;56(6):510–519. PubMed CrossRef
Jann M, Kennedy WK, Lopez G. Benzodiazepines: a major component in unintentional prescription drug overdoses with opioid analgesics. J Pharm Pract. 2014;27(1):5–16. PubMed CrossRef
Brunton LL, Hilal-Dandan R, Knollmann BC, eds. Goodman & Gillman’s The Pharmacological Basis of Therapeutics. 12th ed. The McGraw-Hill Companies, Inc.; 2011.
McCabe SE, West BT. Medical and nonmedical use of prescription benzodiazepine anxiolytics among US high school seniors. Addict Behav. 2014;39(5):959–964. PubMed CrossRef
Gaither JR, Shabanova V, Leventhal JM. US national trends in pediatric deaths from prescription and illicit opioids, 1999–2016. JAMA Netw Open. 2018;1(8):e186558. PubMed CrossRef
Maust DT, Lin LA, Blow FC. Benzodiazepine use and misuse among adults in the United States. Psychiatr Serv. 2019;70(2):97–106. PubMed CrossRef
Schepis TS, West BT, Teter CJ, et al. Prevalence and correlates of co-ingestion of prescription tranquilizers and other psychoactive substances by U.S. high school seniors: Results from a national survey. Addict Behav. 2016;52:8–12. PubMed CrossRef
FDA requiring Boxed Warning updated to improve safe use of benzodiazepine drug class. US Food and Drug Administration. 2020. https://www.fda.gov/drugs/drug-safety-and-availability/fda-requiring-boxed-warning-updated-improve-safe-use-benzodiazepine-drug-class
IBM MarketScan Research Databases. IBM. 2021. Accessed 3/24/2021.https://www.ibm.com/products/marketscan-research-databases.
IBM Watson Health. IBM MarketScan Research Databases for Health Services Researchers. White Paper. 2019. https://www.ibm.com/downloads/cas/6KNYVVQ2
Liu X, Chen Y, Faries DE. Adherence and persistence with branded antidepressants and generic SSRIs among managed care patients with major depressive disorder. Clinicoecon Outcomes Res. 2011;3:63–72. PubMed
Osterberg L, Blaschke T. Adherence to medication. N Engl J Med. 2005;353(5):487–497. PubMed CrossRef
Fontanella CA, Bridge JA, Marcus SC, et al. Factors associated with antidepressant adherence for Medicaid-enrolled children and adolescents. Ann Pharmacother. 2011;45(7-8):898–909. PubMed CrossRef
Paulozzi LJ, Strickler GK, Kreiner PW, et al; Centers for Disease Control and Prevention (CDC). Controlled substance prescribing patterns—prescription behavior surveillance system, eight states, 2013. MMWR Surveill Summ. 2015;64(9):1–14. PubMed CrossRef
Bandelow B, Reitt M, Röver C, et al. Efficacy of treatments for anxiety disorders: a meta-analysis. Int Clin Psychopharmacol. 2015;30(4):183–192. PubMed CrossRef
Wang Z, Whiteside SPH, Sim L, et al. Comparative effectiveness and safety of cognitive behavioral therapy and pharmacotherapy for childhood anxiety disorders: a systematic review and meta-analysis. JAMA Pediatr. 2017;171(11):1049–1056. PubMed CrossRef
Slee A, Nazareth I, Bondaronek P, et al. Pharmacological treatments for generalised anxiety disorder: a systematic review and network meta-analysis. Lancet. 2019;393(10173):768–777. PubMed CrossRef
FDA Drug Safety Communication: FDA warns about serious risks and death when combining opioid pain or cough medicines with benzodiazepines; requires its strongest warning. US Food and Drug Administration. 2016. https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-warns-about-serious-risks-and-death-when-combining-opioid-pain-or
Brent DA, Emslie GJ, Clarke GN, et al. Predictors of spontaneous and systematically assessed suicidal adverse events in the Treatment of SSRI-Resistant Depression in Adolescents (TORDIA) study. Am J Psychiatry. 2009;166(4):418–426. PubMed CrossRef
Neutel CI, Patten SB. Risk of suicide attempts after benzodiazepine and/or antidepressant use. Ann Epidemiol. 1997;7(8):568–574. PubMed CrossRef
Cato V, Holländare F, Nordenskjöld A, et al. Association between benzodiazepines and suicide risk: a matched case-control study. BMC Psychiatry. 2019;19(1):317. PubMed CrossRef
Schulenberg JEJL, O’Malley PM, Bachman JG, et al. Monitoring the Future: National Survey Results on Drug Use, 1975–2017—College Students & Adults Ages 19–55. Volume II. Ann Arbor, MI: Institute for Social Research, The University of Michigan; 2018.
Altmann H, Stahl ST, Gebara MA, et al. Coprescribed benzodiazepines in older adults receiving antidepressants for anxiety and depressive disorders: association with treatment outcomes. J Clin Psychiatry. 2020;81(6):20m13283. PubMed CrossRef
Weisberg RB, Dyck I, Culpepper L, et al. Psychiatric treatment in primary care patients with anxiety disorders: a comparison of care received from primary care providers and psychiatrists. Am J Psychiatry. 2007;164(2):276–282. PubMed CrossRef
Dark T, Flynn HA, Rust G, et al. Epidemiology of emergency department visits for anxiety in the United States: 2009–2011. Psychiatr Serv. 2017;68(3):238–244. PubMed CrossRef
Fischer MA, Stedman MR, Lii J, et al. Primary medication non-adherence: analysis of 195,930 electronic prescriptions. J Gen Intern Med. 2010;25(4):284–290. PubMed CrossRef