Effects of Stimulant Medications in PTSD

Summary

While there have been advances in understanding post-traumatic stress disorder (PTSD) as a disorder and its biological features, unfortunately only one out of five traumatized persons with PTSD reach remission after cycling through evidence-based and/or FDA-approved medications. This is especially unfortunate given that people with PTSD are often from vulnerable populations, or those whose professions entail personal sacrifice. It is clear that new serotonergic antidepressants and atypical antipsychotics will not be sufficient to fix this gap, and new mechanisms of action need to be tested. In the current proposal, the investigators test the hypothesis that mixed amphetamine salts (brand name Adderall), FDA-approved for treating attention deficit hyperactivity disorder (ADHD), can improve PTSD outcomes.

Timeline

Start

2026-09-15

Primary completion

2027-09-15

Completion

2027-09-15

Publications

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• Background Blevins CA, Weathers FW, Davis MT, Witte TK, Domino JL. The Posttraumatic Stress Disorder Checklist for DSM-5 (PCL-5): Development and Initial Psychometric Evaluation. J Trauma Stress. 2015 Dec;28(6):489-98. doi: 10.1002/jts.22059. Epub 2015 Nov 25.
• Background Brenner LA, Betthauser LM, Penzenik M, Germain A, Li JJ, Chattopadhyay I, Frank E, Kupfer DJ, Gibbons RD. Development and Validation of Computerized Adaptive Assessment Tools for the Measurement of Posttraumatic Stress Disorder Among US Military Veterans. JAMA Netw Open. 2021 Jul 1;4(7):e2115707. doi: 10.1001/jamanetworkopen.2021.15707.
• Background Guina J, Rossetter SR, DeRHODES BJ, Nahhas RW, Welton RS. Benzodiazepines for PTSD: A Systematic Review and Meta-Analysis. J Psychiatr Pract. 2015 Jul;21(4):281-303. doi: 10.1097/PRA.0000000000000091.
• Background Weyandt LL, White TL, Gudmundsdottir BG, Nitenson AZ, Rathkey ES, De Leon KA, Bjorn SA. Neurocognitive, Autonomic, and Mood Effects of Adderall: A Pilot Study of Healthy College Students. Pharmacy (Basel). 2018 Jun 27;6(3):58. doi: 10.3390/pharmacy6030058.
• Background Wendt FR, Garcia-Argibay M, Cabrera-Mendoza B, Valdimarsdottir UA, Gelernter J, Stein MB, Nivard MG, Maihofer AX; Post-Traumatic Stress Disorder Working Group of the Psychiatric Genomics Consortium; Nievergelt CM, Larsson H, Mattheisen M, Polimanti R, Meier SM. The Relationship of Attention-Deficit/Hyperactivity Disorder With Posttraumatic Stress Disorder: A Two-Sample Mendelian Randomization and Population-Based Sibling Comparison Study. Biol Psychiatry. 2023 Feb 15;93(4):362-369. doi: 10.1016/j.biopsych.2022.08.012. Epub 2022 Aug 24.
• Background Weafer J, Van Hedger K, Keedy SK, Nwaokolo N, de Wit H. Methamphetamine acutely alters frontostriatal resting state functional connectivity in healthy young adults. Addict Biol. 2020 May;25(3):e12775. doi: 10.1111/adb.12775. Epub 2019 May 16.
• Background Tsai J, Harpaz-Rotem I, Pilver CE, Wolf EJ, Hoff RA, Levy KN, Sareen J, Pietrzak RH. Latent class analysis of personality disorders in adults with posttraumatic stress disorder: results from the National Epidemiologic Survey on Alcohol and Related Conditions. J Clin Psychiatry. 2014 Mar;75(3):276-84. doi: 10.4088/JCP.13m08466.
• Background Stein DJ, Ipser JC, Seedat S. Pharmacotherapy for post traumatic stress disorder (PTSD). Cochrane Database Syst Rev. 2006 Jan 25;2006(1):CD002795. doi: 10.1002/14651858.CD002795.pub2.
• Background Steenkamp MM, Litz BT, Hoge CW, Marmar CR. Psychotherapy for Military-Related PTSD: A Review of Randomized Clinical Trials. JAMA. 2015 Aug 4;314(5):489-500. doi: 10.1001/jama.2015.8370.
• Background Soder HE, Cooper JA, Lopez-Gamundi P, Hoots JK, Nunez C, Lawlor VM, Lane SD, Treadway MT, Wardle MC. Dose-response effects of d-amphetamine on effort-based decision-making and reinforcement learning. Neuropsychopharmacology. 2021 May;46(6):1078-1085. doi: 10.1038/s41386-020-0779-8. Epub 2020 Jul 28.
• Background Shiner B, Westgate CL, Gui J, Maguen S, Young-Xu Y, Schnurr PP, Watts BV. A Retrospective Comparative Effectiveness Study of Medications for Posttraumatic Stress Disorder in Routine Practice. J Clin Psychiatry. 2018 Sep 18;79(5):18m12145. doi: 10.4088/JCP.18m12145.
• Background Shiner B, Forehand JA, Rozema L, Kulldorff M, Watts BV, Trefethen M, Jiang T, Huybrechts KF, Schnurr PP, Vincenti M, Gui J, Gradus JL. Mining Clinical Data for Novel Posttraumatic Stress Disorder Medications. Biol Psychiatry. 2022 Apr 1;91(7):647-657. doi: 10.1016/j.biopsych.2021.10.008. Epub 2021 Oct 20.
• Background Seidemann R, Duek O, Jia R, Levy I, Harpaz-Rotem I. The Reward System and Post-Traumatic Stress Disorder: Does Trauma Affect the Way We Interact With Positive Stimuli? Chronic Stress (Thousand Oaks). 2021 Feb 25;5:2470547021996006. doi: 10.1177/2470547021996006. eCollection 2021 Jan-Dec.
• Background Schultz W. Dopamine reward prediction-error signalling: a two-component response. Nat Rev Neurosci. 2016 Mar;17(3):183-95. doi: 10.1038/nrn.2015.26. Epub 2016 Feb 11.
• Background Reece A, Cooney G, Bull P, Chung C, Dawson B, Fitzpatrick C, Glazer T, Knox D, Liebscher A, Marin S. The CANDOR corpus: Insights from a large multimodal dataset of naturalistic conversation. Sci Adv. 2023 Mar 31;9(13):eadf3197. doi: 10.1126/sciadv.adf3197. Epub 2023 Mar 31.
• Background Platt J, Keyes KM, Koenen KC. Size of the social network versus quality of social support: which is more protective against PTSD? Soc Psychiatry Psychiatr Epidemiol. 2014 Aug;49(8):1279-86. doi: 10.1007/s00127-013-0798-4. Epub 2013 Dec 6.
• Background Okabe-Miyamoto K, Folk D, Lyubomirsky S, Dunn EW. Changes in social connection during COVID-19 social distancing: It's not (household) size that matters, it's who you're with. PLoS One. 2021 Jan 20;16(1):e0245009. doi: 10.1371/journal.pone.0245009. eCollection 2021.
• Background Martin WR, Sloan JW, Sapira JD, Jasinski DR. Physiologic, subjective, and behavioral effects of amphetamine, methamphetamine, ephedrine, phenmetrazine, and methylphenidate in man. Clin Pharmacol Ther. 1971 Mar-Apr;12(2):245-58. doi: 10.1002/cpt1971122part1245. No abstract available.
• Background Markowitz JC, Petkova E, Neria Y, Van Meter PE, Zhao Y, Hembree E, Lovell K, Biyanova T, Marshall RD. Is Exposure Necessary? A Randomized Clinical Trial of Interpersonal Psychotherapy for PTSD. Am J Psychiatry. 2015 May;172(5):430-40. doi: 10.1176/appi.ajp.2014.14070908. Epub 2015 Feb 13.
• Background Markowitz JC, Petkova E, Biyanova T, Ding K, Suh EJ, Neria Y. EXPLORING PERSONALITY DIAGNOSIS STABILITY FOLLOWING ACUTE PSYCHOTHERAPY FOR CHRONIC POSTTRAUMATIC STRESS DISORDER. Depress Anxiety. 2015 Dec;32(12):919-26. doi: 10.1002/da.22436. Epub 2015 Oct 6.
• Background Malikowska-Racia N, Salat K, Nowaczyk A, Fijalkowski L, Popik P. Dopamine D2/D3 receptor agonists attenuate PTSD-like symptoms in mice exposed to single prolonged stress. Neuropharmacology. 2019 Sep 1;155:1-9. doi: 10.1016/j.neuropharm.2019.05.012. Epub 2019 May 11.
• Background Lee R. Mistrustful and Misunderstood: A Review of Paranoid Personality Disorder. Curr Behav Neurosci Rep. 2017 Jun;4(2):151-165. doi: 10.1007/s40473-017-0116-7. Epub 2017 May 18.
• Background Krystal JH, Davis LL, Neylan TC, A Raskind M, Schnurr PP, Stein MB, Vessicchio J, Shiner B, Gleason TC, Huang GD. It Is Time to Address the Crisis in the Pharmacotherapy of Posttraumatic Stress Disorder: A Consensus Statement of the PTSD Psychopharmacology Working Group. Biol Psychiatry. 2017 Oct 1;82(7):e51-e59. doi: 10.1016/j.biopsych.2017.03.007. Epub 2017 Mar 14. No abstract available.
• Background Kirschner H, Molla HM, Nassar MR, de Wit H, Ullsperger M. Methamphetamine-induced adaptation of learning rate dynamics depend on baseline performance. Elife. 2025 Jul 21;13:RP101413. doi: 10.7554/eLife.101413.
• Background Kern DM, Teneralli RE, Flores CM, Wittenberg GM, Gilbert JP, Cepeda MS. Revealing Unknown Benefits of Existing Medications to Aid the Discovery of New Treatments for Post-Traumatic Stress Disorder. Psychiatr Res Clin Pract. 2021 Dec 20;4(1):12-20. doi: 10.1176/appi.prcp.20210019. eCollection 2022 Spring.
• Background Howlett JR, Stein MB. Post-Traumatic Stress Disorder: Relationship to Traumatic Brain Injury and Approach to Treatment. In: Laskowitz D, Grant G, editors. Translational Research in Traumatic Brain Injury. Boca Raton (FL): CRC Press/Taylor and Francis Group; 2016. Chapter 16. Available from http://www.ncbi.nlm.nih.gov/books/NBK326723/
• Background Howlett JR, Campbell-Sills L, Jain S, Heeringa SG, Nock MK, Sun X, Ursano RJ, Stein MB. Attention Deficit Hyperactivity Disorder and Risk of Posttraumatic Stress and Related Disorders: A Prospective Longitudinal Evaluation in U.S. Army Soldiers. J Trauma Stress. 2018 Dec;31(6):909-918. doi: 10.1002/jts.22347. Epub 2018 Nov 21.
• Background Houlihan DJ. Psychostimulant treatment of combat-related posttraumatic stress disorder. J Psychopharmacol. 2011 Nov;25(11):1568-72. doi: 10.1177/0269881110385600. Epub 2010 Oct 8.
• Background Holder N, Woods A, Neylan TC, Maguen S, Seal KH, Bernardy N, Wiechers I, Ryder A, Urbieta AM, Cohen BE. Trends in Medication Prescribing in Patients With PTSD From 2009 to 2018: A National Veterans Administration Study. J Clin Psychiatry. 2021 May 4;82(3):20m13522. doi: 10.4088/JCP.20m13522.
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• Background Gibbons RD, Kupfer DJ, Frank E, Lahey BB, George-Milford BA, Biernesser CL, Porta G, Moore TL, Kim JB, Brent DA. Computerized Adaptive Tests for Rapid and Accurate Assessment of Psychopathology Dimensions in Youth. J Am Acad Child Adolesc Psychiatry. 2020 Nov;59(11):1264-1273. doi: 10.1016/j.jaac.2019.08.009. Epub 2019 Aug 26.
• Background Endicott J, Nee J, Harrison W, Blumenthal R. Quality of Life Enjoyment and Satisfaction Questionnaire: a new measure. Psychopharmacol Bull. 1993;29(2):321-6.
• Background de Wit H, Enggasser JL, Richards JB. Acute administration of d-amphetamine decreases impulsivity in healthy volunteers. Neuropsychopharmacology. 2002 Nov;27(5):813-25. doi: 10.1016/S0893-133X(02)00343-3.
• Background Daly OE. The use of stimulants in the treatment of post traumatic stress disorder: case report. Hum Psychopharmacol. 2000 Jun;15(4):295-300. doi: 10.1002/1099-1077(200006)15:43.0.CO;2-O.
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