Travma Sonrası Stres Bozukluğu Psikofarmakolojisi
Özet
Travma sonrası stres bozukluğu (TSSB), travmatik olayların ardından gelişen ve en az bir ay süren fizyolojik, psikolojik ve duygusal belirtilerle karakterize, işlevselliği bozan bir ruhsal bozukluktur. Dünya genelinde yaşam boyu yaygınlığı %3,9 olan bu hastalıkta genç yaş, kadın cinsiyet ve işsizlik gibi sosyodemografik faktörler risk artışıyla ilişkilidir. Tedavide travma odaklı psikoterapiler birinci basamak müdahale olarak tüm uluslararası klinik rehberler tarafından ilk sırada önerilmektedir. Farmakolojik tedaviler ise psikoterapiye direnç, şiddetli komorbidite veya hasta isteksizliği gibi durumlarda ikincil bir seçenek, güçlendirme ya da kombinasyon tedavisi olarak devreye girmektedir. İlaç tedavilerinde en güçlü kanıt tabanına sahip ajanlar SSRI grubundan fluoksetin, paroksetin, sertralin ile bir SNRI olan venlafaksindir. Atipik antipsikotikler belirli semptomlar ve özel popülasyonlar için tercih edilebilirken, benzodiazepinlerin kullanımı etkisiz bulunmuş ve taşıdığı riskler nedeniyle önerilmemiştir. Prazosin, TSSB ile ilişkili kabusların ve uyku bozukluklarının yönetiminde en güçlü kanıtlara sahip ajandır. Son dönemde MDMA ve ketamin gibi psikedelik maddelerin psikoterapiyi destekleyici kullanımı umut verici yeni yaklaşımlar olarak araştırılmaktadır. Klinik kılavuzlar farmakoterapinin semptom bazlı seçilmesini ve kanıta dayalı yönetimini önermektedir.
Post-traumatic stress disorder (PTSD) is a psychological disorder characterized by physiological, psychological, and emotional symptoms developing after traumatic events, lasting for at least one month, and impairing functionality. With an international lifetime prevalence of 3.9%, risk factors such as young age, female gender, and unemployment are associated with an increased risk of PTSD. In treatment, trauma-focused psychotherapies are recommended as the first-line intervention by all international clinical practice guidelines. Pharmacological treatments serve as a secondary option, augmentation, or combination therapy in cases of psychotherapy resistance, severe comorbidity, or patient reluctance. The medications with the strongest evidence base are SSRIs including fluoxetine, paroxetine, sertraline, and the SNRI venlafaxine. While atypical antipsychotics may be preferred for specific symptoms and distinct populations, the use of benzodiazepines has been found ineffective and is not recommended due to associated risks. Prazosin remains the agent with the strongest evidence base for treating PTSD-related nightmares and sleep disturbances. Recently, the use of psychedelics such as MDMA and ketamine as catalysts for psychotherapy is being investigated as promising novel approaches. Clinical guidelines advise symptom-based selection and evidence-based management of pharmacotherapy.
Referanslar
Diagnostic and Statistical Manual of Mental Disorders. 5th ed. Washington D.C: American Psychiatric Association.; 2013.
Koenen KC, Ratanatharathorn A, Ng L, et al. Posttraumatic stress disorder in the World Mental Health Surveys. Psychol Med. 2017 Oct;47(13):2260–74.
Fulton JJ, Calhoun PS, Wagner HR, et al. The prevalence of posttraumatic stress disorder in Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) Veterans: a meta-analysis. J Anxiety Disord. 2015 Apr;31:98–107.
Kapfhammer HP. Patient-reported outcomes in post-traumatic stress disorder Part II: Focus on pharmacological treatment. Dialogues in Clinical Neuroscience. 2014 Jun 30;16(2):227–37.
Forman-Hoffman V, Middleton JC, Feltner C, et al. Psychological and Pharmacological Treatments for Adults With Posttraumatic Stress Disorder: A Systematic Review Update. Agency for Healthcare Research and Quality (US), Rockville MD. 2018 May.
Bisson JI, Wright LA, Jones KA, et al. Preventing the onset of post traumatic stress disorder. Clinical Psychology Review. 2021 Jun;86:102004.
Lewis C, Roberts NP, Andrew M, et al. Psychological therapies for post-traumatic stress disorder in adults: systematic review and meta-analysis. European Journal of Psychotraumatology. 2020 Dec 31;11(1):1729633.
Pitman RK. Harnessing Reconsolidation to Treat Mental Disorders. Biol Psychiatry. 2015 Dec 15;78(12):819–20.
Bertolini F, Robertson L, Bisson JI, et al. Early pharmacological interventions for universal prevention of post-traumatic stress disorder (PTSD). Cochrane Database of Systematic Reviews. 2022 Feb 10;2022(2).
Wallace D, Cooper J. Update on the management of post traumatic stress disorder. Australian Prescriber. 2015 Apr 1;38(2):55–9.
Thakur A, Choudhary D, Kumar B, et al. A Review on Post-traumatic Stress Disorder (PTSD): Symptoms, Therapies and Recent Case Studies. Current Molecular Pharmacology. 2022 Jun;15(3):502–16.
Williams T, Phillips NJ, Stein DJ, et al. Pharmacotherapy for post traumatic stress disorder (PTSD). Cochrane Database of Systematic Reviews. 2022 Mar 2;2022(3).
Hoskins M, Pearce J, Bethell A, et al. Pharmacotherapy for post-traumatic stress disorder: Systematic review and meta-analysis. British Journal of Psychiatry. 2015 Feb 2;206(2):93–100.
Huang ZD, Zhao YF, Li S, et al. Comparative Efficacy and Acceptability of Pharmaceutical Management for Adults With Post-Traumatic Stress Disorder: A Systematic Review and Meta-Analysis. Frontiers in Pharmacology. 2020 May 8;11.
Hoskins MD, Bridges J, Sinnerton R, et al. Pharmacological therapy for post-traumatic stress disorder: a systematic review and meta-analysis of monotherapy, augmentation and head-to-head approaches. Eur J Psychotraumatol. 2021;12(1):1802920.
Guina J, Rossetter SR, DeRhodes BJ, et al. Benzodiazepines for PTSD. Journal of Psychiatric Practice. 2015 Jul;21(4):281–303.
Geldenhuys C, van den Heuvel LL, Steyn P, et al. Pharmacological Management of Nightmares Associated with Posttraumatic Stress Disorder. CNS Drugs. 2022 Jul 10;36(7):721–37.
Phoenix Australia Centre for Posttraumatic Mental Health . Australian Guidelines for the Prevention and Treatment of Acute Stress Disorder, Posttraumatic Stress Disorder, and Complex Posttraumatic Stress Disorder. National Health and Medical Research Council; Canberra, Australia: 2020.
Reist C, Streja E, Tang CC, et al. Prazosin for treatment of post-traumatic stress disorder: a systematic review and meta-analysis. CNS Spectrums. 2021 Aug 4;26(4):338–44.
Raskind MA, Peskind ER, Chow B, et al. Trial of Prazosin for Post-Traumatic Stress Disorder in Military Veterans. New England Journal of Medicine. 2018 Feb 8;378(6):507–17.
Raskind MA, Peterson K, Williams T, et al. A trial of prazosin for combat trauma PTSD with nightmares in active-duty soldiers returned from Iraq and Afghanistan. Am J Psychiatry. 2013 Sep;170(9):1003–10.
Vermetten E, Krediet E, Bostoen T, et al. Psychedelics in the treatment of PTSD. Tijdschr Psychiatr. 2020;62(8):640–9.
Mithoefer MC, Feduccia AA, Jerome L, et al. MDMA-assisted psychotherapy for treatment of PTSD: study design and rationale for phase 3 trials based on pooled analysis of six phase 2 randomized controlled trials. Psychopharmacology (Berl). 2019 Sep;236(9):2735–45.
Feder A, Parides MK, Murrough JW, et al. Efficacy of intravenous ketamine for treatment of chronic posttraumatic stress disorder: a randomized clinical trial. JAMA Psychiatry. 2014 Jun;71(6):681–8.
Albott CS, Lim KO, Forbes MK, et al. Efficacy, Safety, and Durability of Repeated Ketamine Infusions for Comorbid Posttraumatic Stress Disorder and Treatment-Resistant Depression. The Journal of Clinical Psychiatry. 2018 Jun 27;79(3).
Pradhan B, Wainer I, Moaddel R, et al. Trauma Interventions using Mindfulness Based Extinction and Reconsolidation (TIMBER) psychotherapy prolong the therapeutic effects of single ketamine infusion on post-traumatic stress disorder and comorbid depression: a pilot randomized, placebo-controlled, crossover clinical trial. Asia Pacific Journal of Clinical Trials: Nervous System Diseases. 2017;2(3):80.
Jetly R, Heber A, Fraser G, et al. The efficacy of nabilone, a synthetic cannabinoid, in the treatment of PTSD-associated nightmares: A preliminary randomized, double-blind, placebo-controlled cross-over design study. Psychoneuroendocrinology. 2015 Jan;51:585–8.
Krediet E, Bostoen T, Breeksema J, et al. Reviewing the Potential of Psychedelics for the Treatment of PTSD. International Journal of Neuropsychopharmacology. 2020 Jun 24;23(6):385–400.
Moore BA, Pujol L, Waltman S, et al.Management of Post-traumatic Stress Disorder in Veterans and Military Service Members: A Review of Pharmacologic and Psychotherapeutic Interventions Since 2016. Curr Psychiatry Rep. 2021;23(2):9.
Courtois, CA, Brown, LS, Cook J, et al. Clinical Practice Guideline for the Treatment of Posttraumatic Stress Disorder (PTSD) in Adults American Psychological Association Guideline Development Panel for the Treatment of PTSD in Adults Adopted as APA Policy February 24, 2017.
ISTSS PTSD prevention and treatment guidelines: methodology and recommendation. International Society for Traumatic Stress Studies. 2018.
National Institute for Health and Care Excellence (NICE) Post-Traumatic Stress Disorder. National Institute for Health and Care Excellence (NICE); London, UK: 2018.
Department of Veterans Affairs, Department of Defense. VA/DOD Clinical Practice Guideline for the Management of Posttraumatic Stress Disorder and Acute Stress Disorder. Department of Veterans Affairs, Department of Defense; Washington DC, USA: 2017.
