Tonix Pharmaceuticals Holding Corp. (TNXP)

Tonix Pharmaceuticals is currently enrolling participants in a Phase 3 trial for posttraumatic stress disorder (PTSD). For more information, please visit www.recoverystudy.com or www.clinicaltrials.gov (NCT03841773).

Therapeutic Areas
: Posttraumatic Stress Disorder

Posttraumatic Stress Disorder

What is Posttraumatic stress disorder (PTSD)?

PTSD is a serious chronic psychiatric illness defined as a maladaptive prolonged stress response which occurs after experiencing severely injurious traumatic event(s). While initially recognized as a stress response to military combat ('shell shock') it is now known that many civilians exposed to life-threatening events, sexual assault, natural disasters or accidents, can develop PTSD.1,2

Globally, the vast majority of people (~70%) will experience or witness one or more life-threatening traumatic events in their life-time.3 For many, the response to an isolated traumatic event will dissipate over days or a few weeks and have little or no long-term consequences.

For some individuals, however, the response to trauma will become chronic, lasting for more than one month and persisting for years, and, in many cases, decades. These individuals are considered to have PTSD and will experience psychiatric symptoms (flashbacks, intense anxiety and avoidance, emotional numbness, intense guilt or worry, agitation, sleep disturbances), and as a consequence, experience impaired social functioning, occupational disability, and an overall poor quality of life. PTSD is also characterized by overall high utilization of healthcare services, adding to the significant economic burden from the condition.4,5

How prevalent is PTSD?

PTSD is a global problem, with the lifetime prevalence of PTSD estimated to be 3.9%,6 or affecting an estimated 200-300 million individuals, on a global basis.

Based on U.S. 12-month prevalence rates,1,2 it is estimated that about 11.0 million American adults suffer from DSM-5-defined PTSD in a given year. Similar to other psychiatric disorders, only approximately half of these individuals will seek treatment at some point in the course of the disease,7 and of these, approximately 40% (~1.8 million) will be formally diagnosed with PTSD in any given year.8 Lack of awareness, the negative stigma associated with PTSD (like other mental disorders), as well as the limitations of existing treatment options, may be addressed by increased societal awareness and acceptance as well as the introduction of new therapeutic options.

What are the current treatments for PTSD and what are their limitations?

In the U.S., almost all newly diagnosed patients (91%) receive treatment, most commonly with psychotherapy and pharmacotherapy combined (59%), or as psychotherapy (20%) or pharmacotherapy (16%) alone.8

Various forms of psychotherapy, including cognitive-behavioral therapy (CBT), are used to treat PTSD, although there is an extreme paucity of appropriately trained mental health professionals available to administer these therapies on an on-going basis. Furthermore, although particular trauma-focused behavioral therapies have been shown to be efficacious in PTSD, the gains are modest for most patients, particularly for combat veterans.9

Pharmacotherapy is also used to reduce the symptoms of PTSD. A wide variety of psychiatric drug classes are used to treat PSTD, frequently in combinations.8,10 Only the SSRIs have been extensively studied in large clinical trials, and two have been approved by the regulatory authorities (FDA (U.S.), EMA (EU)) for the treatment of PTSD. The benzodiazepines are frequently used off-label and in combination with the SSRI,8 potentially to address sleep problems not addressed by SSRIs.10

The SSRIs have several limitations for the treatment of PTSD. While the two approved SSRIs have been shown to be efficacious in studies involving predominantly civilians and females, studies are lacking or have been negative in a predominantly male population with combat-related PTSD.11 Second, based on clinical trial results, approximately 40% of patients will not respond to an SSRI, and the majority (70%) do not achieve complete remission.12 As a result, many receive augmentation or combination therapies, especially hypnotic sleep medications,8 despite little or no evidence of benefit.13 Finally, intolerant side-effects including loss of sexual drive, gastrointestinal disturbances and weight gain also limit the utility of SSRIs for the treatment of PTSD, highlighting the major unmet need.14 Currently, 44% of newly diagnosed patients receive an SSRI.8

Similar to the SSRIs, benzodiazepines are used in 44% of newly diagnosed patients.8 Despite their relatively high frequency of use, they have not been shown to offer long-term benefit, and may be abused as well as interfere with psychotherapy, and are thus not recommended by treatment guidelines for PTSD.15

New therapeutic options are needed to offer viable alternatives to the SSRIs, the benzodiazepines and the other classes of drugs which are used off-label with little or no clinical evidence of benefit.15,16


To learn about Tonmya for PTSD

To learn about TNX-601 for PTSD

  1. Goldstein RB, Smith SM, Chou SP, Saha TD, Jung J, Zhang H, Pickering RP, Ruan WJ, Huang B, Grant BF. The epidemiology of DSM-5 posttraumatic stress disorder in the United States: results from the National Epidemiologic Survey on Alcohol and Related Conditions-III. Soc Psychiatry Psychiatr Epidemiol. 2016;51(8):1137-1148.
  2. Pietrzak RH, Goldstein RB, Southwick SM, Grant BF. Prevalence and Axis I comorbidity of full and partial posttraumatic stress disorder in the United States: results from Wave 2 of the National Epidemiologic Survey on Alcohol and Related Conditions. J Anxiety Disord. 2011;25(3):456-465.
  3. Kessler RC, Aguilar-Gaxiola S, Alonso J, Benjet C, Bromet EJ, Cardoso G, Degenhardt L, de Girolamo G, Dinolova RV, Ferry F, Florescu S, Gureje O, Haro JM, Huang Y, Karam EG, Kawakami N, Lee S, Lepine JP, Levinson D, Navarro-Mateu F, Pennell BE, Piazza M, Posada-Villa J, Scott KM, Stein DJ, Ten Have M, Torres Y, Viana MC, Petukhova MV, Sampson NA, Zaslavsky AM, Koenen KC. Trauma and PTSD in the WHO World Mental Health Surveys. Eur J Psychotraumatol. 2017;8(sup5):1353383.
  4. Affairs V. Analysis of VA Health Care Utilization among Operation Enduring Freedom (OEF), Operation Iraqi Freedom (OIF), and Operation New Dawn (OND) Veterans: Cumulative from 1st Qtr FY 2002 through 2nd Qtr FY 2015 (October 1, 2001 – March 31, 2015). In: Group EPP-DH, Health OoP, eds; 2015.
  5. Congressional Budget Office. The Veterans Health Administration's Treatment of PTSD and Traumatic Brain Injury Among Recent Combat Veterans. Washington, D.C.; 2012.
  6. Koenen KC, Ratanatharathorn A, Ng L, McLaughlin KA, Bromet EJ, Stein DJ, Karam EG, Meron Ruscio A, Benjet C, Scott K, Atwoli L, Petukhova M, Lim CCW, Aguilar-Gaxiola S, Al-Hamzawi A, Alonso J, Bunting B, Ciutan M, de Girolamo G, Degenhardt L, Gureje O, Haro JM, Huang Y, Kawakami N, Lee S, Navarro-Mateu F, Pennell BE, Piazza M, Sampson N, Ten Have M, Torres Y, Viana MC, Williams D, Xavier M, Kessler RC. Posttraumatic stress disorder in the World Mental Health Surveys. Psychol Med. 2017;47(13):2260-2274.
  7. Roberts AL, Gilman SE, Breslau J, Breslau N, Koenen KC. Race/ethnic differences in exposure to traumatic events, development of post-traumatic stress disorder, and treatment-seeking for post-traumatic stress disorder in the United States. Psychol Med. 2011;41(1):71-83.
  8. IMS. Market Sizing and Treatment Dynamics: PTSD Patients. On file 2016.
  9. Schnurr PP, Friedman MJ, Foy DW, Shea MT, Hsieh FY, Lavori PW, Glynn SM, Wattenberg M, Bernardy NC. Randomized trial of trauma-focused group therapy for posttraumatic stress disorder: results from a department of veterans affairs cooperative study. Arch Gen Psychiatry. 2003;60(5):481-489.
  10. Bernardy NC, Lund BC, Alexander B, Friedman MJ. Prescribing trends in veterans with posttraumatic stress disorder. J Clin Psychiatry. 2012;73(3):297-303.
  11. Friedman MJ, Marmar CR, Baker DG, Sikes CR, Farfel GM. Randomized, double-blind comparison of sertraline and placebo for posttraumatic stress disorder in a Department of Veterans Affairs setting. J Clin Psychiatry. 2007;68(5):711-720.
  12. Kelmendi B, Adams TG, Yarnell S, Southwick S, Abdallah CG, Krystal JH. PTSD: from neurobiology to pharmacological treatments. Eur J Psychotraumatol. 2016;7:31858.
  13. Ipser JC, Stein DJ. Evidence-based pharmacotherapy of post-traumatic stress disorder (PTSD). Int J Neuropsychopharmacol. 2012;15(6):825-840.
  14. Steckler T, Risbrough V. Pharmacological treatment of PTSD - established and new approaches. Neuropharmacology. 2012;62(2):617-627.
  15. TMoPSD Work Group. VA/DoD Clinical Practice Guideline for the Management of Posttraumatic Stress Disorder and Acute Stress Disorder. In: Veterans Affairs, DoD, eds. Version 3.0; 2017.
  16. Krystal JH, Davis LL, Neylan TC, M AR, Schnurr PP, Stein MB, Vessicchio J, Shiner B, Gleason TD, 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;82(7):e51-e59.