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).
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
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.
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