According to the US National Vietnam Veterans’ Readjustment Study, in excess of 25% of those who served during that war experienced PTSD, and more than half were still experiencing symptoms over twenty years after the fighting ended.
The numbers for more recent conflicts are equally stark, with an estimated one in five of veterans returning from Iraq and Afghanistan suffering from PTSD. With so many affected, finding effective treatments for this debilitating condition has an obvious priority.
Disturbed sleep cycles and recurrent nightmares are amongst some of the most pernicious symptoms; while poor sleep quality in the aftermath of trauma is linked to the onset of PTSD in the first place, and has also been implicated in subsequent depression, substance abuse and suicide. If the trials of a new drug from Tonix Pharmaceuticals go according to plan, however, help could soon be on hand.
Officially granted ‘Breakthrough Therapy’ designation by the US Food and Drug Administration (FDA) for the treatment of PTSD in December 2016, Tonmya is currently undergoing Phase 3 trials. The product is a small, fast disintegrating tablet, designed to be dissolved under the tongue and which Tonix says targets mechanisms in the brain which are typically associated with disturbed sleep and nightmares.
The active pharmaceutical ingredient (API) is cyclobenzaprine hydrochloride. Taken daily at bedtime in the earlier Phase 2 dose-finding clinical study, Tonmya 5.6mg demonstrated both its efficacy and safety for the treatment of military-related PTSD against a placebo, achieving a reduction in the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) score – described as ‘the gold standard’ for assessment by the US National Center for PTSD.
Cyclobenzaprine is not itself a new drug; it was first approved by the FDA in 1977. What gives this new product the edge is that Tonmya solves a long-standing problem with its slow oral ingestion. Previous attempts to speed up its absorption have tended to interfere with the stability of the API, but according to US patent number 9636408 B2 that covers the new drug – esoterically titled “Eutectic formulations of cyclobenzaprine hydrochloride and amitriptyline hydrochloride” – that has now been overcome.
The Phase 3 study, involving 550 participants, ends in October 2018 and, if the topline data proves what the FDA terms “statistically very persuasive”, a single-study new drug application approval for use in PTSD could well be on the cards. Even as this very new pharmaceutical preparation gradually progresses towards acceptance, at the other end of the scale, there is a growing chorus calling for one of the oldest drugs known to humanity to be made more readily available to PTSD sufferers today.
Although the medicinal effects of cannabis were understood by the ancient Chinese by at least 2737 BCE – and probably earlier – in recent times the therapeutic use of prescribed cannabis and cannabinoid-based drugs has been an enduring topic of debate, and a sure-fire headline-grabber. California became the first state to legalise medical marijuana in defiance of US federal law back in 1996, and as of April 2017, no fewer than 29 other states have followed the Californian lead, even though cannabis remains illegal at the federal level. A further 16 allow the use of cannabidiol (CBD) products.
“Cannabis has proven remarkably effective as a palliative treatment for PTSD” says Michael Krawitz, executive director of Veterans for Medical Cannabis Access. “The VA [US Department of Veterans Affairs] at our request passed a policy that allows for veterans to utilise state-legal cannabis in their treatment plans.”
Nevertheless, it seems that not everyone has equal access to it. The illnesses and conditions which qualify for the medical marijuana program (MMP) of individual states differ, with 24 of the 29 permitting cannabis usage for PTSD, while the rest do not, although calls are mounting for this to change. Active service personnel face additional difficulties, since the US military establishment is, understandably, not entirely comfortable endorsing the use of ‘weed’ amongst the armed forces.
“[The] Department of Defense mostly views cannabis through the lens of drug abuse treatment and will likely require FDA approved medications before deploying them in the field,” Krawitz explains.
For now at least, the number of drugs specifically available to treat PTSD remains small, and the evidence base for pharmaceuticals in this condition limited. According to Krawitz, in the US only two are approved for the condition by the FDA, and “each carries a black box suicide warning and fails to provide relief for many patients.” In the UK, according to the National Institute for Health and Care Excellence (NICE) Clinical guideline CG26, only one drug in the list of recommendations holds a product licence for PTSD.
Other pharmaceuticals are, of course, used ‘off-label’ to treat PTSD, but as Krawitz noted in a recent
opinion piece for City & State New York, in the view of the US Army surgeon general, they commonly carry risks that far outweigh their potential benefit.
While drugs may have a place as part of some individual treatment regimes, there is a long way to go before a routine, first-resort pharmaceutical route will be available – if ever. For most sufferers, trauma-focused psychological therapy is the frontline treatment.
Cognitive behavioural therapy
Trauma-focused cognitive behavioural therapy (TFCBT) is one of the most often used of these approaches, and as the name suggests, combines elements of two effective and well established psychotherapies.
According to the UK veterans’ mental health charity, Combat Stress, the goal of behavioural therapy is to “weaken the connections between troublesome situations and our habitual reactions to them” through exposure to those situations, usually through guided imagery, to reduce and eventually remove the anxiety they evoke. Cognitive therapy enables patients to understand how their thinking patterns affect their symptoms, and by helping to then challenge those patterns, replace them with more constructive and healthy thoughts.
TFCBT also helps address the feelings of shame, blame, guilt and stigma, which Combat Stress say are common barriers to recovery in those suffering from PTSD, and to help sufferers confront their experiences and question the automatic assumptions linked to those traumatic events.
The successes of this and similar programmes of therapy are impressive. According to a spokesman for the specialist UK charity, PTSD Resolution, of the more than 1,000 veterans they have treated, “nearly eight out of 10 report that they need no further treatment, confirmed by the therapist providing treatment. This is with an average of five sessions of treatment.”
He explains that the approach avoids some of the pitfalls that can occur with group and other forms of ‘talking’ therapy, such as the possible traumatisation of other members of the group or the presiding counsellor or therapist, while some sufferers can feel inhibited talking about extremely disturbing, violent experiences. “Veterans are not required to talk about the traumatic events with Resolution,” he says. “The programme policy is that re-exposure is better done in the client’s visual imagination and while in a relaxed state, protecting confidentiality and reducing distress. This is a relatively new development of TFCBT, similar to imagery re-scripting and reprocessing therapy (IRRT).”
While there are some veterans that this approach cannot help as a result of additional complications, such as substance-related or other psychological difficulties, Resolution say they can deliver their programme for just £550 on average. The saving to sufferers, their families and to the state in terms of the cost family breakdown, lost jobs and benefits, they point out, runs into considerably more.
Mental trauma has, of course, been a feature of warfare throughout the ages, but at least now there is greater understanding, viable treatments and ongoing research to help heal the invisible wounds the modern battlefield so often inflicts.