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By: Aniruddha M. Railkar

Ani Railkar Imagine being treated for a disorder but still not seeing improvement in symptoms. Imagine not being able to discontinue treatment. Now imagine being treated with something that not only relieves the symptoms, but keeps you symptom-free four years after discontinuing treatment. This is exactly what some war veterans are experiencing.

PTSD, or posttraumatic stress disorder, is an anxiety disorder experienced by individuals who are victims of traumatic situations like accidents, violence, rape, or combat.

Stress can be of two types: acute or chronic. Acute stress is experienced by victims immediately after the trauma has occurred, for example a terrorist attack or natural disaster.Soldier - blog post image - final

But this blog post will focus on chronic stress, which is experienced by victims long after the trauma has occurred. According to the American Psychiatric Association (APA), psychotherapy is the first recommended approach. Excellent results have been obtained with cognitive behavioral therapy (CBT), but when patients don’t respond well to psychotherapy, psychopharmacology (treatment with medication) is the next approach. Among the medications used to treat PTSD, the selective serotonin reuptake inhibitors (SSRi’s) are the first line of therapy and have been very successful. Tricyclic antidepressants and monoamine oxidase inhibitors (MAOI’s) have also been used with some success in male combat veterans, but they were never used in women. Some of the symptoms of PTSD, like anxiety and sleeplessness, have been effectively treated with benzodiazepines, but the return of symptoms upon discontinuation of therapy, dependence, and abuse potential have limited their use. Anticonvulsants, antipsychotics, and adrenergic inhibitors have been used with some success as well. Antipsychotics seem to work when SSRi’s have not been effective. But large controlled clinical trials have not been conducted with these three classes of drugs.

However, it seems like a much maligned party drug called ecstasy is showing promise. The chemical name of ecstasy is 3,4-methylenediamine methamphetamine (MDMA), also known as “Molly.” In a proof of concept (phase 1) study, 83% of the people given MDMA in conjunction with psychotherapy reported symptom relief as compared to 25% who got a placebo and psychotherapy. The MDMA group was symptom-free for up to four years after treatment. A phase 2 study consisting of 136 patients was recently completed, but the data are still being analyzed. Phase 3 could start sometime in 2017, and if all goes well, Food and Drug Administration approval could be obtained by 2021.

Chemical structure of ecstasy

Chemical structure of ecstasy

People who have undergone treatment with SSRi’s and MDMA say that their experience with MDMA is better and without the side effects associated with the SSRi’s. Similar studies are being carried out in Switzerland, Israel, and Britain using lysergic acid diethylamide (LSD), MDMA, and marijuana. But so far these studies are being funded by nonprofit groups. But there is mounting evidence that MDMA is beneficial for treatment of PTSD. If more successful studies get reported, there is a possibility that the government might fund a larger study. In order for it to be approved, large scale double-blind, placebo-controlled studies are needed. Sometimes it is not possible to get a grasp for the full spectrum of side effects unless a larger population has been tested. If these studies are indeed successful, then by all means, MDMA should be approved for that indication. I believe we owe it to the survivors of severe trauma.

Aniruddha (Ani) M. Railkar is director, CMC, at Tarsa Therapeutics. He is the current chair of the PHILADELPHIA PHARMACEUTICAL FORUM discussion group.