It Is Time to Address the Crisis in the Pharmacotherapy of Posttraumatic Stress Disorder: A Consensus Statement of the PTSD Psychopharmacology Working Group

Krystal, John H.; Davis, Lori L.; Neylan, Thomas C.; Raskind, Murray A.; Schnurr, Paula P.; Stein, Murray B.; Vessicchio, Jennifer C.; Shiner, Brian; Gleason, Theresa; Huang, Grant D.

doi:10.1016/j.biopsych.2017.03.007

Cited by 210 publications

(133 citation statements)

References 58 publications

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“…PTSD has a chronic and often severe time course, with only a minority of patients achieving full remission (2). The therapeutic needs of this group are great, and currently available treatment options are limited (3). Prolonged exposure (PE) therapy, a clinical implementation of extinction learning, has strong support for clinical efficacy in PTSD.…”

mentioning

confidence: 99%

Elevated Anandamide, Enhanced Recall of Fear Extinction, and Attenuated Stress Responses Following Inhibition of Fatty Acid Amide Hydrolase: A Randomized, Controlled Experimental Medicine Trial

Mayo

Asratian

Lindé

et al. 2020

Biological Psychiatry

162

105

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BACKGROUND: Posttraumatic stress disorder, an area of large unmet medical needs, is characterized by persistence of fear memories and maladaptive stress responses. In rodents, elevation of the endocannabinoid anandamide due to inhibition of fatty acid amide hydrolase (FAAH) facilitates fear extinction and protects against the anxiogenic effects of stress. We recently reported that elevated anandamide levels in people homozygous for a loss-of-function FAAH mutation are associated with a similar phenotype, suggesting a translational validity of the preclinical findings. METHODS: In this double-blind, placebo-controlled experimental medicine study, healthy adults were randomized to an FAAH inhibitor (PF-04457845, 4 mg orally, once daily; n = 16) or placebo (n = 29) for 10 days. On days 9 and 10, participants completed a task battery assessing psychophysiological indices of fear learning, stress reactivity, and stress-induced affective responses. RESULTS: FAAH inhibition produced a 10-fold increase in baseline anandamide. This was associated with potentiated recall of fear extinction memory when tested 24 hours after extinction training. FAAH inhibition also attenuated autonomic stress reactivity, assessed via electrodermal activity, and protected against stress-induced negative affect, measured via facial electromyography. CONCLUSIONS: Our data provide preliminary human evidence that FAAH inhibition can improve the recall of fear extinction memories and attenuate the anxiogenic effects of stress, in a direct translation of rodent findings. The beneficial effects of FAAH inhibition on fear extinction, as well as stress-and affect-related behaviors, provide a strong rationale for developing this drug class as a treatment for posttraumatic stress disorder.

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mentioning

confidence: 99%

Elevated Anandamide, Enhanced Recall of Fear Extinction, and Attenuated Stress Responses Following Inhibition of Fatty Acid Amide Hydrolase: A Randomized, Controlled Experimental Medicine Trial

Mayo

Asratian

Lindé

et al. 2020

Biological Psychiatry

162

105

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“…This scenario has pushed clinicians to adopt poly-pharmacological approaches for the vast majority of their patients, using off-label medications regarding which there is little empirical guidance concerning risks or benefits. 26 Among these medications, we find benzodiazepines, which are not only ineffective but are also associated with negative psychotherapy outcomes, aggression, depression, and illicit substance use in PTSD patients. 29 While the situation is especially troubling in terms of depression and PTSD, the psychiatric drugs crisis is widespread.…”

Section: Examples Of the Crisismentioning

confidence: 89%

“…[23][24][25] The pharmacological treatment of PTSD is also in crisis, as the PTSD Psychopharmacology Working Group of the US Department of Veteran Affairs recently stated. 26 The prevalence of lifetime PTSD among the general population is approximately 6.8%. 27 Despite this high prevalence, there are only two medications approved for the treatment of PTSD, sertraline and paroxetine, which only produce reduction in symptom severity rather than remission of PTSD.…”

Section: Examples Of the Crisismentioning

confidence: 99%

“…27 Despite this high prevalence, there are only two medications approved for the treatment of PTSD, sertraline and paroxetine, which only produce reduction in symptom severity rather than remission of PTSD. 26 The fact that antidepressants cannot produce remission of PTSD symptomatology may be because PTSD is not an aberrant response of the brain, but a normal response to an aberrant situation. This is why patients with PTSD tend to respond better to psychosocial treatments than to pharmacotherapy.…”

Section: Examples Of the Crisismentioning

confidence: 99%

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Can Psychedelics be the Treatment for the Crisis in Psychopharmacology?

Oña¹,

Bouso²

2019

Preprint

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“…A recent letter to the editor Krystal et al (2017) reported a 2017 consensus statement of the PTSD Psychopharmacology Working Group. They advise that "there seems to be no visible horizon for advancements in medications that treat symptoms or enhance outcomes in persons with a diagnosis of PTSD" (p. e51).…”

Section: Remediation Of Ptsdmentioning

confidence: 99%

Remediation of PTSD in a Combat Veteran: A Case Study

Lindenfeld¹,

Rozelle²,

Hummer

et al. 2019

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The posttraumatic stress disorder (PTSD) condition is a systemic neuroinflammatory state that emanates from a failure to recover from traumatic occurrence(s). Major complications associated with PTSD include problems with impulse control and issues related to verbal and physical outbursts of anger and rage. The Veteran's Administration (VA) projects a post-9/11 veteran population of around 3.5 million by 2019. Emotional problems are prevalent among combat service members and veterans with about half of the group suffering from various symptoms of PTSD. Three in four among them report they are reliving traumas in the form of flashbacks and nightmares. Current mental health treatments have not fully remediated the negative impact that results from PTSD. We present a case study of a novel and transformative treatment approach called Reconsolidation Enhancement by Stimulation of Emotional Triggers (RESET) Therapy. The intervention uses binaural sound to unlock the memory reconsolidation process, thereby releasing the emotional component of experienced trauma. RESET Therapy offers a compelling therapeutic adjunct to the practicing biofeedback/neurofeedback clinician, who is under constant pressure to deliver interventions that are rapid, tolerable, and cost-effective. Additionally, the treatment spares the therapist from repeated exposures to the raw limbic activity of traumatized patients, thereby minimizing the potential for vicarious traumatization.

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It Is Time to Address the Crisis in the Pharmacotherapy of Posttraumatic Stress Disorder: A Consensus Statement of the PTSD Psychopharmacology Working Group

Cited by 210 publications

References 58 publications

Elevated Anandamide, Enhanced Recall of Fear Extinction, and Attenuated Stress Responses Following Inhibition of Fatty Acid Amide Hydrolase: A Randomized, Controlled Experimental Medicine Trial

Elevated Anandamide, Enhanced Recall of Fear Extinction, and Attenuated Stress Responses Following Inhibition of Fatty Acid Amide Hydrolase: A Randomized, Controlled Experimental Medicine Trial

Can Psychedelics be the Treatment for the Crisis in Psychopharmacology?

Remediation of PTSD in a Combat Veteran: A Case Study

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