Basant Pradhan

Nonconventional interventions for chronic post-traumatic stress disorder: Ketamine, repetitive trans-cranial magnetic stimulation (rTMS), and alternative approaches

ABSTRACT It is alarming that only 59% of those who have post-traumatic stress disorder (PTSD) respond to selective serotonin reuptake inhibitors. Many existing treatments, both pharmacological and nonpharmacological, do not directly target trauma memories that lay at the core of the PTSD pathogenesis. Notable exceptions are medications like ketamine and propranolol and trauma-focused psychotherapies like eye-movement desensitization and reprocessing therapy (developed by Shapiro) and Trauma Interventions using Mindfulness Based Extinction and Reconsolidation (TIMBER) for trauma memories (developed by Pradhan). Although the antidepressant effects of ketamine are no longer news, ketamine’s effects on treatment refractory PTSD (TR-PTSD) is a recent concept. As TR-PTSD has a marked public health burden and significant limitations in terms of treatment interventions, a thorough assessment of current strategies is required. Research to bring clarity to the underlying pathophysiology and neurobiology of TR-PTSD delineating the chemical, structural, and circuitry abnormalities will take time. In the interim, in the absence of a 1-size-fits-all therapeutic approach, pragmatically parallel lines of research can be pursued using the pharmacological and nonpharmacological treatments that have a strong theoretical rationale for efficacy. This article aims to review the current literature on interventions for PTSD, most notably ketamine, trans-cranial magnetic stimulation treatment, yoga and mindfulness interventions, and TIMBER. We present an outline for their future use, alone as well as in combination, with a hope of providing additional insights as well as advocating for developing more effective therapeutic intervention for this treatment-resistant and debilitating condition.

Ketamine, Transcranial Magnetic Stimulation, and Depression Specific Yoga and Mindfulness Based Cognitive Therapy in Management of Treatment Resistant Depression: Review and Some Data on Efficacy

Depression affects about 121 million people worldwide and prevalence of major depressive disorder (MDD) in US adults is 6.4%. Treatment resistant depression (TRD) accounts for approximately 12–20% of all depression patients and costs

Role of Repetitive Transcranial Magnetic Stimulation (rTMS) in Treatment of Addiction and Related Disorders: A Systematic Review

29–

d-Serine is a potential biomarker for clinical response in treatment of post-traumatic stress disorder using (R,S)-ketamine infusion and TIMBER psychotherapy: A pilot study

48 billion annually. Ketamine and repetitive transcranial magnetic stimulation (rTMS) have useful roles in TRD, but their utility in long term is unknown. As per the latest literature, the interventions using Yoga and meditation including the mindfulness based cognitive therapy (MBCT) have been useful in treatment of depression and relapse prevention. We present a review of rTMS, ketamine, and MBCT and also report efficacy of a depression specific, innovative, and translational model of Yoga and mindfulness based cognitive therapy (DepS Y-MBCT), developed by the first author. DepS Y-MBCT as an adjunctive treatment successfully ameliorated TRD symptoms in 27/32 patients in an open label pilot trial in TRD patients. Considering the limitations of existing treatment options, including those of ketamine and rTMS when used as the sole modality of treatment, we suggest a “tiered approach for TRD” by combining ketamine and rTMS (alone or along with antidepressants) for rapid remission of acute depression symptoms and to use DepS Y-MBCT for maintaining remission and preventing relapse.

Yoga: Original Concepts and History

BACKGROUND Addiction and related disorders are devastating with their tremendous social, psychological, and physical consequences for which development of optimally effective treatments is long overdue. Repetitive Transcranial Magnetic Stimulation (rTMS) is relatively safe and is becoming an emerging therapeutic tool for these conditions. METHODS This systematic review was conducted using PubMed, PsycINFO, PsychiatryOnline and Cochrane Library ranging from year 2001 to 2017. RESULTS Our search selected 70 related articles of which, based on the Strength of Recommendation Taxonomy (SORT) guidelines, 11 indicated Level-1 study quality and class-B strength of recommendation for rTMS in nicotine addiction (effective in 218/289 subjects who received rTMS as found in 11 studies). Level-2/Class-B evidence was found for alcohol and cocaine addictions (Alcohol: effective in 126/193 subjects who received rTMS as found in 8 studies; Cocaine: effective in 86/128 subjects, as found in 5 studies). For food cravings, Level-3/Class-B evidence was noted (effective in 134/169, found in 7 studies). However, the evidence was limited to Level-3/Class-C for heroin (10/20 subjects received active rTMS, effective in 1 study), methamphetamine (33/48 subjects received active rTMS, effective in 2 studies), cannabis (18/18 subjects received active rTMS, effective in 1 study), and pathological gambling (31/31 subjects received active rTMS, effective in 2 studies). CONCLUSION rTMS may serve as an emerging therapeutic option for addiction and related disorders. The major lacunae include important methodological limitations and dearth of knowledge about precise mechanism of action that need to be addressed in the future studies.

Limiting progressive hippocampal metabolic abnormalities after smoke inhalation injury

Post-traumatic stress disorder (PTSD) is a chronic and debilitating condition that is often refractory to standard frontline antidepressant therapy. A promising new approach to PTSD therapy is administration of a single sub-anesthetic dose of (R,S)-ketamine (Ket). The treatment produces rapid and significant therapeutic response, which lasts for only 4-7 days. In one of our studies, the mean duration of response was increased to 33 days when Ket administration was combined with a mindfulness-based cognitive therapy, Trauma Interventions using Mindfulness Based Extinction and Reconsolidation (TIMBER). We now report the results from a 20-patient study, which examined the duration of sustained response with combined TIMBER-Ket therapy, TIMBER-K arm, relative to the response observed in a placebo-controlled arm, TIMBER-P. A significant difference in the duration of response was observed between TIMBER-K and TIMBER-P arms: 34.44 ± 19.12 days and 16.50 ± 11.39 days, respectively (p = 0.022). Previous studies identified a negative correlation between antidepressant response to Ket and basal plasma concentrations of d-serine (DSR). In this study, the basal DSR levels positively correlated with the pre-treatment severity of PTSD symptoms (Pearsons r = 0.42, p = 0.07) and patients with basal DSR level ≥ 3.5 μM displayed not only higher PTSD severity but also shorter duration of response. The data indicate that basal DSR levels may serve as a biomarker of the severity of PTSD symptoms and as a predictor of clinical response. This article is part of a Special Issue entitled: d-Amino acids: biology in the mirror, edited by Dr. Loredano Pollegioni, Dr. Jean-Pierre Mothet and Dr. Molla Gianluca.

Psychiatric Aspects in Chronic Pain and Utility of Yoga and Mindfulness-Based Cognitive Behavioral Therapy for Pain (Y-MBCT Pain) as a Translational Model

Yoga is not that new to the Western world. In fact, studying about the Transcendentalist Movement in the eighteenth-century West, one can see the deep influence of the ancient Indian Yogic scriptures (Upanishad) on notable Western philosophers like Arthur Schopenhauer, author of the famous book, The World as Will and Representation (Payne 1958). Schopenhauer’s deep considerations that a lifestyle of negating desires, similar to the ascetic teachings of Upanishads, was the way to attain liberation and he keeping a copy of the Upanishad by his side all the time attest to the above fact. Unfortunately, despite its immense popularity, Yoga is a profoundly misunderstood subject, more so in the West. The experiential essence of Yoga is to pass beyond the world of intellectual distinctions and into the world of the unthinkable, where reality appears as undivided and undifferentiated. For most, this seems too difficult to grasp. Yoga is often mistaken for unclearness or un-objectiveness, mainly due to its experiential nature. Ancient Indian philosophies elude even the greatest Western thinkers. For example, in his letters to Romaine Rolland, Sigmund Freud’s mystic friend, Freud himself comments on his own difficulty with the philosophy and practice of Yoga. He writes: “…let me admit once more that it is very difficult for me to work with these almost intangible quantities…” (Freud 1930, p. 72). Being exclusively experiential and subjective in nature, Yogic experiences, while documented over many centuries and millennia, cannot be verified using concrete measures. Unlike scientific methodology, Eastern mysticism regards intellect as merely a means for clearing the path to direct mystical experience. This is called direct because it is experiential and thus bypasses the interpretive and intellectual interference of the ordinary mind. Yogic experiential knowledge is intuitive and non-conceptual and not based on a concrete sensorial experience. In essence, one must transcend taxonomies and multiplicity in order to experience a reality void of arbitrary distinctions. Yoga’s disregard for concrete concepts, reductionism, and the mind/body dichotomy is partially responsible for the grave misunderstanding of Yoga. Here follows the fundamental difficulty with understanding Yoga. As Suzuki (1963, p. 11) writes: “… the scientific method in the study of reality is to view an object from the so-called objective point of view. For example, suppose a flower on the table is the object of a scientific study. The chief characteristic in this scientific (or objective) approach is to put this object (flower) to all kinds of analyses, to talk about it, to go around it, to catch anything that attracts our sense–intellect and abstract it away from the object (flower) itself, and, when all is supposedly finished, to synthesize these analytically formulated abstractions and take the outcome of the analysis for the object (flower) itself. But the question still remains: Has the complete object really been caught? The answer is no. These objective observations are mere descriptions of the object, in this case the flower, but in reality not the flower itself.

Trauma Interventions using Mindfulness Based Extinction and Reconsolidation (TIMBER) psychotherapy prolong the therapeutic effects of single ketamine infusion on post-traumatic stress disorder and comorbid depression: a pilot randomized, placebo-controlled, crossover clinical trial

A 46-year-old man had a smoke inhalation injury. Within 1 month, he developed neuropsychiatric problems including toxic encephalopathy, cognitive disorder, depression symptoms and personality change. From 3 to 14 years after the toxic inhalation injury, the patient received treatment with sertraline and methylphenidate. The 18F-fluorodeoxyglucose positron emission tomography scan at 3 years after injury showed deterioration of glucose metabolism in the hippocampus and orbital frontal region; at 14 years after injury, the hippocampus had no significant change but the orbital frontal region had deterioration of glucose metabolism. It was hypothesised that sertraline may have provided selective hippocampal neuroprotection. Further study is justified to evaluate sertraline as a possible neuroprotective agent after smoke inhalation injury.

Attempts at Standardization

One may agree that under-treated pain is an epidemic and over-treated pain is a nightmare for clinicians. It is a major public health problem. Chronic pain in the United States has a national economic cost of approximately

Brain, Mind, and Soul: Bridging the Gap

600 billion per year [57]; pain costs society