Efficacy of Ketamine in the Treatment of Substance Use Disorders: A Systematic Review

Background: Despite advances in behavioral and pharmacotherapy interventions, substance use disorders (SUDs) are frequently refractory to treatment. Glutamatergic dysregulation has received increasing attention as one common neuropathology across multiple substances of abuse. Ketamine is a potent N-methyl-D-aspartate (NMDA) glutamatergic receptor antagonist which has been found to be effective in the treatment of severe depression. Here we review the literature on the efficacy of ketamine in the treatment of SUDs.Methods: A systematic review of the PubMed, Scopus, and ClinicalTrials.gov databases was undertaken to identify completed and ongoing human studies of the effectiveness of ketamine in the treatment of SUDs between January 1997 and January 2018.Results and conclusion: Seven completed studies were identified. Two studies focused on alcohol use disorder, two focused on cocaine use disorder, and three focused on opioid use disorder. Both cocaine studies found improvements in craving, motivation, and decreased cocaine use rates, although studies were limited by small sample sizes, a homogeneous population and short follow-up. Studies of alcohol and opioid use disorders found improvement in abstinence rates in the ketamine group, with significant between-group effects noted for up to two years following a single infusion, although these were not placebo-controlled trials. These results suggest that ketamine may facilitate abstinence across multiple substances of abuse and warrants broader investigation in addiction treatment. We conclude with an overview of the six ongoing studies of ketamine in the treatment of alcohol, cocaine, cannabis, and opioid use disorders and discuss future directions in this emerging area of research

Habituation of Distress and Craving During Treatment as Predictors of Change in PTSD Symptoms and Substance Use Severity

Objective—Increasing evidence supports the efficacy of trauma-focused exposure therapy in the treatment of posttraumatic stress disorder (PTSD) and co-occurring substance use disorders. Little is known, however, about the mechanisms of change in treatment for patients with PTSD and co-occurring substance use disorders. The aim of the present study was to examine whether within- and between-session habituation of distress and substance craving during imaginal exposure relates to treatment outcomes among U.S. military veterans with PTSD and a co-occurring substance use disorder (N = 54). Method—Veterans received Concurrent Treatment of PTSD and Substance Use Disorders Using Prolonged Exposure, a manualized integrated treatment combining prolonged exposure with cognitive-behavioral therapy for substance use disorders as part of a larger randomized clinical trial. Self-reported distress and craving ratings were collected during each imaginal exposure session. Results—Data were analyzed using a series of random intercept and slope multilevel linear and generalized linear models. Results revealed that between-session habituation of distress and craving was associated with greater improvement in PTSD symptoms during treatment. Between-session habituation of craving was also associated with a marginally greater reduction in frequency of substance use among participants still reporting use during treatment. Within-session habituation of distress was unrelated to treatment outcome. Conclusions—Together, these findings indicate that habituation in both distress and craving may be important in maximizing treatment outcome for patients with PTSD and comorbid substance use disorders

Differential symptom weighting in estimating empirical thresholds for underlying PTSD severity: Toward a “platinum” standard for diagnosis?

Objective: Symptom counts as the basis for Post-Traumatic Stress Disorder (PTSD) diagnoses in the DSM presume each symptom is equally reflective of underlying disorder severity. However, the “equal weight” assumption fails to fit PTSD symptom data when tested. The present study developed an enhanced PTSD diagnosis based on (a) a conventional PTSD diagnosis from a clinical interview and (b) an empirical classification of full PTSD that reflected the relative clinical weights of each symptom. Method: Baseline structured interview data from Project Harmony (N = 2658) was used. An enhanced diagnosis for full PTSD was estimated using an empirical threshold from moderated nonlinear factor analysis (MNLFA) latent PTSD scale scores, in combination with a full conventional PTSD diagnosis based on interview data. Results: One in 4 patients in the sample had a PTSD diagnosis that was inconsistent with their empirical PTSD grouping, such that the enhanced diagnostic standard reduced the diagnostic discrepancy rate by 20%. Veterans, and in particular female Veterans, were at greatest odds for discrepancy between their underlying PTSD severity and DSM diagnosis. Conclusion: Psychometric methodologies that differentially weight symptoms can complement DSM criteria and may serve as a platform for symptom prioritization for diagnoses in future editions of DSM

Laboratory-induced cue reactivity among individuals with prescription opioid dependence

Prescription opioid (PO) dependence is a critical health problem. Although examination of drug cue reactivity paradigms has advanced the understanding of risk factors for relapse for a variety of substances (e.g., cocaine, alcohol, nicotine), no PO specific drug cue paradigm has been developed. The current study addressed this gap in the literature and evaluated the ability of a newly developed PO drug cue paradigm to elicit subjective, physiological, and neuroendocrine changes among PO-dependent participants (n = 20) as compared to controls (n = 17). The drug cue paradigm included an induction script, viewing and handling paraphernalia (e.g., bottle of oxycontin pills, pill crusher) and watching a video depicting people using POs as well as places related to POs (e.g., pharmacies). Consistent with hypotheses, the PO group demonstrated significant pre- to post-cue increases on subjective ratings of craving, difficulty resisting POs, stress, and anger. The control group did not demonstrate significant changes on any of the subjective measures. Both the PO group and the control group evidenced significant pre- to post-cue increases in physiological responses (e.g., blood pressure, skin conductance), as expected given the arousing nature of the drug cue stimuli. The PO group, but not the control group, evidenced a significant pre- to post-cue increase in heart rate and salivary cortisol levels. The development and validation of a drug cue paradigm for POs may help inform future research and treatment development efforts for patients with PO dependence

Posttraumatic Stress Disorder: Overview of Evidence-Based Assessment and Treatment

Posttraumatic stress disorder (PTSD) is a chronic psychological disorder that can develop after exposure to a traumatic event. This review summarizes the literature on the epidemiology, assessment, and treatment of PTSD. We provide a review of the characteristics of PTSD along with associated risk factors, and describe brief, evidence-based measures that can be used to screen for PTSD and monitor symptom changes over time. In regard to treatment, we highlight commonly used, evidence-based psychotherapies and pharmacotherapies for PTSD. Among psychotherapeutic approaches, evidence-based approaches include cognitive-behavioral therapies (e.g., Prolonged Exposure and Cognitive Processing Therapy) and Eye Movement Desensitization and Reprocessing. A wide variety of pharmacotherapies have received some level of research support for PTSD symptom alleviation, although selective serotonin reuptake inhibitors have the largest evidence base to date. However, relapse may occur after the discontinuation of pharmacotherapy, whereas PTSD symptoms typically remain stable or continue to improve after completion of evidence-based psychotherapy. After reviewing treatment recommendations, we conclude by describing critical areas for future research

Assessment Of Club Drug Use In A Treatment-Seeking Sample Of Individuals With Marijuana Dependence

Club drug use is becoming increasingly popular in the United States and has been associated with chronic psychiatric symptoms and neuropsychological abnormalities. Patterns of club drug use and characteristics of club drug users are not homogeneous. Thus, treatment-seeking marijuana-dependent individuals may have a differential pattern of club drug use. Baseline assessments collected from 55 individuals participating in a pharmacological treatment study for marijuana dependence were examined. Individuals completed a 16-item self-report questionnaire assessing club drugs used, frequency and patterns of use, problems associated with use, and reasons for use. Subjects were primarily male (87.3%) and Caucasian (81.8%), with a mean age of 32.1 (±9.1 years). As expected, a large number of individuals had used ecstasy (75%). However, LSD and methamphetamine use was also reported by many users (82.5% and 47.5% respectively), with many individuals reporting the use of more than one club drug. Notably, 31.6% of individuals reported tolerance to club drugs. These results emphasize the significant co-occurrence of club drug use in marijuana-dependent individuals. This appears to be the first study to report on club drug use in treatment-seeking marijuana-dependent individuals. Clinical implications and directions for future research are discussed. Copyright © American Academy of Addiction Psychiatry