Does D-Cycloserine Enhance Exposure Therapy for Anxiety Disorders in Humans? A Meta-Analysis

Abstract

The treatment of anxiety is on the edge of a new era of combinations of pharmacologic and psychosocial interventions. A new wave of translational research has focused on the use of pharmacological agents as psychotherapy adjuvants using neurobiological insights into the mechanism of the action of certain psychological treatments such as exposure therapy. Recently, d-cycloserine (DCS) an antibiotic used to treat tuberculosis has been applied to enhance exposure-based treatment for anxiety and has proved to be a promising, but as yet unproven intervention. The present study aimed to evaluate the efficacy of DCS in the enhancement of exposure therapy in anxiety disorders. A systematic review/meta-analysis was conducted. Electronic searches were conducted in the databases ISI-Web of Science, Pubmed and PsycINFO. We included only randomized, double-blind, placebo-controlled trials with humans, focusing on the role of DCS in enhancing the action of exposure therapy for anxiety disorders. We identified 328 references, 13 studies were included in our final sample: 4 on obsessive-compulsive disorder, 2 on panic disorder, 2 on social anxiety disorder, 2 on posttraumatic stress disorder, one on acrophobia, and 2 on snake phobia. The results of the present meta-analysis show that DCS enhances exposure therapy in the treatment of anxiety disorders (Cohen d = −0.34; CI: −0.54 to −0.14), facilitating the specific process of extinction of fear. DCS seems to be effective when administered at a time close to the exposure therapy, at low doses and a limited number of times. DCS emerges as a potential new therapeutic approach for patients with refractory anxiety disorders that are unresponsive to the conventional treatments available. When administered correctly, DCS is a promising strategy for augmentation of CBT and could reduce health care costs, drop-out rates and bring faster relief to patients.

Gutsy Moves: The Amygdala as a Critical Node in Microbiota to Brain Signaling

“…[97,98] While there have also [5,9,10,88,90] Anxiolytic effects, sometimes sex-specific, in mice (light-dark box, elevated-plus maze) [72,113] Anxiolytic effects in mice (open field, defensive marble burying, elevated-plus maze, light-dark box) [91,93] Strain-specific anxiolytic effects in humans (e.g., Beck Anxiety Index, Hospital Anxiety & Depression Scale) and rodents (defensive marble burying, elevated-plus maze, open field) [11,62,133,134] Transplant from humans with depression or comorbid IBS and anxiety increases anxietylike behavior in mice (open field, step-down test, light-dark box) [96,125] Heightened anxiety in rats (open field) [89] Depression Increased depressive-like behavior in mice (forced swim) [90] Increased depressive-like behavior in rats (forced swim) [94] Antidepressant effects in mice and rats (forced swim, tail suspension, learned helplessness after inescapable shock) [91,92] Strain-specific antidepressant effects in humans (e.g. Beck Depression Inventory, Hospital Anxiety & Depression Scale) and rodents (tail suspension test, forced swim, sucrose preference) [11,97,98,133,134] Transplant from depressed human donors induces depressive-like behavior in mice (sucrose preference, forced swim [varied results], tail suspension test) [90,96] Learned fear Impaired fear recall in adult mice [101] Acute administration enhances fear extinction in rodents and exposure therapy in humans, [103,104] reduces fear recall in humans [102] Enhanced fear learning and memory or slow fear extinction in adult rats [62,105] Re...…”

“…Specifically, it has been shown to enhance fear extinction in rodents and exposure therapy in clinical anxiety disorders. [103,104] Although it is unclear whether a microbial mechanism is at play in these cases of acute antibiotic administration, it is certainly a hypothesis worth considering.…”

Anorexia nervosa as a motivated behavior: Relevance of anxiety, stress, fear and learning

“…These include d-cycloserine, a cognitive enhancer and NMDA partial agonist, used to boost fear extinction [107], propranolol to weaken fear memory; and several serotonin reuptake inhibitors [60,63]. However, consistent, well-replicated results are lacking.…”

Extinction learning as a moderator of d-cycloserine efficacy for enhancing exposure therapy in posttraumatic stress disorder

“…Accumulating evidence points to the efficacy of this novel augmentation strategy (see for meta-analyses: Bontempo, Panza, & Bloch, 2012;Norberg, Krystal, & Tolin, 2008;Rodrigues et al, 2014), but results of these clinical studies have been mixed, especially in the treatment of posttraumatic stress disorder (PTSD). Difede et al (2014), who investigated DCS enhanced virtual reality exposure therapy (VRET) for civilian PTSD patients following the WTC-attacks, showed faster and greater symptom decline for those who received DCS.…”