Effects of D-cycloserine administration on weekly nonemotional memory tasks in healthy participants.

BACKGROUND: The application of weekly doses of D-cycloserine (DCS) to the enhancement of exposure-based treatments has been a particular achievement of translational research. It is not known, however, whether this enhancement effect can be extended to other forms of learning. In this study, we investigated the relative benefit of DCS versus placebo for enhancing nonemotional verbal and nonverbal memory across weekly trials. METHODS: We randomized healthy participants to weekly doses of 50 mg DCS or placebo, with 33 participants completing a 5-week protocol. Participants completed baseline neuropsychological evaluation and then 4 subsequent weeks of repeated learning tasks. RESULTS: No improvement was found in immediate or delayed memory following single doses of DCS for the memory tasks repeated on a weekly basis. Trends for an advantage of DCS were evident for novel word lists given each week. CONCLUSIONS: The learning tasks in our study were particularly distinct from the extinction learning paradigms that have shown strong DCS effects, and we were unable to demonstrate useful DCS effects with these nonemotional stimuli. Additional research is needed to elucidate the bounds of DCS augmentation effects on therapeutic learning.

A meta-analytic review of psychosocial interventions for substance use disorders.

OBJECTIVE: Despite significant advances in psychosocial treatments for substance use disorders, the relative success of these approaches has not been well documented. In this meta-analysis, the authors provide effect sizes for various types of psychosocial treatments, as well as abstinence and treatment-retention rates for cannabis, cocaine, opiate, and polysubstance abuse and dependence treatment trials. METHOD: With a comprehensive series of literature searches, the authors identified a total of 34 well-controlled treatment conditions-five for cannabis, nine for cocaine, seven for opiate, and 13 for polysubstance users-representing the treatment of 2,340 patients. Psychosocial treatments evaluated included contingency management, relapse prevention, general cognitive behavior therapy, and treatments combining cognitive behavior therapy and contingency management. RESULTS: Overall, controlled trial data suggest that psychosocial treatments provide benefits reflecting a moderate effect size according to Cohen's standards. These interventions were most efficacious for cannabis use and least efficacious for polysubstance use. The strongest effect was found for contingency management interventions. Approximately one-third of participants across all psychosocial treatments dropped out before treatment completion compared to 44.6% for the control conditions. CONCLUSIONS: Effect sizes for psychosocial treatments for illicit drugs ranged from the low-moderate to high-moderate range, depending on the substance disorder and treatment under study. Given the long-term social, emotional, and cognitive impairments associated with substance use disorders, these effect sizes are noteworthy and comparable to those for other efficacious treatments in psychiatry.

Clinical perspectives on the combination of D-cycloserine and cognitive-behavioral therapy for the treatment of anxiety disorders.

In a particular success for translational research agendas, characterization of the neuronal circuits underlying fear extinction, and basic research in animal extinction paradigms, has led to intervention studies examining the use of D-cycloserine (DCS) to enhance therapeutic learning from exposure-based cognitive-behavioral therapy (CBT). In this article, we review these intervention studies, and discuss DCS augmentation of CBT relative to more traditional combination-treatment strategies in the treatment of anxiety disorders. We offer an accounting, based on evidence for internal context effects, of current limitations in the combination of antidepressant or benzodiazepine medications with CBT and discuss the advantages of isolated-dosing strategies with DCS relative to these limitations. This strategy is contrasted with the chronic-dosing applications of DCS for schizophrenia and Alzheimer's disease, and future directions for isolated-dosing strategies are discussed.