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1. D-cycloserine augmentation of exposure-based cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders: A systematic review and meta-analysis of individual participant data

Author

David F. Tolin, Page L. Anderson, Anja Siewert-Siegmund, Paolo Frumento, Daniel A. Geller, Michael W. Otto, Agnes van Minnen, Eric J. Lenze, Tanya K. Murphy, Benedetta Monzani, Cassidy A. Gutner, David Mataix-Cols, Lorena Fernández de la Cruz, Thomas L. Rodebaugh, Ana Pérez-Vigil, Stefan G. Hofmann, Boadie W. Dunlop, Isobel Heyman, Seth D. Norrholm, Mark H. Pollack, Maryrose Gerardi, Joseph P. H. McNamara, Claudia Finck, Katarzyna Wyka, Tanja Jovanovic, Carl F. Weems, Judith Cukor, Cheri A. Levinson, Matt G. Kushner, Gary R. Geffken, David Rosenfield, Adam J. Guastella, Jens Plag, Gert-Jan Hendriks, Allison M. Waters, Sabine Wilhelm, Fabian Golfels, Jasper A. J. Smits, Lara J. Farrell, Barbara O. Rothbaum, Adam B. Lewin, JoAnn Difede, Wayne K. Goodman, Harry McConnell, Rianne A. de Kleine, Andreas Ströhle, Christian Rück, Francis S. Lee, Erik Andersson, Paul Thuras, Michael S. Scheeringa, Kerry J. Ressler, Eric A. Storch, Margaret Altemus, Michael Davis, and Candyce D. Tart

Subjects
Obsessive-Compulsive Disorder, N-Methylaspartate, medicine.medical_treatment, Stress-related disorders Donders Center for Medical Neuroscience [Radboudumc 13], Placebo-controlled study, Implosive Therapy, Specific phobia, Stress Disorders, Post-Traumatic, Experimental Psychopathology and Treatment, 03 medical and health sciences, 0302 clinical medicine, Outcome Assessment, Health Care, Excitatory Amino Acid Agonists, medicine, Humans, 10. No inequality, Panic disorder, Social anxiety, Repeated measures design, Drug Synergism, medicine.disease, Anxiety Disorders, Combined Modality Therapy, Antidepressive Agents, 030227 psychiatry, 3. Good health, Cognitive behavioral therapy, Psychiatry and Mental health, Cycloserine, Anxiety, medicine.symptom, Psychology, 030217 neurology & neurosurgery, Clinical psychology, Agoraphobia
Abstract

Contains fulltext : 174490.pdf (Publisher’s version ) (Open Access) Importance: Whether and under which conditions D-cycloserine (DCS) augments the effects of exposure-based cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders is unclear. Objective: To clarify whether DCS is superior to placebo in augmenting the effects of cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders and to evaluate whether antidepressants interact with DCS and the effect of potential moderating variables. Data Sources: PubMed, EMBASE, and PsycINFO were searched from inception to February 10, 2016. Reference lists of previous reviews and meta-analyses and reports of randomized clinical trials were also checked. Study Selection: Studies were eligible for inclusion if they were (1) double-blind randomized clinical trials of DCS as an augmentation strategy for exposure-based cognitive behavior therapy and (2) conducted in humans diagnosed as having specific phobia, social anxiety disorder, panic disorder with or without agoraphobia, obsessive-compulsive disorder, or posttraumatic stress disorder. Data Extraction and Synthesis: Raw data were obtained from the authors and quality controlled. Data were ranked to ensure a consistent metric across studies (score range, 0-100). We used a 3-level multilevel model nesting repeated measures of outcomes within participants, who were nested within studies. Results: Individual participant data were obtained for 21 of 22 eligible trials, representing 1047 of 1073 eligible participants. When controlling for antidepressant use, participants receiving DCS showed greater improvement from pretreatment to posttreatment (mean difference, -3.62; 95% CI, -0.81 to -6.43; P = .01; d = -0.25) but not from pretreatment to midtreatment (mean difference, -1.66; 95% CI, -4.92 to 1.60; P = .32; d = -0.14) or from pretreatment to follow-up (mean difference, -2.98, 95% CI, -5.99 to 0.03; P = .05; d = -0.19). Additional analyses showed that participants assigned to DCS were associated with lower symptom severity than those assigned to placebo at posttreatment and at follow-up. Antidepressants did not moderate the effects of DCS. None of the prespecified patient-level or study-level moderators was associated with outcomes. Conclusions and Relevance: D-cycloserine is associated with a small augmentation effect on exposure-based therapy. This effect is not moderated by the concurrent use of antidepressants. Further research is needed to identify patient and/or therapy characteristics associated with DCS response. 10 p.

Published
2017

2. D-Cycloserine Augmentation of Exposure-Based Cognitive Behavior Therapy for Anxiety, Obsessive-Compulsive, and Posttraumatic Stress Disorders: A Systematic Review and Meta-analysis of Individual Participant Data

Author

Mataix-Cols, D, Fernández de la Cruz, L, Monzani, B, Rosenfield, D, Andersson, E, Pérez-Vigil, A, Frumento, P, de Kleine RA, Difede, J, Dunlop, Bw, Farrell, Lj, Geller, D, Gerardi, M, Guastella, Aj, Hofmann, Sg, Hendriks, Gj, Kushner, Mg, Lee, Fs, Lenze, Ej, Levinson, Ca, Mcconnell, H, Otto, Mw, Plag, J, Pollack, Mh, Ressler, Kj, Rodebaugh, Tl, Rothbaum, Bo, Scheeringa, Ms, Siewert-Siegmund, A, Smits, Jaj, Storch, Ea, Ströhle, A, Tart, Cd, Tolin, Df, van Minnen, A, Waters, Am, Weems, Cf, Wilhelm, S, Wyka, K, Davis, M, Rück, C, and the DCS Anxiety Consortium, Altemus, M, Anderson, P, Cukor, J, Finck, C, Geffken, Gr, Golfels, F, Goodman, Wk, Gutner, C, Heyman, I, Jovanovic, T, Lewin, Ab, Mcnamara, Jp, Murphy, Tk, Norrholm, S, and Thuras, P.

Published
2017

3. D-Cycloserine Augmentation of Exposure-Based Cognitive Behavior Therapy for Anxiety, Obsessive-Compulsive, and Posttraumatic Stress Disorders: A Systematic Review and Meta-analysis

Author

Mataix-Cols, D., Fernandez de la Cruz, L., Monzani, B., Rosenfield, D., Andersson, E., Perez-Vigil, A., Frumento, P., De Kleine, R.A., Difede, J., Dunlop, B.W., Farrell, L.J., Geller, D., Gerardi, M., Guastella, A.J., Hofmann, S.G., Hendriks, G.J., Kushner, M.G., Lee, F.S., Lenze, E.J., Levinson, C.A., McConnell, H., Otto, M.W., Plag, J., Pollack, M.H., Ressler, K.J., Rodebaugh, T.L., Rothbaum, B.O., Scheeringa, M.S., Siewert-Siegmund, A., Smits, J.A.J., Storch, E.A., Strohle, A., Tart, C.D., Tolin, D.F., Van Minnen, A., Waters, A.M., Weems, C.F., Wilhelm, S., Wyka, K. Davis, and Ruck

Published
2017

4. D-cycloserine augmentation of exposure-based cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders: A systematic review and meta-analysis of individual participant data

Author

Mataix-Cols, D., Fernández de la Cruz, L., Monzani, B., Rosenfield, D., Andersson, E., Pérez-Vigil, A., Frumento, P., Kleine, R.A. de, Difede, J., Dunlop, B.W., Farrell, L.J., Geller, D., Gerardi, M., Guastella, A.J., Hofmann, S.G., Hendriks, G.J., Kushner, M.G., Lee, F.S., Lenze, E.J., Levinson, C.A., McConnell, H., Otto, M.W., Plag, J., Pollack, M.H., Ressler, K.J., Rodebaugh, T.L., Rothbaum, B.O., Scheeringa, M.S., Siewert-Siegmund, A., Smits, J.A.J., Storch, E.A., Ströhle, A., Tart, C.D., Tolin, D.F., Minnen, A. van, Waters, A.M., Weems, C.F., Wilhelm, S., Wyka, K., Davis, M., Rück, C., Altemus, M., Anderson, P., Cukor, J., Finck, C., Geffken, G.R., Golfels, F., Goodman, W.K., Gutner, C., Heyman, I., Jovanovic, T., Lewin, A.B., McNamara, J.P., Murphy, T.K., Norrholm, S., Thuras, P., Mataix-Cols, D., Fernández de la Cruz, L., Monzani, B., Rosenfield, D., Andersson, E., Pérez-Vigil, A., Frumento, P., Kleine, R.A. de, Difede, J., Dunlop, B.W., Farrell, L.J., Geller, D., Gerardi, M., Guastella, A.J., Hofmann, S.G., Hendriks, G.J., Kushner, M.G., Lee, F.S., Lenze, E.J., Levinson, C.A., McConnell, H., Otto, M.W., Plag, J., Pollack, M.H., Ressler, K.J., Rodebaugh, T.L., Rothbaum, B.O., Scheeringa, M.S., Siewert-Siegmund, A., Smits, J.A.J., Storch, E.A., Ströhle, A., Tart, C.D., Tolin, D.F., Minnen, A. van, Waters, A.M., Weems, C.F., Wilhelm, S., Wyka, K., Davis, M., Rück, C., Altemus, M., Anderson, P., Cukor, J., Finck, C., Geffken, G.R., Golfels, F., Goodman, W.K., Gutner, C., Heyman, I., Jovanovic, T., Lewin, A.B., McNamara, J.P., Murphy, T.K., Norrholm, S., and Thuras, P.

Abstract

Contains fulltext : 174490.pdf (publisher's version ) (Open Access), Importance: Whether and under which conditions D-cycloserine (DCS) augments the effects of exposure-based cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders is unclear. Objective: To clarify whether DCS is superior to placebo in augmenting the effects of cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders and to evaluate whether antidepressants interact with DCS and the effect of potential moderating variables. Data Sources: PubMed, EMBASE, and PsycINFO were searched from inception to February 10, 2016. Reference lists of previous reviews and meta-analyses and reports of randomized clinical trials were also checked. Study Selection: Studies were eligible for inclusion if they were (1) double-blind randomized clinical trials of DCS as an augmentation strategy for exposure-based cognitive behavior therapy and (2) conducted in humans diagnosed as having specific phobia, social anxiety disorder, panic disorder with or without agoraphobia, obsessive-compulsive disorder, or posttraumatic stress disorder. Data Extraction and Synthesis: Raw data were obtained from the authors and quality controlled. Data were ranked to ensure a consistent metric across studies (score range, 0-100). We used a 3-level multilevel model nesting repeated measures of outcomes within participants, who were nested within studies. Results: Individual participant data were obtained for 21 of 22 eligible trials, representing 1047 of 1073 eligible participants. When controlling for antidepressant use, participants receiving DCS showed greater improvement from pretreatment to posttreatment (mean difference, -3.62; 95% CI, -0.81 to -6.43; P = .01; d = -0.25) but not from pretreatment to midtreatment (mean difference, -1.66; 95% CI, -4.92 to 1.60; P = .32; d = -0.14) or from pretreatment to follow-up (mean difference, -2.98, 95% CI, -5.99 to 0.03; P = .05; d = -0.19). Additional analyses showed that participants ass

Published
2017

5. D-Cycloserine Augmentation of Exposure-Based Cognitive Behavior Therapy for Anxiety, Obsessive-Compulsive, and Posttraumatic Stress Disorders: A Systematic Review and Meta-analysis of Individual Participant Data.

Author

Mataix-Cols D, Fernández de la Cruz L, Monzani B, Rosenfield D, Andersson E, Pérez-Vigil A, Frumento P, de Kleine RA, Difede J, Dunlop BW, Farrell LJ, Geller D, Gerardi M, Guastella AJ, Hofmann SG, Hendriks GJ, Kushner MG, Lee FS, Lenze EJ, Levinson CA, McConnell H, Otto MW, Plag J, Pollack MH, Ressler KJ, Rodebaugh TL, Rothbaum BO, Scheeringa MS, Siewert-Siegmund A, Smits JAJ, Storch EA, Ströhle A, Tart CD, Tolin DF, van Minnen A, Waters AM, Weems CF, Wilhelm S, Wyka K, Davis M, Rück C, Altemus M, Anderson P, Cukor J, Finck C, Geffken GR, Golfels F, Goodman WK, Gutner C, Heyman I, Jovanovic T, Lewin AB, McNamara JP, Murphy TK, Norrholm S, and Thuras P

Subjects
Anxiety Disorders drug therapy, Combined Modality Therapy, Drug Synergism, Humans, Obsessive-Compulsive Disorder drug therapy, Stress Disorders, Post-Traumatic drug therapy, Antidepressive Agents therapeutic use, Anxiety Disorders therapy, Cycloserine pharmacology, Excitatory Amino Acid Agonists pharmacology, Implosive Therapy methods, N-Methylaspartate agonists, Obsessive-Compulsive Disorder therapy, Outcome Assessment, Health Care statistics & numerical data, Stress Disorders, Post-Traumatic therapy
Abstract

Importance: Whether and under which conditions D-cycloserine (DCS) augments the effects of exposure-based cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders is unclear., Objective: To clarify whether DCS is superior to placebo in augmenting the effects of cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders and to evaluate whether antidepressants interact with DCS and the effect of potential moderating variables., Data Sources: PubMed, EMBASE, and PsycINFO were searched from inception to February 10, 2016. Reference lists of previous reviews and meta-analyses and reports of randomized clinical trials were also checked., Study Selection: Studies were eligible for inclusion if they were (1) double-blind randomized clinical trials of DCS as an augmentation strategy for exposure-based cognitive behavior therapy and (2) conducted in humans diagnosed as having specific phobia, social anxiety disorder, panic disorder with or without agoraphobia, obsessive-compulsive disorder, or posttraumatic stress disorder., Data Extraction and Synthesis: Raw data were obtained from the authors and quality controlled. Data were ranked to ensure a consistent metric across studies (score range, 0-100). We used a 3-level multilevel model nesting repeated measures of outcomes within participants, who were nested within studies., Results: Individual participant data were obtained for 21 of 22 eligible trials, representing 1047 of 1073 eligible participants. When controlling for antidepressant use, participants receiving DCS showed greater improvement from pretreatment to posttreatment (mean difference, -3.62; 95% CI, -0.81 to -6.43; P = .01; d = -0.25) but not from pretreatment to midtreatment (mean difference, -1.66; 95% CI, -4.92 to 1.60; P = .32; d = -0.14) or from pretreatment to follow-up (mean difference, -2.98, 95% CI, -5.99 to 0.03; P = .05; d = -0.19). Additional analyses showed that participants assigned to DCS were associated with lower symptom severity than those assigned to placebo at posttreatment and at follow-up. Antidepressants did not moderate the effects of DCS. None of the prespecified patient-level or study-level moderators was associated with outcomes., Conclusions and Relevance: D-cycloserine is associated with a small augmentation effect on exposure-based therapy. This effect is not moderated by the concurrent use of antidepressants. Further research is needed to identify patient and/or therapy characteristics associated with DCS response.

Published
2017
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