Table 1.
Placebo-controlled studies of DCS to augment exposure therapy in adults with anxiety spectrum disorders, addiction, schizophrenia, or anorexia nervosa.
| Publication | Sample Size Randomized | Condition | # of Total Sessions / Exposure Sessions / DCS administered | DCS Dose (mg) | Description of Findings |
|---|---|---|---|---|---|
|
Anxiety
Spectrum | |||||
| Ressler 2004 (11) | 27 | Specific phobia | 2/2/2 | 50 or 500 | DCS (50mg and 500mg combined) group displayed significantly greater improvement than the PBO group on all main outcome measures at post-treatment and 3- month follow up. No significant difference between 50mg or 500mg DCS groups. |
| Hofmann 2006 (12) | 32 | Social anxiety disorder | 5/4/4 | 50 | DCS group displayed significantly greater improvement than the PBO group on 2/3 outcome measures at post-treatment and 1-month follow up (medium-large effects). |
| Guastella 2007 (82), study 1 | 63 | Spider-fearful | 1/1/1 | 50 | No differences in improvement between DCS and PBO group on all outcomes at post- treatment or 3.5- week follow up |
| Guastella 2007 (82), study 2 | 37 | Spider-fearful | 1/1/1 | 50 or 500 | No differences in improvement between DCS and PBO group on all outcomes at post- treatment or 3.5- week follow up |
| Kushner 2007 (35) | 32 | Obsessive-compulsive disorder | 10/10/10 | 125 | No differences in improvement between DCS and PBO group on all outcomes measures at post-treatment and 3-month follow up. Some evidence of faster improvement and lower dropout. |
| Storch 2007 (86) | 24 | Obsessive-compulsive disorder | 12/12/12 | 250 | No differences in improvement between DCS and PBO group on main outcome measures at post-treatment. |
| Guastella 2008 (37) | 56 | Social anxiety disorder | 5/4/4 | 50 | DCS group displayed significantly greater improvement than the PBO group on 4/5 outcome measures at post- treatment and 1- month follow up (mostly medium effects). |
| Wilhelm 2008 (87) | 23 | Obsessive-compulsive disorder | 10/10/10 | 100 | No differences in improvement between DCS and PBO group on main outcome measures at post-treatment and 1- month follow up. Some evidence of faster improvement and improvement in depressive symptoms. Reanalysis indicated significant faster response for participants receiving DCS (88). |
| Otto 2010 (13) | 31 | Panic disorder | 5/4/3 | 50 | DCS group displayed significantly greater improvement than the PBO group on all main outcome measures at post- treatment and 1- month follow up (large effects). |
| Seigmund 2011 (39) | 44 | Panic disorder, Agoraphobia | 8/3/3 | 50 | No differences in improvement between DCS and PBO group on main outcome measures at post-treatment and 1- month follow up. Some evidence of faster improvement for more severe patients. |
| De Kleine 2012 (41) | 67 | Posttraumatic stress disorder | 10/9/9 | 50 | No differences in improvement between DCS and PBO group on main outcome measures at post-treatment and 3- month follow up; some evidence of higher post-treatment response rate. Some evidence of benefit for participants with severe pretreatment symptoms who needed longer treatment. |
| Litz 2012 (17) | 26 | Posttraumatic stress disorder | 6/4/4 | 50 | PBO group displayed significantly greater improvement than DCS group on all main outcome measures at post- treatment. |
| Nave 2012 (89) | 20 | Specific phobia | 1/1/1 | 50 | No differences in improvement between DCS and PBO group on main outcome measures at post-treatment. Some evidence of faster improvement. |
| Tart 2013 (59) | 29 | Specific phobia | 2/2/2 | 50a | No differences in improvement between DCS and PBO group on main outcome measures at post-treatment or 1- month follow up. Evidence of exposure success as moderator. Reanalysis indicated significant greater DCS benefits for participants achieving low fear during exposure sessions (21). |
| Hofmann 2013 (38) | 169 | Social anxiety disorder | 12/5/5 | 50 | No differences between DCS and PBO in completion, response, and remission rates and post-treatment and 1, 3, 6-month follow up. Evidence of faster (24–33%) improvement. Reanalysis indicated significant greater DCS benefits for participants achieving low fear during exposure sessions (20). |
| Rothbaum 2014 (56) | 106 | Posttraumatic stress disorder | 6/5/5 | 50 | No differences in improvement between DCS and PBO group on main outcome measures at post-treatment or 3, 6, 12-month follow up. Between-session extinction learning was a treatment- specific enhancer of outcome for DCS group. |
| Andersson 2015 (62) | 128 | Obsessive-compulsive disorder | 12/5/5 | 50 | No differences between DCS and PBO in main outcome measures at post-treatment and 3- month follow up. Evidence of significant interaction of DCS effects with antidepressant medication. |
| Addiction | |||||
| Santa Ana 2009 (67) | 25 | Nicotine dependence | 2/2/2 | 50 | DCS group displayed significantly greater improvement than PBO group on 3 out of 7 main outcomes at post-treatment and 1-week follow up (large effect at follow up). |
| Kamboj 2011 (72) | 40 | Heavy drinkers | 2/2/2 | 125 | No differences in improvement between DCS and PBO group on main outcome measures at two sessions or follow up ~4 days later. |
| Watson 2011 (70) | 16 | Alcohol dependence | 3/3/2 | 250 | No differences in improvement between DCS and PBO group on main outcome measures at all 3 sessions. |
| Hofmann 2012 (71) | 20 | Heavy drinkers | 3/3/3 | 50 | No differences in DCS and PBO group on most outcomes. Some evidence of poorer outcomes in DCS group than PBO group at first of 2 post-treatment test sessions. |
| Kamboj 2012 (18) | 32 | Heavy smokers | 2/2/2 | 125 | No differences in improvement between DCS and PBO group on main outcome measures at post-treatment or 2- week follow up. |
| Price 2013 (19) | 32 | Cocaine dependence | 3/3/3 | 50 | No differences in improvement between DCS and PBO group on main outcome measures at post-treatment. Some evidence of significantly poorer session-specific outcomes and 5–12 day follow up outcomes in DCS group. |
| Yoon 2013 (68) | 47 | Cocaine and nicotine dependence | 12/12/4 | 50 | No differences in improvement between DCS and PBO group on main outcome measures at post-treatment or 6- month follow up. |
| Kiefer 2015 (73) | 76 | Alcohol dependence | 9/9/9 | 50 | No differences in improvement between DCS and PBO group on subjective outcome measures at post- treatment. PBO group displayed higher fMRI activation than DCS group in brain regions associated with negative outcomes. |
| MacKillop 2015 (74) | 37 | Alcohol use disorder | 4/2/2 | 50 | DCS group displayed greater improvements than PBO group on session-specific measures and post- treatment outcomes but not 3-week follow up. |
| Schizophreniab | |||||
| Gottlieb 2011 (96) | 21 | Schizophrenia/schizoaffective | 2/2/2 | 50 | No differences in improvement between DCS and PBO on main outcome measures at post-treatment. Significant order effectsc; DCS first displayed greater improvements than PBO first on some outcomes at post- treatment (moderate- large effects). |
| Cain 2014 (97) | 40 | Schizophrenia | 24–40/8d | 50 | DCS group displayed greater improvements than PBO on one outcome, while PBO displayed greater improvement than DCS on another. Some evidence of more improvement for subjects with more severe pretreatment symptoms. |
|
Anorexia
Nervosa | |||||
| Levinson 2015 (76) | 36 | Anorexia nervosa | 4/4/3 | 250 | DCS group displayed greater improvements than PBO on main outcome measure at post-treatment but not 1-month follow up. |
Notes. PBO = placebo
a
All studies administered DCS prior to CBT sessions, except for the designated study, which administered DCS immediately after session;
b
See supplemental information for discussion of the application of DCS to therapeutic learning in schizophrenia;
c
Within-participant cross-over design;
d
This study did not utilize exposure but utilized a "Brain Fitness" cognitive remediation program which took place 3–5x/week across 8 weeks.