Table 2.

Placebo-controlled, randomized, double-blind clinical trials of d-cycloserie as augmentation of psychotherapy in OCD patients

Study & Drug		Duration, dose and Temporal Relationship to CBT Sessions		Subjects		Mode of Therapy		Endpoint Results on Efficacy			Side Effects		Effect on Primary Outcome: (yes/no)
Studies in adults
Storch et al., 2007		12 CBT sessions with DCS 4 h prior to each session Dose: 250 mg/CBT session		24 adult OCD patients		In person 1 session hierarchy and education, 1 session practice exposure and 9 sessions exposure and response prevention exercises		No significant difference between the DCS and placebo groups in terms of OCD severity post-treatment.			Well tolerated		Y-BOCS change: no
Kushner et al., 2007		10 CBT sessions with DCS 2 h prior to each session Dose: 125 mg/CBT session		25 adult OCD patients		In person Hierarchy at baseline, 10 sessions of exposure/ritual prevention techniques		No differences in Y-BOCS scores or between the DCS and placebo groups at the end of the trial. The DCS group achieved > 50% SUDS scores reduction significantly faster and showed improved compliance.			Well tolerated Mild gastrointestinal distress, fatigue, anxiety and dizziness		Y-BOCS change: no
Wilhelm et al., 2008		10 CBT sessions with DCS 1 h before each session Dose: 100 mg/CBT session		23 adult OCD patients (Including patients with continuing stable psychotropic treatment regimen)		In person 1 psychoeducational /treatment planning session, 10 behavior therapy sessions		No significant differences in Y-BOCS scores between the DCS and placebo groups at post-treatment (p = 0.14) or 1 month follow up (p = 0.12) Significantly lower Y-BOCS scores in the DCS group at mid-treatment (p = 0.009) Significantly fewer depressive symptoms at post-treatment (p=0.04)			Well tolerated		Y-BOCS change: no at post-treatment or 1 mo follow up; yes at mid-treatment
Andersson et al., 2015		DCS 1 h before 5 CBT tasks during a 12 weeks internet-based CBT Dose: 50 mg/CBT task		128 adult OCD outpatients (In some stable antidepressant regimen)		Therapist-supported internet 12 weeks of therapist-supported internet-based CBT		No difference between the DCS and placebo group in Y-BOCS scores at the trial end and 3 months follow up In the DCS group significantly more antidepressant-free patients achieved remission at the trial’s end compared to antidepressant-medicated patients (p = 0.008).			Well tolerated		Y-BOCS change: no
de Leeuw et al., 2017		6 guided exposure sessions with DCS 1 h before each session Dose: 125 mg/session		39 adult OCD patients		In person 6 weekly guided exposure sessions		No significant difference in the Y-BOCS score change between the groups at the end of the trial, although decrease in DCS group was numerically greater (p = 0.076). A significant effect of DCS in the “cleaning/contamination” subgroup (p = 0.033).			Well tolerated		Y-BOCS change: no
Studies in children and adolescents
Storch et al., 2010		10 CBT sessions with DCS 1 h before each session for 7 of the sessions Dose: weight-adjusted		30 children and adolescents with OCD		In person 10 CBT sessions including psychoeducation, cognitive therapy, hierarchy development, and ERP		No significant differences in CY-BOCS and ADIS-CSR scores changes at the end of the trial.			Well tolerated		CY-BOCS: no CGI-S: significant time and group, but no significant time by group interaction ADIS-CSR: no
Study & Drug	Duration, dose and Temporal Relationship to CBT Sessions		Subjects		Mode of Therapy		Endpoint Results on Efficacy		Side Effects	Effect on Primary Outcome: (yes/no)
Studies in children and adolescents
Farrell et al., 2013	9 CBT sessions with DCS 1 h before each of 5 sessions Dose: weight-adjusted		17 children and adolescents with OCD		In person 9 CBT sessions, including 4 sessions with instruction on cognitive-behavioural techniques and 5 ERP sessions		No significant difference in CY-BOCS between the DCS and placebo groups at the end of the trial Greater improvement from end of the trial until 1 month follow up in the DCS compared to the placebo group was detected for CY-BOCS obsessions subscale (p < 0.05), GOCS scale (p < 0.05) and CGI-S (p = 0.05).		Well tolerated	CY-BOCS scores: no at post treatment or 2 mo follow up; yes at 1 mo follow up for some of the measures CSR: no GOCS: yes at 1 mo follow up; no at post treatment or 3 mo follow up CGI-S: yes at 1 mo follow up; no at post treatment or 3 mo follow up
Mataix-Cols et al., 2014	14 CBT sessions, 10 of them with DCS immediately after each session Dose: 50 mg		27 children and adolescents with OCD (In some patients stable psychotropic regimen)		In person 14-session manualised treatment, including 2 sessions psychoeducation, 10 sessions ERP and 2 sessions relapse prevention.		No significant differences in CY-BOCS scores between the DCS and placebo group at any time point		Well tolerated	CY-BOCS change: no
Storch et al., 2016	10 CBT sessions with DCS administered 1 h prior to 7 of the sessions Dose: weight-adjusted		142 children and adolescents with OCD		In person 10 CBT sessions		No significant difference in the rate of CY-BOCS scores decline between the groups. No moderation effect for antidepressant medication observed.		Well tolerated	CY-BOCS change: no

Abbreviations: ADIS = Anxiety Disorders Interview Schedule, ASD = autism spectrum disorder, CBT = cognitive behavioural therapy, CSR = clinical severity rating, CY-BOCS = Children's Yale-Brown Obsessive Compulsive Scale, CGAS = Children's Global Assessment Scale, CGI-I = Clinical Global Impression – Improvement, CGI-S = Clinical Global Impression - Severity, GOCS = Global Obsessive-Compulsive Scale, HDRS = Hamilton Rating Scale for Depression, NAC = N-acetylcysteine, OCD-VAS = OCD visual analog scale, SSRI = selective serotonin reuptake inhibitor, SUDS = Subjective Units of Distress Scale, Y-BOCS = Yale-Brown Obsessive Compulsive Scale.