Antiglutamatergic agents for obsessive-compulsive disorder: Where are we now and what are possible future prospects?

Table 1 Glutamate-modulating randomized controlled trials for refractory obsessive-compulsive disorder

Ref.	Drugs	Adjunctive/monotherapy	Subjects	Duration & dose	Results
Haghighi et al[48], 2013	Memantine	Adjunctive to SRIs	40 pt	12 wk. Dose: 5-10 mg/d	Significant reduction. Y-BOCS score
Ghaleiha et al[49], 2013	Memantine	Adjunctive to fluvoxamine	42 pt	8 wk. Dose: 20 mg/d	Significant reduction. Y-BOCS score
Modarresi et al[50], 2018	Memantine	Adjunctive to SRIs	32 pt	12 wk. Dose: 20 mg/d	Significant reduction. Y-BOCS score
Farnia et al[51], 2018	Memantine	Adjunctive to SRIs	99 pt	8 wk. Dose: 10 mg/d	No significant reduction. Y-BOCS score
Naderi et al[56] , 2019	Amantadine	Adjunctive to SRIs	100 pt	12 wk. Dose: 100 mg/d	Significant reduction. Y-BOCS score
Grant et al[59], 2014	Riluzole	Adjunctive to SRIs	60 pt	12 wk. Final dose: 100 mg/d	No significant reduction. Y-BOCS score
Pittenger et al[58], 2015	Riluzole	Adjunctive to SRIs	38 pt	12 wk. Final dose: 100 mg/d	No significant reduction. Y-BOCS score
Emamzadehfar et al[60], 2016	Riluzole	Adjunctive to fluvoxamine	50 pt	10 wk. Final dose: 100 mg/d	Significant reduction. Y-BOCS score
Rodriguez et al[61], 2013	Ketamine	Monotherapy	15 pt	Intravenous infusions dose: 0.5 mg/kg	Significant reduction. Y-BOCS score
Greenberg et al[46], 2009	Glycine	Adjunctive pharmacological or psychotherapeutic treatment	24 pt	12 wk. Dose: 60 mg/d	No significant reduction. Y-BOCS score
Afshar et al[44], 2012	N-acetylcysteine	Adjunctive to SRIs	48 pt	12 wk. Dose: 2.4 g/d	Significant reduction. Y-BOCS score
Sarris et al[68], 2015	N-acetylcysteine	Adjunctive to SRIs	44 pt	16 wk. Dose: 3 g/d	No significant reduction. Y-BOCS score
Paydary et al[45], 2016	N-acetylcysteine	Adjunctive to fluvoxamine	44 pt	10 wk. Dose: 2 g/d	Significant reduction. Y-BOCS score
Costa et al[69], 2017	N-acetylcysteine	Adjunctive to SRIs	40 pt	16 wk. Dose: 3 g/d	No significant reduction. Y-BOCS score
Ghanizadeh et al[70], 2017	N-acetylcysteine	Adjunctive to SRIs	34 pt	10 wk. Dose: 2.4 g/d	Significant reduction. Y-BOCS score
Li et al[71], 2020	N-acetylcysteine	Adjunctive to SRIs	11 pt	12 wk. Dose: 2.7 g/d	Significant reduction. Y-BOCS score
Esalatmanesh et al[75], 2016	Minocycline	Adjunctive to fluvoxamine	102 pt	10 wk. Dose: 200 mg/d	Significant reduction. Y-BOCS score
Kushner et al[78], 2007	D-cycloserine	Adjunctive to CBT	32 pt	125 mg	Significant reduction. Y-BOCS score
Wilhelm et al[79], 2008	D-cycloserine	Adjunctive to CBT	23 pt	100 mg	Significant reduction. Y-BOCS score
Farrell et al[80], 2013	D-cycloserine	Adjunctive to CBT	17 pt	25-50 mg	Significant reduction. Y-BOCS score
Andersson et al[81], 2015	D-cycloserine	Adjunctive to CBT	128 pt	12 wk. Dose: 50 mg	Significant reduction. Y-BOCS score
Mataix-Cols et al[82], 2014	D-cycloserine	Adjunctive to CBT	27 pt	50 mg	Significant reduction. Y-BOCS score
Storch et al[83], 2007	D-cycloserine	Adjunctive to CBT	24 pt	250 mg	No significant reduction. Y-BOCS score
Storch et al[85], 2010	D-cycloserine	Adjunctive to CBT	30 pt	25 mg	No significant reduction. Y-BOCS score
Storch et al[84], 2016	D-cycloserine	Adjunctive to CBT	142 pt	50 mg	No significant reduction. Y-BOCS score

RCT: Randomized controlled trials; OCD: Obsessive-compulsive disorder; SRIs: Serotonin reuptake inhibitors; CBT: Cognitive behaviour therapy; pt: Patients; Y-BOCS: Yale-Brown Obsessive Compulsive Scale.