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EV0940

Efficacy and safety of D-cycloserine-augmented transcranial magnetic stimulation in obsessive-compulsive disorder: a structured literature review

EFFICACY AND SAFETY OF D-CYCLOSERINE-AUGMENTED TRANSCRANIAL MAGNETIC STIMULATION FOR OBSESSIVE-COMPULSIVE DISORDER: A STRUCTURED LITERATURE REVIEW

Limited evidence from three studies suggests that adding D-cycloserine may enhance the therapeutic effects of TMS in obsessive-compulsive disorder and is generally well tolerated.

This review aimed to synthesize the evidence on the efficacy and safety of D-cycloserine-augmented repetitive transcranial magnetic stimulation (rTMS) in obsessive-compulsive disorder (OCD). PubMed was searched using keywords and MeSH terms; studies involving adults aged 18 years or older diagnosed with OCD who received D-cycloserine alongside rTMS and reporting obsessive-compulsive symptom outcomes or adverse events were considered eligible, and three publications met the criteria. In the triple-blind, sham- and placebo-controlled randomized controlled trial by McGirr and colleagues (2025) (n = 24; sham n = 8, iTBS + placebo n = 6, iTBS + D-cycloserine n = 10), intermittent theta burst stimulation (iTBS), with 600 pulses per session, was administered 5 days a week for 4 weeks alongside 100 mg of D-cycloserine; baseline Y-BOCS scores were 23.88 ± 3.64, 21.50 ± 1.04, and 24.10 ± 4.09, respectively, and a significant between-group difference was found at week 4 (p < 0.001), with reported effect sizes of d = 1.34 for iTBS + D-cycloserine versus sham and d = 1.18 for iTBS + D-cycloserine versus iTBS + placebo. In the retrospective case series by Marino and colleagues (2026) (n = 18; baseline Y-BOCS 22.5 ± 6.0), 20 TMS sessions and 125 mg of D-cycloserine were administered over 1 to 2 days, and 16 of the 18 patients also received 20 mg of lisdexamfetamine; 12/18 patients (66.7%) achieved a reduction of at least 35% in their Y-BOCS score, and 5/18 patients (27.8%) reached subclinical symptom severity (Y-BOCS < 8). In the single case report by Weiss and Stine (2025), 20 iTBS sessions were administered over 9.5 hours alongside 125 mg of D-cycloserine and 20 mg of lisdexamfetamine; the Y-BOCS score decreased from 26 at baseline to 7 at week 1 and remained at 7 at week 12. Regarding safety, no serious adverse events were reported in any of the three publications; one hypomanic episode occurred in the study by McGirr and colleagues, but its relationship to treatment remained unclear because the participant subsequently disclosed a diagnosis of bipolar disorder and was taking an unopposed serotonin reuptake inhibitor. Limitations included the early termination of the study by McGirr and colleagues because of an interruption in the supply of D-cycloserine, resulting in small, unequal groups; the heterogeneous stimulation protocols used in the series by Marino and colleagues; and the use of lisdexamfetamine, which made it difficult to attribute the benefits solely to D-cycloserine-augmented iTBS. In conclusion, although the preliminary findings were considered promising, larger, adequately powered randomized controlled trials are needed to confirm efficacy and safety, identify the optimal protocol, and assess the durability of response.

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