Abstract
Background Treatment-resistant obsessive-compulsive disorder (tr-OCD) remains a significant clinical challenge, as many patients fail to respond to conventional serotonergic therapies despite multiple augmentation strategies. Emerging evidence from neurobiological research suggests that dopaminergic dysfunction, particularly in the prefrontal cortex, may contribute to the persistence of OCD symptoms. The objective of this study was to evaluate the efficacy and tolerability of methylphenidate (MPH), a dopamine and norepinephrine reuptake inhibitor, as an adjunct in patients with tr-OCD. Methodology This case series examines six individuals with tr-OCD who remained symptomatic despite adequate trials of first-line selective serotonin reuptake inhibitors (SSRIs) and various augmentation strategies. MPH was introduced as an adjunct to their existing pharmacotherapy regimens. Clinical outcomes were assessed using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) at baseline and during follow-up over several weeks, with additional clinical judgment supporting therapeutic decisions. Results All six patients demonstrated significant clinical improvement following MPH augmentation. The mean baseline Y-BOCS score was 27.4, which reduced to a mean post-treatment score of 15.1, representing a mean reduction of 12.3 points. Reductions in obsessive thoughts and compulsive behaviors were observed, alongside improvements in cognitive flexibility and impulse control. The treatment was generally well-tolerated, with no serious adverse effects reported. Conclusion These preliminary findings suggest that dopaminergic augmentation with MPH may offer therapeutic benefits in cases of tr-OCD. The observed improvements support the hypothesis that enhancing prefrontal dopamine availability can positively influence OCD symptomatology. Further randomized controlled trials are necessary to confirm these results, define optimal dosing strategies, and establish long-term safety and efficacy.