Unexpected Improvement in Obsessive-Compulsive Disorder Symptoms Following Initiation of Bupropion

Obsessive-compulsive disorder (OCD) is characterized by intrusive obsessions and compulsions that cause distress and functional impairment.¹ First-line treatments include selective serotonin reuptake inhibitors (SSRIs) and cognitive-behavioral therapy incorporating exposure and response prevention.² However, despite these interventions, 25%–40% of patients demonstrate partial or inadequate symptom response,³ underscoring the need to better understand alternative treatment approaches.

Bupropion, a norepinephrine-dopamine reuptake inhibitor, is not a standard treatment for OCD and is generally avoided due to concerns regarding potential symptom exacerbation. Evidence regarding bupropion in OCD is limited and mixed.⁴ However, research suggests that nonserotonergic mechanisms, including dopaminergic modulation of frontostriatal circuits, may play a role in OCD pathophysiology.^5–8 This raises the possibility that dopaminergic agents such as bupropion may influence obsessive-compulsive symptoms. Here, we present a case of a young adult with OCD and comorbid major depressive disorder (MDD) who experienced an unexpected improvement in OCD symptoms following initiation of bupropion.

Case Report

A 23-year-old woman with OCD, MDD, and unspecified anxiety presented for management of persistent obsessive-compulsive and depressive symptoms. Her OCD was characterized by intrusive obsessions involving aversions to the smell and textures of fruit and fixations on song lyrics. Compulsions included repeatedly wiping surfaces with detergent, mentally replaying songs until she could stop thinking about them, and meticulously repeating her bedtime routine until performed in a precise order. These symptoms resulted in significant functional impairment, including avoidance of any jobs that involved handling fruit.

SSRIs, including sertraline and fluoxetine, were tried, but both were discontinued due to adverse effects. Adjunctive N-acetylcysteine (NAC) at 600 mg daily had been initiated prior to SSRI discontinuation without substantial remission of obsessive-compulsive symptoms. Given ongoing depression with prominent amotivation, as well as reports of her mother’s depression previously responding well to bupropion, bupropion extended release 150 mg daily was initiated but caused insomnia, which resolved after switching to bupropion sustained release 150 mg daily.

At 1-month follow-up, the patient reported marked improvement in depressive symptoms, including energy, mood, and sleep. She also noted a reduction in the frequency and intensity of obsessive thoughts and compulsive behaviors, which were no longer distressing or impairing. She tolerated previously avoided stimuli, including being around fruit in occupational settings without any distress or compulsions. Over 3 years of follow-up, she continued to report minimal to no OCD symptoms without recurrence of functional impairment and remained stable on bupropion.

Discussion

This case highlights a sustained improvement in OCD following initiation of bupropion in a patient with OCD and MDD. While serotonergic mechanisms have historically guided pharmacologic treatment of OCD, literature suggests that dopaminergic signaling contributes to compulsivity, cognitive rigidity, and habit formation in OCD.^7,8 Limited research also shows a bimodal response to bupropion.⁴ Therefore, bupropion’s dopaminergic and noradrenergic effects may have contributed to the observed reduction in symptoms. Although improvement in depressive symptoms may have helped, the patient’s OCD predated the depressive episode, and improved tolerance of previously avoided stimuli further suggests a functional recovery from OCD.

Limitations include a reliance on patient-reported outcomes and concurrent use of adjunctive NAC. As a single case, this does not support routine deviation from first-line treatments for OCD. However, this case does suggest that bupropion may warrant consideration in select patients when comorbid depression with amotivation is present and serotonergic agents are poorly tolerated. Bupropion’s differing adverse effect profile, with respect to decreased sexual dysfunction and weight gain, may also influence adherence and patient preference.⁹ Primary care clinicians often serve as the first point of contact for patients with OCD, and this case highlights the potential role of bupropion as part of an individualized treatment approach for patients with refractory symptoms.

Article Information

Published Online: August 18, 2026. https://doi.org/10.4088/PCC.26cr04209
© 2026 Physicians Postgraduate Press, Inc.
Prim Care Companion CNS Disord 2026;28(4):26cr04209
Submitted: February 7, 2026; accepted April 10, 2026.
To Cite: Riestra JM, Munsar Z, Opler DJ. Unexpected improvement in obsessive-compulsive disorder symptoms following initiation of bupropion. Prim Care Companion CNS Disord 2026;28(4):26cr04209.
Author Affiliations: Department of Psychiatry, Rutgers New Jersey Medical School, Newark, New Jersey (all authors).
Corresponding Author: Zoya Munsar, BS, Rutgers New Jersey Medical School, 185 S Orange Ave, Newark, NJ 07103 ([email protected]).
Financial Disclosure: None.
Funding/Support: None
Patient Consent: Consent was received from the patient to publish this case report, and information has been deidentified to protect patient anonymity.