Obsessive-compulsive disorder affects roughly one in forty adults in the United States, and between thirty and forty percent of those diagnosed do not achieve adequate symptom control through first-line treatments — SSRIs at therapeutic doses and cognitive-behavioral therapy incorporating exposure and response prevention (ERP). For patients across Middle Tennessee and the Nashville metro area, OCD that has resisted standard treatment can be profoundly disabling, affecting work, relationships, and daily functioning across every dimension. At Three Rivers Wellness in Gallatin, we evaluate patients with refractory OCD and assess whether IV ketamine infusions may offer a meaningful option when conventional treatments have failed.
The Neurobiology of OCD and Why Glutamate Matters
OCD involves dysregulation within the cortico-striato-thalamo-cortical (CSTC) circuit — a feedback loop running through the orbitofrontal cortex, caudate nucleus, thalamus, and back to the cortex. In OCD, this circuit becomes locked in a state of chronic overactivation. The obsessive thought pattern and the compulsive behavior are, in neural terms, a dysfunctional CSTC loop that has lost the inhibitory control that would allow it to quiet down.
Serotonergic pathways are clearly involved, which explains why SSRIs are effective for a substantial proportion of OCD patients. But glutamatergic signaling within the CSTC circuit is increasingly recognized as a central driver of treatment-refractory OCD. Research from the National Institute of Mental Health has documented abnormal glutamate levels in the caudate nucleus of OCD patients. This biological picture has generated serious scientific interest in NMDA receptor antagonists — including ketamine — as potential treatments for OCD that conventional serotonergic agents have not adequately addressed.
What the Clinical Evidence Shows
The most commonly cited clinical trial on IV ketamine for OCD was published in Biological Psychiatry in 2013 by Dr. Carolyn Rodriguez and colleagues at Columbia University and the New York State Psychiatric Institute. In that randomized, double-blind study, patients with OCD who received a single IV ketamine infusion showed rapid reductions in obsessive-compulsive symptoms within hours — effects that were significantly greater than the placebo group and were detectable the same day as infusion.
These findings are preliminary and were based on a small sample receiving a single infusion. Larger trials examining multi-infusion protocols for OCD are ongoing. The evidence base is promising but early, and we present it to patients without embellishment. IV ketamine for OCD is off-label — the FDA has not approved ketamine for OCD. Results vary by individual, and not every patient with OCD who receives ketamine infusions will experience meaningful symptom reduction. Discuss with your provider what the current state of evidence means for your specific clinical situation. Our blog post on ketamine for OCD in Gallatin, TN provides additional background on how we approach this treatment locally.
Our Evaluation Process for OCD Patients
OCD takes many forms — contamination fears with compulsive washing, symmetry obsessions, intrusive violent or sexual thoughts, harm OCD, pure-O presentations, and more. Each presentation has different phenomenological features, and careful clinical characterization shapes our approach to every evaluation. We review the full history of OCD symptoms, the progression from onset to current severity, the range of treatments attempted (including specific SSRIs, clomipramine, augmentation strategies, and ERP exposure history), and any documented responses or partial responses.
We also screen carefully for comorbidities. MDD, anxiety disorders, and PTSD co-occur with OCD at elevated rates and must be factored into treatment planning. For patients whose OCD co-occurs with treatment-resistant depression, the intersection of these conditions with our treatment menu — IV ketamine infusions and SPRAVATO® — becomes particularly relevant. SPRAVATO® is FDA-approved for treatment-resistant depression, not OCD; but patients who carry both diagnoses may benefit from a nuanced conversation about which conditions drive the most impairment and which treatment targets are most appropriate to prioritize.
Integration with Ongoing OCD Therapy
IV ketamine is not a substitute for ERP therapy. ERP — exposure and response prevention, the structured form of CBT that is the gold-standard behavioral treatment for OCD — works by retraining the fear circuitry that sustains obsessions and compulsions. The neuroplasticity that IV ketamine may promote creates a potential window for more effective ERP engagement, particularly for patients whose anxiety has historically been too high to tolerate exposures adequately.
We encourage patients to pursue ERP with a trained therapist either during or immediately following their ketamine series. We can assist with referrals to OCD-specialized therapists in the Nashville and Middle Tennessee area. The combination of a neurologically targeted intervention with evidence-based behavioral therapy is, in our view, the most clinically rational approach to refractory OCD. For a broader look at OCD and its relationship to other mood-spectrum conditions, our team has written further resources that may be helpful context.
FAQ
Is IV ketamine approved for OCD?
No. IV ketamine is not FDA-approved for OCD. Its use for OCD is off-label. Preliminary clinical research, including a randomized controlled trial, suggests rapid anti-obsessional effects, but the evidence base is early-stage. Discuss with your provider whether this is appropriate for your history.
Can SPRAVATO® help OCD symptoms?
SPRAVATO® is FDA-approved for treatment-resistant depression and MDD with acute suicidal ideation or behavior — not OCD. If a patient has both TRD and OCD, the treatment plan would be individualized. SPRAVATO® would be considered for the TRD component; IV ketamine would be evaluated for the OCD component. Discuss with your provider.
How many ketamine infusions are in the standard OCD protocol?
Our standard protocol is six IV ketamine infusions over two to three weeks, followed by individualized maintenance as needed. This protocol is based on the same framework as our depression and PTSD protocols; specific dosing may be adjusted for OCD.
How quickly might OCD symptoms respond to ketamine?
The Rodriguez 2013 trial documented same-day reductions in OCD symptoms. Duration of effect from a single infusion was limited. A multi-infusion series may produce more sustained results, but response timelines vary considerably by individual.
Are there OCD patients who should not receive IV ketamine?
Patients with certain medical conditions, psychiatric contraindications (such as active psychosis or a history of mania), or contraindicated medications may not be appropriate candidates. Our intake process reviews all relevant clinical factors before any treatment recommendation is made.
Key Takeaways
- OCD involves CSTC circuit dysregulation with a documented glutamatergic component that SSRIs may not adequately address.
- Preliminary randomized controlled trial data documents rapid anti-obsessional effects from IV ketamine, though the evidence base is early and derives from small samples.
- IV ketamine for OCD is off-label; patients should review the current evidence carefully and honestly with their provider.
- Three Rivers Wellness coordinates IV ketamine therapy with ERP therapy referrals for a behaviorally integrated treatment approach.
- Results vary by individual; SPRAVATO® is not indicated for OCD but may be relevant for patients with co-occurring treatment-resistant depression.
Conclusion
Refractory OCD is one of the most disabling conditions we treat, and the relief that standard options have failed to deliver deserves a serious alternative. IV ketamine therapy targets the glutamatergic component of OCD’s neural circuitry in a way that SSRIs and other conventional agents do not, and the preliminary evidence for its effectiveness is genuinely encouraging. At Three Rivers Wellness in Gallatin, we evaluate OCD patients carefully, discuss the evidence honestly, and build treatment plans that integrate infusion therapy with behavioral work. If you are in the Nashville area and living with OCD that hasn’t responded to standard care, we welcome you to schedule a consultation with our team.
References
Rodriguez CI et al., Randomized Controlled Trial of IV Ketamine in OCD — Biological Psychiatry. https://pubmed.ncbi.nlm.nih.gov/23452685/
International OCD Foundation. https://iocdf.org
National Institute of Mental Health. https://www.nimh.nih.gov
American Psychiatric Association. https://www.psychiatry.org
About Darwin Sunday
Darwin Sunday, MSN, ACNP-BC, RN, is a co-founder of Three Rivers Wellness in Gallatin, TN. Alongside co-founder David Baloun, he is a Vanderbilt University–trained Acute Care Nurse Practitioner with deep experience in emergency and critical care medicine. Sunday brings the clinical precision and vigilance of emergency nursing to each ketamine infusion, applying the same standard of monitoring and decisive response that defines acute care to the treatment of patients with OCD, depression, anxiety, and PTSD. The standard protocol at Three Rivers Wellness begins with a six-infusion series over two to three weeks, followed by individualized maintenance as needed.
Medical Disclaimer
The content on this page is provided for educational purposes only and does not constitute medical advice, diagnosis, or treatment. IV ketamine therapy is an off-label treatment for OCD and other psychiatric conditions. SPRAVATO® is FDA-approved for treatment-resistant depression and MDD with acute suicidal ideation or behavior — not for OCD. Results vary by individual, and not all patients will experience the same outcomes. Always discuss treatment options, potential risks, and your personal health history with a qualified healthcare provider before making any medical decisions.