The Depression and Anxiety Experts

Ketamine for OCD

Accumulating evidence for augmenting obsessive compulsive disorder (OCD) treatments with ketamine has emerged over the past decade.

This article discusses where ketamine fits into the OCD treatment pathway and describes two successful case studies.

First-Tier Treatment

Step one of treating OCD is psychotherapy. CBT that focuses on exposure and response/ritual prevention (ERP) is very effective.

Second-Tier Treatments

Second tier treatments are antidepressant medications that work via serotonin and norepinephrine. Fluvoxamine, clomipramine, desvenlafaxine, sertraline, etc. are the staples. Often, adding one of these medications to the psychotherapy improves symptoms dramatically.

Third-Tier Treatments

These treatments are used for the one in ten patients that have been treatment resistant thus far.

Third tier treatments involve augmenting the second-tier antidepressants with medications that attack the OCD circuit from a different receptor angle. Examples include atypical mood stabilizers, amantadine, ondansetron, memantine, topiramate, pregabalin and NAC.

When these augmenting strategies work, they are great but when they don’t, the shared agony is spread over many months of failed drug trials. Indeed, refractory OCD is one of the hardest conditions to treat.

There is accumulating evidence for treating refractory OCD with ketamine. Ketamine modulates the glutamate system, which is thought to be dysregulated in OCD. It also promotes neuronal plasticity and connectiveness. This fits neatly into the ERP psychotherapy where patients are taught to tolerate or think differently about ruminative thoughts.

These two case histories illustrate how ketamine can be effective for treatment resistant OCD. Identifying details have been changed.

Case 1.

A 65-year-old teacher had a lifelong history of severe, typical OCD and comorbid unipolar depression. Initial treatment with desvenlafaxine was switched to clomipramine with a small improvement. Clomipramine was augmented sequentially with amantadine, quetiapine, and pregabalin in conjunction with five days/week CBT and DBT with a partial response.

After the first dose of ketamine, she was noticeably more relaxed with less prominent OCD rumination.

After the fourth infusion, reassurance seeking was moderate. She was transitioned to consolidation phase infusions every two weeks.

At four weeks, obsessions and compulsions were intermittently present, but she was able to resist them. Reassurance seeking was mild or appropriate. Quality of life was full.

Case 2.

A 39-year-old lawyer had a life-long history of OCD complicated by bipolar II depression. The OCD was largely ruminative with few compulsions. Going down a rabbit hole of “What if …?” left her paralyzed with doubt.

Numerous mood stabilizers, anti-psychotics, and SSRIs were used over the years. Under my care, the depression settled down with lamotrigine and desvenlafaxine but there was never a full resolution of the anxious rumination. Quality of life and relationships were severely impaired.

After the first ketamine infusion, the patient said that they felt normal again for the first time since age 16. It was a transforming experience.

Four induction infusions over two weeks transitioned to consolidation therapy every two to three weeks with moderate dose increases to prolong the positive treatment effect.

This was a complicated case due to the comorbidity of OCD and bipolar disorder. Nevertheless, it was heartening to see inner tension melt away and for the patient to thank me for changing her life.

Where Does Ketamine Fit into the OCD Treatment Pathway?

Ketamine fits into the treatment pathway as a third-tier augmentation medication. There is not enough data to say whether ketamine should be added early in tier three or later, once all other third-tier options have been exhausted.


Ketamine’s use for treating OCD is off-label, i.e. it’s not FDA approved. Spravato (esketamine) is only FDA approved for depression treatment at this time and cannot be used for OCD.

There is a lack of long-term data for ketamine treatment in psychiatry.

Additionally, there are potential side-effects such as unpleasant dissociations, transient hypertension, and abuse potential that must be carefully weighed up before using ketamine.

Take Away

For psychiatrists, the ability to target the glutamate system effectively with ketamine is potentially a game changer for treatment resistant OCD. Having a 50% chance of a positive reaction to the first infusion offers the promise of rapid relief, which has hitherto been elusive for psychiatry.

If you are a patient with OCD who thinks you may benefit from ketamine treatment, please call our office to discuss setting up a consultation.

If you are a psychiatrist or therapist interested in referring a patient please call me to personally discuss the case.

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