In my latest professional newsletter, read about patients’ real-world journeys using ketamine and Spravato as we navigate the depression-care pathway
Understanding how Ketamine and Spravato Work
Ketamine has historically been used in anesthesia and for pain management, but recent research has shown a powerful anti-depressant effect. Spravato is a new FDA-approved formulation of esketamine, a variant of ketamine that is administered as a nasal spray.
Ketamine and Spravato antagonize NMDA receptors, which are involved in pain, mood and cognition pathways. These drugs may also stimulate neuronal plasticity and modulate glutamate, serotonin and opioid receptors.
Ketamine Case Study*
A 45-year-old manager presented for treatment of long-standing dysthymia. Her depression score was moderate. She was a daily cannabis user and a regular drinker, with an AUDIT score in the hazardous range.
Through counseling, she stopped alcohol and cannabis. I treated her with maximum-dose fluoxetine that was further augmented with bupropion, but she had a tepid response. Fluoxetine was changed to desvenlafaxine. Depression scores dropped somewhat but she remained perpetually morose. After four ketamine induction infusions, her depression score had dropped by 50%.
The ketamine worsened pre-existing hypertension; anti-hypertensives were increased.
She elected not to have consolidation therapy because she did not want to miss work. Dysthymia re-emerged one month later. With monthly maintenance infusions, remission was maintained.
“The initial dissociation was helpful in jettisoning my preoccupation with depression or anxiety,” she reflected. “For the first time in quite a while, all the restrictions I normally impose on myself had dissolved and I felt optimistic and hopeful.”
Spravato Case Study
A college graduate presented in crisis with one year of severe depression, frantic and paralyzed with intrusive suicidal thoughts but no intent. I noted a family history of bipolar disorder and a prior hypomanic response to an antidepressant. A diagnosis of Bipolar II was made.
I treated the patient with valproate, venlafaxine and clonazepam but he developed valproate toxicity and it was stopped. Pharmacogenomic testing later showed him to be a slow metabolizer of valproate. I prescribed Ziprasidone instead but it was not tolerated and I switched him to lamotrigine, lurasidone and desvenlafaxine, but depression remained unchanged.
Inpatient admission was considered.
After six weeks of intense struggle, Spravato was started. By the sixth treatment, the depression score had dropped by 50%. By treatment 11, the patient was in remission, which remained sustained with monthly maintenance inhalations.
The Role of Ketamine and Spravato in the Depression Treatment Pathway
Ketamine and Spravato fit into the depression treatment pathway via two categories: Treatment-Resistant Depression (at least two medications have been tried, without remission) and suicidality.
There is a 50% response rate to the first infusion of ketamine, so there is validity to trying it out once, but many patients improve progressively though the induction cycle. As case 1 shows, responders benefit from consolidation and maintenance treatment, otherwise relapse is more likely.
I like that ketamine provides relieves the pain of depression. I don’t think we psychiatrists speak enough about its pain although there is a strong medical mandate to relieve other types of pain.
My hope is to reduce suicidal risk and prevent in-patient admissions by providing timely treatment with ketamine or Spravato. Shortly after an assessment, a depressed patient who meets treatment criteria can be receiving their first ketamine infusion with a 50% chance that they will leave feeling somewhat better.
This is an exciting new paradigm in the depression treatment pathway.
If you are interested in discussing or referring a potential case for ketamine or Spravato treatment, please call me on 646 830 0131.
* Identifying details were changed to preserve anonymity