Appeal type: Experimental/Investigational
Decision: Overturned

Diagnosis: Recurrent Major Depression, Autism Spectrum Disorder, Ulcerative Colitis.
Treatment: Intravenous (IV) Ketamine.
The insurer denied: Intravenous (IV) Ketamine.
The denial is upheld.

The patient is an adolescent male. He was reported to have been diagnosed with autism spectrum disorder, major depressive disorder, recurrent, severe without psychotic features and ulcerative colitis. The patient's provider is requesting intravenous ketamine infusions for treatment of symptoms related to major depressive disorder. The requested intravenous ketamine infusions were denied as the treatment was noted to be experimental/investigational. The provider indicates that the patient is unable to tolerate serotonergic antidepressants and bupropion due to ulcerative colitis. The patient was reported to have persistent depression and suicidal ideations. The patient was reported to have been treated with twice weekly intravenous ketamine and was reported to have responded well to treatments. The patient was previously treated with Vyvanse (lisdexamfetamine), methylphenidate, atomoxetine, bupropion, nortriptyline, escitalopram, fluoxetine, lamotrigine and guanfacine. The patient was reported to have significant abdominal pain with antidepressant medications.

The health plan should not cover the requested intravenous Ketamine.

The patient was reported to have been unable to take oral antidepressant medications due to abdominal pain and other symptoms related to ulcerative colitis. However, there was no indication that the patient was adequately maintained on dosages of antidepressant medication and augmenting agents for antidepressant such as atypical antipsychotic medications. Ketamine currently indicated as a general anesthetic agent. Ketamine has also been shown to improve symptoms of depression and suicidal thoughts. However, there is no clear evidence in current peer-reviewed, evidence-based medical literature to indicate the safety or efficacy of intravenous ketamine infusions for treatment resistant major depressive disorder (1-5). The medication is currently not approved by the Food and Drug Administration (FDA) for treatment of major depressive disorder. Esketamine (Spravato) a S-enantiomer of racemic ketamine is the only form of ketamine that is currently approved for treatment of major depressive disorder. A randomized control trial reported by Phillips et al. (2018) indicated that ketamine infusions have cumulative and sustained antidepressant effects. However, the authors concluded that future studies should further expand on optimizing administration to better translate the use of ketamine into clinical settings (1). A review by Lent et al. (2019) indicated that ketamine infusion therapy was generally well tolerated, with minimal untoward effects. However, the authors conclude that large, randomized controlled trials are needed to discern the longer-term efficacy, tolerance, and dependence profiles of ketamine infusions (2). A meta-analysis of effect sizes of different formulations of ketamine for treatment of mood disorders reported by McIntyre et al. (2020) indicated that no conclusions could be made regarding comparative efficacy of the disparate formulations and routes of delivery (3). A review by Memom et al. (2020) concluded that the short-lived antidepressant effect of ketamine is a potential limitation and therefore further studies administering multiple infusions for acute treatment and maintenance are necessary (4). A recent review by Dean et al. (2021) concluded that ketamine may be more efficacious than placebo at 24 hours. How these findings translate into clinical practice, however, is not entirely clear (5). Therefore, due to the lack of clear evidence in current peer-reviewed, evidence-based medical literature for the safety or efficacy of intravenous ketamine infusions for treatment of major depressive disorder in children, the health plan should not cover the requested intravenous Ketamine.