Juvenile Bipolar Disorder: Intranasal Ketamine Effective, Well-Tolerated

nasal spray bottle
nasal spray bottle
Ketamine improves social function and academic performance in juvenile patients with bipolar disorder with a fear of harm phenotype.

According to the results of a study published in the Journal of Affective Disorders, intranasal ketamine was shown to clinically improve social function and academic performance in juvenile patients with bipolar disorder with a fear of harm phenotype.

In this single-site study, researchers enrolled 45 young patients (mean, 15 ± 6.7 years; range, 6-37 years) with bipolar disorder and a fear of harm phenotype who were refractory to treatment. Patients were treated with intranasal ketamine (0.1 mL sprays of 50-200 mg/mL; mean, 165 ± 75 mg) for up to 6.5 years (mean, 1.71 ± 1.36 years). Effectiveness and adverse events were monitored by patient or parent responses to survey questions, as well as a chart review.

After treatment with intranasal ketamine, Clinical Global Impression Severity scores significantly improved from baseline (5.7 ± 0.7 vs 3.2 ± 1.1; P <.001), correlating with a shift from severely ill to mildly ill. Of the 39 charts reviewed, 8 patients were considered very much improved, 26 much improved, 5 mildly improved or unchanged, and none worsened.

Based on open-ended written reports, treatment improved researcher clinical global impressions, resulting in a Clinical Global Impressions improvement score of 1.44 (95% CI, 1.23-1.64). All patients treated with intranasal ketamine were considered easier to get along with and had improved family life. Most patients also had better academic and work performance (n = 20/21).

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Persistent adverse events included sensory changes (n = 2), urination problems (n = 5), and torso acne (n = 4). Acute time-limited reactions included a sense of relaxation calm and bodily warmth, dizziness, wobbly gait, and a stinging sensation in the nose. The intensity of the adverse events decreased over time but remained present. No adverse events led to the discontinuation of the treatment. 

Demitri Papolos, MD, lead author on the study, called the results of the study “important,” as they provide evidence for the treatment of a refractory bipolar disorder phenotype in adolescents. Dr Papolos noted that racemic ketamine is “a generic drug that is affordable, readily available, and appears safe and highly efficacious, at least in this specific population [bipolar disorder with a fear of harm phenotype].”


Papolos D, Frei M, Rossignol D, Mattis S, Hernandez-Garcia LC, Teicher MH. Clinical experience using intranasal ketamine in the longitudinal treatment of juvenile bipolar disorder with fear of harm phenotype. J Affect Disord. 2017;225:545-551