Clinical experience using intranasal ketamine in the longitudinal treatment of juvenile bipolar disorder with fear of harm phenotype

J Affect Disord. 2018 Jan 1;225:545-551. doi: 10.1016/j.jad.2017.08.081. Epub 2017 Aug 30.


Objectives: Fear of Harm (FOH) is a pediatric onset phenotype of bipolar disorder (BD) characterized by BD plus treatment resistance, separation anxiety, aggressive obsessions, parasomnias, and thermal dysregulation. Intranasal ketamine (InK) in 12 youths with BD-FOH produced marked improvement during a two-week trial. Here we report on the open effectiveness and safety of InK in maintenance treatment of BD-FOH from the private practice of one author.

Methods: As part of a chart review, patients 18 years or older and parents of younger children responded to a clinical effectiveness and safety survey. Effectiveness was assessed from analysis of responses to 49 questions on symptomatology plus qualitative content analyses of written reports and chart review. Adverse events (AEs) were analyzed by frequency, duration and severity. Peak InK doses ranged from 20 to 360mg per administration.

Results: Surveys were completed on 45 patients treated with InK for 3 months to 6.5 years. Almost all patients were "much" to "very much" improved clinically and in ratings of social function and academic performance. Significant reductions were reported in all symptom categories. There were 13 reports of persistent AEs, none of which resulted in discontinuation. Acute emergence reactions were sporadically observed in up to 75%, but were mild and of brief duration.

Limitations: Retrospective review from a single practice without placebo control with potential for response and recall bias.

Conclusions: InK every 3-4 days at sub-anesthetic doses appeared to be a beneficial and well-tolerated treatment. Use of InK may be considered as a tertiary alternative in treatment refractory cases. Randomized control trials are warranted.

Keywords: Fear of Harm Phenotype; Intranasal ketamine; Pediatric bipolar disorder; Treatment resistant mood disorder.

MeSH terms

  • Administration, Intranasal
  • Adolescent
  • Adult
  • Bipolar Disorder / drug therapy*
  • Bipolar Disorder / psychology
  • Child
  • Excitatory Amino Acid Antagonists / administration & dosage*
  • Fear / drug effects*
  • Fear / psychology
  • Female
  • Humans
  • Ketamine / administration & dosage*
  • Male
  • Phenotype
  • Retrospective Studies
  • Surveys and Questionnaires
  • Young Adult


  • Excitatory Amino Acid Antagonists
  • Ketamine