• Data captured before and after treatment by ketamine show that the drug is able to provide a rapid and significant reduction of most, if not all of the symptoms described in the FOH phenotype and that it is well tolerated with no clinically significant side effects.
  • There seems to be an important association between body temperature regulation and the profile of behavioral symptoms described by FOH: Resolution of behavioral symptoms follows a resolution of symptoms related to body temperature dysregulation.
  • The reduction and return of symptoms as a group supports the notion that they are associated with each other as a single syndrome.


As discussed in FOH and Intranasal Ketamine, Dr. Papolos, Director of Research for JBRF has used intranasal ketamine to treat children with FOH. Full data sets from questionnaires given pre- and post- treatment were available from 12 of those patients. The data were analyzed and published as a preliminary, retrospective report of the efficacy and safety of ketamine for children with FOH.

The data came from three questionnaires which measure symptom severity (CBQ, OAS, Y-BOCS) and one which measures dissociative side effects (CADSS). The symptom severity questionnaires were answered by parents 1-2 weeks before treatment and all questionnaires were again answered by the same parent over a two month period after the start of treatment. The data was assessed and the results published in 2012. (Click here to access the article.)

The patients ranged in age from 6 to 19 and all of them had psychotic symptoms, met criteria for DSM-IV bipolar disorder, were characterized by the FOH syndrome and were not helped by previous treatments. They shared the experiences of school refusal, comorbid anxiety, obsessive rituals, and a moderate to major degree of decreased functioning in most social areas or severe impairment of functioning in one area.

Analysis of the data showed that once a therapeutic dose was reached, the response was immediate and it brought about a significant reduction in all of the key dimensions of FOH. Specifically, improvement was seen in symptoms of: (hypo)manic hyperactivity, mood instability, hyperarousal, aggressive behaviors and obsessions, anxiety, sleep, inattention, racing thoughts and carbohydrate craving, fear of harm, sleep-onset and sleep-offset disturbances, parasomnias, and other thermoregulatory symptoms associated with this syndrome. Side effects were minimal, well tolerated, and diminished over time for 90% of the patients whose data was used in the study.

Three Important Take-Away Findings

  • Remission of behavioral symptoms followed the remission of the thermoregulatory symptoms. This relationship, and the order in which it occurs, underscores the relevance of thermoregulation to the expression of the illness. Interestingly, for 2 patients (not included in the paper) who did not achieve a therapeutic response, the ketamine was not able to control their thermoregulatory symptoms.
  • The fact that the FOH symptoms, as a group, leave when the ketamine hits its target, and then return as a group 1 to 3 days later, when the effect of the ketamine wears off, supports the notion that the broad range of symptoms are all associated with each other as a single syndrome.
  • The fact that low-dose intranasal ketamine has been able to effectively treat the symptoms of bipolar disorder and FOH, and can do so over an extended period of time without unacceptable side effects and without the emergence of new known symptoms (to date), suggests that it may be an effective drug for the long-term management of severe mood disorder. (Other studies [A3] with ketamine and mood disorder focus upon its ability to be used as an emergency intervention.)



 [A2]Link to IN Ketamine paper


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