In addition, most reported daily naps and unrefreshing sleep.4 They had not responded to adequate trials of antidepressants and the duration of symptoms ranged from 6-96 months. There was no history of abuse or neglect, although this has been suggested as an etiology of SEID in the past.6,7 Patients completed the Children’s Depression Inventory8 and the mean score was 14 (+2.83), below the typical cut-off for depression.

Patients were treated with the antiviral, valacyclovir (Valtrex), at a dose of 1000 mg twice a day. Only one patient experienced nausea and discontinued the antiviral. Improvement occurred over the course of 3-5 months. Eighty-six percent of the patients responded by 3 months, and 92% responded by 5 months. Symptoms of fatigue, exertion induced malaise, excessive sleep, napping, unrefreshing sleep, headaches, cognitive symptoms, and emotional symptoms all resolved.


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Fatigue was specifically measured with the Fatigue Severity Scale,9 the Fatigue Symptom Inventory,10 and the Multidimensional Fatigue Symptom Inventory-Short Version (MFSI),11 which also allows assessment of cognitive symptoms, emotional symptoms, pain, and vigor. The general score on the MFSI dropped from 23.31 (+1.11) to 1.1 (+1.37) and the vigor score rose from 4.54 (+2.40) to 16.50 (+3.37). All changes were statistically significant.4 All of the responders had improved school performance, and five of seven who had previously dropped out of school had re-enrolled.

These data stand in stark contrast to the trials of cognitive-behavioral therapy (CBT) or graded exercise therapy (GET) wherein a response rate of about 60% is reported and response is defined as an approximate 10% improvement in fatigue scores.2,3,12 Moreover, the PACE trial, the largest study of CBT/GET,12 was an unblinded study whose data has garnered criticism for its biasing of the score threshold.

While these data are from a subset of 15 adolescent patients, it accurately reflects the experience with a much larger subset of clinic patients. Patients who present with depression include a subset who instead have SEID. This is particularly true for patients with treatment-resistant depression as seen in our ketamine infusion therapy clinic (www.ketamineinfusioncenters.com).

As discussed in the National Academy of Science report, these patients can be differentiated by symptoms of fatigue, post-exertional malaise, frequent naps, unrefreshing sleep, headache, lightheadedness, and cognitive dysfunction.