Archive for September, 2014

Treatment Resistant Depression or Chronic Fatigue Syndrome? Child Psychiatrist Finds Success With Antivirals

September 23, 2014

A Different Kind of Psychiatrist

“I have now treated dozens of adults and adolescents who came to me with the diagnosis of “treatment-resistant depression” and instead they had Chronic Fatigue Syndrome. With proper treatment, this viral illness can be successfully controlled.”

ted-henderson

Dr. Henderson is one of the rare psychiatrists to acknowledge the role the immune system and viruses can play in producing symptoms many associate with psychiatric disorders like fatigue

Chronic Fatigue Syndrome in all its forms is difficult to treat, but one doctor in Centennial, Colorado is apparently having some success with antivirals. Dr. Theodore Henderson is not a virologist or even an infectious disease specialist. He’s a child psychiatrist – perhaps the last profession one might expect to be open to viral theories of ME/CFS or childhood depression.  (I remember Environmental Medicine specialist Dr. William Rea telling me that he could count on the fingers of one hand the number of psychiatrists who didn’t believe environmental illness was mental.)

On his website Dr. Henderson descries the DSM approach that attempts to pigeonhole patients and put them in one category or the other. Instead he tries to approach the neurobiological problems of each patient uniquely.

I approach psychiatry from a brain-based biological perspective.. Most people cannot be pigeon-holed into a single category and most psychiatric conditions are actually a range of disturbed neurobiological processes. As a result, I approach each patient, child or adult, as an individual with a unique brain.

While Dr. Henderson uses traditional approaches to treat mental  disorders, he also recognizes the role the immune system and  viruses can play in producing some psychiatric symptoms.

“More importantly, growing evidence suggests that not all psychiatric symptoms, such as anxiety, fatigue, listlessness, low mood, or poor concentration, result from intrinsic flaws in the patient’s brain. Extrinsic causes, such as infections and toxins, can cause these psychiatric symptoms. The resulting cluster of symptoms might mimic anxiety, depression and other psychiatric disorders, leading to misdiagnosis and ineffective treatment.

Certain rare autoimmune disorders can lead to the formation of antibodies against specific neurotransmitter receptors. Much more widespread autoimmune disorders, such as systemic lupus erythematosus, can lead to cognitive changes, anxiety, seizures, and mood disorders”

Dr. Henderson reported he has been effectively treating both adolescent and adult Chronic Fatigue Syndrome patients with antivirals for several years. He recently published a paper describing his results with adolescents.

The Paper

Henderson TA.  Adv Mind Body Med. 2014 Winter;28(1):4-14. Valacyclovir treatment of chronic fatigue in adolescents.
pathogens

Dr. Henderson cites Dr. Lerner’s work with antivirals and ME/CFS on his website

In the paper, Dr. Henderson first cites the low diagnostic rates for Chronic Fatigue Syndrome (20%).  Then he argues that studies suggest reactivated herpesvirus infections, particularly HHV-6, are common in ME/CFS.  Arguing – as did Dr. Brewer at the Simmaron Research Foundation’s Immunology Workshop in San Francisco – that IgM antibodies are not diagnostic in this disease, Dr. Henderson asserted that primary cell cultures in combination with antibody or PCR tests indicate HHV-6 infection rates are very high in ME/CFS.

The Antiviral Subset?

In Dr. Henderson’s experience (approximately 65 patients treated) ME/CFS patients whose illness began with flu-like onset and who have:

  • have elevated IgG levels against a herpesvirus
  • low natural killer cell activity
  • high ribonuclease activity
  • high levels of angiotensin converting  enzyme (>35)
  • high TNF-a levels
  • elevated total IgM or IgG levels

responded well to antivirals.  He undertook a retrospective chart review of 15 adolescents he had treated with valacyclovir (Valtrex) between 2007 and 2013.

Valtrex is used to treat herpes zoster and herpes simplex and, in Chronic Fatigue Syndrome, Epstein-Barr Virus reactivation. Two studies by Lerner suggest Valtrex can be effective in ME/CFS.

young-man

Many of the adolescents who responded to antivirals had been referred to Dr. Henderson for treatment resistant depression

Dr. Henderson evaluated these patients like any good child psychiatrist would: He looked for mood disorders, a history of childhood abuse, assessed their sleep quality, and reviewed their school performance. He looked for any other significant symptoms and did laboratory work.  He noted that most of them had been referred to him for having ‘treatment-resistant depression’. All experienced fatigue, low motivation, academic problems, and unrefreshing sleep. Most had tried antidepressants or other mood altering drugs without effect. They did not, however, meet the CDI self-report test for depression.

Upon further evaluation six were given a diagnosis of Chronic Fatigue Syndrome, four were given an ME/CFS diagnosis plus anxiety, and three were given a diagnosis of ME/CFS diagnosis plus mood disorders.

Eleven were receiving failing grades in at least one class, and almost half had dropped out of school.  A third were sleeping more than 12 hours a day.

Ten could remember an infectious event they didn’t recover from.  Interestingly, a third of the group reported that they had always experienced significant fatigue.

fatigued-young-woman

The fatigue levels of his young patients were incredibly high

Their self-reported fatigue levels were almost off the charts.  While ‘significant fatigue’ is indicated by a score of 39 on the Fatigue Symptom Index (FSI), their mean score was 95. Similarly, they topped out on the Fatigue Severity Scale with almost two-thirds of the participants scoring near maximum fatigue levels (56 out of a possible 63).

The doctor provided them with the option of going on Valacyclovir, noting that the published evidence that it would work was small and confined to adults, not adolescents.  They began on an oral dose 500 mg BID and worked their way up to 1000 mg BID over a couple of weeks.

Results

“The medical understanding of CFS has been impeded to a degree by the resistance to the concept  of chronic viral infections of the central nervous system.”

Almost all of the adolescents responded quickly to the antivirals. Within three months 12 out of 15 reported greater than an 80% improvement in symptoms. After 8 months 14 out of 15 adolescents reported increased energy, improved sleep, increased motivation, and “return to normal functioning”. Ten of the 14 reported a “complete resolution of fatigue” and their depressive symptoms disappeared. Five of the seven who had dropped out of school returned to school and ultimately enrolled in college.

upwards graph

Fatigue scores generally dropped dramatically in response to antiviral therapies

The changes in the fatigue self-report scores were astonishing. Mean Fatigue Symptom Index (FSI) scores for nine of the fifteen dropped from the whole group FSI score of 56 to and FSI score of 12.  Fatigue Severity Scale scores dropped from 95 to 19. All ME/CFS symptoms measured by the MFSI dropped significantly.

The impressive results bring to mind Dr. Montoya’s initial Stanford valganciclovir trial in adults (9/12 recover) and the reminder that the results of his more rigorous double blinded, placebo-controlled trial, while positive, were much less successful.  Still, Dr. Henderson has clearly experienced real success with his adolescent ME/CFS patients, none of whom had responded to other approaches.

Noting that his adolescent patients were more likely to have acute infectious onset than adults and less likely to experience depression, Dr. Henderson suggested adolescents might have more success with antivirals.

While he didn’t mention it, one wonders if late exposure to Epstein-Barr Virus is playing a major role in adolescent onset ME/CFS.  Adolescence is becoming a more and more likely time of first exposure to Epstein-Barr virus (EBV).  Early exposure to EBV (during childhood) often doesn’t cause symptoms, but as cytotoxic T-cells decline after early childhood, later exposure causes a much more virulent illness. Some researchers believe delayed exposure to EBV is behind the increased levels of autoimmune disorders seen.

As do some others in the field, Dr. Henderson, took issue with the medical community’s unwillingness to more fully investigate the impact central nervous system viruses have on a range of disorders including ME/CFS, multiple sclerosis, schizophrenia, Alzheimer’s, and Autism.

Follow-up

The average duration on the drug was over two years.  Four patients discontinued treatment after about 18 months and remained well at the time of this report. Five patients who discontinued treatment in a similar time frame, however, immediately relapsed and had to go back on the drug.

Treatment Resistant Depression = Chronic Fatigue Syndrome?

“The authors secondary hypothesis is that treatment-resistant depression may often, in fact, be CFS that has been misdiagnosed.”

Dr. Henderson proposed that a significant number of adolescents diagnosed with treatment-resistant depression actually have a form of chronic fatigue syndrome that may respond to antivirals.

question-mark

Remarkably, most of the adolescent referred to Henderson for treatment resistant depression….did not meet the criteria for it

The medical profession’s eagerness to diagnose adolescents experiencing severe fatigue with depression was evident. Despite the fact that most of his adolescent patients did not met the DSM criteria for depression nor did they have CDI scores consistent with depression, many of them were still diagnosed with depression.  Other findings, such as low cortisol and cerebral hypoperfusion, were at odds with a depression diagnosis, yet over half the adolescents had been treated for depression and had not responded.

One is reminded of the saying that if your only tool is a hammer, everything begins to look like a nail.  But Dr. Henderson’s specialty is psychiatry.  He recognizes true depression when he sees it.

In fact, adults with inflammation-associated depression who make up perhaps a third of all cases of depression – do not respond to antidepressants either. Interestingly, a subset of depressed patients without inflammation-associated depression get worse when given anti-inflammatories. (For them some inflammation is good!)

The doctor provided a case report involving an adolescent experiencing fatigue, brain fog, and depression diagnosed with ‘treatment resistant depression’ who had failed to respond to either SSRIs or SNRIds.  Tests showed she had reduced NK cell counts and high IgG titers to EBV and HHV-6. Three months after going on 1000 mg a day of Valacyclovir she had experienced a complete resolution of all her symptoms. Three months later, after forgetting her meds on a trip to Disneyland, her symptoms quickly returned and she spent most of the vacation in bed at her hotel. One week after resuming the medication her symptoms completely disappeared again.

Dr. Henderson proposed a placebo-controlled trial be done involving seropositive (antibody positive) and seronegative ME/CFS patients. The trial should not, he emphasized, employ acyclovir, an antiviral he asserted has low bioavailability and is rapidly eliminated by the body.

Conclusion

In a retrospective case analysis Dr. Henderson reported very high response rates to Valacyclovir (Valcyte) in a small group of adolescents with ME/CFS. Fatigue and other symptoms virtually disappeared for many in the study, a significant portion of whom had been diagnosed with treatment-resistant depression.

He proposed that that many adolescents diagnosed with treatment-resistant depression may have Chronic Fatigue Syndrome.  Dr. Henderson also suggested that the high incidence of infectious onset and low incidence of depression in adolescents with ME/CFS made them good targets for antiviral therapy.

Check out Dr. Henderson’s website and blog here.