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Ask the Mental Health Expert Archives 2001-2004

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Allergic to Serotonin

Q. I have a 35-year-old female patient with dysthymia and chronic fatigue syndrome. Her progress has been slow; she's unable to return to work after 6 months. As part of her workup, she was evaluated for allergies and it was found she is allergic to serotonin. Can you be allergic to serotonin? What treatment strategies would you recommend?

A. Interesting question! There are some data showing evidence of antibodies against serotonin (5HT) in patients with primary fibromyalgia syndrome (Klein et al, Psychoneuroendocrinology 1992; 17:593-8) and in patients with panic disorder (Coplan et al, Neuropsychopharmacology 1999; 20:386-91). But what these findings mean in general terms, or how they might apply to your patient, is the $64 thousand dollar question! (This is assuming the work-up for serotonin allergy was valid, of course).

As Klein et al put it, "?.it remains to be determined whether these antibodies are of pathogenetic relevance?" or are related to actual symptoms associated with fibromyalgia. Coplan et al concluded that, "?potential interruption of 5-HT neurotransmission through autoimmune mechanisms may be of pathophysiologic significance in certain patients with panic disorder?[but] it remains to be demonstrated if the peripheral autoimmunity is representative of CNS 5HT?"

I am not aware of any well-validated therapeutic strategies for dysthymia or chronic fatigue syndrome (CFS) that specifically make use of these arcane findings. On the other hand, if your patient really has some auto-immune based disruption of serotonin transmission, it could suggest a role for pro-serotonergic agents, such as SSRIs--at least, in theory.

The analogy might be with myasthenia gravis (MG), in which autoantibodies are directed against the receptor for acetylcholine (Ach). One strategy is to compensate for this by giving the person drugs that boost Ach, which may help temporarily.

Immunosuppressive strategies and plasmapheresis may also be helpful in MG--and I suppose that, in theory, one might consider similar approaches to a patient who truly made autoantibodies against 5HT. But, I'm not aware of any studies showing that such strategies are effective for depression/dysthymia, or for chronic fatigue syndrome, which is itself rather an enigma! (There are some studies suggesting benefits of plasmapheresis in streptococcal-related obsessive compulsive disorders, but I think they are pretty weak findings).

You might want to run all this by an immunologist (or neuroimmunologist), but I wouldn't bet on reaping tremendous benefits for your efforts. On the other hand, since SSRIs are known to be helpful for dysthymic disorder, it's a reasonable strategy to consider.

By the way, I have seen a couple of cases in which chronic fatigue syndrome/fibromyalgia was associated with a peculiar sleep anomaly called alpha-delta sleep. This is essentially the intrusion of the waking rhythm into deep sleep, and was originally described by Moldofsky. If this pattern is detected on polysomnogram (PSG), treatment with a low dose tricyclic at bedtime may be helpful.

I have also seen other patients (usually older males with hypertension and obesity) diagnosed with CFS, who turned out to have obstructive sleep apnea or periodic leg movements of sleep which, when corrected, led to an improvement in mood and energy. So--you might consider getting a PSG in this case.

There are also some studies finding that cognitive-behavioral therapy may be helpful for CFS, so that may be worth pursuing. Good luck with this "fascinoma"!

December 2003

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