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to Treat Chronic Fatigue Syndrome
By Charles Lapp,
have proven to be
useful in treating chronic fatigue syndrome (CFS). They can help improve sleep,
energy levels and cognitive impairment, and alleviate
It needs to be
emphasized that these
drugs are helpful not because patients are primarily depressed (although
depression may occur as a result of the illness), but because they often have
low levels of the neurotransmitters serotonin and
I find that almost all of my patients
benefit from treatment with antidepressants. The
chart at this link is not intended to
be comprehensive, but rather to represent classes of drugs that may be helpful.
Following is a brief discussion of research on the benefits of antidepressants
and the process that I use when deciding which drug to try with a
A small number of trials have
been conducted to assess the possible value of antidepressants for CFS, and for
the most part have provided evidence of their usefulness in treating specific
A minority of patients in a six-week
treatment study of Nardil (phenelzine), a monoamine oxidase inhibitor (MAOI),
reported significant improvement, although some had to drop out of the trial due
to side effects.1 Trials of Manerix (moclobemide), another MAOI, with
CFS patients have showed significant reductions in fatigue.3,4
Unfortunately, moclobemide is not available in the United States.
antidepressant (TCA), was tested in a single-case, double-blind study for CFS. A
60 mg-per day dose significantly reduced CFS symptom scores.5 In
controlled trials, TCAs have also proven beneficial in the treatment of
fibro-myalgia (FM), an illness that shares many clinical features with
earlier case studies, a trial of Prozac (fluoxetine) conducted in the
Netherlands with 44 CFS patients with concomitant depression and 52 with CFS but
no evidence of depression failed to show significant beneficial effects. The
researchers suggested that the fact that even the depressed group failed to
improve indicates chemical changes in the brain in CFS that are very dissimilar
In an uncontrolled
trial, 79 patients
with CFS who showed no signs of depression reported seeing major improvement
(particularly regarding levels of fatigue, muscle pain and sleep disturbance)
after treatment with Zoloft (sertraline).8
may also benefit the
immune system in CFS. Dr. Nancy Klimas at the University of Miami has studied
the effect of selective serotonin reuptake inhibitors (SSRIs) on the immune
system. She has reported that CFS patients given Prozac for three months showed
moderate to marked improvement in the number of natural killer cells
The first question I ask when
deciding which antidepressant to prescribe for a CFS patient is whether the
individual is having difficulty sleeping. Three drugs listedin the chart
at this link, Desyrel (trazadone), Remeron (mirtazapine) and Serzone
(nefazadone) are more sedating and may be useful in assisting sleep. Desyrel in
particular increases stage 3 and 4 (or "deep") sleep.
Wellbutrin (bupropion), Prozac and
are more activating drugs in terms of increasing CFS patients' perceived energy
levels, but they may actually interfere with deep sleep. Some stimulating drugs
may also increase the risk of seizure activity by causing hyperexcitability in
the central nervous system.
Pain control is another factor that
consider. TCAs increase levels of norepinephrine in the central nervous system,
which will increase the patient's pain threshold. This is why Elavil
(amitriptyline) is often used to treat FM and CFS. However, while Elavil has a
soporific effect, it reduces deep sleep and in the long run may not be the best
choice for patients having trouble sleeping. Effexor (venlafaxine) is a
serotonin and norepinephrine reuptake inhibitor that mayalso increase the pain
Wellbutrin is the first antidepressant
the market to increase levels of the neurotransmitter dopamine, which is
typically "balanced" with serotonin in the brain. If a patient has tried
serotonin agonists and does not tolerate them well, then Wellbutrin may be a
good choice. Wellbutrin may be taken alone or with other
Remeron is another
unique drug in
that it affects alpha 2 receptors and histamine receptors in the brain. At lower
doses (7.5 to 30 mg), the histaminic effect can induce sleep. Starting at 30 mg, the alpha 2 effect
appears, which can give patients increased energy levels. Clinicians should be
aware that 30 mg is the highest recommended dose according to the manufacturer,
although psychiatrists occasionally prescribe45 or 60 mg
effect of Remeron can
stimulate appetite, so patients on low-dose therapy with this drug usually gain weight rapidly. Clinicians may
want to use Remeron only with individuals who are low weight or losing
If the patient has neurally mediated
hypotension or orthostatic intolerance, which can cause fluctuations in blood
pressure and heart rate, clinicians may want to choose an antidepressant that
can improve those symptoms as well. Prozac, Zoloft and Paxil (paroxetine) have
been shown in controlled, blinded studies to improve autonomic
Antidepressant drugs have been associated
with numerous side effects. Wellbutrin, Desyrel, Remeron and Serzone show the
least incidence of sexual dysfunction as a side effect, while Prozac, Zoloft and
Paxil are most likely to suppress libido. The drugs with the highest
anitcholinergic effect, Paxil, Elavil and Desyrel, can lead to dry eyes and
mouth and blurred vision.
Some antidepressants can also affect
cytochrome P450 system, which detoxifies the liver. If that system is blocked by
the drug, other medications cannot be metabolized and build up in the body,
leading to a higher risk of adverse effects.
Selecting the most
efficacious agent depends upon taking a good patient history and tailoring drug
therapy to the patient's specific symptoms. Clinicians should be aware that CFS
patients often have sensitivities and idiosyncratic reactions to medication.
They also may show a therapeutic response at much lower doses than individuals
suffering from major depression.
start low and go slow, using one-half to one-third of the usual dose at first
for specific dose suggestions).
Some patients require even lower doses. Using medications that are available in
the liquid form, such as Sinequan (doxepin), may be helpful, since the dose is
- Natelson BH et al. Randomized,
double blind, controlled placebo-phase in trial of low dose phenelzine in the
chronic fatigue syndrome. Psychopharmacol. 1996; 124: 226-30.
- Goodnick PJ. Treatment of CFS with
verlafaxine. Am J Psychiatry. 1996; 153: 294.
- White PD and Cleary KJ. An open
study of the efficacy and adverse effects of moclobemide in patients with the
chronic fatigue syndrome. Int Clin Psychopharmacol. 1997; 12:
- Hickie IB et al. A randomized,
double-blind, placebo-controlled trial of moclobemide in patients with chronic
fatigue syndrome. J Clin Psych. 2000; 61: 643-8.
- Goodnick PJ and Sandoval R.
Psychotropic treatment of chronic fatigue syndrome and related disorders. J
Clin Psych. 1993; 54: 13-20.
- Blondel-Hill E and Shafran SD.
Treatment of chronic fatigue syndrome. A review and practical guide.
Drugs. 1993; 46: 639-51.
- Vercoulen J et al. Randomized,
double-blind, placebo-controlled study of fluoxetine in chronic fatigue
syndrome. Lancet. 1996; 347: 858-61 and 1770-2.
- Behan P et al. A pilot study of
sertraline for the treatment of chronic fatigue syndrome. Clin Infect
Dis. 1994; 18 (suppl 1): S111.
- Information presented by Nancy Klimas at
The CFIDS Association of America's 1990 research conference in Charlotte,
Dr. Lapp practices
at the Hunter-Hopkins Center in Charlotte, NC. He is also a Clinical Associate
Professor of Family and Community Medicine at Duke University.