CHRONIC FATIGUE SYNDROME - Pharmacologic Therapy

Posted by Alex

No treatment has been proved to benefit patients with CFS in large randomized controlled trials that have been replicated by other investigators in other populations of patients. Moreover, without a better understanding of the pathogenesis of CFS, it is unlikely that definitive treatment will be identified. Indeed, the pharmacologic treatment of CFS primarily involves the treatment of the symptoms associated with CFS. In my experience, patients with CFS are unusually sensitive to any drug or substance (e.g., alcohol) that affects the central nervous system; one should start with a low dose and then gradually escalate it as necessary.

Low-Dose Tricyclic Agents

The most widely used treatment of CFS is sedating tricyclic antidepressant agents in low doses: amitriptyline (Elavil)* or doxepin (Sinequan),* 5 to 20 mg at bedtime. For unusually low doses, the liquid form of the medication may be necessary. Low-dose tricyclic agents have been proved efficacious in randomized trials of a similar illness (fibromyalgia) and in a number of sleep disorders. No such trials have been conducted in patients with CFS. In my anecdotal experience, most patients immediately notice that their sleep is less frequently interrupted and that they awaken feeling somewhat more refreshed.

Patients with concomitant depression do not report an improvement in the core symptoms of depression when given these low doses of tricyclic agents. Patients should be warned that during the first week of therapy, even extremely low doses of tricyclics may cause them to feel groggy in the morning; that reaction usually dissipates after about 1 week. When this reaction does not dissipate, patients can be switched to a less sedating tricyclic agent, such as desipramine (Norpramin),* 20 to 50 mg at bedtime, or to the triazolopyridine antidepressant trazodone (Desyrel),* 25 to 50 mg at bedtime.

Antidepressant Agents

Half or more of patients with CFS develop major depression in the months and years after the onset of their illness, although only a minority have experienced an episode of depression in the years before their illness. When patients are suffering from depression, antidepressant therapy is indicated. Again, one should start any antidepressant at an unusually low dose and gradually increase it. In my experience, tricyclic agents can rarely be tolerated in conventional antidepressant doses, but selective serotonin reuptake inhibitors are better tolerated. Sertraline (Zoloft), fluoxetine (Prozac), and paroxetine (Paxil) have been used the most. Some colleagues have reported good results with the combined serotonin and norepinephrine uptake inhibitor venlafaxine (Effexor). Despite this, the only randomized trial of antidepressant therapy in CFS, which used fluoxetine, found no benefit in either the fatigue or depression.

Although I have seen many patients with CFS and depression in whom the depression is successfully treated, I have seen no patient whose entire symptom complex appears to have been cured by antidepressant therapy.

Anxiolytic Agents

Panic disorder and generalized anxiety disorder may be more common in patients with CFS, after the onset of the illness, than in the general population. In such patients, careful use of alprazolam (Xanax), clonazepam (Klonopin), or other benzodiazepines is indicated–with care taken to start at a low dose and to avoid escalating the regimen beyond normal dose levels.

Nonsteroidal Anti-inflammatory Drugs

The majority of patients with CFS experience myalgias, arthralgias, headaches, and migratory paresthesias. For some, the pain is the most debilitating aspect of their illness. In most patients, nonsteroidal anti-inflammatory drugs (NSAIDs) seem to provide a measure of relief. The less expensive NSAIDs, particularly naproxen (Naprosyn) and ibuprofen (Motrin), appear to be just as efficacious as the more expensive NSAIDs.

Antimicrobial Therapy

Because there is no proven infectious cause of CFS, it is not surprising that antimicrobial agents are rarely used. One randomized controlled study found no benefit from acyclovir (Zovirax); however, that antiviral drug has little or no in vitro efficacy against those viruses that studies have found to be reactivated in patients with CFS.

Immunomodulation Therapy

Several controlled trials of intravenous immune globulin* have been tried, on the premise that some kind of immune dysregulation may explain CFS. However, only one study showed a small benefit, and the same investigators have subsequently published a second study with negative findings. There are no data supporting the use of other immunomodulation treatments such as interferon or transfer factor.

Antiallergy Therapy

Many patients with CFS have experienced atopic symptoms since childhood, and the atopic symptoms often flare in CFS. Nonsedating antihistamines* are useful in such patients. Elimination diets have not been studied.

Antihypotensive Therapy

A substantial fraction of patients with CFS have modest abnormalities of the autonomic nervous system, leading to neurally mediated hypotension. Whereas syncope is relatively uncommon in patients with CFS, dizziness and dysequilibrium-particularly associated with postural change - are common. It has been my anecdotal experience that these symptoms may benefit from therapy that increases the vascular space: adding salt to the diet, or taking fludrocortisone (Florinef),* a salt-retaining steroid.