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DRUGS: For Better or For Worse

  [ 31 votes ]   [ Discuss This Article ]
By By: Kristin Thorson • • April 1, 1993

Reprinted with permission of the Fibromyalgia Network, October, 1992.

Serotonin is involved in sleep, pain modulation and a whole host of other body functions. But just because a drug impacts serotonin, it may not reduce your symptoms, and in some instances, it may leave you feeling worse. Your response to a particular drug may be completely different from what someone else with FMS/CFS experiences. Several medications or drug categories that your doctor might prescribe for you are discussed below to help you understand why certain therapies work for you while others simply don't.

Selective Serotonin Re-uptake Inhibitors

Drugs in this category include fluoxitine (Prozac), sertraline (Zoloft), fluvoxamine and others (1). When serotonin is released at your nerve endings, these medications enable this neurotransmitter to exert a longer lasting effect by blocking its re-uptake so as to offset its deficiency (i.e., like giving it more power to its punch). And, they are selective, meaning that they don't disrupt the function of other neurotransmitters which often leads to unwanted side effects. But will these drugs improve your sleep, lessen your pain and reduce your fatigue?

Take Prozac, for example. A small dose in the morning may boost your energy level and take the edge off of your pain, but it can have a detrimental impact on your sleep. According to the research data in the book Serotonin, Sleep and Mental Disorder (2), Prozac reduces the time you spend in sleep as well as the quality of your sleep. So, if this drug gives you an initial burst of energy, only to put you flat on your back a week or two later, it is possible that Prozac could be interfering with your deep level sleep.

Naturally, if the above response happens, consult your physician immediately. Or, if you have cancelled out the possibility of using any of the drugs in this category because you had a bad response to Prozac, you should still talk to your doctor. Based on a theory offered in the book mentioned above, some medications which block serotonin uptake may eventually lead to a lower amount of this neurotransmitter being released at the nerve endings. You can't fool Mother Nature—your nerves see all that serotonin at their endings and decide to release less of it! But not all drugs in his class are alike.

Fenfluramine is not only an uptake inhibitor but It also facilitates the release of serotonin, thereby producing sedation in humans. Unfortunately, this drug produces undesirable and possibly toxic problems when taken on a regular basis, rendering it unsuitable for treating the chronic symptoms of FMS.

Keep the faith. Zoloft, released for prescription sale in the U.S. earlier this year, may not be as damaging to your sleep as Prozac can be. Fluvoxamine, which will be released later in the year, isn't expected to disturb sleep at all, but it may cause nausea in some people.

If you discover that medications in this class (i.e., Prozac or Zoloft) significantly decrease your pain, you may want to talk to your doctor about combination therapies. Perhaps he or she can prescribe something for you to take at night to counteract the negative effects that these medications might have on your sleep.

Tricyclic Antidepressants (TCAs)

These drugs (Eleavil, Flexeril, Pamelor, Sinequan, etc.) are often prescribed in small quantities for FMS/CFS patients based on their serotonin altering effects. However, they block the re-uptake of other neurotransmitters as well (that's right, they aren't selective). In addition, TCAs may lead to increased wakefulness in some people, whereas they might also have potent sedative properties in others (2). The drowsy-inducing nature of TCAs may be due to their blocking of histamine. The net effect can be similar to the antihistamine that you take for colds or allergies—they impair your day-time alertness but have little affect on normal sleep.

Testing the effects of Flexeril on sleep, Harvey Moldofsky, M.D., of Toronto, Canada, found that this drug did not alter the poor quality of sleep that FMS patients were experiencing. But, medications in this class may still work to reduce pain, and when taken before bedtime, their sedative property can be a plus for some patients.

Antihistamines (H1 and H12)

Histamine receptor #1 antagonists (H-1) are in the cold remedies mentioned above. Most of them (except for those that don't cross the blood/brain barrier) will make you feel sluggish. If you are frustrated with trying to fall asleep, H-1 medications may benefit you at night.

Histamine receptor #2 antagonists (H-2) are commonly prescribed as ulcer medicines, such as Tagamet and Zantac. They block the histamine released into your stomach (not your sinuses) and this also reduces other gastric secretions that could irritate an ulcer. These drugs won't make you drowsy but one study has shown that Tagamet increases slow wave (deep level) sleep (2). Other studies have demonstrated that H-2 blockers also alter immune system function, which could prove beneficial.

Maybe it is time you talked to your physician about H-l and H-2 blockers. FMS treatment is unpredictable. You never know when something is going to help!

Anti-anxiety Meds

Serotonin receptor #1A appears to be involved in anxiety, memory, the control of food intake and temperature regulation. Buspirone (or Buspar) is an anti-anxiety drug that acts by partially activating this S1A receptor. It probably won't affect your pain or sleep directly, but because anxiety is an aggravent to FMS symptoms, Buspar may favorably impact the way you feel. Unlike traditional benzodiazepines (which can also relieve anxiety), this drug is not thought to cause addiction problems.


Alprozolam (Xanax) and clonazepam (Klonopin) are both in this class of drugs. In general, they work on GABA receptors to increase their inhibitory transmission in the central nervous system (less signals interfering with sleep—this could be a plus). Xanax also works on platelet serotonin stores to increase its availability in the blood while Klonopin has anti-seizure properties (helpful for patients with sleep myoclonus, restless leg syndrome and nighttime teeth grinding).

Abstracting a section by lan Oswald, M.D., from the above referenced book (page 242): "A benzodiazepine drug (or alcohol or a barbiturate) acts on the brain to reduce anxiety, reduce the likelihood of fits, reduce restlessness, reduce the intensity of dreams and increase sleep. As the days and weeks go by, if the foreign chemical continues to impinge upon the brain, the brain reacts to the foreign agent by modifying its own machinery in such a way as to counteract the drug. The loose expression is to say 'the drug loses its effect.' But it is the brain that has changed, and the net reduction in the observed action of the drug constitutes tolerance." Tolerance to a drug may explain why it worked last year but now it no longer helps.

In this same chapter (page 241), Dr. Oswald also commented that, "There are a great many anxious patients who sleep badly, who feel that they are helped by drugs like benzodiazepines, taken for long periods of time; and this is especially true of older people with physical disorders." He stated that people who slept less than 6 hours per night tended to be anxious (who wouldn't be!). Prescribing them a benzodiazepine increased their longevity while going without equated to a significantly shorter life span... hum, these drugs must be doing something beneficial.

Ritanserin and Sumatriptan

These two medications effect different serotonin receptors but are lumped together because neither of them is FDA approved. Ritanserin is a serotonin receptor #2 antagonist and has been shown to increase the amount of time spent in deep level (slow wave) sleep in humans (2). It may also reduce pain but additional studies are needed.

Sumatriptan, an S-ID receptor antagonist (or inhibitor), has been reported to stop migraine attacks and may possibly relieve other forms of pain as well (3). Only formal testing will tell!

Selective Serotonin Re-Uptake Inhibitors Perspectives in Psychiatry, Volume 1, John Wiley & Sons Ltd, 1991.
Serotonin, Sleep and Mental Disorder Janssen Biomedical Science Series, Wrightson Biomedical Publishing Ltd., 1991.
Serotonin and Pain International Congress Series 879, Excerpta Medica, 1990.

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