Alternative medications may be the first choice for chronic fatigue syndrome (ME/CFS) patients but they are often not effective enough. A panel of prominent ME/CFS doctors indicated that while they were open to the use of over-the-counter products such as melatonin, Benadryl and Tylenol, these products don’t usually provide enough relief. Prescription drugs may have some side effects but most doctors regard the tradeoff as acceptable.
I’ve come to believe that while natural is best, if you don’t sleep, if you cannot develop some kind of restorative sleep, even medicated sleep, it’s one of the worst things about your illness.” Dr. Bateman
As with any treatment there will be a broad spectrum of responses. Dr. Bateman says, “Every drug has this spectrum of how it will work; every drug on here has proven value, proven safety, yet it could be horrible for any one person […] Topamax (for instance) is really hard for some people, but for others, it’s incredible, so you can’t generalize about a drug.”
Several physicians reported that their patients often need two types of sleep drugs: one to put them to sleep and one to keep them asleep. Dr. Teitelbaum goes further, arguing that getting a solid eight to ten hours of restful sleep is worth taking the time and effort to settle on as many as five or six different sleep aids if necessary. Since most of the side effects (and fewer of the benefits) come at higher doses, he believes patients can maximize their benefits by taking small amounts of several sleep aids at once.
“Many people […] are afraid to take enough medication to get adequate sleep. They are so grateful to get five hours of sleep a night that they settle for that. That’s a bad idea. I recommend taking whatever is necessary to get eight to nine hours of solid sleep […] even if it means taking several of these medications at one time”.
Dr. Teitlebaum writes about this approach here.
Prescription and OTC Drugs
These drugs have shown promise in assisting sleep in chronic fatigue syndrome (ME/CFS). See the chart below for more recommendations from ME/CFS physicians.
- 5-HTP (5-Hydroxytryptophan)
- Ambien (Zolpidem)
- Amytryptiline (Elavil)
- Antihistamines (Benadryl, Claritin, etc.)
- Clonezpam (Klonopin)
- Cyclobenzaprine (Flexeril)
- Doxepin Elixir (Sinequan)
- Gabapentin (Neurontin)
- Melatonin
- Quetiapine (Seroquel, Xeroquel)
- Sodium Oxybate (Xyrem)
- Trazodone (Desreyel)
- Zolpidem (Ambien)
Prescription Drug Chart
The IACFS/ME ME/CFS Primer For Clinical Practitioners (2014) written by CFS physicians provides the following recommendations for sleep medications.
| Medication | Dose | Comments |
| Tricyclics: Amitriptyline, Doxepin, Nortriptyline | 5-100 mg | Take 5 hours before bedtime. May worsen dry mouth, constipation, orthostatic intolerance, or cause daytime sedation |
| Cyclobenzaprine | 5-10 mg | Same comments as for tricyclics above |
| Trazodone | 12.5-200 mg | May be the least likely to lose effectiveness for sleep |
| Quetiapine | 12.5-100 mg | May cause weight gain or extrapyramidal symptoms |
| Gabapentin | 100-1500 mg | May help nocturnal pain and restless legs syndrome |
| Pregabalin | 50-450 mg | Helpful for nocturnal pain, but very sedating for some |
| Antihistamines: Promethazine, Diphenhydramine | 10 mg/50 mg | Anticholinergic side effects |
| Clonazepam | 0.25-1 mg | For restless legs, muscle spasms or anxiety. |
| Orphenadrine | 100 mg | For restless legs or muscle spasms (not available everywhere) |
| Ropinirole or pramipexole | 0.125-0.25 mg | For restless legs or muscle spasms (not available every-where) |
| Melatonin | 1-3 mg or more, 2-3 hours before bedtime | May help patients who have altered circadian rhythms |
| Zolpidem | 2.5-10 mg | Short duration of action may lead to rebound insomnia |
| Zopiclone | 7.5 mg | Short duration of action may lead to rebound insomnia |
| Mirtazapine | 7.5-15 mg | May cause daytime sedation; tolerance may develop |
ME/CFS physician recommendations for prescription sleep medications
The chart below provides recommendations from nine prominent ME/CFS physicians. While their recommendations vary they display a general consistency that is encouraging.
ME/CFS Physician | Sleep Initiators | Sleep Prolongers |
Dr. Bateman | Ambien, Sonata, Lunesta, Restoril, Melatonin, Rozarem, Zyprexa | Trazodone, Remeron, Neurontin, Lyrica, Amytriptyline |
Dr. Bell | Flexeril, Carisoprodol, Elavil, Klonopin, Ambien, Sonata | Trazodone |
Dr. Klimas | Sinequan (Doxepin) elixir, Elavil, Flexeril, Klonopin | |
Dr. Lapp | Clonzepam, Sonata, Lunesta, Ambien, Klonopin | Trazodone |
Dr. Levine | Sinequam (Doxepin), Klonopin | Trazodone, Amytriptyline, Norpramin, Neurontin, Cyclobezaprine |
Dr. Pocinki | Ambien/Ambien CR | Amitryptyine, Trazodone |
Dr. Rosenbaum | Elavil, Sinequan (Doxepin) elixir, Sonata | |
Dr. Teitelbaum | Ambien, Klonopin, Sinequam, Flexeril, Zanaflex | Trazodone, Neurontin, Sonata, Amitryptyline |
Dr. Wallace | Ambien, Klonopin | Neurontin |
Recommendations are discussed in the following sources:
Lucinda Bateman, MD., 2006. “Tips and Travails of Treatment“, an abridged version of a seminar transcript of a Nov. Lecture in Auckland, New Zealand by Pat Fero and David Thompson.
David S. Bell, M.D., 2002, “Medications for Chronic Fatigue Syndrome and Chronic Pain Control”.
Charles Lapp, MD., 1999. “The Treatment of Chronic Fatigue Syndrome and Fibromyalgia”.
Carol Sieverling, 2000. Paul Cheney, M.D on “Klonopin: Protecting Your Brain”.
Jacob Teitelbaum, 2007. From Fatigued to Fantastic, Avery Publishers.