Sunday, October 18, 2009

Current and Future Approaches to Treatment

Treatment options for Fibromyalgia and CFIDS sufferers are currently few and far between. There are no FDA approved medications specifically indicated for treating Chronic Fatigue Syndrome, and Lyrica is the only drug approved for Fibromyalgia thus far, with few options coming down the pipeline. Drugs currently prescribed for the condition include:
  • Amitryptilline - Based on the theory that Chronic fatigue is caused by a neurotransmitter imbalance, Amitryptilline is frequently part of the drug regiment offered to Chronic Fatigue patients, whereby it is postulated that it helps regulate sleep, as it is thought that in CFS or FM, very little time is spent in stage 4 sleep. Controlled blind studies show that it is not very effective, providing only a slight benefit over placebo.
  • Ritalin (methylphenidate), Desoxyn (methamphetamine), Dexedrine (dextroamphetamine), Provigil (Modafinil) - Drugs in this category act as CNS stimulants. The first three have the effect of raising blood pressure, and are indicated in treating postural hypotension, and promote wakefulness in CFIDS individuals. Modafinil does not address postural hypotension, therefore it is of limited use. For these patients, stimulants make it possible to perform daily tasks, however they do not seem to have an appreciable effect on cognitive impairment.
  • Lyrica (Pregabalin) and Gabapentin - Gabapentin is a drug used to treat epilepsy, which gained off-label use to treat neuropathic pain, Lyrica being the active metabolite of Gabapentin. Lyrica was the first drug approved for Fibromyalgia, until the approval of the antidepressant Cymbalta (duloxetine). Response to Lyrica has not resulted in statistically significant improvement in quality of life in FM patients. The cost of the drug is high, and many insurers will not cover its cost, and the opioid analgesics like Dilaudid (hydromorphone), and fentanyl seem to confer the greatest benefits. Lyrica is known to cause marked weight gain, and can be very sedating (CNS depressant).
Current experimental treatments have shifted towards anti-viral compounds. Anti-virals currently being prescribed off-label include Valtrex (Valacyclovir), Valcyte (Valgancavir), and Acyclovir - all targeted towards herpesviruses. Some patients note significant improvement, lending to the theory that having high viral titers of herpesviruses adds to the disease burden of XMRV. Equally significant results have been obtained with Isoprinosine, which is available on both sides of the border at a reasonable cost. Valcyte has the distinction of being extraordinarily expensive - >$1500 a month, and it is not without severe side effects. Ampligen is a drug if approved that would be the first drug approved specifically for treating Chronic Fatigue Syndrome - it is expected to cost ~$1500 a month for treatment.

Future treatment will likely involve treatment with anti-retrovirals. As the link between Chronic Fatigue Syndrome and XMRV becomes more clearly established, likely more practitioners will be willing to try current anti-retrovirals on Chronic Fatigue and Fibromyalgia patients. Three potential viral targets might include reverse-transcriptase, XMRV polymerase, and intergrase. Initially, AZT has shown activity in vitro against XMRV, however the toxicity of AZT limits its use - it's fine for someone who would otherwise die of AIDS, but it leads to an ethical dilemma when prescribing it in a situation where the side effects may be worse than the disease. Most NRT's and NNRT's are fraught with side effects such as lipodystrophy - which can be quite disfiguring. Protease inhibitors are slightly more benign, although some are known to cause dramatic increase in blood lipids. Integrase inhibitors are prehaps the most benign, being well tolerated, producing few metabolic abnormalities. Protease inhibitors may not work against XMRV, as the catalytic site may be sufficiently different than the HIV protease - being the case, it would require determining the atomic structure of the XMRV protease, in order to develop effective drugs. As the function of other proteins of XMRV become unravelled, other drug targets could conceivably be developed - one of these being the androgen responsive element or ard.

1 comment:

  1. Just thought I'd let you know the title of your blog contains a spelling error..."sufferers" is the correct spelling :)