'Acquaintance Rape Drug' May One Day Help Instead of Hurt
'Acquaintance Rape Drug' May One Day Help Instead of Hurt
With the publication of a Federal Register notice on March 13, gamma-hydroxybutyrate (GHB) joined the ranks of heroin and other illicit substances as a Schedule I drug. Illicit use and distribution is now subject to federal penalties, including imprisonment and fines. The scheduling, the result of a bill signed by President Clinton in February, will curb abuse of the substance which, despite being linked to 65 deaths, in still widely used by partygoers as an intoxicant. The central nervous system depressant is also known as an "acquaintance rape drug" because it has been used to incapacitate victims prior to sexual assault.
However, GHB is proving to have a positive use, too. The compound appears to be a therapeutic breakthrough for a group of patients who currently have few effective treatment options -- the estimated 125,000 people in the United States with narcolepsy.
"GHB is absolutely irreplaceable," Debbie Hicks, a researcher and writer in Washington, D.C., told Pharmacy Today. Hicks has had narcolepsy her entire life and has received GHB through an investigational study. "No other drug offers me the quality of life that GHB offers. With GHB, I don't have the fatigue. I also enjoy increased energy, alertness, and muscle control. In terms of controlling the cataplexy, it cannot be replaced." Cataplexy, the sudden loss of muscle control triggered by emotion, is a hallmark of the disorder.
Treating Both Cataplexy and EDs
"We looked at this at first with quite a skeptical eye," said Patti Engel, vice president of marketing and sales at Orphan Medical, a small, specialty drugs company in Minnetonka, Minn. "We recognized narcolepsy patients are frantic for effective therapy and were concerned about the possible placebo effect."
But after two placebo-controlled trials, Orphan found that medically formulated GHB, sodium oxybate (Xyrem), reduced the median number of cataplexy episodes per week by 68.6%. The drug had a positive effect on excessive daytime sleepiness (EDS) as well, a second major narcolepsy symptom. "Patients on Xyrem actually wept the results were so dramatic," Engel said.
The cause of narcolepsy is unknown, but it seems related to a perhaps-inherited disruption of the sleep cycle. "Patients with narcolepsy get as much sleep as you and I, but it is fragmented over a 24-hour period like a newborn baby's," Engel said. "GHB seems to have sleep-consolidation effects."
"Patients take a dose before bedtime and go to sleep. They wake up spontaneously 4 hours later and take a second dose," she explained. "Patients wake rested and refreshed in the morning. They don't feel drugged the next day like they would with sleeping pills because GHB does not have the same effect on REM sleep." A dosage of 9 grams per night, divided into two doses, proved most effective in trials.
Orphan will submit a new drug application for sodium oxybate to FDA later this year. The agency has committed to a priority review because of the lack of effective agents against cataplexy. Orphan anticipates full approval of its medical GHB for the treatment of narcolepsy symptoms by mid-2001. The scheduling of GHB as an illicit drug does not affect ongoing clinical trials. Sodium oxybate will be a Schedule III drug if approved.
Multiple Stigmas
"People with narcolepsy face multiple stigmas," Hicks said. "We have a disability that is not well understood by the health care community or the general public. Many insist that sleepiness and fatigue reflect a lack of will power or motivation. So our symptoms are too often prejudged as character defects or misattributed to mental illness."
At present, cataplexy is treated with either SSRIs or tricyclic antidepressants to mute strong emotions. EDS is treated with central nervous system stimulants such as methylphenidate (Ritalin). In early 1999, FDA approved the first nonstimulant, modafinil (Provigil), to treat EDS associated with narcolepsy, but the drug does not address cataplexy. "Right now, there are many drugs we are using, but they all have side effects and patients build up tolerance. None of them are very effective for cataplexy," Engel said.
With the publication of a Federal Register notice on March 13, gamma-hydroxybutyrate (GHB) joined the ranks of heroin and other illicit substances as a Schedule I drug. Illicit use and distribution is now subject to federal penalties, including imprisonment and fines. The scheduling, the result of a bill signed by President Clinton in February, will curb abuse of the substance which, despite being linked to 65 deaths, in still widely used by partygoers as an intoxicant. The central nervous system depressant is also known as an "acquaintance rape drug" because it has been used to incapacitate victims prior to sexual assault.
However, GHB is proving to have a positive use, too. The compound appears to be a therapeutic breakthrough for a group of patients who currently have few effective treatment options -- the estimated 125,000 people in the United States with narcolepsy.
"GHB is absolutely irreplaceable," Debbie Hicks, a researcher and writer in Washington, D.C., told Pharmacy Today. Hicks has had narcolepsy her entire life and has received GHB through an investigational study. "No other drug offers me the quality of life that GHB offers. With GHB, I don't have the fatigue. I also enjoy increased energy, alertness, and muscle control. In terms of controlling the cataplexy, it cannot be replaced." Cataplexy, the sudden loss of muscle control triggered by emotion, is a hallmark of the disorder.
Treating Both Cataplexy and EDs
"We looked at this at first with quite a skeptical eye," said Patti Engel, vice president of marketing and sales at Orphan Medical, a small, specialty drugs company in Minnetonka, Minn. "We recognized narcolepsy patients are frantic for effective therapy and were concerned about the possible placebo effect."
But after two placebo-controlled trials, Orphan found that medically formulated GHB, sodium oxybate (Xyrem), reduced the median number of cataplexy episodes per week by 68.6%. The drug had a positive effect on excessive daytime sleepiness (EDS) as well, a second major narcolepsy symptom. "Patients on Xyrem actually wept the results were so dramatic," Engel said.
The cause of narcolepsy is unknown, but it seems related to a perhaps-inherited disruption of the sleep cycle. "Patients with narcolepsy get as much sleep as you and I, but it is fragmented over a 24-hour period like a newborn baby's," Engel said. "GHB seems to have sleep-consolidation effects."
"Patients take a dose before bedtime and go to sleep. They wake up spontaneously 4 hours later and take a second dose," she explained. "Patients wake rested and refreshed in the morning. They don't feel drugged the next day like they would with sleeping pills because GHB does not have the same effect on REM sleep." A dosage of 9 grams per night, divided into two doses, proved most effective in trials.
Orphan will submit a new drug application for sodium oxybate to FDA later this year. The agency has committed to a priority review because of the lack of effective agents against cataplexy. Orphan anticipates full approval of its medical GHB for the treatment of narcolepsy symptoms by mid-2001. The scheduling of GHB as an illicit drug does not affect ongoing clinical trials. Sodium oxybate will be a Schedule III drug if approved.
Multiple Stigmas
"People with narcolepsy face multiple stigmas," Hicks said. "We have a disability that is not well understood by the health care community or the general public. Many insist that sleepiness and fatigue reflect a lack of will power or motivation. So our symptoms are too often prejudged as character defects or misattributed to mental illness."
At present, cataplexy is treated with either SSRIs or tricyclic antidepressants to mute strong emotions. EDS is treated with central nervous system stimulants such as methylphenidate (Ritalin). In early 1999, FDA approved the first nonstimulant, modafinil (Provigil), to treat EDS associated with narcolepsy, but the drug does not address cataplexy. "Right now, there are many drugs we are using, but they all have side effects and patients build up tolerance. None of them are very effective for cataplexy," Engel said.