Nicholas Mulcahy

PHILADELPHIA — The rate of fluoroquinolone resistance in Neisseria gonorrhoeae doubled from 2.2% in 2002 to greater than 4% in 2003, and resistant isolates are now surfacing at several sites around the country, according to an official with the Centers for Disease Control and Prevention.

In the past, the problem of quinolone-resistant Neisseria gonorrhoeae (QRNG) was limited to Hawaii and California, “but we now have big increases in Massachusetts, New Hampshire, New York City, Seattle, and Washington state.

“We also have increased frequency of resistance to a lesser extent in Chicago, Philadelphia, Las Vegas, and many other cities and states,” reported Susan Wang, M.D., national coordinator, gonococcal resistance, in the division of STD prevention at the CDC.

According to preliminary estimates of 2003 data, the national rate of QRNG is about 4%, while the rate is about 12% in Hawaii, 19% in California, and 14% in Massachusetts, she said at a conference on STD prevention sponsored by the CDC.

It's not clear how widespread the problem is, because only a limited number of cities and counties participate in the CDC-sponsored Gonococcal Isolate Surveillance Project (GISP), which monitors the susceptibilities of N. gonorrhoeae strains to antimicrobial agents, including ciprofloxacin and cephalosporins.

“In most places, susceptibility testing is not done at the local level. So you and your local health department may not know if gonococcal resistance is a problem for your area, unless you are in a GISP city,” Dr. Wang said.

GISP sites include Albuquerque; Atlanta; Baltimore; Birmingham, Ala.; Chicago; Cincinnati; Cleveland; Dallas; Denver; Detroit; Greensboro, N.C.; Honolulu; Los Angeles; Las Vegas; Long Beach County, Calif.; Miami; Minneapolis; New Orleans; Oklahoma City; Orange County, Calif.; Philadelphia; Phoenix, Ariz.; Portland, Ore.; San Diego; San Francisco; Seattle; and St. Louis.

“The prevalence of QRNG in women is increasing but is generally lower than in men who have sex with men [MSM],” Dr. Wang said.

The latter group accounts for a “big portion” of the cases of QRNG. “According to 2002 data, in New York City, Seattle, and Massachusetts, QRNG is especially emerging in MSM,” she said.

The lack of data regarding women and QRNG concerns the CDC, Dr. Wang said in an interview.

“Data on women are especially important because the long-term sequelae of the disease have the greatest impact on women in terms of pelvic inflammatory disease, infertility, and chronic pelvic pain,” she said.

The lack of QRNG data on women is partly a technical issue, she explained. The national GISP surveillance system uses N. gonorrhoeae isolates from the first 25 men with gonorrhea attending sexually transmitted diseases clinics at GISP sites each month; the isolates are then sent for testing at regional labs. “GISP surveillance is limited to male urethral specimens in part because these specimens are less complicated to evaluate than female specimens,” she said.

The problem of poor data in women and related treatment problems also is worsened by the increasing inability of community-based physicians and labs to perform culture-based testing, Dr. Wang said.

“To monitor resistance you cannot perform DNA-based testing. You need culture-based testing. Physicians and labs increasingly only perform DNA-based testing.”

Physicians who believe that a patient is not responding to treatment with a fluoroquinolone should perform a culture and send the sample to a private lab or local health department for susceptibility testing.

For the primary treatment of uncomplicated gonorrhea, the CDC recommends regimens of fluoroquinolones (single-dose, oral therapy with 500 mg ciprofloxacin or 400 mg ofloxacin or 250 mg levofloxacin); or a single oral dose of cefexime 400 mg; or a 125-mg IM injection of ceftriaxone.

The CDC also recommends that clinicians check with their local health departments to learn if treatment recommendations have changed, as is the case in Massachusetts, Washington, and other locales.

Resistance to ciprofloxacin and other fluoroquinolones limits treatment options because of the current absence of cefixime from the market.

“Basically, QRNG threatens the physician's ability to treat with an oral agent. Currently our only other available treatment is a cephalosporin, ceftriaxone, which is an intramuscular injection and doctors may not stock it in private practice,” Dr. Wang said.

“Cefixime is also an oral agent and is recommended by the CDC for the treatment of gonorrhea.

But it was taken off the market by Wyeth Laboratories in 2002. However, the Food and Drug Administration recently approved a generic manufacturer of cefixime from India to sell the drug here. Cefixime is also an option for QRNG,” she said.

Gonococcal resistance has repeatedly occurred in the United States, noted Dr. Wang.

“Gonococcal resistance has been ongoing since the 1940s, starting with resistance to sulfanilamide. In the 1980s, tetracycline and penicillin were abandoned due to resistance, which led the CDC to recommend treatment with ciprofloxacin or other fluoroquinolones in 1987,” Dr. Wang said.

The future of treatment of drug-resistant gonorrhea is cloudy, P. Frederick Sparling, M.D., observed in his plenary lecture at the meeting.

“What drugs will replace ciprofloxacin and cefixime? Pharmaceuticals are abandoning such areas, as they are price-controlled markets, with government as the main buyer. The future of treating gonorrhea is bleak,” said Dr. Sparling, J. Herbert Bate Professor of Medicine and Microbiology and Immunology, Emeritus, University of North Carolina at Chapel Hill.

Dr. Sparling added that the implications of emerging vaccines for STDs and attacks from conservative groups on research related to STDs both add to the difficulties in developing new drugs for gonorrhea.

PHILADELPHIA — The rate of fluoroquinolone resistance in Neisseria gonorrhoeae doubled from 2.2% in 2002 to greater than 4% in 2003, and resistant isolates are now surfacing at several sites around the country, according to an official with the Centers for Disease Control and Prevention.

In the past, the problem of quinolone-resistant Neisseria gonorrhoeae (QRNG) was limited to Hawaii and California, “but we now have big increases in Massachusetts, New Hampshire, New York City, Seattle, and Washington state.

“We also have increased frequency of resistance to a lesser extent in Chicago, Philadelphia, Las Vegas, and many other cities and states,” reported Susan Wang, M.D., national coordinator, gonococcal resistance, in the division of STD prevention at the CDC.

According to preliminary estimates of 2003 data, the national rate of QRNG is about 4%, while the rate is about 12% in Hawaii, 19% in California, and 14% in Massachusetts, she said at a conference on STD prevention sponsored by the CDC.

It's not clear how widespread the problem is, because only a limited number of cities and counties participate in the CDC-sponsored Gonococcal Isolate Surveillance Project (GISP), which monitors the susceptibilities of N. gonorrhoeae strains to antimicrobial agents, including ciprofloxacin and cephalosporins.

“In most places, susceptibility testing is not done at the local level. So you and your local health department may not know if gonococcal resistance is a problem for your area, unless you are in a GISP city,” Dr. Wang said.

GISP sites include Albuquerque; Atlanta; Baltimore; Birmingham, Ala.; Chicago; Cincinnati; Cleveland; Dallas; Denver; Detroit; Greensboro, N.C.; Honolulu; Los Angeles; Las Vegas; Long Beach County, Calif.; Miami; Minneapolis; New Orleans; Oklahoma City; Orange County, Calif.; Philadelphia; Phoenix, Ariz.; Portland, Ore.; San Diego; San Francisco; Seattle; and St. Louis.

“The prevalence of QRNG in women is increasing but is generally lower than in men who have sex with men [MSM],” Dr. Wang said.

The latter group accounts for a “big portion” of the cases of QRNG. “According to 2002 data, in New York City, Seattle, and Massachusetts, QRNG is especially emerging in MSM,” she said.

The lack of data regarding women and QRNG concerns the CDC, Dr. Wang said in an interview.

“Data on women are especially important because the long-term sequelae of the disease have the greatest impact on women in terms of pelvic inflammatory disease, infertility, and chronic pelvic pain,” she said.

The lack of QRNG data on women is partly a technical issue, she explained. The national GISP surveillance system uses N. gonorrhoeae isolates from the first 25 men with gonorrhea attending sexually transmitted diseases clinics at GISP sites each month; the isolates are then sent for testing at regional labs. “GISP surveillance is limited to male urethral specimens in part because these specimens are less complicated to evaluate than female specimens,” she said.

The problem of poor data in women and related treatment problems also is worsened by the increasing inability of community-based physicians and labs to perform culture-based testing, Dr. Wang said.

“To monitor resistance you cannot perform DNA-based testing. You need culture-based testing. Physicians and labs increasingly only perform DNA-based testing.”

Physicians who believe that a patient is not responding to treatment with a fluoroquinolone should perform a culture and send the sample to a private lab or local health department for susceptibility testing.

For the primary treatment of uncomplicated gonorrhea, the CDC recommends regimens of fluoroquinolones (single-dose, oral therapy with 500 mg ciprofloxacin or 400 mg ofloxacin or 250 mg levofloxacin); or a single oral dose of cefexime 400 mg; or a 125-mg IM injection of ceftriaxone.

The CDC also recommends that clinicians check with their local health departments to learn if treatment recommendations have changed, as is the case in Massachusetts, Washington, and other locales.

Resistance to ciprofloxacin and other fluoroquinolones limits treatment options because of the current absence of cefixime from the market.

“Basically, QRNG threatens the physician's ability to treat with an oral agent. Currently our only other available treatment is a cephalosporin, ceftriaxone, which is an intramuscular injection and doctors may not stock it in private practice,” Dr. Wang said.

“Cefixime is also an oral agent and is recommended by the CDC for the treatment of gonorrhea.

But it was taken off the market by Wyeth Laboratories in 2002. However, the Food and Drug Administration recently approved a generic manufacturer of cefixime from India to sell the drug here. Cefixime is also an option for QRNG,” she said.

Gonococcal resistance has repeatedly occurred in the United States, noted Dr. Wang.

“Gonococcal resistance has been ongoing since the 1940s, starting with resistance to sulfanilamide. In the 1980s, tetracycline and penicillin were abandoned due to resistance, which led the CDC to recommend treatment with ciprofloxacin or other fluoroquinolones in 1987,” Dr. Wang said.

The future of treatment of drug-resistant gonorrhea is cloudy, P. Frederick Sparling, M.D., observed in his plenary lecture at the meeting.

“What drugs will replace ciprofloxacin and cefixime? Pharmaceuticals are abandoning such areas, as they are price-controlled markets, with government as the main buyer. The future of treating gonorrhea is bleak,” said Dr. Sparling, J. Herbert Bate Professor of Medicine and Microbiology and Immunology, Emeritus, University of North Carolina at Chapel Hill.

Dr. Sparling added that the implications of emerging vaccines for STDs and attacks from conservative groups on research related to STDs both add to the difficulties in developing new drugs for gonorrhea.

PHILADELPHIA — The rate of fluoroquinolone resistance in Neisseria gonorrhoeae doubled from 2.2% in 2002 to greater than 4% in 2003, and resistant isolates are now surfacing at several sites around the country, according to an official with the Centers for Disease Control and Prevention.

In the past, the problem of quinolone-resistant Neisseria gonorrhoeae (QRNG) was limited to Hawaii and California, “but we now have big increases in Massachusetts, New Hampshire, New York City, Seattle, and Washington state.

“We also have increased frequency of resistance to a lesser extent in Chicago, Philadelphia, Las Vegas, and many other cities and states,” reported Susan Wang, M.D., national coordinator, gonococcal resistance, in the division of STD prevention at the CDC.

According to preliminary estimates of 2003 data, the national rate of QRNG is about 4%, while the rate is about 12% in Hawaii, 19% in California, and 14% in Massachusetts, she said at a conference on STD prevention sponsored by the CDC.

It's not clear how widespread the problem is, because only a limited number of cities and counties participate in the CDC-sponsored Gonococcal Isolate Surveillance Project (GISP), which monitors the susceptibilities of N. gonorrhoeae strains to antimicrobial agents, including ciprofloxacin and cephalosporins.

“In most places, susceptibility testing is not done at the local level. So you and your local health department may not know if gonococcal resistance is a problem for your area, unless you are in a GISP city,” Dr. Wang said.

GISP sites include Albuquerque; Atlanta; Baltimore; Birmingham, Ala.; Chicago; Cincinnati; Cleveland; Dallas; Denver; Detroit; Greensboro, N.C.; Honolulu; Los Angeles; Las Vegas; Long Beach County, Calif.; Miami; Minneapolis; New Orleans; Oklahoma City; Orange County, Calif.; Philadelphia; Phoenix, Ariz.; Portland, Ore.; San Diego; San Francisco; Seattle; and St. Louis.

“The prevalence of QRNG in women is increasing but is generally lower than in men who have sex with men [MSM],” Dr. Wang said.

The latter group accounts for a “big portion” of the cases of QRNG. “According to 2002 data, in New York City, Seattle, and Massachusetts, QRNG is especially emerging in MSM,” she said.

The lack of data regarding women and QRNG concerns the CDC, Dr. Wang said in an interview.

“Data on women are especially important because the long-term sequelae of the disease have the greatest impact on women in terms of pelvic inflammatory disease, infertility, and chronic pelvic pain,” she said.

The lack of QRNG data on women is partly a technical issue, she explained. The national GISP surveillance system uses N. gonorrhoeae isolates from the first 25 men with gonorrhea attending sexually transmitted diseases clinics at GISP sites each month; the isolates are then sent for testing at regional labs. “GISP surveillance is limited to male urethral specimens in part because these specimens are less complicated to evaluate than female specimens,” she said.

The problem of poor data in women and related treatment problems also is worsened by the increasing inability of community-based physicians and labs to perform culture-based testing, Dr. Wang said.

“To monitor resistance you cannot perform DNA-based testing. You need culture-based testing. Physicians and labs increasingly only perform DNA-based testing.”

Physicians who believe that a patient is not responding to treatment with a fluoroquinolone should perform a culture and send the sample to a private lab or local health department for susceptibility testing.

For the primary treatment of uncomplicated gonorrhea, the CDC recommends regimens of fluoroquinolones (single-dose, oral therapy with 500 mg ciprofloxacin or 400 mg ofloxacin or 250 mg levofloxacin); or a single oral dose of cefexime 400 mg; or a 125-mg IM injection of ceftriaxone.

The CDC also recommends that clinicians check with their local health departments to learn if treatment recommendations have changed, as is the case in Massachusetts, Washington, and other locales.

Resistance to ciprofloxacin and other fluoroquinolones limits treatment options because of the current absence of cefixime from the market.

“Basically, QRNG threatens the physician's ability to treat with an oral agent. Currently our only other available treatment is a cephalosporin, ceftriaxone, which is an intramuscular injection and doctors may not stock it in private practice,” Dr. Wang said.

“Cefixime is also an oral agent and is recommended by the CDC for the treatment of gonorrhea.

But it was taken off the market by Wyeth Laboratories in 2002. However, the Food and Drug Administration recently approved a generic manufacturer of cefixime from India to sell the drug here. Cefixime is also an option for QRNG,” she said.

Gonococcal resistance has repeatedly occurred in the United States, noted Dr. Wang.

“Gonococcal resistance has been ongoing since the 1940s, starting with resistance to sulfanilamide. In the 1980s, tetracycline and penicillin were abandoned due to resistance, which led the CDC to recommend treatment with ciprofloxacin or other fluoroquinolones in 1987,” Dr. Wang said.

The future of treatment of drug-resistant gonorrhea is cloudy, P. Frederick Sparling, M.D., observed in his plenary lecture at the meeting.

“What drugs will replace ciprofloxacin and cefixime? Pharmaceuticals are abandoning such areas, as they are price-controlled markets, with government as the main buyer. The future of treating gonorrhea is bleak,” said Dr. Sparling, J. Herbert Bate Professor of Medicine and Microbiology and Immunology, Emeritus, University of North Carolina at Chapel Hill.

Dr. Sparling added that the implications of emerging vaccines for STDs and attacks from conservative groups on research related to STDs both add to the difficulties in developing new drugs for gonorrhea.

PHILADELPHIA – Modafinil in patients with obstructive sleep apnea and excessive daytime sleepiness despite positive airway pressure therapy was effective in improving wakefulness for at least 17 weeks in a small study presented at the annual meeting of the Associated Professional Sleep Societies.

Previous studies of the wakefulness drug and obstructive sleep apnea (OSA) had been limited to 12 weeks, Juan Moralejo, M.D., reported.

“In our study population, modafinil was more likely to be effective in the elderly and those with high Epworth Sleepiness Scale scores at the time of diagnosis” of daytime sleepiness, said Dr. Moralejo, a pulmonary medicine fellow at Graduate Hospital, Philadelphia.

The study sample consisted of 22 patients (13 males and 9 females), mean age 53.9 years. Of the 18 patients receiving “conventional treatment,” 9 were using continuous positive airway pressure, 8 were using bilevel positive airway pressure, and 1 was using a dental device. At the time of the survey, four patients were not using any conventional treatment for OSA.

The mean Epworth Sleepiness Scale score was 15.9 at diagnosis, 13.6 after treatment with conventional modalities, and 8.9 after treatment with modafinil (Provigil). A lower Epworth score is indicative of improved wakefulness, and reduction of 4 points is considered a response to treatment. No statistical difference was found between the Epworth scores before and after conventional treatment, but the change after modafinil treatment was significant, Dr. Moralejo said.

The improvement in Epworth Sleepiness Scale score was similar whether patients were on modafinil for more than or less than 12 weeks. The average duration of treatment was 17 weeks (range 1–40).

On univariate analysis, factors associated with response to modafinil were higher Epworth Sleepiness Scale score at diagnosis, higher Epworth score while on conventional therapy, and male gender, said Dr. Moralejo, who has no affiliation with Cephalon, maker of Provigil. But on multivariate analysis, a high Epworth score at diagnosis of OSA and increasing age correlated best with response to modafinil.

The average dosage of modafinil was 227.3 mg once daily (range 100–800). No significant side effects were documented.

Epworth Sleepiness Scale scores at the diagnosis of OSA and after treatment with conventional modalities were obtained from the patients' records. A telephone survey was conducted and included questions about patients' demographics, modafinil treatment, and type of ongoing conventional treatment for OSA as well as patient compliance with this treatment.

PHILADELPHIA – Modafinil in patients with obstructive sleep apnea and excessive daytime sleepiness despite positive airway pressure therapy was effective in improving wakefulness for at least 17 weeks in a small study presented at the annual meeting of the Associated Professional Sleep Societies.

Previous studies of the wakefulness drug and obstructive sleep apnea (OSA) had been limited to 12 weeks, Juan Moralejo, M.D., reported.

“In our study population, modafinil was more likely to be effective in the elderly and those with high Epworth Sleepiness Scale scores at the time of diagnosis” of daytime sleepiness, said Dr. Moralejo, a pulmonary medicine fellow at Graduate Hospital, Philadelphia.

The study sample consisted of 22 patients (13 males and 9 females), mean age 53.9 years. Of the 18 patients receiving “conventional treatment,” 9 were using continuous positive airway pressure, 8 were using bilevel positive airway pressure, and 1 was using a dental device. At the time of the survey, four patients were not using any conventional treatment for OSA.

The mean Epworth Sleepiness Scale score was 15.9 at diagnosis, 13.6 after treatment with conventional modalities, and 8.9 after treatment with modafinil (Provigil). A lower Epworth score is indicative of improved wakefulness, and reduction of 4 points is considered a response to treatment. No statistical difference was found between the Epworth scores before and after conventional treatment, but the change after modafinil treatment was significant, Dr. Moralejo said.

The improvement in Epworth Sleepiness Scale score was similar whether patients were on modafinil for more than or less than 12 weeks. The average duration of treatment was 17 weeks (range 1–40).

On univariate analysis, factors associated with response to modafinil were higher Epworth Sleepiness Scale score at diagnosis, higher Epworth score while on conventional therapy, and male gender, said Dr. Moralejo, who has no affiliation with Cephalon, maker of Provigil. But on multivariate analysis, a high Epworth score at diagnosis of OSA and increasing age correlated best with response to modafinil.

The average dosage of modafinil was 227.3 mg once daily (range 100–800). No significant side effects were documented.

Epworth Sleepiness Scale scores at the diagnosis of OSA and after treatment with conventional modalities were obtained from the patients' records. A telephone survey was conducted and included questions about patients' demographics, modafinil treatment, and type of ongoing conventional treatment for OSA as well as patient compliance with this treatment.

PHILADELPHIA – Modafinil in patients with obstructive sleep apnea and excessive daytime sleepiness despite positive airway pressure therapy was effective in improving wakefulness for at least 17 weeks in a small study presented at the annual meeting of the Associated Professional Sleep Societies.

Previous studies of the wakefulness drug and obstructive sleep apnea (OSA) had been limited to 12 weeks, Juan Moralejo, M.D., reported.

“In our study population, modafinil was more likely to be effective in the elderly and those with high Epworth Sleepiness Scale scores at the time of diagnosis” of daytime sleepiness, said Dr. Moralejo, a pulmonary medicine fellow at Graduate Hospital, Philadelphia.

The study sample consisted of 22 patients (13 males and 9 females), mean age 53.9 years. Of the 18 patients receiving “conventional treatment,” 9 were using continuous positive airway pressure, 8 were using bilevel positive airway pressure, and 1 was using a dental device. At the time of the survey, four patients were not using any conventional treatment for OSA.

The mean Epworth Sleepiness Scale score was 15.9 at diagnosis, 13.6 after treatment with conventional modalities, and 8.9 after treatment with modafinil (Provigil). A lower Epworth score is indicative of improved wakefulness, and reduction of 4 points is considered a response to treatment. No statistical difference was found between the Epworth scores before and after conventional treatment, but the change after modafinil treatment was significant, Dr. Moralejo said.

The improvement in Epworth Sleepiness Scale score was similar whether patients were on modafinil for more than or less than 12 weeks. The average duration of treatment was 17 weeks (range 1–40).

On univariate analysis, factors associated with response to modafinil were higher Epworth Sleepiness Scale score at diagnosis, higher Epworth score while on conventional therapy, and male gender, said Dr. Moralejo, who has no affiliation with Cephalon, maker of Provigil. But on multivariate analysis, a high Epworth score at diagnosis of OSA and increasing age correlated best with response to modafinil.

The average dosage of modafinil was 227.3 mg once daily (range 100–800). No significant side effects were documented.

Epworth Sleepiness Scale scores at the diagnosis of OSA and after treatment with conventional modalities were obtained from the patients' records. A telephone survey was conducted and included questions about patients' demographics, modafinil treatment, and type of ongoing conventional treatment for OSA as well as patient compliance with this treatment.

PHILADELPHIA – The combination of caffeine and evening naps has only modest positive effects on performance and subjective sleepiness of night shift workers, Paula Schweitzer, Ph.D., reported at the annual meeting of the Associated Professional Sleep Societies.

In a rare field study of night shift workers, 39 participants (28 males; mean age 33 years) completed a 4-consecutive-night crossover study comparing two conditions: an evening nap prior to the night shift on the first 2 nights plus caffeine 300 mg on all 4 nights and placebo without napping on all 4 nights.

Three times during each night (start of shift, midway, and end of shift), participants completed a 15-minute psychomotor vigilance task (PVT) using a handheld PVT electronic device that measured the subject's reaction times to tasks. The study subjects also completed subjective sleepiness and mood tests three times a night, said Dr. Schweitzer, associate director of the Sleep Medicine and Research Center at St. Luke's Hospital, St. Louis.

RT10, or the reaction time of the slowest 10% of the PVT responses, worsened across nights 1–4 for both the nap/caffeine treatment group and the placebo group.

“Alertness and performance did not improve across successive night shifts–as has been found in some laboratory studies. People are not getting used to things [on the night shift],” Dr. Schweitzer said.

But some evidence indicated that the caffeine and naps did help somewhat.

Only the placebo group had a worsening of RT10 from shift start to shift end. Additionally, at shift end, the placebo group's RT10 was worse than that of the caffeine/nap treatment group.

The study also evaluated PVT lapses, which are unacceptably long delays in PVT reaction time. Again, the nap/caffeine group outperformed the placebo group. PVT lapse frequency increased from shift start to end for the placebo group, with no change for the treatment group. But both the placebo and treatment groups had an increase in lapse frequency across nights 1–4, which, in effect, was further proof of Dr. Schweitzer's observation that workers are not getting accustomed to night shift work.

Subjective sleepiness as measured by the Karolinska Sleepiness Scale also indicated some benefit of the caffeine and naps. The placebo group showed increased sleepiness at shift end, but the treatment group did not. There was no change in sleepiness ratings across nights 1–4, Dr. Schweitzer said.

Actigraph-estimated total sleep time for daytime sleep did not differ between the two groups.

PHILADELPHIA – The combination of caffeine and evening naps has only modest positive effects on performance and subjective sleepiness of night shift workers, Paula Schweitzer, Ph.D., reported at the annual meeting of the Associated Professional Sleep Societies.

In a rare field study of night shift workers, 39 participants (28 males; mean age 33 years) completed a 4-consecutive-night crossover study comparing two conditions: an evening nap prior to the night shift on the first 2 nights plus caffeine 300 mg on all 4 nights and placebo without napping on all 4 nights.

Three times during each night (start of shift, midway, and end of shift), participants completed a 15-minute psychomotor vigilance task (PVT) using a handheld PVT electronic device that measured the subject's reaction times to tasks. The study subjects also completed subjective sleepiness and mood tests three times a night, said Dr. Schweitzer, associate director of the Sleep Medicine and Research Center at St. Luke's Hospital, St. Louis.

RT10, or the reaction time of the slowest 10% of the PVT responses, worsened across nights 1–4 for both the nap/caffeine treatment group and the placebo group.

“Alertness and performance did not improve across successive night shifts–as has been found in some laboratory studies. People are not getting used to things [on the night shift],” Dr. Schweitzer said.

But some evidence indicated that the caffeine and naps did help somewhat.

Only the placebo group had a worsening of RT10 from shift start to shift end. Additionally, at shift end, the placebo group's RT10 was worse than that of the caffeine/nap treatment group.

The study also evaluated PVT lapses, which are unacceptably long delays in PVT reaction time. Again, the nap/caffeine group outperformed the placebo group. PVT lapse frequency increased from shift start to end for the placebo group, with no change for the treatment group. But both the placebo and treatment groups had an increase in lapse frequency across nights 1–4, which, in effect, was further proof of Dr. Schweitzer's observation that workers are not getting accustomed to night shift work.

Subjective sleepiness as measured by the Karolinska Sleepiness Scale also indicated some benefit of the caffeine and naps. The placebo group showed increased sleepiness at shift end, but the treatment group did not. There was no change in sleepiness ratings across nights 1–4, Dr. Schweitzer said.

Actigraph-estimated total sleep time for daytime sleep did not differ between the two groups.

PHILADELPHIA – The combination of caffeine and evening naps has only modest positive effects on performance and subjective sleepiness of night shift workers, Paula Schweitzer, Ph.D., reported at the annual meeting of the Associated Professional Sleep Societies.

In a rare field study of night shift workers, 39 participants (28 males; mean age 33 years) completed a 4-consecutive-night crossover study comparing two conditions: an evening nap prior to the night shift on the first 2 nights plus caffeine 300 mg on all 4 nights and placebo without napping on all 4 nights.

Three times during each night (start of shift, midway, and end of shift), participants completed a 15-minute psychomotor vigilance task (PVT) using a handheld PVT electronic device that measured the subject's reaction times to tasks. The study subjects also completed subjective sleepiness and mood tests three times a night, said Dr. Schweitzer, associate director of the Sleep Medicine and Research Center at St. Luke's Hospital, St. Louis.

RT10, or the reaction time of the slowest 10% of the PVT responses, worsened across nights 1–4 for both the nap/caffeine treatment group and the placebo group.

“Alertness and performance did not improve across successive night shifts–as has been found in some laboratory studies. People are not getting used to things [on the night shift],” Dr. Schweitzer said.

But some evidence indicated that the caffeine and naps did help somewhat.

Only the placebo group had a worsening of RT10 from shift start to shift end. Additionally, at shift end, the placebo group's RT10 was worse than that of the caffeine/nap treatment group.

The study also evaluated PVT lapses, which are unacceptably long delays in PVT reaction time. Again, the nap/caffeine group outperformed the placebo group. PVT lapse frequency increased from shift start to end for the placebo group, with no change for the treatment group. But both the placebo and treatment groups had an increase in lapse frequency across nights 1–4, which, in effect, was further proof of Dr. Schweitzer's observation that workers are not getting accustomed to night shift work.

Subjective sleepiness as measured by the Karolinska Sleepiness Scale also indicated some benefit of the caffeine and naps. The placebo group showed increased sleepiness at shift end, but the treatment group did not. There was no change in sleepiness ratings across nights 1–4, Dr. Schweitzer said.

Actigraph-estimated total sleep time for daytime sleep did not differ between the two groups.

PHILADELPHIA – Children who had attention-deficit hyperactivity disorder had a shorter time to sleep onset and more actual sleep time when they were treated with atomoxetine than with methylphenidate, according to a study comparing the two ADHD treatments that was presented at the annual meeting of the Associated Professional Sleep Societies.

Children were able to get to sleep more quickly and slept longer during a drug-free baseline period.

Methylphenidate caused fewer awakenings and produced less awake time during the night than did atomoxetine.

“The results of the study may not be a big surprise to clinicians familiar with these drugs, as methylphenidate is a stimulant and atomoxetine is not.

“However, the half-life of methylphenidate is so short that, by bedtime, it is gone. So there is some question about its effects,” said Bart Sangal, M.D., director of the Sleep Disorders Institute, Troy, Mich.

The current study was a randomized, double-blind, crossover trial of 85 children with ADHD. The average age of the children was 10.1 years. After a treatment-free baseline period of up to 12 days, patients underwent treatment for up to 7 weeks on one drug. After another drug-free period (10–20 days), patients in the study then crossed over to the other drug for treatment up to 7 weeks.

When compared with the initial treatment-free baseline period, ADHD children who were treated with atomoxetine fell asleep within 12.1 minutes of their baseline, compared with 39.2 minutes for the methylphenidate group. Researchers measured the time to sleep onset by actigraphy, which is a monitor worn like a watch on the wrist at home by the child.

“Both atomoxetine and methylphenidate caused an increase in time to fall asleep, but it was significantly more so with methylphenidate,” Dr. Sangal said.

Actual sleep time also was negatively affected by both drugs. Children who were on atomoxetine slept 15.3 minutes less than at baseline and children who were on methylphenidate slept 29.6 minutes less than at baseline. The difference in sleep times was statistically significant, Dr. Sangal said.

On a positive note, the numbers of wake bouts or awakenings experienced by the participants were decreased, compared with baseline, by the two drugs. But that decrease was more significant with methylphenidate, according to Dr. Sangal.

Children who were on atomoxetine had 1.3 fewer awakenings than at baseline and children on methylphenidate had 4.4 fewer awakenings.

The total awake time was significantly decreased from baseline by 6.3 minutes with methylphenidate, while atomoxetine decreased awake time by only 0.3 minutes, Dr. Sangal said.

“It is possible that the subjects in the study had a worse sleep initiation with methylphenidate and then a compensatory improvement in sleep maintenance,” he said.

The mean final dosages were 1.56 mg/kg per day for atomoxetine and 1.12 mg/kg per day for methylphenidate. Dosage was based on weight and started at 0.5 mg /kg per day for atomoxetine and 0.45 mg/kg per day for methylphenidate. Each subject was titrated upwards to a maximum of 1.8 mg/kg per day for each drug.

There were 21 (25%) female and 64 (75%) male subjects. The ADHD subtypes were: 2 (2%) hyperactive/impulsive; 25 (29%) inattentive; and 57 (68%) combined. In terms of race, 21 (25%) of the participants were of African descent; 62 (73%) were of European descent; and 2 (2%) were categorized as other. Thirty-seven (43.5%) of the participants had previous stimulant exposure and 48 (56.5%) did not.

Only a subset of patients in the study underwent polysomnography in a sleep lab, which Dr. Sangal said was a “limitation of the study.” With polysomnography, atomoxetine compared favorably again with methylphenidate with regard to time to persistent sleep, a polysomnography measure that is akin to sleep onset.

ADHD children treated with atomoxetine fell asleep 0.2 minutes ahead of their baseline, compared with 16.8 minutes after their baseline for the methylphenidate group; the difference was statistically significant. Both atomoxetine and methylphenidate were well-tolerated, he said.

Dr. Sangal is a paid consultant to Lilly Pharmaceuticals. Lilly Pharmaceuticals sponsored the study and manufactures atomoxetine.

PHILADELPHIA – Children who had attention-deficit hyperactivity disorder had a shorter time to sleep onset and more actual sleep time when they were treated with atomoxetine than with methylphenidate, according to a study comparing the two ADHD treatments that was presented at the annual meeting of the Associated Professional Sleep Societies.

Children were able to get to sleep more quickly and slept longer during a drug-free baseline period.

Methylphenidate caused fewer awakenings and produced less awake time during the night than did atomoxetine.

“The results of the study may not be a big surprise to clinicians familiar with these drugs, as methylphenidate is a stimulant and atomoxetine is not.

“However, the half-life of methylphenidate is so short that, by bedtime, it is gone. So there is some question about its effects,” said Bart Sangal, M.D., director of the Sleep Disorders Institute, Troy, Mich.

The current study was a randomized, double-blind, crossover trial of 85 children with ADHD. The average age of the children was 10.1 years. After a treatment-free baseline period of up to 12 days, patients underwent treatment for up to 7 weeks on one drug. After another drug-free period (10–20 days), patients in the study then crossed over to the other drug for treatment up to 7 weeks.

When compared with the initial treatment-free baseline period, ADHD children who were treated with atomoxetine fell asleep within 12.1 minutes of their baseline, compared with 39.2 minutes for the methylphenidate group. Researchers measured the time to sleep onset by actigraphy, which is a monitor worn like a watch on the wrist at home by the child.

“Both atomoxetine and methylphenidate caused an increase in time to fall asleep, but it was significantly more so with methylphenidate,” Dr. Sangal said.

Actual sleep time also was negatively affected by both drugs. Children who were on atomoxetine slept 15.3 minutes less than at baseline and children who were on methylphenidate slept 29.6 minutes less than at baseline. The difference in sleep times was statistically significant, Dr. Sangal said.

On a positive note, the numbers of wake bouts or awakenings experienced by the participants were decreased, compared with baseline, by the two drugs. But that decrease was more significant with methylphenidate, according to Dr. Sangal.

Children who were on atomoxetine had 1.3 fewer awakenings than at baseline and children on methylphenidate had 4.4 fewer awakenings.

The total awake time was significantly decreased from baseline by 6.3 minutes with methylphenidate, while atomoxetine decreased awake time by only 0.3 minutes, Dr. Sangal said.

“It is possible that the subjects in the study had a worse sleep initiation with methylphenidate and then a compensatory improvement in sleep maintenance,” he said.

The mean final dosages were 1.56 mg/kg per day for atomoxetine and 1.12 mg/kg per day for methylphenidate. Dosage was based on weight and started at 0.5 mg /kg per day for atomoxetine and 0.45 mg/kg per day for methylphenidate. Each subject was titrated upwards to a maximum of 1.8 mg/kg per day for each drug.

There were 21 (25%) female and 64 (75%) male subjects. The ADHD subtypes were: 2 (2%) hyperactive/impulsive; 25 (29%) inattentive; and 57 (68%) combined. In terms of race, 21 (25%) of the participants were of African descent; 62 (73%) were of European descent; and 2 (2%) were categorized as other. Thirty-seven (43.5%) of the participants had previous stimulant exposure and 48 (56.5%) did not.

Only a subset of patients in the study underwent polysomnography in a sleep lab, which Dr. Sangal said was a “limitation of the study.” With polysomnography, atomoxetine compared favorably again with methylphenidate with regard to time to persistent sleep, a polysomnography measure that is akin to sleep onset.

ADHD children treated with atomoxetine fell asleep 0.2 minutes ahead of their baseline, compared with 16.8 minutes after their baseline for the methylphenidate group; the difference was statistically significant. Both atomoxetine and methylphenidate were well-tolerated, he said.

Dr. Sangal is a paid consultant to Lilly Pharmaceuticals. Lilly Pharmaceuticals sponsored the study and manufactures atomoxetine.

PHILADELPHIA – Children who had attention-deficit hyperactivity disorder had a shorter time to sleep onset and more actual sleep time when they were treated with atomoxetine than with methylphenidate, according to a study comparing the two ADHD treatments that was presented at the annual meeting of the Associated Professional Sleep Societies.

Children were able to get to sleep more quickly and slept longer during a drug-free baseline period.

Methylphenidate caused fewer awakenings and produced less awake time during the night than did atomoxetine.

“The results of the study may not be a big surprise to clinicians familiar with these drugs, as methylphenidate is a stimulant and atomoxetine is not.

“However, the half-life of methylphenidate is so short that, by bedtime, it is gone. So there is some question about its effects,” said Bart Sangal, M.D., director of the Sleep Disorders Institute, Troy, Mich.

The current study was a randomized, double-blind, crossover trial of 85 children with ADHD. The average age of the children was 10.1 years. After a treatment-free baseline period of up to 12 days, patients underwent treatment for up to 7 weeks on one drug. After another drug-free period (10–20 days), patients in the study then crossed over to the other drug for treatment up to 7 weeks.

When compared with the initial treatment-free baseline period, ADHD children who were treated with atomoxetine fell asleep within 12.1 minutes of their baseline, compared with 39.2 minutes for the methylphenidate group. Researchers measured the time to sleep onset by actigraphy, which is a monitor worn like a watch on the wrist at home by the child.

“Both atomoxetine and methylphenidate caused an increase in time to fall asleep, but it was significantly more so with methylphenidate,” Dr. Sangal said.

Actual sleep time also was negatively affected by both drugs. Children who were on atomoxetine slept 15.3 minutes less than at baseline and children who were on methylphenidate slept 29.6 minutes less than at baseline. The difference in sleep times was statistically significant, Dr. Sangal said.

On a positive note, the numbers of wake bouts or awakenings experienced by the participants were decreased, compared with baseline, by the two drugs. But that decrease was more significant with methylphenidate, according to Dr. Sangal.

Children who were on atomoxetine had 1.3 fewer awakenings than at baseline and children on methylphenidate had 4.4 fewer awakenings.

The total awake time was significantly decreased from baseline by 6.3 minutes with methylphenidate, while atomoxetine decreased awake time by only 0.3 minutes, Dr. Sangal said.

“It is possible that the subjects in the study had a worse sleep initiation with methylphenidate and then a compensatory improvement in sleep maintenance,” he said.

The mean final dosages were 1.56 mg/kg per day for atomoxetine and 1.12 mg/kg per day for methylphenidate. Dosage was based on weight and started at 0.5 mg /kg per day for atomoxetine and 0.45 mg/kg per day for methylphenidate. Each subject was titrated upwards to a maximum of 1.8 mg/kg per day for each drug.

There were 21 (25%) female and 64 (75%) male subjects. The ADHD subtypes were: 2 (2%) hyperactive/impulsive; 25 (29%) inattentive; and 57 (68%) combined. In terms of race, 21 (25%) of the participants were of African descent; 62 (73%) were of European descent; and 2 (2%) were categorized as other. Thirty-seven (43.5%) of the participants had previous stimulant exposure and 48 (56.5%) did not.

Only a subset of patients in the study underwent polysomnography in a sleep lab, which Dr. Sangal said was a “limitation of the study.” With polysomnography, atomoxetine compared favorably again with methylphenidate with regard to time to persistent sleep, a polysomnography measure that is akin to sleep onset.

ADHD children treated with atomoxetine fell asleep 0.2 minutes ahead of their baseline, compared with 16.8 minutes after their baseline for the methylphenidate group; the difference was statistically significant. Both atomoxetine and methylphenidate were well-tolerated, he said.

Dr. Sangal is a paid consultant to Lilly Pharmaceuticals. Lilly Pharmaceuticals sponsored the study and manufactures atomoxetine.

PHILADELPHIA — The median therapeutic dose of modafinil was 300 mg for patients with obstructive sleep apnea and 400 mg for patients with narcolepsy in long-term open-label extensions of placebo-controlled trials, Dr. Jonathan Schwartz said at the annual meeting of the Associated Professional Sleep Societies.

The labeling for modafinil (Provigil) calls for a dosage of 200 mg/day to improve wakefulness in patients with excessive sleepiness associated with either condition. “Modafinil dosing was flexible—between 200 and 400 mg/day—based on the investigators' impressions of clinical efficacy and tolerability [during the open-label extensions]. The dose was slightly higher in patients with narcolepsy, which may be attributable to the underlying differences in severity of excessive sleepiness between the two conditions,” said Dr. Schwartz, a pulmonologist in Oklahoma City.

The open-label extensions involved two double-blind, placebo-controlled trials of modafinil in patients with narcolepsy and one in patients with nasal continuous positive airway pressure (nCPAP)-treated obstructive sleep apnea (OSA).

In the narcolepsy studies, 84% of 478 patients were titrated to a modafinil dose greater than 200 mg, with 50% at 400 mg, 34% at 300 mg, and 16% at 200 mg. In the OSA study, 76% of the 266 patients were titrated to a modafinil dose greater than 200 mg, with 43% at 300 mg, 33% at 400 mg, and 24% at 200 mg.

Modafinil was well tolerated in both populations at all doses, Dr. Schwartz said. Adverse events were similar in the two patient populations. Treatment duration was 40 weeks for both narcolepsy studies and 12 months for the OSA study.

Baseline excessive sleepiness was assessed by mean score on the Epworth Sleepiness Scale (ESS); the score was significantly higher in the narcolepsy patients than in the OSA population (17.4 vs. 14.5, respectively; P < .001).

“Narcolepsy and obstructive sleep apnea are both frequently associated with excessive sleepiness, but patients with narcolepsy are usually sleepier than nCPAP-treated patients with OSA,” said Dr. Schwartz.

In OSA, modafinil is indicated as an adjunct to standard treatments for the underlying obstruction in patients who continue to experience residual excessive sleepiness, despite treatment of the underlying obstruction, he added.

At least 20% of OSA patients are still sleepy despite nCPAP therapy, he said.

The mean change in ESS scores from baseline to final clinic visit in the study populations was virtually identical—about 4.25 points—for the narcolepsy and OSA patients, said Dr. Schwartz. In other words, there was a similar efficacy (mean reduction in sleepiness), despite the difference in the mean dose.

The mean body mass index was significantly lower in the narcolepsy group (28.8 kg/m2) than in the OSA patients (36.2 kg/m2). Despite having significantly lower body mass index than OSA patients, patients with narcolepsy were titrated to higher modafinil doses to achieve clinical improvement, Dr. Schwartz observed.

The mean age for the narcolepsy patients was 42 years; the OSA patients' mean age was 50 years. Of the narcolepsy patients, 46% were male, as were 77% of the OSA patients.

Overall, 84% of patients in the studies completed the specified treatment period, but completion rates were higher in the 40-week narcolepsy studies (95%) than in the single 12-month OSA study (66%).

Clinic visits for both narcolepsy studies were scheduled at baseline and after 1, 2, 6, 8, 16, 24, and 40 weeks.

Clinic visits for the OSA study were scheduled at baseline and at 3, 6, 9, and 12 months.

The study included patients who withdrew after two evaluations if their withdrawal was not due to adverse events.

The study was funded by Cephalon Inc., the maker of modafinil.

PHILADELPHIA — The median therapeutic dose of modafinil was 300 mg for patients with obstructive sleep apnea and 400 mg for patients with narcolepsy in long-term open-label extensions of placebo-controlled trials, Dr. Jonathan Schwartz said at the annual meeting of the Associated Professional Sleep Societies.

The labeling for modafinil (Provigil) calls for a dosage of 200 mg/day to improve wakefulness in patients with excessive sleepiness associated with either condition. “Modafinil dosing was flexible—between 200 and 400 mg/day—based on the investigators' impressions of clinical efficacy and tolerability [during the open-label extensions]. The dose was slightly higher in patients with narcolepsy, which may be attributable to the underlying differences in severity of excessive sleepiness between the two conditions,” said Dr. Schwartz, a pulmonologist in Oklahoma City.

The open-label extensions involved two double-blind, placebo-controlled trials of modafinil in patients with narcolepsy and one in patients with nasal continuous positive airway pressure (nCPAP)-treated obstructive sleep apnea (OSA).

In the narcolepsy studies, 84% of 478 patients were titrated to a modafinil dose greater than 200 mg, with 50% at 400 mg, 34% at 300 mg, and 16% at 200 mg. In the OSA study, 76% of the 266 patients were titrated to a modafinil dose greater than 200 mg, with 43% at 300 mg, 33% at 400 mg, and 24% at 200 mg.

Modafinil was well tolerated in both populations at all doses, Dr. Schwartz said. Adverse events were similar in the two patient populations. Treatment duration was 40 weeks for both narcolepsy studies and 12 months for the OSA study.

Baseline excessive sleepiness was assessed by mean score on the Epworth Sleepiness Scale (ESS); the score was significantly higher in the narcolepsy patients than in the OSA population (17.4 vs. 14.5, respectively; P < .001).

“Narcolepsy and obstructive sleep apnea are both frequently associated with excessive sleepiness, but patients with narcolepsy are usually sleepier than nCPAP-treated patients with OSA,” said Dr. Schwartz.

In OSA, modafinil is indicated as an adjunct to standard treatments for the underlying obstruction in patients who continue to experience residual excessive sleepiness, despite treatment of the underlying obstruction, he added.

At least 20% of OSA patients are still sleepy despite nCPAP therapy, he said.

The mean change in ESS scores from baseline to final clinic visit in the study populations was virtually identical—about 4.25 points—for the narcolepsy and OSA patients, said Dr. Schwartz. In other words, there was a similar efficacy (mean reduction in sleepiness), despite the difference in the mean dose.

The mean body mass index was significantly lower in the narcolepsy group (28.8 kg/m2) than in the OSA patients (36.2 kg/m2). Despite having significantly lower body mass index than OSA patients, patients with narcolepsy were titrated to higher modafinil doses to achieve clinical improvement, Dr. Schwartz observed.

The mean age for the narcolepsy patients was 42 years; the OSA patients' mean age was 50 years. Of the narcolepsy patients, 46% were male, as were 77% of the OSA patients.

Overall, 84% of patients in the studies completed the specified treatment period, but completion rates were higher in the 40-week narcolepsy studies (95%) than in the single 12-month OSA study (66%).

Clinic visits for both narcolepsy studies were scheduled at baseline and after 1, 2, 6, 8, 16, 24, and 40 weeks.

Clinic visits for the OSA study were scheduled at baseline and at 3, 6, 9, and 12 months.

The study included patients who withdrew after two evaluations if their withdrawal was not due to adverse events.

The study was funded by Cephalon Inc., the maker of modafinil.

PHILADELPHIA — The median therapeutic dose of modafinil was 300 mg for patients with obstructive sleep apnea and 400 mg for patients with narcolepsy in long-term open-label extensions of placebo-controlled trials, Dr. Jonathan Schwartz said at the annual meeting of the Associated Professional Sleep Societies.

The labeling for modafinil (Provigil) calls for a dosage of 200 mg/day to improve wakefulness in patients with excessive sleepiness associated with either condition. “Modafinil dosing was flexible—between 200 and 400 mg/day—based on the investigators' impressions of clinical efficacy and tolerability [during the open-label extensions]. The dose was slightly higher in patients with narcolepsy, which may be attributable to the underlying differences in severity of excessive sleepiness between the two conditions,” said Dr. Schwartz, a pulmonologist in Oklahoma City.

The open-label extensions involved two double-blind, placebo-controlled trials of modafinil in patients with narcolepsy and one in patients with nasal continuous positive airway pressure (nCPAP)-treated obstructive sleep apnea (OSA).

In the narcolepsy studies, 84% of 478 patients were titrated to a modafinil dose greater than 200 mg, with 50% at 400 mg, 34% at 300 mg, and 16% at 200 mg. In the OSA study, 76% of the 266 patients were titrated to a modafinil dose greater than 200 mg, with 43% at 300 mg, 33% at 400 mg, and 24% at 200 mg.

Modafinil was well tolerated in both populations at all doses, Dr. Schwartz said. Adverse events were similar in the two patient populations. Treatment duration was 40 weeks for both narcolepsy studies and 12 months for the OSA study.

Baseline excessive sleepiness was assessed by mean score on the Epworth Sleepiness Scale (ESS); the score was significantly higher in the narcolepsy patients than in the OSA population (17.4 vs. 14.5, respectively; P < .001).

“Narcolepsy and obstructive sleep apnea are both frequently associated with excessive sleepiness, but patients with narcolepsy are usually sleepier than nCPAP-treated patients with OSA,” said Dr. Schwartz.

In OSA, modafinil is indicated as an adjunct to standard treatments for the underlying obstruction in patients who continue to experience residual excessive sleepiness, despite treatment of the underlying obstruction, he added.

At least 20% of OSA patients are still sleepy despite nCPAP therapy, he said.

The mean change in ESS scores from baseline to final clinic visit in the study populations was virtually identical—about 4.25 points—for the narcolepsy and OSA patients, said Dr. Schwartz. In other words, there was a similar efficacy (mean reduction in sleepiness), despite the difference in the mean dose.

The mean body mass index was significantly lower in the narcolepsy group (28.8 kg/m2) than in the OSA patients (36.2 kg/m2). Despite having significantly lower body mass index than OSA patients, patients with narcolepsy were titrated to higher modafinil doses to achieve clinical improvement, Dr. Schwartz observed.

The mean age for the narcolepsy patients was 42 years; the OSA patients' mean age was 50 years. Of the narcolepsy patients, 46% were male, as were 77% of the OSA patients.

Overall, 84% of patients in the studies completed the specified treatment period, but completion rates were higher in the 40-week narcolepsy studies (95%) than in the single 12-month OSA study (66%).

Clinic visits for both narcolepsy studies were scheduled at baseline and after 1, 2, 6, 8, 16, 24, and 40 weeks.

Clinic visits for the OSA study were scheduled at baseline and at 3, 6, 9, and 12 months.

The study included patients who withdrew after two evaluations if their withdrawal was not due to adverse events.

The study was funded by Cephalon Inc., the maker of modafinil.

PHILADELPHIA – The median dose of modafinil was 300 mg for patients with obstructive sleep apnea and 400 mg for patients with narcolepsy in long-term open-label extensions of placebo-controlled trials, Jonathan Schwartz, M.D., said at the annual meeting of the Associated Professional Sleep Societies.

The labeling for modafinil (Provigil) calls for a dosage of 200 mg/day to improve wakefulness in patients with excessive sleepiness associated with either condition.

“Modafinil dosing was flexible–between 200 and 400 mg/day–based on the investigators' impressions of clinical efficacy and tolerability [during the open-label extensions]. The dose was slightly higher in patients with narcolepsy, which may be attributable to the underlying differences in severity of excessive sleepiness between the two conditions,” said Dr. Schwartz, a pulmonologist in Oklahoma City.

The open-label extensions involved two double-blind, placebo-controlled trials of modafinil in patients with narcolepsy and one in patients with nasal continuous positive airway pressure (nCPAP)-treated obstructive sleep apnea (OSA).

In the narcolepsy studies, 84% of 478 patients were titrated to a modafinil dose greater than 200 mg, with 50% at 400 mg, 34% at 300 mg, and 16% at 200 mg. In the OSA study, 76% of the 266 patients were titrated to a modafinil dose greater than 200 mg, with 43% at 300 mg, 33% at 400 mg, and 24% at 200 mg.

Modafinil was well tolerated in both populations at all doses, Dr. Schwartz said. Adverse events were similar in the two patient populations.

Treatment duration was 40 weeks for both narcolepsy studies and 12 months for the OSA study.

Baseline excessive sleepiness was assessed by mean score on the Epworth Sleepiness Scale (ESS); the score was significantly higher in the narcolepsy patients than in the OSA population (17.4 vs. 14.5, respectively; P< .001).

“Narcolepsy and obstructive sleep apnea are both frequently associated with excessive sleepiness, but patients with narcolepsy are usually sleepier than nCPAP-treated patients with OSA,” said Dr. Schwartz.

In OSA, modafinil is indicated as an adjunct to standard treatments for the underlying obstruction in patients who continue to experience residual excessive sleepiness, despite treatment of the underlying obstruction, he added.

At least 20% of OSA patients are still sleepy despite nCPAP therapy, he said.

The mean change in ESS scores from baseline to final clinic visit in the study populations was virtually identical–about 4.25 points–for the narcolepsy and OSA patients, said Dr. Schwartz. In other words, there was a similar efficacy (mean reduction in sleepiness), despite the difference in the mean dose.

The mean body mass index was significantly lower in the narcolepsy group (28.8 kg/m2) than in the OSA patients (36.2 kg/m2). Despite having significantly lower body mass indexes than OSA patients, patients with narcolepsy were titrated to higher modafinil doses to achieve clinical improvement, Dr. Schwartz observed.

The mean age for the narcolepsy patients was 42 years; the OSA patients' mean age was 50 years. Of the narcolepsy patients, 46% were male, as were 77% of the OSA patients.

Overall, 84% of patients in the studies completed the specified treatment period, but completion rates were higher in the 40-week narcolepsy studies (95%) than in the single 12-month OSA study (66%).

Clinic visits for both narcolepsy studies were scheduled at baseline and after 1, 2, 6, 8, 16, 24, and 40 weeks.

Clinic visits for the OSA study were scheduled at baseline and at 3, 6, 9, and 12 months.

The study was funded by Cephalon Inc., the maker of modafinil.

PHILADELPHIA – The median dose of modafinil was 300 mg for patients with obstructive sleep apnea and 400 mg for patients with narcolepsy in long-term open-label extensions of placebo-controlled trials, Jonathan Schwartz, M.D., said at the annual meeting of the Associated Professional Sleep Societies.

The labeling for modafinil (Provigil) calls for a dosage of 200 mg/day to improve wakefulness in patients with excessive sleepiness associated with either condition.

“Modafinil dosing was flexible–between 200 and 400 mg/day–based on the investigators' impressions of clinical efficacy and tolerability [during the open-label extensions]. The dose was slightly higher in patients with narcolepsy, which may be attributable to the underlying differences in severity of excessive sleepiness between the two conditions,” said Dr. Schwartz, a pulmonologist in Oklahoma City.

The open-label extensions involved two double-blind, placebo-controlled trials of modafinil in patients with narcolepsy and one in patients with nasal continuous positive airway pressure (nCPAP)-treated obstructive sleep apnea (OSA).

In the narcolepsy studies, 84% of 478 patients were titrated to a modafinil dose greater than 200 mg, with 50% at 400 mg, 34% at 300 mg, and 16% at 200 mg. In the OSA study, 76% of the 266 patients were titrated to a modafinil dose greater than 200 mg, with 43% at 300 mg, 33% at 400 mg, and 24% at 200 mg.

Modafinil was well tolerated in both populations at all doses, Dr. Schwartz said. Adverse events were similar in the two patient populations.

Treatment duration was 40 weeks for both narcolepsy studies and 12 months for the OSA study.

Baseline excessive sleepiness was assessed by mean score on the Epworth Sleepiness Scale (ESS); the score was significantly higher in the narcolepsy patients than in the OSA population (17.4 vs. 14.5, respectively; P< .001).

“Narcolepsy and obstructive sleep apnea are both frequently associated with excessive sleepiness, but patients with narcolepsy are usually sleepier than nCPAP-treated patients with OSA,” said Dr. Schwartz.

In OSA, modafinil is indicated as an adjunct to standard treatments for the underlying obstruction in patients who continue to experience residual excessive sleepiness, despite treatment of the underlying obstruction, he added.

At least 20% of OSA patients are still sleepy despite nCPAP therapy, he said.

The mean change in ESS scores from baseline to final clinic visit in the study populations was virtually identical–about 4.25 points–for the narcolepsy and OSA patients, said Dr. Schwartz. In other words, there was a similar efficacy (mean reduction in sleepiness), despite the difference in the mean dose.

The mean body mass index was significantly lower in the narcolepsy group (28.8 kg/m2) than in the OSA patients (36.2 kg/m2). Despite having significantly lower body mass indexes than OSA patients, patients with narcolepsy were titrated to higher modafinil doses to achieve clinical improvement, Dr. Schwartz observed.

The mean age for the narcolepsy patients was 42 years; the OSA patients' mean age was 50 years. Of the narcolepsy patients, 46% were male, as were 77% of the OSA patients.

Overall, 84% of patients in the studies completed the specified treatment period, but completion rates were higher in the 40-week narcolepsy studies (95%) than in the single 12-month OSA study (66%).

Clinic visits for both narcolepsy studies were scheduled at baseline and after 1, 2, 6, 8, 16, 24, and 40 weeks.

Clinic visits for the OSA study were scheduled at baseline and at 3, 6, 9, and 12 months.

The study was funded by Cephalon Inc., the maker of modafinil.

PHILADELPHIA – The median dose of modafinil was 300 mg for patients with obstructive sleep apnea and 400 mg for patients with narcolepsy in long-term open-label extensions of placebo-controlled trials, Jonathan Schwartz, M.D., said at the annual meeting of the Associated Professional Sleep Societies.

The labeling for modafinil (Provigil) calls for a dosage of 200 mg/day to improve wakefulness in patients with excessive sleepiness associated with either condition.

“Modafinil dosing was flexible–between 200 and 400 mg/day–based on the investigators' impressions of clinical efficacy and tolerability [during the open-label extensions]. The dose was slightly higher in patients with narcolepsy, which may be attributable to the underlying differences in severity of excessive sleepiness between the two conditions,” said Dr. Schwartz, a pulmonologist in Oklahoma City.

The open-label extensions involved two double-blind, placebo-controlled trials of modafinil in patients with narcolepsy and one in patients with nasal continuous positive airway pressure (nCPAP)-treated obstructive sleep apnea (OSA).

In the narcolepsy studies, 84% of 478 patients were titrated to a modafinil dose greater than 200 mg, with 50% at 400 mg, 34% at 300 mg, and 16% at 200 mg. In the OSA study, 76% of the 266 patients were titrated to a modafinil dose greater than 200 mg, with 43% at 300 mg, 33% at 400 mg, and 24% at 200 mg.

Modafinil was well tolerated in both populations at all doses, Dr. Schwartz said. Adverse events were similar in the two patient populations.

Treatment duration was 40 weeks for both narcolepsy studies and 12 months for the OSA study.

Baseline excessive sleepiness was assessed by mean score on the Epworth Sleepiness Scale (ESS); the score was significantly higher in the narcolepsy patients than in the OSA population (17.4 vs. 14.5, respectively; P< .001).

“Narcolepsy and obstructive sleep apnea are both frequently associated with excessive sleepiness, but patients with narcolepsy are usually sleepier than nCPAP-treated patients with OSA,” said Dr. Schwartz.

In OSA, modafinil is indicated as an adjunct to standard treatments for the underlying obstruction in patients who continue to experience residual excessive sleepiness, despite treatment of the underlying obstruction, he added.

At least 20% of OSA patients are still sleepy despite nCPAP therapy, he said.

The mean change in ESS scores from baseline to final clinic visit in the study populations was virtually identical–about 4.25 points–for the narcolepsy and OSA patients, said Dr. Schwartz. In other words, there was a similar efficacy (mean reduction in sleepiness), despite the difference in the mean dose.

The mean body mass index was significantly lower in the narcolepsy group (28.8 kg/m2) than in the OSA patients (36.2 kg/m2). Despite having significantly lower body mass indexes than OSA patients, patients with narcolepsy were titrated to higher modafinil doses to achieve clinical improvement, Dr. Schwartz observed.

The mean age for the narcolepsy patients was 42 years; the OSA patients' mean age was 50 years. Of the narcolepsy patients, 46% were male, as were 77% of the OSA patients.

Overall, 84% of patients in the studies completed the specified treatment period, but completion rates were higher in the 40-week narcolepsy studies (95%) than in the single 12-month OSA study (66%).

Clinic visits for both narcolepsy studies were scheduled at baseline and after 1, 2, 6, 8, 16, 24, and 40 weeks.

Clinic visits for the OSA study were scheduled at baseline and at 3, 6, 9, and 12 months.

The study was funded by Cephalon Inc., the maker of modafinil.