Treatments for Sleepiness Vary in Cost, Side Effects

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Treatments for Sleepiness Vary in Cost, Side Effects 54 Neuropsychiatric Medicine C LINICAL P SYCHIATRY N EWS • April 2006 Treatments for Sleepiness Vary in Cost, Side Effects BY SHERRY BOSCHERT their insomnia, he said. Ironically, a bit of fects than other stimulants. Tolerance is sleepiness is sleep apnea, which occurs in San Francisco Bureau caffeine in the morning may be just what not an issue—it maintains most of its ef- perhaps 10% of the population, he said. they need. “The problem with many of ficacy over time—and use of the drug Restless leg syndrome can interrupt sleep S AN D IEGO — All three main treat- these insomniac patients is that they can’t does not lead to dependence. Side effects and lead to daytime sleepiness. Narcolep- ments for problem sleepiness can perk pa- get going, get functioning in the morn- include headache, nausea, dry mouth, in- sy is fairly uncommon. Insomnia can cause tients up, but they differ in cost and side ing,” he said. Limited caffeine use in the somnia, and hyperactivity. excessive sleepiness, but more often, in- effects, Dr. Milton Erman said at a psy- morning may help them function better. The risk of headache relates to the dos- somniac patients are hypervigilant. “If chopharmacology congress sponsored by Use of CNS stimulants also leads to tol- ing of modafinil. In early research on the anything, they are more alert” than they the Neuroscience Education Institute. erance, and there is a high potential for de- drug, headache appeared primarily in pa- want to be, he said. Caffeine is the cheapest, most accessible, pendence. Side effects include nervousness, tients who titrated up to a dose of 400 Secondary causes of sleepiness include and most widely used stimulant. The two headaches, insomnia, anorexia, GI prob- mg/day by the third day. In subsequent re- chronic pain and any medical condition other treatment options are prescription lems, and mood changes. General CNS search that gave patients 7-9 days to titrate that causes pain or discomfort, which may medications, which are more expensive: stimulants such as amphetamines have a up to 400 mg/day, headache was much interrupt sleep. Medications used to alle- modafinil or CNS stimulants (most com- high risk of abuse and hyperactivity be- less of a problem, Dr. Erman said. viate pain also can lead to daytime sleepi- monly amphetamines or methylphenidate). cause of their broad mechanism of action. “Modafinil works quite well, particu- ness because they affect breathing during Caffeine tolerance develops rapidly, how- One experimental study of sleep depri- larly if we’re not talking about the most sleep and increase the risk for sleep apnea. ever, and there’s a moderate risk for de- vation that compared amphetamines with severely hypersomnolent patients,” such as Check to see if patients who complain pendence. Stopping a daily caffeine habit modafinil treatment to maintain wakeful- narcoleptics who have become accus- of sleepiness are taking drugs that cause too quickly can trigger a “caffeine ness suggested that the two drugs are tomed to taking stimulants, he said. sedation or that disrupt sleep, Dr. Erman headache.” Side effects from regular caf- equally potent. In real life, however, “I Dr. Erman is a speaker and consultant added, and consider alternative therapies. feine use include nervousness, irritability, think amphetamines are more potent,” he for, and has received research funding Lifestyle issues, such as graveyard shift insomnia, and GI problems, said Dr. Erman said. Patients with narcolepsy who have from, the company that makes modafinil, work, also contribute to excessive sleepi- of the University of California, San Diego. used amphetamines in the past often aren’t Cephalon Inc. Modafinil is approved to ness,. The pace of U.S. culture common- “Many of my insomniac patients tell me satisfied with the effects of modafinil. treat sleepiness from shift work, nar- ly leads to chronic sleep deprivation that proudly that they aren’t using caffeine” to Modafinil works more specifically on colepsy, and sleep apnea. affects daytime function. “As a society, we indicate that caffeine can’t be blamed for wakefulness circuits and has fewer side ef- The most common cause of problem really haven’t dealt with this,” he said. ■ PHQ-9 Detects Depression Sodium Oxybate Reduces Daytime After Traumatic Brain Injury Sleepiness in Medicated Narcoleptics BY DAMIAN MC NAMARA The majority (78%) remained on steady BY JANE SALODOF MACNEIL idated for other medical conditions and Miami Bureau doses of preexisting stimulant medica- Southwest Bureau would be easy for nonpsychiatrists to use. tions. “It takes 2-5 minutes,” he said. “We did this M IAMI B EACH — Sodium oxybate “I don’t think we know the mecha- S ANTA A NA P UEBLO, N.M. — The over the phone. It can be filled out by the significantly lessened daytime sleepiness nism of action. We understand GABA- Patient Health Questionnaire is a simple, patients themselves with paper and pencil. and decreased frequency of sleep attacks B [gamma-aminobutyric acid B] mech- reliable tool that any clinician can use to Or it can be done face to face in an inter- in people with narcolepsy concurrently anism regarding nighttime sleep. screen patients for depression after trau- view format.” taking stimulants, compared with place- Sodium oxybate affects a number of matic brain injury, Dr. Jesse R. Fann re- The PHQ-9 asks whether patients had bo, according to study findings present- neurotransmitter systems, and tends to ported at the annual meeting of the Acad- been bothered during the previous 2 ed at the annual meeting of the Ameri- depress dopamine at night,” Dr. Thorpy, emy of Psychosomatic Medicine. weeks by each of nine symptoms of ma- can Academy of Neurology. director of the Sleep-Wake Disorders Dr. Fann and his colleagues at the Uni- jor depressive disorder in the DSM-IV. The Previous studies have shown that Center at the Montefiore Medical Cen- versity of Washington, Seattle, validated multiple-choice answers range from “not nightly administration of sodium oxy- ter, New York, said in response to a the nine-item questionnaire in a prospec- at all” to “nearly every day.” bate (Xyrem, Orphan Medical) effec- question from the audience. Dr. Thorpy tive cohort study with 135 patients who “It has validity for major depression but tively treated cataplexy in people with received support from Orphan Medical were also referred for structured clinical also helps remind nonpsychiatrists what narcolepsy (Sleep 2003;26:31-5; Sleep Inc., sponsor of the study. interviews. the DSM criteria are,” Dr. Fann said. 2002;25:42-9). Dr. Thorpy used the Maintenance of These patients were among 478 patients The study found the optimal criterion The Food and Drug Administration Wakefulness Test (MWT) as an objective enrolled at the time of analysis in a Na- for a positive screen on the PHQ-9 to be approved the agent for treatment of cat- measure of excessive daytime sleepi- tional Institutes of Health-supported study a patient reporting five or more of the aplexy, a sudden loss of muscle tone as- ness, and the Epworth Sleepiness Scale that is using the PHQ-9 to determine the nine symptoms for at least several days. sociated with narcolepsy, in July 2002. Re- (ESS) for a subjective assessment. Par- prevalence of depression in people who The researchers specified that one of these searchers in the two studies observed ticipants also kept diaries to record the have suffered traumatic brain injury. five symptoms should be a cardinal symp- that the drug also decreased excessive incidence of sleep attacks. Changes in “Various studies have estimated 25%- tom: either depressed mood or anhedonia. daytime sleepiness. MWT scores at 8 weeks were signifi- 45% get depressed in the first year. The When patients met the optimal criteri- To confirm this effect, Dr. Michael J. cant, compared with baseline for pa- prevalence drops after the first year, but on, the poster reported the PHQ-9 had a Thorpy conducted an 8-week, double- tients receiving the final doses of either remains significantly higher than the gen- maximum sensitivity of 0.93, maximum blind, placebo-controlled trial of adult 4.5 g or 9 g. “Compared with placebo, eral population,” Dr. Fann, of the de- specificity of 0.89, positive predictive val- narcolepsy patients from 42 sleep clin- patients treated with sodium oxybate partment of psychiatry and behavioral ue of 0.63, and negative predictive value ics in the United States, Canada, and showed a significant median increase in sciences, said in an interview about the of 0.99 in comparison to a Structured Europe. Participants, after being more than 10 minutes in MWT at the 9- poster. Clinical Interview for DSM-IV (SCID). weaned from anticataplectic medica- g dose,” Dr. Thorpy said. Just why this population is more vul- The investigators also found correlations tions, were randomized to receive 4.5 g, Baseline ESS scores were “around 19, nerable to depression is not clear, Dr. Fann of 0.90 with the Hopkins Symptom 6 g, or 9 g of sodium oxybate or place- suggesting a lot of sleepiness,” Dr. Thor- said. Brain lesions could be a factor, he Checklist Depression Subscale and 0.78 bo nightly. py said. The 6-g and 9-g treatment said, but many patients also suffer from with the Hamilton Rating Scale. The drug was administered in two groups experienced statistically signifi- psychosocial stressors, such as unstable Dr. Fann’s group conducted the study at equally divided doses at bedtime and 2.5- cant decreases in median ESS scores af- employment and social support or abuse the Harborview Medical Center in Seattle, 4 hours later. Sodium oxybate was in- ter 8 weeks, compared with baseline.
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