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What interventions can help patients stop using chewing tobacco?
Nicotine replacement therapy (NRT), including gum and patches, decreases cravings and short-term abstinence rates, but does not improve long-term abstinence (strength of recommendation [SOR]: B, meta-analysis of small randomized controlled studies [RCT]).
It is unclear if bupropion has an effect on cessation rates (SOR: B, small RCTs with conflicting results). Behavioral interventions increase abstinence rates for smokeless tobacco users (SOR: B, meta-analysis of small RCTs).
Evidence summary
Use of smokeless tobacco can lead to nicotine dependence and cause periodontal disease, leukoplakia, cancer, and possibly cardiovascular disease.1-3 Patients who abruptly stop using smokeless tobacco may experience withdrawal symptoms similar to that observed in smokers.3
Nicotine gum
A small double-blind study randomized 79 male smokeless tobacco users to chew nicotine gum (0 mg, 2 mg, or 4 mg) for 5 days.4 Sixty patients completed the study. No significant differences in withdrawal symptoms, including cravings, concentration, or restlessness, were noted among the 3 groups (P>.05). However, further analysis demonstrated that patients with high blood levels of cotinine who received nicotine gum 2 mg experienced decreased cravings compared with placebo (P<.001), and a trend towards decreased cravings with 4 mg gum was noted (P<.06). Limitations of this study: quit rates were not reported, participants did not have to be motivated to quit smokeless tobacco in order to enroll, and it is not known if patients were counseled about the appropriate “chew and park” technique for nicotine gum.
Another study randomized 234 male smokeless tobacco users to receive group behavioral treatment plus nicotine gum 2 mg (B/NRT); group behavioral treatment plus placebo (B/Pl); minimal contact plus nicotine gum 2 mg (MC/NRT); or minimal contact plus placebo (MC/Pl).5
Group behavioral treatment consisted of 8 group counseling sessions 45 to 60 minutes in length; minimal contact involved 4 brief one-on-one sessions with a nurse. Patients chewed a minimum of 6 pieces of nicotine or placebo gum per day.
At 4 weeks, point prevalence abstinence rates were as follows: B/NRT, 63.6%; B/Pl, 66%; MC/NRT, 35.3%; and MC/Pl, 48.1% (P<.01). Abstinence rates remained significantly different at 1 and 6 month follow-ups, but not at 12 months. Post-hoc logistic regression favored group behavioral therapy plus NRT at 6 months. Moreover, survival analysis of continuous prevalence rates demonstrated that the least effective treatment was minimal contact plus NRT.
The authors theorized that nicotine gum may actually worsen risk of relapse in smokeless tobacco users due to behavioral similarities associated with use, but that behavioral treatment may help regain abstinence after a lapse. Gum users experienced lessened withdrawal symptoms including cravings, irritability, anxiety, and difficulty concentrating (P<.01). Results indicate that behavioral interventions may be more effective than NRT; however, low doses of nicotine gum were used.
Nicotine transdermal patches
A randomized double-blind study examined nicotine transdermal patches in smokeless tobacco users.6 Researchers recruited 422 participants from a Minnesota college campus and surrounding metropolitan area through advertisements; they were randomly assigned to nicotine patch plus mint snuff (a nicotine-free product), nicotine patch and no mint snuff, placebo patch plus mint snuff, or placebo patch and no mint snuff. The patch was dosed as 21-mg patch for 6 weeks, 14-mg patch for 2 weeks, and 7-mg patch for 2 weeks. All patients participated in 8 weekly individual 10-minute sessions with a therapist.
Continuous 10-week abstinence rates were 69% for nicotine patch and mint snuff, 58% for nicotine patch and no mint snuff, 46% for placebo patch and mint snuff, and 51% for placebo patch and no mint snuff (P=.002). After 15 weeks the abstinence rates were no longer different between the treatment groups. Patch users experienced lower total withdrawal scores (P=.002) as well as decreased craving (P<.001), irritability (P<.001), and restlessness (P=.019). Total withdrawal scores were not improved for mint snuff users; however, subsets of total withdrawal scores were lower for cravings (P=.005), irritability (P=.046), and anxiety (P=.012).
Meta-analysis
The Cochrane Database of Systematic Reviews published a meta-analysis of 6 studies that examined NRT or bupropion in smokeless tobacco users.3 The primary outcome for the meta-analysis was tobacco abstinence 6 months or more after the intervention. Neither nicotine patches (odds ratio [OR]=1.16; 95% confidence interval [CI], 0.88–1.54) nor nicotine gum (OR=0.98; 95% CI, 0.59–1.63) were shown to improve abstinence over placebo at 6 months. The authors highlight the need for larger studies that compare different NRT products, doses, and duration.
One small randomized trial of bupropion was included, but it found no effect on tobacco abstention (OR=1.00; 95% CI, 0.23–4.37). Another small RCT found an effect; however, it was excluded from the meta-analysis because subjects were followed for only 3 months. The meta-analysis also concluded that behavioral interventions appear to be effective for increasing tobacco abstinence rates. Results were heterogeneous, and study quality was mixed. One post-hoc finding appeared to show that most effective behavioral interventions were coupled with an oral exam with direct feedback.
Recommendations from others
The United States Department of Health and Human Services recommends that smokeless tobacco users should be treated with the same counseling and interventions utilized for smokers, but commented that evidence is currently insufficient to suggest that NRT increases long-term abstinence.7 British guidelines concluded that no evidence clearly shows that nicotine gum or patches are effective cessation aids for smokeless tobacco users.2
NRT not recommended for smokeless users; try bupropion, behavioral therapy
Patrick O. Smith, PhD
Professor, Family Medicine, University of Mississippi Medical Center
Smokeless tobacco users are a special tobacco user population with a limited research base. Although it seems counterintuitive, nicotine replacement therapy (nicotine gum and the nicotine patch) is not recommended for this population. Using the tobacco use and quit history, treatment may include bupropion while employing standard behavioral therapies: intra-treatment social support, extra-treatment social support, and problem solving skills training. After setting a quit date, prepare the patient for the quit, and following the quit attempt focus on relapse prevention. Frequent follow-up visits provide intra-treatment social support and promotes development of extra-treatment (eg, telephone or computer based quit lines or individuals) social support while providing practical problem solving.
1. Severson HH, Hatsukami D. Smokeless tobacco cessation. Prim Care 1999;26:529-551.
2. West R, McNeill A, Raw M. Smokeless tobacco cessation guidelines for health professionals in England. Br Dent J 2004;196:611-618.
3. Ebbert JO, Rowland LC, Montori V, et al. Interventions for smokeless tobacco use cessation. Cochrane Database Syst Rev 2005;1:130.-
4. Hatsukami D, Anton D, Keenan R, Callies A. Smokeless tobacco abstinence effects and nicotine gum dose. Psychopharmacology 1992;106:60-66.
5. Hatsukami D, Jensen J, Allen S, Grillo M, Bliss R. Effects on behavioral and pharmacological treatment on smokeless tobacco users. J Consult Clin Psychol 1996;64:153-161.
6. Hatsukami DK, Grillo M, Boyle R, et al. Treatment of spit tobacco users with transdermal nicotine system and mint snuff. J Consult Clin Psychol 2000;68:241-249.
7. Treating tobacco use and dependence: a clinical practice guideline. Rockville, Md: US Department of Health and Human Services, Public Health Service. Last updated 2000. Available at: guidelines.gov/summary/summary.aspx?doc_id=2360&nbr=158 6&string=tobacco. Accessed on March 4, 2005.
Nicotine replacement therapy (NRT), including gum and patches, decreases cravings and short-term abstinence rates, but does not improve long-term abstinence (strength of recommendation [SOR]: B, meta-analysis of small randomized controlled studies [RCT]).
It is unclear if bupropion has an effect on cessation rates (SOR: B, small RCTs with conflicting results). Behavioral interventions increase abstinence rates for smokeless tobacco users (SOR: B, meta-analysis of small RCTs).
Evidence summary
Use of smokeless tobacco can lead to nicotine dependence and cause periodontal disease, leukoplakia, cancer, and possibly cardiovascular disease.1-3 Patients who abruptly stop using smokeless tobacco may experience withdrawal symptoms similar to that observed in smokers.3
Nicotine gum
A small double-blind study randomized 79 male smokeless tobacco users to chew nicotine gum (0 mg, 2 mg, or 4 mg) for 5 days.4 Sixty patients completed the study. No significant differences in withdrawal symptoms, including cravings, concentration, or restlessness, were noted among the 3 groups (P>.05). However, further analysis demonstrated that patients with high blood levels of cotinine who received nicotine gum 2 mg experienced decreased cravings compared with placebo (P<.001), and a trend towards decreased cravings with 4 mg gum was noted (P<.06). Limitations of this study: quit rates were not reported, participants did not have to be motivated to quit smokeless tobacco in order to enroll, and it is not known if patients were counseled about the appropriate “chew and park” technique for nicotine gum.
Another study randomized 234 male smokeless tobacco users to receive group behavioral treatment plus nicotine gum 2 mg (B/NRT); group behavioral treatment plus placebo (B/Pl); minimal contact plus nicotine gum 2 mg (MC/NRT); or minimal contact plus placebo (MC/Pl).5
Group behavioral treatment consisted of 8 group counseling sessions 45 to 60 minutes in length; minimal contact involved 4 brief one-on-one sessions with a nurse. Patients chewed a minimum of 6 pieces of nicotine or placebo gum per day.
At 4 weeks, point prevalence abstinence rates were as follows: B/NRT, 63.6%; B/Pl, 66%; MC/NRT, 35.3%; and MC/Pl, 48.1% (P<.01). Abstinence rates remained significantly different at 1 and 6 month follow-ups, but not at 12 months. Post-hoc logistic regression favored group behavioral therapy plus NRT at 6 months. Moreover, survival analysis of continuous prevalence rates demonstrated that the least effective treatment was minimal contact plus NRT.
The authors theorized that nicotine gum may actually worsen risk of relapse in smokeless tobacco users due to behavioral similarities associated with use, but that behavioral treatment may help regain abstinence after a lapse. Gum users experienced lessened withdrawal symptoms including cravings, irritability, anxiety, and difficulty concentrating (P<.01). Results indicate that behavioral interventions may be more effective than NRT; however, low doses of nicotine gum were used.
Nicotine transdermal patches
A randomized double-blind study examined nicotine transdermal patches in smokeless tobacco users.6 Researchers recruited 422 participants from a Minnesota college campus and surrounding metropolitan area through advertisements; they were randomly assigned to nicotine patch plus mint snuff (a nicotine-free product), nicotine patch and no mint snuff, placebo patch plus mint snuff, or placebo patch and no mint snuff. The patch was dosed as 21-mg patch for 6 weeks, 14-mg patch for 2 weeks, and 7-mg patch for 2 weeks. All patients participated in 8 weekly individual 10-minute sessions with a therapist.
Continuous 10-week abstinence rates were 69% for nicotine patch and mint snuff, 58% for nicotine patch and no mint snuff, 46% for placebo patch and mint snuff, and 51% for placebo patch and no mint snuff (P=.002). After 15 weeks the abstinence rates were no longer different between the treatment groups. Patch users experienced lower total withdrawal scores (P=.002) as well as decreased craving (P<.001), irritability (P<.001), and restlessness (P=.019). Total withdrawal scores were not improved for mint snuff users; however, subsets of total withdrawal scores were lower for cravings (P=.005), irritability (P=.046), and anxiety (P=.012).
Meta-analysis
The Cochrane Database of Systematic Reviews published a meta-analysis of 6 studies that examined NRT or bupropion in smokeless tobacco users.3 The primary outcome for the meta-analysis was tobacco abstinence 6 months or more after the intervention. Neither nicotine patches (odds ratio [OR]=1.16; 95% confidence interval [CI], 0.88–1.54) nor nicotine gum (OR=0.98; 95% CI, 0.59–1.63) were shown to improve abstinence over placebo at 6 months. The authors highlight the need for larger studies that compare different NRT products, doses, and duration.
One small randomized trial of bupropion was included, but it found no effect on tobacco abstention (OR=1.00; 95% CI, 0.23–4.37). Another small RCT found an effect; however, it was excluded from the meta-analysis because subjects were followed for only 3 months. The meta-analysis also concluded that behavioral interventions appear to be effective for increasing tobacco abstinence rates. Results were heterogeneous, and study quality was mixed. One post-hoc finding appeared to show that most effective behavioral interventions were coupled with an oral exam with direct feedback.
Recommendations from others
The United States Department of Health and Human Services recommends that smokeless tobacco users should be treated with the same counseling and interventions utilized for smokers, but commented that evidence is currently insufficient to suggest that NRT increases long-term abstinence.7 British guidelines concluded that no evidence clearly shows that nicotine gum or patches are effective cessation aids for smokeless tobacco users.2
NRT not recommended for smokeless users; try bupropion, behavioral therapy
Patrick O. Smith, PhD
Professor, Family Medicine, University of Mississippi Medical Center
Smokeless tobacco users are a special tobacco user population with a limited research base. Although it seems counterintuitive, nicotine replacement therapy (nicotine gum and the nicotine patch) is not recommended for this population. Using the tobacco use and quit history, treatment may include bupropion while employing standard behavioral therapies: intra-treatment social support, extra-treatment social support, and problem solving skills training. After setting a quit date, prepare the patient for the quit, and following the quit attempt focus on relapse prevention. Frequent follow-up visits provide intra-treatment social support and promotes development of extra-treatment (eg, telephone or computer based quit lines or individuals) social support while providing practical problem solving.
Nicotine replacement therapy (NRT), including gum and patches, decreases cravings and short-term abstinence rates, but does not improve long-term abstinence (strength of recommendation [SOR]: B, meta-analysis of small randomized controlled studies [RCT]).
It is unclear if bupropion has an effect on cessation rates (SOR: B, small RCTs with conflicting results). Behavioral interventions increase abstinence rates for smokeless tobacco users (SOR: B, meta-analysis of small RCTs).
Evidence summary
Use of smokeless tobacco can lead to nicotine dependence and cause periodontal disease, leukoplakia, cancer, and possibly cardiovascular disease.1-3 Patients who abruptly stop using smokeless tobacco may experience withdrawal symptoms similar to that observed in smokers.3
Nicotine gum
A small double-blind study randomized 79 male smokeless tobacco users to chew nicotine gum (0 mg, 2 mg, or 4 mg) for 5 days.4 Sixty patients completed the study. No significant differences in withdrawal symptoms, including cravings, concentration, or restlessness, were noted among the 3 groups (P>.05). However, further analysis demonstrated that patients with high blood levels of cotinine who received nicotine gum 2 mg experienced decreased cravings compared with placebo (P<.001), and a trend towards decreased cravings with 4 mg gum was noted (P<.06). Limitations of this study: quit rates were not reported, participants did not have to be motivated to quit smokeless tobacco in order to enroll, and it is not known if patients were counseled about the appropriate “chew and park” technique for nicotine gum.
Another study randomized 234 male smokeless tobacco users to receive group behavioral treatment plus nicotine gum 2 mg (B/NRT); group behavioral treatment plus placebo (B/Pl); minimal contact plus nicotine gum 2 mg (MC/NRT); or minimal contact plus placebo (MC/Pl).5
Group behavioral treatment consisted of 8 group counseling sessions 45 to 60 minutes in length; minimal contact involved 4 brief one-on-one sessions with a nurse. Patients chewed a minimum of 6 pieces of nicotine or placebo gum per day.
At 4 weeks, point prevalence abstinence rates were as follows: B/NRT, 63.6%; B/Pl, 66%; MC/NRT, 35.3%; and MC/Pl, 48.1% (P<.01). Abstinence rates remained significantly different at 1 and 6 month follow-ups, but not at 12 months. Post-hoc logistic regression favored group behavioral therapy plus NRT at 6 months. Moreover, survival analysis of continuous prevalence rates demonstrated that the least effective treatment was minimal contact plus NRT.
The authors theorized that nicotine gum may actually worsen risk of relapse in smokeless tobacco users due to behavioral similarities associated with use, but that behavioral treatment may help regain abstinence after a lapse. Gum users experienced lessened withdrawal symptoms including cravings, irritability, anxiety, and difficulty concentrating (P<.01). Results indicate that behavioral interventions may be more effective than NRT; however, low doses of nicotine gum were used.
Nicotine transdermal patches
A randomized double-blind study examined nicotine transdermal patches in smokeless tobacco users.6 Researchers recruited 422 participants from a Minnesota college campus and surrounding metropolitan area through advertisements; they were randomly assigned to nicotine patch plus mint snuff (a nicotine-free product), nicotine patch and no mint snuff, placebo patch plus mint snuff, or placebo patch and no mint snuff. The patch was dosed as 21-mg patch for 6 weeks, 14-mg patch for 2 weeks, and 7-mg patch for 2 weeks. All patients participated in 8 weekly individual 10-minute sessions with a therapist.
Continuous 10-week abstinence rates were 69% for nicotine patch and mint snuff, 58% for nicotine patch and no mint snuff, 46% for placebo patch and mint snuff, and 51% for placebo patch and no mint snuff (P=.002). After 15 weeks the abstinence rates were no longer different between the treatment groups. Patch users experienced lower total withdrawal scores (P=.002) as well as decreased craving (P<.001), irritability (P<.001), and restlessness (P=.019). Total withdrawal scores were not improved for mint snuff users; however, subsets of total withdrawal scores were lower for cravings (P=.005), irritability (P=.046), and anxiety (P=.012).
Meta-analysis
The Cochrane Database of Systematic Reviews published a meta-analysis of 6 studies that examined NRT or bupropion in smokeless tobacco users.3 The primary outcome for the meta-analysis was tobacco abstinence 6 months or more after the intervention. Neither nicotine patches (odds ratio [OR]=1.16; 95% confidence interval [CI], 0.88–1.54) nor nicotine gum (OR=0.98; 95% CI, 0.59–1.63) were shown to improve abstinence over placebo at 6 months. The authors highlight the need for larger studies that compare different NRT products, doses, and duration.
One small randomized trial of bupropion was included, but it found no effect on tobacco abstention (OR=1.00; 95% CI, 0.23–4.37). Another small RCT found an effect; however, it was excluded from the meta-analysis because subjects were followed for only 3 months. The meta-analysis also concluded that behavioral interventions appear to be effective for increasing tobacco abstinence rates. Results were heterogeneous, and study quality was mixed. One post-hoc finding appeared to show that most effective behavioral interventions were coupled with an oral exam with direct feedback.
Recommendations from others
The United States Department of Health and Human Services recommends that smokeless tobacco users should be treated with the same counseling and interventions utilized for smokers, but commented that evidence is currently insufficient to suggest that NRT increases long-term abstinence.7 British guidelines concluded that no evidence clearly shows that nicotine gum or patches are effective cessation aids for smokeless tobacco users.2
NRT not recommended for smokeless users; try bupropion, behavioral therapy
Patrick O. Smith, PhD
Professor, Family Medicine, University of Mississippi Medical Center
Smokeless tobacco users are a special tobacco user population with a limited research base. Although it seems counterintuitive, nicotine replacement therapy (nicotine gum and the nicotine patch) is not recommended for this population. Using the tobacco use and quit history, treatment may include bupropion while employing standard behavioral therapies: intra-treatment social support, extra-treatment social support, and problem solving skills training. After setting a quit date, prepare the patient for the quit, and following the quit attempt focus on relapse prevention. Frequent follow-up visits provide intra-treatment social support and promotes development of extra-treatment (eg, telephone or computer based quit lines or individuals) social support while providing practical problem solving.
1. Severson HH, Hatsukami D. Smokeless tobacco cessation. Prim Care 1999;26:529-551.
2. West R, McNeill A, Raw M. Smokeless tobacco cessation guidelines for health professionals in England. Br Dent J 2004;196:611-618.
3. Ebbert JO, Rowland LC, Montori V, et al. Interventions for smokeless tobacco use cessation. Cochrane Database Syst Rev 2005;1:130.-
4. Hatsukami D, Anton D, Keenan R, Callies A. Smokeless tobacco abstinence effects and nicotine gum dose. Psychopharmacology 1992;106:60-66.
5. Hatsukami D, Jensen J, Allen S, Grillo M, Bliss R. Effects on behavioral and pharmacological treatment on smokeless tobacco users. J Consult Clin Psychol 1996;64:153-161.
6. Hatsukami DK, Grillo M, Boyle R, et al. Treatment of spit tobacco users with transdermal nicotine system and mint snuff. J Consult Clin Psychol 2000;68:241-249.
7. Treating tobacco use and dependence: a clinical practice guideline. Rockville, Md: US Department of Health and Human Services, Public Health Service. Last updated 2000. Available at: guidelines.gov/summary/summary.aspx?doc_id=2360&nbr=158 6&string=tobacco. Accessed on March 4, 2005.
1. Severson HH, Hatsukami D. Smokeless tobacco cessation. Prim Care 1999;26:529-551.
2. West R, McNeill A, Raw M. Smokeless tobacco cessation guidelines for health professionals in England. Br Dent J 2004;196:611-618.
3. Ebbert JO, Rowland LC, Montori V, et al. Interventions for smokeless tobacco use cessation. Cochrane Database Syst Rev 2005;1:130.-
4. Hatsukami D, Anton D, Keenan R, Callies A. Smokeless tobacco abstinence effects and nicotine gum dose. Psychopharmacology 1992;106:60-66.
5. Hatsukami D, Jensen J, Allen S, Grillo M, Bliss R. Effects on behavioral and pharmacological treatment on smokeless tobacco users. J Consult Clin Psychol 1996;64:153-161.
6. Hatsukami DK, Grillo M, Boyle R, et al. Treatment of spit tobacco users with transdermal nicotine system and mint snuff. J Consult Clin Psychol 2000;68:241-249.
7. Treating tobacco use and dependence: a clinical practice guideline. Rockville, Md: US Department of Health and Human Services, Public Health Service. Last updated 2000. Available at: guidelines.gov/summary/summary.aspx?doc_id=2360&nbr=158 6&string=tobacco. Accessed on March 4, 2005.
Evidence-based answers from the Family Physicians Inquiries Network
What is the best hypnotic for use in the elderly?
Short-acting hypnotics such as zolpidem (Ambien) or zaleplon (Sonata) are the preferred hypnotics in the elderly because of an improved side-effect profile compared with traditional hypnotics such as benzodiazepines (strength of recommendation: B, based on extrapolations of randomized controlled trials). Zolpidem and zaleplon have a quick onset and short duration of action, making them less likely to cause residual sedation, cognitive changes, and falls than benzodiazepines. More comparative clinical trials in the elderly are needed to determine if zolpidem and zaleplon are truly safer than benzodiazepines in this population. Hypnotics should be prescribed on a short-term, intermittent basis as part of a comprehensive treatment plan that addresses any underlying causes of poor sleep.
Evidence summary
Zolpidem and zaleplon
Zolpidem and zaleplon differ structurally from benzodiazepines but act at the benzodiazepine receptor.1 Due to their rapid absorption and short half-lives, they are particularly helpful for patients who have trouble falling asleep.2 They have been shown to decrease sleep latency, increase total sleep time, and increase sleep efficiency without disturbing sleep architecture or adversely affecting memory.1
Comparative studies in the elderly have demonstrated that zolpidem is as effective as triazolam,3 and that zaleplon is more effective than placebo at decreasing sleep latency and improving sleep quality.4 Tolerance, withdrawal symptoms, or rebound insomnia occur less frequently than with benzodi-azepines,1 but zolpidem increased risk of hip fracture in a case control study (adjusted odds ratio=1.95, 95% confidence interval, 1.09–3.51).5
Side effects of zolpidem and zaleplon are considered dose-related, and a lower dose of 5 mg is recommended for older patients.2 Efficacy of intermittent use of zolpidem has been demonstrated in clinical studies,1 a practice that could potentially decrease risk of side effects. Overall, if a hypnotic is desired for an older adult, zolpidem and zaleplon are preferred because of their improved side-effect profiles compared with older hypnotics such as benzodiazepines, chloral hydrate, over-the-counter sleep aids, and antidepressants (see Table ).
TABLE 1
Adverse effects of hypnotics in the elderly
| Hypnotic | Adverse effect |
|---|---|
| Benzodiazepines | Somnolence, anterograde amnesia, falls, hip fracture, rebound insomnia, tolerance, dependence, impaired sleep architecture2,3,5 |
| Antihistamines | Somnolence, dry mouth, constipation, urinary retention, blurred vision, cognitive changes3 |
| Valerian | Headache, excitability, uneasiness, cardiac disturbances, insomnia, drowsiness, withdrawal symptoms10 |
| Melatonin | Headache, depressive symptoms, daytime fatigue and drowsiness, dizziness, abdominal cramps, reduced alertness10 |
| Chloral hydrate | Nausea, vomiting, diarrhea, may increase effects of warfarin, overdose potential3,8 |
| Tricyclic antidepressants | Dry mouth, constipation, urinary retention, blurred vision, cognitive changes, orthostatic hypotension, somnolence, worsening of chronic heart failure, overdose potential, cardiac conduction abnormalities2,3 |
| Trazodone | Somnolence, orthostatic hypotension, dry mouth, priapism3 |
| Zolpidem | Drowsiness, headache, dizziness, somnolence, fatigue, agitation, nightmares, diarrhea, myalgia, arthralgia, anterograde amnesia1,10 |
| Zaleplon | Headache, dizziness, somnolence, short-term amnesic effects, next-day memory impairment, mild rebound insomnia1,10 |
Benzodiazepines
Benzodiazepines have been used since the 1960s for their hypnotic, anxiolytic, anticonvulsant, muscle-relaxing, and amnesic properties. A recent meta-analysis showed that benzodiazepines improve sleep latency by only 4.2 minutes compared with placebo.6 Although benzodiazepines increase sleep time and efficiency, patients quickly develop tolerance to the hypnotic effects.7 Additional problems associated with benzodiazepines include dependence, rebound insomnia, residual sedation, falls, hip fractures, and detrimental effects on sleep architecture.7
Chloral hydrate
Chloral hydrate has a narrow therapeutic index and is not recommended for the treatment of insomnia.8 Tolerance to its effects develops after only 2 weeks of use, and drug interactions with warfarin can occur.2
Over-the-counter sleep aids
Most over-the-counter sleep aids contain diphen-hydramine, a long-acting antihistamine that is considered less effective than benzodiazepines. The anticholinergic properties of antihistamines can result in cognitive changes and urinary retention in the elderly.8 Melatonin and valerian are “natural” hypnotics that are available without a prescription,9 but their safety and efficacy are not regulated by the FDA.8
Antidepressants
Antidepressants with sedative effects, such as tricyclic antidepressants and trazodone, have been used for insomnia, but minimal data support the efficacy or safety of this approach.8 Tricyclic antidepressants may exacerbate restless legs syndrome and periodic limb movement disorder,8 cause anticholinergic side effects, worsen chronic heart failure, and cause ortho-static hypotension and falls.2 Although tra-zodone is not a tricyclic antidepressant, it can cause dry mouth, orthostatic hypotension, and (rarely) priapism.2
Recommendations from others
A Canadian consensus statement published in 2003 supports the use of non-benzodiazepines such as zolpidem and zaleplon due to improved tolerability, and less withdrawal and abuse potential compared with benzodiazepines.7 The National Heart, Lung and Blood Institute Working Group on Insomnia recommends the use of short-acting hypnotics for short-term management of insomnia, but does not differentiate between short-acting benzodiazepines and the newer hypnotics such as zolpidem and zale-plon.8 Geriatric experts recommend that long-acting benzodiazepines, barbiturates, and amitriptyline be avoided in the elderly due to the risk of adverse drug events.10
Question the patient about sleep habits
David Cravens, MD, MSPH
Department of Family & Community Medicine, University of Missouri–Columbia
Sleep complaints are common in the elderly. However, before prescribing a hypnotic, determine the elderly patient’s sleep habits: often daytime naps plus nighttime sleep add up to adequate sleep. Encourage measures to avoid daytime naps if nighttime sleep is more important. Second, discuss sleep hygiene, such as avoiding evening caffeine or excessive alcohol, and avoiding using bed for activities other than sleeping, such as watching TV, reading, and the like. Determine whether sleep problems are part of a larger problem requiring evaluation, such as medication effects, depression, or obstructive sleep apnea. Finally, consider costs: although not a true hypnotic, trazodone at doses of 25–50 mg is a very effective and well-tolerated soporific at about one-tenth the cost of 5 mg of zolpidem or zaleplon.
1. Terzano MG, Rossi M, Palomba V, Smerien A, Parrino L. New drugs for insomnia: comparative tolerability of zopiclone, zolpi-dem and zaleplon. Drug Saf 2003;26:261-282.
2. McEvoy GK, Miller J, Litvak K, et al. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists; 2003;2400-2405.
3. Roger M, Attali P, Coquelin JP. Multicenter, double-blind, controlled comparison of zolpidem and triazolam in elderly patients with insomnia. Clin Ther 1993;15:127-136.
4. Hedner J, Yaeche R, Emilien G, Farr I, Salinas E. Zaleplon shortens subjective sleep latency and improves subjective sleep quality in elderly patients with insomnia. The Zaleplon Clinical Investigator Study Group. Int J Geriatr Psychiatry 2000;15:704-712.
5. Wang PS, Bohn RL, Glynn RJ, Mogun H, Avom J. Zolpidem use and hip fractures in older people. J Am Geriatr Soc 2001;49:1685-1690.
6. Holbrook AM, Crowther R, Lotter A, Cheng C, King D. Meta-analysis of benzodiazepine use in the treatment of insomnia. CMAJ 2000;162:225-233.
7. Montplaisir J, Hawa R, Moller H, et al. Zopiclone and zaleplon vs benzodiazepines in the treatment of insomnia: Canadian consensus statement. Hum Psychopharmacol 2003;18:29-38.
8. Insomnia: assessment and management in primary care. National Heart, Lung, and Blood Institute Working Group on Insomnia. Am Fam Physician 1999;59:3029-3038.
9. Jellin JM, Gregory P, Batz F, et al. Pharmacist’s Letter/Prescriber’s Letter Natural Medicines Comprehensive Database. 3rd ed. Stockton, Calif: Therapeutic Research Faculty; 2000;723-7251052-1053.
10. Beers MH. Explicit criteria for determining potentially inappropriate medication use by the elderly. An update. Arch Intern Med 1997;157:1531-1536.
Short-acting hypnotics such as zolpidem (Ambien) or zaleplon (Sonata) are the preferred hypnotics in the elderly because of an improved side-effect profile compared with traditional hypnotics such as benzodiazepines (strength of recommendation: B, based on extrapolations of randomized controlled trials). Zolpidem and zaleplon have a quick onset and short duration of action, making them less likely to cause residual sedation, cognitive changes, and falls than benzodiazepines. More comparative clinical trials in the elderly are needed to determine if zolpidem and zaleplon are truly safer than benzodiazepines in this population. Hypnotics should be prescribed on a short-term, intermittent basis as part of a comprehensive treatment plan that addresses any underlying causes of poor sleep.
Evidence summary
Zolpidem and zaleplon
Zolpidem and zaleplon differ structurally from benzodiazepines but act at the benzodiazepine receptor.1 Due to their rapid absorption and short half-lives, they are particularly helpful for patients who have trouble falling asleep.2 They have been shown to decrease sleep latency, increase total sleep time, and increase sleep efficiency without disturbing sleep architecture or adversely affecting memory.1
Comparative studies in the elderly have demonstrated that zolpidem is as effective as triazolam,3 and that zaleplon is more effective than placebo at decreasing sleep latency and improving sleep quality.4 Tolerance, withdrawal symptoms, or rebound insomnia occur less frequently than with benzodi-azepines,1 but zolpidem increased risk of hip fracture in a case control study (adjusted odds ratio=1.95, 95% confidence interval, 1.09–3.51).5
Side effects of zolpidem and zaleplon are considered dose-related, and a lower dose of 5 mg is recommended for older patients.2 Efficacy of intermittent use of zolpidem has been demonstrated in clinical studies,1 a practice that could potentially decrease risk of side effects. Overall, if a hypnotic is desired for an older adult, zolpidem and zaleplon are preferred because of their improved side-effect profiles compared with older hypnotics such as benzodiazepines, chloral hydrate, over-the-counter sleep aids, and antidepressants (see Table ).
TABLE 1
Adverse effects of hypnotics in the elderly
| Hypnotic | Adverse effect |
|---|---|
| Benzodiazepines | Somnolence, anterograde amnesia, falls, hip fracture, rebound insomnia, tolerance, dependence, impaired sleep architecture2,3,5 |
| Antihistamines | Somnolence, dry mouth, constipation, urinary retention, blurred vision, cognitive changes3 |
| Valerian | Headache, excitability, uneasiness, cardiac disturbances, insomnia, drowsiness, withdrawal symptoms10 |
| Melatonin | Headache, depressive symptoms, daytime fatigue and drowsiness, dizziness, abdominal cramps, reduced alertness10 |
| Chloral hydrate | Nausea, vomiting, diarrhea, may increase effects of warfarin, overdose potential3,8 |
| Tricyclic antidepressants | Dry mouth, constipation, urinary retention, blurred vision, cognitive changes, orthostatic hypotension, somnolence, worsening of chronic heart failure, overdose potential, cardiac conduction abnormalities2,3 |
| Trazodone | Somnolence, orthostatic hypotension, dry mouth, priapism3 |
| Zolpidem | Drowsiness, headache, dizziness, somnolence, fatigue, agitation, nightmares, diarrhea, myalgia, arthralgia, anterograde amnesia1,10 |
| Zaleplon | Headache, dizziness, somnolence, short-term amnesic effects, next-day memory impairment, mild rebound insomnia1,10 |
Benzodiazepines
Benzodiazepines have been used since the 1960s for their hypnotic, anxiolytic, anticonvulsant, muscle-relaxing, and amnesic properties. A recent meta-analysis showed that benzodiazepines improve sleep latency by only 4.2 minutes compared with placebo.6 Although benzodiazepines increase sleep time and efficiency, patients quickly develop tolerance to the hypnotic effects.7 Additional problems associated with benzodiazepines include dependence, rebound insomnia, residual sedation, falls, hip fractures, and detrimental effects on sleep architecture.7
Chloral hydrate
Chloral hydrate has a narrow therapeutic index and is not recommended for the treatment of insomnia.8 Tolerance to its effects develops after only 2 weeks of use, and drug interactions with warfarin can occur.2
Over-the-counter sleep aids
Most over-the-counter sleep aids contain diphen-hydramine, a long-acting antihistamine that is considered less effective than benzodiazepines. The anticholinergic properties of antihistamines can result in cognitive changes and urinary retention in the elderly.8 Melatonin and valerian are “natural” hypnotics that are available without a prescription,9 but their safety and efficacy are not regulated by the FDA.8
Antidepressants
Antidepressants with sedative effects, such as tricyclic antidepressants and trazodone, have been used for insomnia, but minimal data support the efficacy or safety of this approach.8 Tricyclic antidepressants may exacerbate restless legs syndrome and periodic limb movement disorder,8 cause anticholinergic side effects, worsen chronic heart failure, and cause ortho-static hypotension and falls.2 Although tra-zodone is not a tricyclic antidepressant, it can cause dry mouth, orthostatic hypotension, and (rarely) priapism.2
Recommendations from others
A Canadian consensus statement published in 2003 supports the use of non-benzodiazepines such as zolpidem and zaleplon due to improved tolerability, and less withdrawal and abuse potential compared with benzodiazepines.7 The National Heart, Lung and Blood Institute Working Group on Insomnia recommends the use of short-acting hypnotics for short-term management of insomnia, but does not differentiate between short-acting benzodiazepines and the newer hypnotics such as zolpidem and zale-plon.8 Geriatric experts recommend that long-acting benzodiazepines, barbiturates, and amitriptyline be avoided in the elderly due to the risk of adverse drug events.10
Question the patient about sleep habits
David Cravens, MD, MSPH
Department of Family & Community Medicine, University of Missouri–Columbia
Sleep complaints are common in the elderly. However, before prescribing a hypnotic, determine the elderly patient’s sleep habits: often daytime naps plus nighttime sleep add up to adequate sleep. Encourage measures to avoid daytime naps if nighttime sleep is more important. Second, discuss sleep hygiene, such as avoiding evening caffeine or excessive alcohol, and avoiding using bed for activities other than sleeping, such as watching TV, reading, and the like. Determine whether sleep problems are part of a larger problem requiring evaluation, such as medication effects, depression, or obstructive sleep apnea. Finally, consider costs: although not a true hypnotic, trazodone at doses of 25–50 mg is a very effective and well-tolerated soporific at about one-tenth the cost of 5 mg of zolpidem or zaleplon.
Short-acting hypnotics such as zolpidem (Ambien) or zaleplon (Sonata) are the preferred hypnotics in the elderly because of an improved side-effect profile compared with traditional hypnotics such as benzodiazepines (strength of recommendation: B, based on extrapolations of randomized controlled trials). Zolpidem and zaleplon have a quick onset and short duration of action, making them less likely to cause residual sedation, cognitive changes, and falls than benzodiazepines. More comparative clinical trials in the elderly are needed to determine if zolpidem and zaleplon are truly safer than benzodiazepines in this population. Hypnotics should be prescribed on a short-term, intermittent basis as part of a comprehensive treatment plan that addresses any underlying causes of poor sleep.
Evidence summary
Zolpidem and zaleplon
Zolpidem and zaleplon differ structurally from benzodiazepines but act at the benzodiazepine receptor.1 Due to their rapid absorption and short half-lives, they are particularly helpful for patients who have trouble falling asleep.2 They have been shown to decrease sleep latency, increase total sleep time, and increase sleep efficiency without disturbing sleep architecture or adversely affecting memory.1
Comparative studies in the elderly have demonstrated that zolpidem is as effective as triazolam,3 and that zaleplon is more effective than placebo at decreasing sleep latency and improving sleep quality.4 Tolerance, withdrawal symptoms, or rebound insomnia occur less frequently than with benzodi-azepines,1 but zolpidem increased risk of hip fracture in a case control study (adjusted odds ratio=1.95, 95% confidence interval, 1.09–3.51).5
Side effects of zolpidem and zaleplon are considered dose-related, and a lower dose of 5 mg is recommended for older patients.2 Efficacy of intermittent use of zolpidem has been demonstrated in clinical studies,1 a practice that could potentially decrease risk of side effects. Overall, if a hypnotic is desired for an older adult, zolpidem and zaleplon are preferred because of their improved side-effect profiles compared with older hypnotics such as benzodiazepines, chloral hydrate, over-the-counter sleep aids, and antidepressants (see Table ).
TABLE 1
Adverse effects of hypnotics in the elderly
| Hypnotic | Adverse effect |
|---|---|
| Benzodiazepines | Somnolence, anterograde amnesia, falls, hip fracture, rebound insomnia, tolerance, dependence, impaired sleep architecture2,3,5 |
| Antihistamines | Somnolence, dry mouth, constipation, urinary retention, blurred vision, cognitive changes3 |
| Valerian | Headache, excitability, uneasiness, cardiac disturbances, insomnia, drowsiness, withdrawal symptoms10 |
| Melatonin | Headache, depressive symptoms, daytime fatigue and drowsiness, dizziness, abdominal cramps, reduced alertness10 |
| Chloral hydrate | Nausea, vomiting, diarrhea, may increase effects of warfarin, overdose potential3,8 |
| Tricyclic antidepressants | Dry mouth, constipation, urinary retention, blurred vision, cognitive changes, orthostatic hypotension, somnolence, worsening of chronic heart failure, overdose potential, cardiac conduction abnormalities2,3 |
| Trazodone | Somnolence, orthostatic hypotension, dry mouth, priapism3 |
| Zolpidem | Drowsiness, headache, dizziness, somnolence, fatigue, agitation, nightmares, diarrhea, myalgia, arthralgia, anterograde amnesia1,10 |
| Zaleplon | Headache, dizziness, somnolence, short-term amnesic effects, next-day memory impairment, mild rebound insomnia1,10 |
Benzodiazepines
Benzodiazepines have been used since the 1960s for their hypnotic, anxiolytic, anticonvulsant, muscle-relaxing, and amnesic properties. A recent meta-analysis showed that benzodiazepines improve sleep latency by only 4.2 minutes compared with placebo.6 Although benzodiazepines increase sleep time and efficiency, patients quickly develop tolerance to the hypnotic effects.7 Additional problems associated with benzodiazepines include dependence, rebound insomnia, residual sedation, falls, hip fractures, and detrimental effects on sleep architecture.7
Chloral hydrate
Chloral hydrate has a narrow therapeutic index and is not recommended for the treatment of insomnia.8 Tolerance to its effects develops after only 2 weeks of use, and drug interactions with warfarin can occur.2
Over-the-counter sleep aids
Most over-the-counter sleep aids contain diphen-hydramine, a long-acting antihistamine that is considered less effective than benzodiazepines. The anticholinergic properties of antihistamines can result in cognitive changes and urinary retention in the elderly.8 Melatonin and valerian are “natural” hypnotics that are available without a prescription,9 but their safety and efficacy are not regulated by the FDA.8
Antidepressants
Antidepressants with sedative effects, such as tricyclic antidepressants and trazodone, have been used for insomnia, but minimal data support the efficacy or safety of this approach.8 Tricyclic antidepressants may exacerbate restless legs syndrome and periodic limb movement disorder,8 cause anticholinergic side effects, worsen chronic heart failure, and cause ortho-static hypotension and falls.2 Although tra-zodone is not a tricyclic antidepressant, it can cause dry mouth, orthostatic hypotension, and (rarely) priapism.2
Recommendations from others
A Canadian consensus statement published in 2003 supports the use of non-benzodiazepines such as zolpidem and zaleplon due to improved tolerability, and less withdrawal and abuse potential compared with benzodiazepines.7 The National Heart, Lung and Blood Institute Working Group on Insomnia recommends the use of short-acting hypnotics for short-term management of insomnia, but does not differentiate between short-acting benzodiazepines and the newer hypnotics such as zolpidem and zale-plon.8 Geriatric experts recommend that long-acting benzodiazepines, barbiturates, and amitriptyline be avoided in the elderly due to the risk of adverse drug events.10
Question the patient about sleep habits
David Cravens, MD, MSPH
Department of Family & Community Medicine, University of Missouri–Columbia
Sleep complaints are common in the elderly. However, before prescribing a hypnotic, determine the elderly patient’s sleep habits: often daytime naps plus nighttime sleep add up to adequate sleep. Encourage measures to avoid daytime naps if nighttime sleep is more important. Second, discuss sleep hygiene, such as avoiding evening caffeine or excessive alcohol, and avoiding using bed for activities other than sleeping, such as watching TV, reading, and the like. Determine whether sleep problems are part of a larger problem requiring evaluation, such as medication effects, depression, or obstructive sleep apnea. Finally, consider costs: although not a true hypnotic, trazodone at doses of 25–50 mg is a very effective and well-tolerated soporific at about one-tenth the cost of 5 mg of zolpidem or zaleplon.
1. Terzano MG, Rossi M, Palomba V, Smerien A, Parrino L. New drugs for insomnia: comparative tolerability of zopiclone, zolpi-dem and zaleplon. Drug Saf 2003;26:261-282.
2. McEvoy GK, Miller J, Litvak K, et al. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists; 2003;2400-2405.
3. Roger M, Attali P, Coquelin JP. Multicenter, double-blind, controlled comparison of zolpidem and triazolam in elderly patients with insomnia. Clin Ther 1993;15:127-136.
4. Hedner J, Yaeche R, Emilien G, Farr I, Salinas E. Zaleplon shortens subjective sleep latency and improves subjective sleep quality in elderly patients with insomnia. The Zaleplon Clinical Investigator Study Group. Int J Geriatr Psychiatry 2000;15:704-712.
5. Wang PS, Bohn RL, Glynn RJ, Mogun H, Avom J. Zolpidem use and hip fractures in older people. J Am Geriatr Soc 2001;49:1685-1690.
6. Holbrook AM, Crowther R, Lotter A, Cheng C, King D. Meta-analysis of benzodiazepine use in the treatment of insomnia. CMAJ 2000;162:225-233.
7. Montplaisir J, Hawa R, Moller H, et al. Zopiclone and zaleplon vs benzodiazepines in the treatment of insomnia: Canadian consensus statement. Hum Psychopharmacol 2003;18:29-38.
8. Insomnia: assessment and management in primary care. National Heart, Lung, and Blood Institute Working Group on Insomnia. Am Fam Physician 1999;59:3029-3038.
9. Jellin JM, Gregory P, Batz F, et al. Pharmacist’s Letter/Prescriber’s Letter Natural Medicines Comprehensive Database. 3rd ed. Stockton, Calif: Therapeutic Research Faculty; 2000;723-7251052-1053.
10. Beers MH. Explicit criteria for determining potentially inappropriate medication use by the elderly. An update. Arch Intern Med 1997;157:1531-1536.
1. Terzano MG, Rossi M, Palomba V, Smerien A, Parrino L. New drugs for insomnia: comparative tolerability of zopiclone, zolpi-dem and zaleplon. Drug Saf 2003;26:261-282.
2. McEvoy GK, Miller J, Litvak K, et al. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists; 2003;2400-2405.
3. Roger M, Attali P, Coquelin JP. Multicenter, double-blind, controlled comparison of zolpidem and triazolam in elderly patients with insomnia. Clin Ther 1993;15:127-136.
4. Hedner J, Yaeche R, Emilien G, Farr I, Salinas E. Zaleplon shortens subjective sleep latency and improves subjective sleep quality in elderly patients with insomnia. The Zaleplon Clinical Investigator Study Group. Int J Geriatr Psychiatry 2000;15:704-712.
5. Wang PS, Bohn RL, Glynn RJ, Mogun H, Avom J. Zolpidem use and hip fractures in older people. J Am Geriatr Soc 2001;49:1685-1690.
6. Holbrook AM, Crowther R, Lotter A, Cheng C, King D. Meta-analysis of benzodiazepine use in the treatment of insomnia. CMAJ 2000;162:225-233.
7. Montplaisir J, Hawa R, Moller H, et al. Zopiclone and zaleplon vs benzodiazepines in the treatment of insomnia: Canadian consensus statement. Hum Psychopharmacol 2003;18:29-38.
8. Insomnia: assessment and management in primary care. National Heart, Lung, and Blood Institute Working Group on Insomnia. Am Fam Physician 1999;59:3029-3038.
9. Jellin JM, Gregory P, Batz F, et al. Pharmacist’s Letter/Prescriber’s Letter Natural Medicines Comprehensive Database. 3rd ed. Stockton, Calif: Therapeutic Research Faculty; 2000;723-7251052-1053.
10. Beers MH. Explicit criteria for determining potentially inappropriate medication use by the elderly. An update. Arch Intern Med 1997;157:1531-1536.
Evidence-based answers from the Family Physicians Inquiries Network