Newer Sedative and Hypnotic Agents

In recent years, a variety of alternatives to the benzodiazepines have become available to treat both anxiety and insomnia. Buspirone (Buspar) has been shown to reduce anxiety in generalized anxiety disorders, but it does not suppress panic attacks, and is not used as a primary treatment of obsessive-compulsive disorder. Buspirone is not abused by alcoholics and drug addicts, and it does not produce withdrawal symptoms on abrupt discontinuation. Like the antidepressants, buspirone requires several weeks of daily dosing to produce antianxiety effects, which are less dramatic from patients' point of view than are the effects produced by the benzodiazepines (Sussman & Stein, 2002).

The antidepressants as a class have been shown to possess antipanic and antianxiety effects opening a new range of uses for these medicines in the treatment of anxiety disorders. The selective serotonin reuptake inhibitors (SSRIs) have emerged as the first-line treatment for many anxiety disorders (Davidson, 2003; DuPont, 1997; Jefferson, 1997). Although the earlier antianxiety and anti-insomnia medicines focused exclusively on the benzodiazepine receptors in the GABA system, the recognition of the importance of serotonin and norepinephrine neurotransmitters in the management of anxiety and insomnia, and the success of buspirone, have stimulated a search for a new generation of antianxiety medicines that are not controlled substances (e.g., they are not abused by alcoholics and drug addicts). Recognition of the withdrawal symptoms associated with abrupt discontinuation of some antidepressants (especially those with shorter half-lives and more anticholinergic properties) have shown that withdrawal is not limited to controlled stubstances (DuPont, 1997).

Two nonbenzodiazepine hypnotic agents have been introduced. Zolpidem (Ambien) and Zaleplon (Sonata) are rapid-onset, short duration of action medicines that act on the benzodiazepine receptors of the GABA system. They have been shown to reduce insomnia. They have largely replaced the benzo-diazepines as hypnotic medicines, although they lack the anxiolytic, anti-convulsant, and muscle-relaxant properties of the benzodiazepines (Scharf, Mayleben, Kaffeman, Krall, & Ochs, 1991). Zolpidem and zaleplon are reinforcing to alcoholics and drug addicts, underscoring the fact that the abuse potential of both drugs appears to be similar to that of benzodiazepines. Both medicines impair memory and performance of complex tasks in ways that are similar to the acute effects of benzodiazepines. They do not affect stage 4 sleep, as do the benzodiazepines.

Both zaleplon and Zolpidem are effective in relieving sleep-onset insomnia, and both have been approved by the FDA for use up to 7-10 days at a time. Both medicines clinically appear to have sustained hypnotic activity over longer periods of time. Zolpidem has a half-life of about 2 hours, which is consistent with therapeutic activity over a typical 8 hours of sleep. Zaleplon has a 1hour half-life that offers the possibility of dosing in the middle of the night for broken sleep. For this reason zaleplon is approved for use both at bedtime and in midsleep periods of insomnia.

In recent years, the antiepilepsy medicines, including valproate (Depakote) and gabapentin (Neurontin), have been used as augmenting agents in the treatment of anxiety (Lydiard, 2002).

REFERENCES

Allgulander, C., Borg, S., & Vikander, B. (1984). A 4-6 year follow-up of 50 patients with primary dependence on sedative and hypnotic drugs. Am J Psychiatry, 141, 1580-1582.

American Psychiatric Association. (2000). Diagnostic and statistical manual of mental disorders (4th text rev. ed.). Washington, DC: Author.

Baldessarini, R. J. (2001). Depression and anxiety disorders. In J. G. Hardman & L. E. Limbird, (Eds.), Goodman and Gilman's, the pharmacological basis of therapeutics (10th ed., pp. 447-483). New York: McGraw-Hill.

Burt, D. R., & Kamatchi, G. L. (1991). GABA receptor subtypes: From pharmacology to molecular biology. FASEB, 5, 2916-2923.

Busto, U., Simpkins, J., & Sellers, E. M. (1983). Objective determination of benzodiazepine use and abuse in alcoholics. Br J Addict, 48, 429-435.

Charney, D. S., Minic, S. J., & Harris, R. A. (2001). Hypnotics and sedatives. In J. G. Hardman & L. E. Limbird, (Eds.), Goodman and Gilman's, the pharmacological basis of therapeutics (10th ed., pp. 399-427). New York: McGraw-Hill.

Chouninard, G., Lefko-Singh, K., & Teboul, E. (1999). Metabolism of anxiolytics and hypnotics: Benzodiazepines, buspirone, zopliclone, and Zolpidem. Cell Mol Neuro-biol, 19, 533-552.

Ciraulo, D. A., Sarid-Segal, O., Knapp, C., Ciraulo, A. M., Greenblatt, D. J., & Shader, R. I. (1996). Liability to alprazolam abuse in daughters of alcoholics. Am J Psychiatry, 153, 956-958.

Davidson, J. (2003). The anxiety book. New York: Penguin/Putnam.

Davidson, J. R. T. (1997). Use of benzodiazepines in panic disorder. J Clin Psychiatry, 58(Suppl. 2), 26-31.

DuPont, R. L. (1984). Getting tough on gateway drugs: A guide for the family. Washington, DC: American Psychiatric Press.

DuPont, R. L. (1986). Benzodiazepines: The social issues. Rockville, MD: Institute for Behavior and Health.

DuPont, R. L. (Ed.). (1988). Abuse of benzodiazepines: The problems and the solutions. Am J Drug Alcohol Abuse, 14(Suppl 1), 1-69.

DuPont, R. L. (1995). Anxiety and addiction: A clinical perspective on comorbidity. Bull Menninger Clin, 59(Suppl A), A53-A72.

DuPont, R. L. (1997). The pharmacology and drug interactions of the newer antidepressants. Essential Psychopharmacology, 2, 7-31.

DuPont, R. L. (1998). Addiction: A new paradigm. Bull Menninger Clin, 62, 231-242.

DuPont, R. L. (2000). The selfish brain: Learning from addiction (rev. ed.). Center City, MN: Hazelden.

DuPont, R. L., DuPont, C. M., & Rice, D. P. (2002). Economic costs of anxiety disorders. In D. J. Stein & E. Hollander (Eds.), Textbook of anxiety disorders (pp. 365374). Washington, DC: American Psychiatric Press

DuPont R. L., & Gold, M. S. (1995). Withdrawal and reward: implications for detoxification and relapse prevention. Psychiatr Ann, 25, 663-668.

DuPont, R. L., Spencer, E. D., & DuPont, C. M. (2004). The anxiety cure: An eight step program for getting well (rev. ed.). New York: Wiley.

DuPont, R. L., Swinson, R. P., Ballenger, J. C., Burrows, G. D., Noyes, R., Rubin, R. T., Rifkin, A., & Pecknold, J. C. (1992). Discontinuation effects of alprazolam after long-term treatment of panic-related disorders. J Clin Psychopharmacol, 12, 352354.

Golombok, S., Moodley, P., & Lader, M. (1988). Cognitive impairment in long-term benzodiazepine users. Psychol Med, 18, 365-374.

Griffiths, R. R., & Sannerud, C. A. (1987). Abuse of and dependence on benzodiazepines and other anxiolytic/sedative drugs. In H. Meltzer, B. S. Bunney, & J. T. Coyle (Eds.), Psychopharmacology: The third generation of progress (pp. 1535-1541). New York: Raven Press.

Griffiths, R. R., & Weerts, E. M. (1994). Benzodiazepine self-administration in humans and laboratory animals: Implications for problems of long-term use and abuse. Psy-chopharmacology, 134, 1-37.

Handelsman, L. (2002). Anxiety in the context of substance abuse. In D. J. Stein & E. Hollander (Eds.), Textbook of anxiety disorders (pp. 441-448). Washington, DC: American Psychiatric Press.

Hemmelgarn, B., Suissa, S., Huang, A., Boivin, J.-F., & Pinard, G. (1997). Benzodiazepine use and the risk of motor vehicle crash in the elderly. JAMA, 278, 27-31.

Jefferson, J. W. (1997). Antidepressants in panic disorder. J Clin Psychiatry, 58(Suppl 2), 20-25.

Juergens, S. M., & Cowley, D.S. (2003). The pharmacology of benzodiazepines and other sedative-hypnotics. In A. W. Graham, T. K. Schultz, M. F. Mayo Smith, & R. K. Ries (Eds.), Principles of addiction medicine (3rd ed., pp. 119-139). Chevy Chase, MD: American Society of Addiction Medicine.

Kessler, R. C., McGonagle, K. A., Zhao, S., Nelson, C. B., Hughes, M., Eshleman, S., et al. (1994). Lifetime and 12-month prevalence of DSM-III-R psychiatric disorders in the United States: Results from the National Comorbidity Survey. Arch Gen Psychiatry, 51, 8-19.

Lydiard, R. B. (2002). Pharmacotherapy for panic disorder. In D. J. Stein & E. Hollander (Eds.), Textbook of anxiety disorders (pp. 257-273). Washington, DC: American Psychiatric Press.

MacDonald, D. I., DuPont, R. L., & Ferguson, J. L. (2003). The role of the medical review officer. In A. W. Graham, T. K. Schultz, M. F. Mayo Smith, & R. K. Ries

(Eds.), Principles of addiction medicine (3rd ed., pp. 977-985). Chevy Chase, MD: American Society of Addiction Medicine.

Medical Economics Data Production. (2003). Physicians' desk reference. Montvale, NJ:

Author.

Mellinger, G. D., & Balter, M. B. (1981). Prevalence and patterns of use of psychotherapeutic drugs: Results from a 1979 national survey of American adults. In G. Tognoni, C. Bellantuono, & M. Lader (Eds.), Epidemiological impact of psycho-tropic drugs (pp. 117-135). Amsterdam: Elsevier.

Mendelson, W. B., Roth, T., Casella, J., Roehrs, T., Walsh, J., Woods, J. H., et al. (2001). Report on a conference: The treatment of chronic insomnia: Drug indication, chronic use and abuse liability. Paper presented at the NCDEU meeting, Phoenix, AZ.

Noyes, R., Garvey, M. J., Cook, B. L., & Perry, P. J. (1988). Benzodiazepine withdrawal: A review of the evidence. J Clin Psychiatry, 49, 382-389.

Rickels, K., Schweizer, E., Csanalosi, I., Case, G. W., & Chung, H. (1988). Long-term treatment of anxiety and risk of withdrawal. Arch Gen Psychiatry, 45, 444-450.

Ross, J. (1994). Triumph over fear: A book of help and hope for people with anxiety, panic attacks, and phobias. New York: Bantam.

Sattar, S. P., & Bhatia, S. (2003). Benzodiazepines for substance abusers. Curr Psychiatry, l2(5), 25-34.

Savage, S. R. (2003). Principles of pain management in the addicted patient. In A. W. Graham, T. K. Schultz, M. F. Mayo Smith, & R. K. Ries (Eds.), Principles of addiction medicine (3rd ed., pp. 1405-1419). Chevy Chase, MD: American Society of Addiction Medicine.

Scharf, M. B., Mayleben, D. W., Kaffeman, M., Krall, R., & Ochs, R. (1991). Dose response effects of zolpidem in normal geriatric subjects. J Clin Psychiatry, 52, 7783.

Schenck, C. H., & Mahowald, M. W. (1996). Long-term, nightly benzodiazepine treatment of injurious parasomnias and other disorders of disrupted nocturnal sleep in 170 adults. Am J Med, 100, 333-337.

Sellers, E. M., Ciraulo, D. A., DuPont, R. L., Griffiths, R. R., Kosten, T. R., Romach, M. K., & Woody, G. E. (1993). Alprazolam and benzodiazepine dependence. J Clin Psychiatry, 54(Suppl), 64-74.

Spencer, E. D., DuPont, R. L., & DuPont, C. M. (2004). The anxiety cure for kids: A guide for parents. New York: Wiley.

Stahl, S. M. (2003). At long last, long-lasting psychiatric medications: An overview of controlled-released technologies. J Clin Psychiatry, 64, 4.

Sussman, N., & Stein, D. J. (2002). Pharmacotherapy for generalized anxiety disorder. In D. J. Stein & E. Hollander (Eds.), Textbook of anxiety disorders (pp. 135-141). Washington, DC: American Psychiatric Press.

Tyrer, P., Rutherford, D., & Huggett, D. (1981). Benzodiazepine withdrawal symptoms and propranolol. Lancet, 1, 520-522.

U.S. Department of Health and Human Services. (2001, March). Monitoring the Future—overview of key findings (NIH Publication No. 02-5105). Rockville, MD: National Institutes of Health, National Institute on Drug Abuse.

U.S. Department of Health and Human Services. (2002). Results from the 2001 National Household Survey on Drug Abuse (DHHS Publication No. SMA 02-3758). Rock-

ville, MD: Substance Abuse and Mental Health Services Administration, Office of Applied Studies.

Wang, P. S., Bohn, R. L., Glynn, R. J., Mogun, H., & Avom, J. (2001). Hazardous benzodiazepine regimes in the elderly: Effects of half-life, dosage, and duration on risk of hip fracture. Am J Psychiatry, 158, 892-898. Wesson, D. R., Smith, D. E., & Ling, W. (2003). Pharmacologic interventions for benzodiazepine and other sedative-hypnotic addiction. In A. W. Graham, T. K. Schultz, M. F. Mayo Smith, & R. K. Ries (Eds.), Principles of addiction medicine (3rd ed., pp. 721-735). Chevy Chase, MD: American Society of Addiction Medicine. World Health Organization. (1988). The use of essential drugs: Third report of the World Health Organization expert committee (WHO Technical Report Series No. 770). Geneva: Author.

Dealing With Drugs

Dealing With Drugs

Get All The Support And Guidance You Need To Be A Success At Dealing With Drugs. This Book Is One Of The Most Valuable Resources In The World When It Comes To A Parents Guide To The Drug Talk.

Get My Free Ebook


Post a comment