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Withdrawal Reaction From Long-term, Low-dosage Administration of Diazepam: A Double-blind, Placebo-Controlled Case Study

Withdrawal Reaction From Long-term, Low-dosage Administration of Diazepam: A Double-blind,... Abstract • Symptoms of diazepam withdrawal developed in a young man who had been taking diazepam in dosages of 15 to 25 mg/day during a six-year period. This was verified in a study conducted under placebo-controlled, double-blind conditions, with plasma levels of diazepam and its major metabolite, desmethyldiazepam, monitored throughout the course of the study. Severe symptoms of physiological withdrawal were observed within two days of replacement of diazepam with placebo capsules. The patient recovered promptly on reinstitution of diazepam administration, and relapsed during a second withdrawal phase. During an additional two week-period of placebo administration, the patient's condition first worsened, then gradually improved. Examination of plasma levels of diazepam and desmethyldiazepam indicated no obvious pharmacokinetic abnormalities. Thus, with long-term administration of diazepam, even in therapeutically accepted doses, withdrawal reactions can be encountered on abrupt termination. References 1. Blackwell B: Psychotropic drugs in use toady: The role of diazepam in medical practice . JAMA 225:1637-1691, 1973.Crossref 2. Greenblatt DJ, Shader RI, Koch-Weser J: Psychotropic drug use in the Boston area: A report from the Boston Collaborative Drug Surveillance Program . Arch Gen Psychiatry 32:518-521, 1975.Crossref 3. Greenblatt DJ, Shader RI: Benzodiazepines in Clinical Practice . New York, Raven Press, 1974. 4. Klerman GL: Psychotropic drugs as therapeutic agents . Hastings Cent Stud 2:81-93, 1974.Crossref 5. Greenblatt DJ, Shader RI: Pharmacotherapy of anxiety with benzodiazepines and β-adrenergic blockers , in Lipton MA, DiMascio A, Killam KF (eds): Psychopharmacology: A Generation of Progress . New York, Raven Press, 1978, pp 1381-1389. 6. Rickels K: Antineurotic agents: Specific and non-specific effects , in Efron DH, Cole JO, Levine J, et al (eds): Psychopharmacology: A Review of Progress , 1957-1967. US Public Health Service Publication No. 1836, pp 231-247. 7. Rickels K, Downing RW, Winokur A: Antianxiety drugs: Clinical use in psychiatry , in Iversen LL, Iversen SD, Snyder SH (eds): Handbook of Psychopharmacology . New York, Plenum Press, 1978, vol 13. 8. Greenblatt DJ, Allen MD, Noel BJ, et al: Acute overdosage with benzodiazepine derivatives . Clin Pharmacol Ther 21:497-514, 1977. 9. Greenblatt DJ, Woo E, Allen MD, et al: Rapid recovery from massive diazepam overdose . JAMA 240:1872-1874, 1978.Crossref 10. Greenblatt DJ, Shader RI: Dependence, tolerance, and addiction to benzodiazepines: Clinical and pharmacokinetic considerations . Drug Metab Rev 8:13-28, 1978.Crossref 11. Haskell D: Withdrawal of diazepam . JAMA 233:135, 1975.Crossref 12. Covi L, Lipman RS, Pattison JH, et al: Length of treatment with anxiolytic sedatives and response to their sudden withdrawal . Acta Psychiatry Scand 49:51-64, 1973.Crossref 13. Woody GE, O'Brien CP, Greenstein R: Misuse and abuse of diazepam: An increasingly common medical problem . Int J Addict 10:843-845, 1975. 14. Preskorn SH, Denner LJ: Benzodiazepines and withdrawal psychosis: Report of three cases . JAMA 237:36-38, 1977.Crossref 15. Dusken MW, Chan CH: Diazepam withdrawal psychosis: A case report . Am J Psychiatry 134:573, 1977. 16. Hollister LE, Motzenbecker FP, Degan RO: Withdrawal reactions from chlordiazepoxide . Psychopharmacologia 2:63-68, 1961.Crossref 17. Pevnick JS, Jasinski DR, Haertzen CA: Abrupt withdrawal from therapeutically administered diazepam: Report of a case . Arch Gen Psychiatry 35:995-998, 1978.Crossref 18. Eysenck HT, Eysenck SBG: EITS Manual . San Diego, Educational and Industrial Testing Service, 1968. 19. Covi L, Park LC, Lipman RS, et al: Factors affecting withdrawal response to certain minor tranquilizers , in Cole JO, Wittenborn JR (eds): Drug Abuse: Social and Psychopharmacological Aspects . Springfield, Ill, Charles C Thomas Publisher Inc, 1969, pp 93-108. 20. Hamilton M: A rating scale for depression . J Neurol Neurosurg Psychiatry 23:56-62, 1960.Crossref 21. Hamilton M: The assessment of anxiety states by rating . Br J Med Psychol 32:50-55, 1959.Crossref 22. Derogatis LR, Lipman BS, Covi L: The SCL-90: An outpatient psychiatric rating scale . Psychopharm Bull 9:13-28, 1973. 23. Derogatis LR: SCL-90 revised . Baltimore, Johns Hopkins University School of Medicine, Manual 1, 1977. 24. Greenblatt DJ: Simultaneous gas chromatographic analysis of diazepam and its major metabolite, desmethyldiazepam, with use of double internal standardization . Clin Chem 24:1838-1841, 1978. 25. Rutherford DM, Okoko A, Tyrer PJ: Plasma concentration of diazepam and desmethyldiazepam during chronic diazepam therapy . Br J Clin Pharmacology 6:69-73, 1978.Crossref 26. Greenblatt DJ, Shader RI: Pharmacokinetic understanding of antianxiety drug therapy . South Med J 71( (suppl 2) ):2-9, 1978.Crossref 27. Maletsky BM, Klotter J: Addiction to diazepam . Int J Addict 11:95-115, 1976. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of General Psychiatry American Medical Association

Withdrawal Reaction From Long-term, Low-dosage Administration of Diazepam: A Double-blind, Placebo-Controlled Case Study

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Publisher
American Medical Association
Copyright
Copyright © 1980 American Medical Association. All Rights Reserved.
ISSN
0003-990X
eISSN
1598-3636
DOI
10.1001/archpsyc.1980.01780140103012
Publisher site
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Abstract

Abstract • Symptoms of diazepam withdrawal developed in a young man who had been taking diazepam in dosages of 15 to 25 mg/day during a six-year period. This was verified in a study conducted under placebo-controlled, double-blind conditions, with plasma levels of diazepam and its major metabolite, desmethyldiazepam, monitored throughout the course of the study. Severe symptoms of physiological withdrawal were observed within two days of replacement of diazepam with placebo capsules. The patient recovered promptly on reinstitution of diazepam administration, and relapsed during a second withdrawal phase. During an additional two week-period of placebo administration, the patient's condition first worsened, then gradually improved. Examination of plasma levels of diazepam and desmethyldiazepam indicated no obvious pharmacokinetic abnormalities. Thus, with long-term administration of diazepam, even in therapeutically accepted doses, withdrawal reactions can be encountered on abrupt termination. References 1. Blackwell B: Psychotropic drugs in use toady: The role of diazepam in medical practice . JAMA 225:1637-1691, 1973.Crossref 2. Greenblatt DJ, Shader RI, Koch-Weser J: Psychotropic drug use in the Boston area: A report from the Boston Collaborative Drug Surveillance Program . Arch Gen Psychiatry 32:518-521, 1975.Crossref 3. Greenblatt DJ, Shader RI: Benzodiazepines in Clinical Practice . New York, Raven Press, 1974. 4. Klerman GL: Psychotropic drugs as therapeutic agents . Hastings Cent Stud 2:81-93, 1974.Crossref 5. Greenblatt DJ, Shader RI: Pharmacotherapy of anxiety with benzodiazepines and β-adrenergic blockers , in Lipton MA, DiMascio A, Killam KF (eds): Psychopharmacology: A Generation of Progress . New York, Raven Press, 1978, pp 1381-1389. 6. Rickels K: Antineurotic agents: Specific and non-specific effects , in Efron DH, Cole JO, Levine J, et al (eds): Psychopharmacology: A Review of Progress , 1957-1967. US Public Health Service Publication No. 1836, pp 231-247. 7. Rickels K, Downing RW, Winokur A: Antianxiety drugs: Clinical use in psychiatry , in Iversen LL, Iversen SD, Snyder SH (eds): Handbook of Psychopharmacology . New York, Plenum Press, 1978, vol 13. 8. Greenblatt DJ, Allen MD, Noel BJ, et al: Acute overdosage with benzodiazepine derivatives . Clin Pharmacol Ther 21:497-514, 1977. 9. Greenblatt DJ, Woo E, Allen MD, et al: Rapid recovery from massive diazepam overdose . JAMA 240:1872-1874, 1978.Crossref 10. Greenblatt DJ, Shader RI: Dependence, tolerance, and addiction to benzodiazepines: Clinical and pharmacokinetic considerations . Drug Metab Rev 8:13-28, 1978.Crossref 11. Haskell D: Withdrawal of diazepam . JAMA 233:135, 1975.Crossref 12. Covi L, Lipman RS, Pattison JH, et al: Length of treatment with anxiolytic sedatives and response to their sudden withdrawal . Acta Psychiatry Scand 49:51-64, 1973.Crossref 13. Woody GE, O'Brien CP, Greenstein R: Misuse and abuse of diazepam: An increasingly common medical problem . Int J Addict 10:843-845, 1975. 14. Preskorn SH, Denner LJ: Benzodiazepines and withdrawal psychosis: Report of three cases . JAMA 237:36-38, 1977.Crossref 15. Dusken MW, Chan CH: Diazepam withdrawal psychosis: A case report . Am J Psychiatry 134:573, 1977. 16. Hollister LE, Motzenbecker FP, Degan RO: Withdrawal reactions from chlordiazepoxide . Psychopharmacologia 2:63-68, 1961.Crossref 17. Pevnick JS, Jasinski DR, Haertzen CA: Abrupt withdrawal from therapeutically administered diazepam: Report of a case . Arch Gen Psychiatry 35:995-998, 1978.Crossref 18. Eysenck HT, Eysenck SBG: EITS Manual . San Diego, Educational and Industrial Testing Service, 1968. 19. Covi L, Park LC, Lipman RS, et al: Factors affecting withdrawal response to certain minor tranquilizers , in Cole JO, Wittenborn JR (eds): Drug Abuse: Social and Psychopharmacological Aspects . Springfield, Ill, Charles C Thomas Publisher Inc, 1969, pp 93-108. 20. Hamilton M: A rating scale for depression . J Neurol Neurosurg Psychiatry 23:56-62, 1960.Crossref 21. Hamilton M: The assessment of anxiety states by rating . Br J Med Psychol 32:50-55, 1959.Crossref 22. Derogatis LR, Lipman BS, Covi L: The SCL-90: An outpatient psychiatric rating scale . Psychopharm Bull 9:13-28, 1973. 23. Derogatis LR: SCL-90 revised . Baltimore, Johns Hopkins University School of Medicine, Manual 1, 1977. 24. Greenblatt DJ: Simultaneous gas chromatographic analysis of diazepam and its major metabolite, desmethyldiazepam, with use of double internal standardization . Clin Chem 24:1838-1841, 1978. 25. Rutherford DM, Okoko A, Tyrer PJ: Plasma concentration of diazepam and desmethyldiazepam during chronic diazepam therapy . Br J Clin Pharmacology 6:69-73, 1978.Crossref 26. Greenblatt DJ, Shader RI: Pharmacokinetic understanding of antianxiety drug therapy . South Med J 71( (suppl 2) ):2-9, 1978.Crossref 27. Maletsky BM, Klotter J: Addiction to diazepam . Int J Addict 11:95-115, 1976.

Journal

Archives of General PsychiatryAmerican Medical Association

Published: Jan 1, 1980

References

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