Effects of long-term benzodiazepine use

Benzodiazepines
Chemical structure diagram of a benzene ring fused to a diazepine ring. Another benzene ring is attached to the bottom of the diazepine ring via a single line. Attached to the first benzene ring is a side chain labeled R7; to the second, a side chain labeled R2'; and attached to the diazepine ring, two side chains labeled R1 and R2.
The core structure of benzodiazepines. "R" labels denote common locations of side chains, which give different benzodiazepines their unique properties.

The effects of long-term benzodiazepine use include drug dependence as well as the possibility of adverse effects on cognitive function, physical health, and mental health.[1] Long-term use is sometimes described as use not shorter than three months.[2] Benzodiazepines are generally effective when used therapeutically in the short term,[3] but even then the risk of dependency can be significantly high. There are significant physical, mental and social risks associated with the long-term use of benzodiazepines.[3] Although anxiety can temporarily increase as a withdrawal symptom, there is evidence that a reduction or withdrawal from benzodiazepines can lead in the long run to a reduction of anxiety symptoms.[4][5] Due to these increasing physical and mental symptoms from long-term use of benzodiazepines, slow withdrawal is recommended for long-term users.[6][7][8][9] Not everyone, however, experiences problems with long-term use.[10]

Some of the symptoms that could possibly occur as a result of a withdrawal from benzodiazepines after long-term use include emotional clouding,[1] flu-like symptoms,[5] suicide,[11] nausea, headaches, dizziness, irritability, lethargy, sleep problems, memory impairment, personality changes, aggression, depression, social deterioration as well as employment difficulties, while others never have any side effects from long-term benzodiazepine use. Abruptly or rapidly stopping benzodiazepines can be dangerous; when withdrawing, a gradual reduction in dosage is recommended, under professional supervision.[7][12][9]

While benzodiazepines are highly effective in the short term, adverse effects associated with long-term use, including impaired cognitive abilities, memory problems, mood swings, and overdoses when combined with other drugs, may make the risk-benefit ratio unfavourable. In addition, benzodiazepines have reinforcing properties in some individuals and thus are considered to be addictive drugs, especially in individuals that have a "drug-seeking" behavior; further, a physical dependence can develop after a few weeks or months of use.[13] Many of these adverse effects associated with long-term use of benzodiazepines begin to show improvements three to six months after withdrawal.[14][15]

Other concerns about the effects associated with long-term benzodiazepine use, in some, include dose escalation, benzodiazepine use disorder, tolerance and benzodiazepine dependence and benzodiazepine withdrawal problems. Both physiological tolerance and dependence can be associated with worsening the adverse effects associated with benzodiazepines. Increased risk of death has been associated with long-term use of benzodiazepines in several studies; however, other studies have not found increased mortality. Due to conflicting findings in studies regarding benzodiazepines and increased risks of death including from cancer, further research in long-term use of benzodiazepines and mortality risk has been recommended; most of the available research has been conducted in prescribed users, even less is known about illicit misusers.[16][17] The long-term use of benzodiazepines is controversial and has generated significant debate within the medical profession. Views on the nature and severity of problems with long-term use of benzodiazepines differ from expert to expert and even from country to country; some experts even question whether there is any problem with the long-term use of benzodiazepines.[18]

  1. ^ a b Ayers, Susan (23 August 2007). Baum, Andrew; McManus, Chris; Newman, Stanton; Wallston, Kenneth; Weinman, John (eds.). Cambridge Handbook of Psychology, Health and Medicine (2nd ed.). Cambridge University Press. p. 677. ISBN 978-0-521-87997-2.
  2. ^ "Discontinuation of long-term benzodiazepine use: 10-year follow-up". Oxford Academic Journals. 30 December 2010. Retrieved 22 October 2020.
  3. ^ a b Ford C, Law F (July 2014). "Guidance for the use and reduction of misuse of benzodiazepines and other hypnotics and anxiolytics in general practice". smmgp.org.uk. Archived from the original on 9 June 2020. Retrieved 9 June 2020.
  4. ^ Galanter, Marc (1 July 2008). The American Psychiatric Publishing Textbook of Substance Abus Treatment (American Psychiatric Press Textbook of Substance Abuse Treatment) (4 ed.). American Psychiatric Publishing, Inc. p. 197. ISBN 978-1-58562-276-4.
  5. ^ a b Lindsay, S.J.E.; Powell, Graham E., eds. (28 July 1998). The Handbook of Clinical Adult Psychology (2nd ed.). Routledge. p. 173. ISBN 978-0-415-07215-1.
  6. ^ Cite error: The named reference asapdacg was invoked but never defined (see the help page).
  7. ^ a b Onyett SR (April 1989). "The benzodiazepine withdrawal syndrome and its management". The Journal of the Royal College of General Practitioners. 39 (321): 160–3. PMC 1711840. PMID 2576073.
  8. ^ National Drug Strategy; National Drug Law Enforcement Research Fund (2007). "Benzodiazepine and pharmaceutical opioid misuse and their relationship to crime - An examination of illicit prescription drug markets in Melbourne, Hobart and Darwin" (PDF). Archived from the original (PDF) on 25 June 2012. Retrieved 27 December 2008.
  9. ^ a b Juergens SM, Morse RM (May 1988). "Alprazolam dependence in seven patients". The American Journal of Psychiatry. 145 (5): 625–7. doi:10.1176/ajp.145.5.625. PMID 3258735.
  10. ^ Hammersley D, Beeley L (1996). "The effects of medication on counselling". In Palmer S, Dainow S, Milner P (eds.). Counselling: The BACP Counselling Reader. Vol. 1. Sage. pp. 211–4. ISBN 978-0-8039-7477-7.
  11. ^ Cite error: The named reference pmid28257172 was invoked but never defined (see the help page).
  12. ^ National Drug Strategy; National Drug Law Enforcement Research Fund (2007). "Benzodiazepine and pharmaceutical opioid misuse and their relationship to crime - An examination of illicit prescription drug markets in Melbourne, Hobart and Darwin" (PDF). Archived from the original (PDF) on 25 June 2012. Retrieved 27 December 2008.
  13. ^ Denis C, Fatséas M, Lavie E, Auriacombe M (July 2006). Denis C (ed.). "Pharmacological interventions for benzodiazepine mono-dependence management in outpatient settings". The Cochrane Database of Systematic Reviews (3): CD005194. doi:10.1002/14651858.CD005194.pub2. PMID 16856084. (Retracted, see doi:10.1002/14651858.CD005194.pub3, PMID 23780681,  Retraction Watch. If this is an intentional citation to a retracted paper, please replace {{retracted|...}} with {{retracted|...|intentional=yes}}.)
  14. ^ Rickels K, Lucki I, Schweizer E, García-España F, Case WG (April 1999). "Psychomotor performance of long-term benzodiazepine users before, during, and after benzodiazepine discontinuation". Journal of Clinical Psychopharmacology. 19 (2): 107–13. doi:10.1097/00004714-199904000-00003. PMID 10211911.
  15. ^ Cite error: The named reference pmid18377143 was invoked but never defined (see the help page).
  16. ^ Darke S, Torok M, Duflou J (May 2014). "Circumstances and toxicology of sudden or unnatural deaths involving alprazolam". Drug and Alcohol Dependence. 138: 61–6. doi:10.1016/j.drugalcdep.2014.01.023. PMID 24629629.
  17. ^ Charlson F, Degenhardt L, McLaren J, Hall W, Lynskey M (February 2009). "A systematic review of research examining benzodiazepine-related mortality". Pharmacoepidemiology and Drug Safety. 18 (2): 93–103. doi:10.1002/pds.1694. PMID 19125401. S2CID 20125264.
  18. ^ Uzun S, Kozumplik O, Jakovljević M, Sedić B (March 2010). "Side effects of treatment with benzodiazepines". Psychiatria Danubina. 22 (1): 90–3. PMID 20305598.