WikiDoc Resources for Opioid withdrawal
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Opioid withdrawal occurs due to the discontinuation or reduction of opioid use in individuals with heavy and prolonged opioid use or may be precipitated by the administration of an opioid antagonist in an individual with prolonged opioid use or by the administration of an opioid partial agonist in an individual that is currently using a full opioid agonist. Symptoms of withdrawal from opiates include, but are not limited to, depression, anxiety, irritability, leg cramps, abdominal cramps, nausea, vomiting, diarrhea, insomnia, pain, tremor, rhinorrhea, sweating, and cravings for the drug itself. Depending on the opioid's half-life, the symptoms of opioid withdrawal usually resolve within 5 to 14 days, however, many patients require appropriate treatment. The DSM-V diagnostic criteria is used for the diagnosis of opioid withdrawal. The medications for treatment include methadone, clonidine, buprenorphine, and adjunctive drugs.
- Opium and its derivatives have been used as medical therapies since 5,000 years ago.
- In the United States, in the early 20th century, opiates were over-the-counter drugs and were commonly used in medical therapy of various disorders.
- In the early 1900s, the federal restrictions on opioid access caused suffering and death since there were no effective treatments for the opioid withdrawal symptoms that happened with sudden discontinuation of opioids.
|Half-life of Opioids||Onset of Withdrawal Symptoms||Duration of the syndrome|
- Gastrointestinal (GI) tract:
- Mesolimbic reward circuits (the ventral tegmental area and its projections to nucleus accumbens, prefrontal cortex and amygdala):
- Ascending reticular activating system (in the brainstem, thalamus, and hypothalamus):
- Different brain pathways (the locus coeruleus (LC) in the brainstem and its projections including those to the reticular activating system):
- Physical dependence symptoms
Locus coeruleus (LC)
- Has norepinephrine (NE) neurons
- Input to several areas of the brain (prefrontal cortex, hippocampus and amygdala)
- Regulates attention, vigilance and autonomic nervous system
Acute opioid effects:
- Drowsiness, hypotension, reduced respiration and muscle tone
- Binding of an opioid to mu-opioid receptors on the neurons in LC causes:
Chronic opioid use:
- Upregulation of the cAMP pathway and production of normal cAMP levels:
Abrupt discontinuation of opioids after opioid tolerance:
- Discontinuation or reduction of opioid use in individuals with heavy and prolonged opioid use.
- Precipitation by administrating of an opioid antagonist (such as naloxone or naltrexone) to an individual with prolonged opioid use.
- Precipitation by administrating of an opioid partial agonist (such as buprenorphine) to an individual that is currently using a full opioid agonist.
Differentiating opioid withdrawal from other diseases and conditions
- Sedative-hypnotic withdrawal
- Hallucinogen intoxication
- Stimulant intoxication
- Opioid-induced depressive disorder
|Disease||Prominent clinical features||Investigations|
|Hyperthyroidism||The main symptoms include:|
|Essential hypertension||Most patients with hypertension are asymptomatic at the time of diagnosis. Common symptoms are listed below:||JNC 7 recommends the following routine laboratory tests before initiation of therapy for hypertension:|
|Generalized anxiety disorder||According to DSM V, the following criteria should be present to fit the diagnosis of generalized anxiety disorder:
|Menopause||The perimenopausal symptoms are caused by an overall drop, as well as dramatic but erratic fluctuations, in the levels of estrogens, progestin, and testosterone. Some of these symptoms such as formication, etc. may be associated with the hormone withdrawal process.
|Opioid withdrawal disorder||According to DSM V, the following criteria should be present to fit the diagnosis of opioid withdrawal:
|Pheochromocytoma||The hallmark symptoms of pheochromocytoma are those of sympathetic nervous system hyperactivity, symptoms usually subside in less than one hour and they may include:
Please note that not all patients with pheochromocytoma experience all of the classical symptoms.
|Diagnostic lab findings associated with pheochromocytoma include:|
Epidemiology and Demographics
- The prevalence of opioid withdrawal is 6,000 per 100,000 (60%) of the population that have used heroin one or more time in the prior 12 months.
- In the USA, the amount of opioids prescribed has increased from 43.8 million prescriptions in 2000 to 89.2 million in 2010.
- About 4% of adults in the USA regularly use opioids for pain.
- Medical therapy of pain
- Opioid agonist therapy for opioid use disorder
- Recreational use
- Self-treating the symptoms of mental disorders
Natural History, Complications and Prognosis
- Depending on the opioid's half-life, the symptoms of opioid withdrawal usually resolve within 5 to 14 days.
- However, many patients require appropriate treatment since the symptoms and distress is severe in the first days after the cessation of opioid use.
- Potential complications of discontinuing opioid use may include:
DSM-V Diagnostic Criteria for Opioid Withdrawal
History and Symptoms
- Hot flashes
- Pupillary dilatation
- Heart pounding
- Nausea, vomiting
- Abdominal cramps
- Aches, pain
- Muscle spasms, twitching
- Piloerection (such as goose bumps)
- Nausea, vomiting
- Muscle spasms, twitching
- Laboratory tests
- Viral hepatitis (especially B and C)
- Other sexually transmitted diseases
- Opportunistic infections
Echocardiography or Ultrasound
Other Imaging Findings
Other Diagnostic Studies
- Short Opioid Withdrawal Scale (SOWS)
- Objective Opiate Withdrawal Scale (OOWS)
- Opiate Craving Scale (OCS)
- Opiate Withdrawal Scale (OWS)
- Methadone is a long-acting agonist at the μ-opioid receptor
- Methadone is the most commonly used medication, but patients require adjunctive drugs for nausea, vomiting, diarrhea, and stomach cramps
- Refraining from sudden and abrupt discontinuation of opioid use in individuals with opioid dependence.
- Opioid replacement therapy (replace short-acting opioids with long-acting opioids).
- Opioid tapering (gradual reduction in opioid dose).
- Early diagnosis and treatment of opioid use dependence.
- Long-term treatment of opioid use dependence.
- Kosten TR, Baxter LE (2019). "Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment". Am J Addict. 28 (2): 55–62. doi:10.1111/ajad.12862. PMC 6590307 Check
|pmc=value (help). PMID 30701615.
- Srivastava AB, Mariani JJ, Levin FR (2020). "New directions in the treatment of opioid withdrawal". Lancet. 395 (10241): 1938–1948. doi:10.1016/S0140-6736(20)30852-7. PMC 7385662 Check
|pmc=value (help). PMID 32563380 Check
- Kosten TR, O'Connor PG (2003). "Management of drug and alcohol withdrawal". N Engl J Med. 348 (18): 1786–95. doi:10.1056/NEJMra020617. PMID 12724485.
- Kleber HD (2007). "Pharmacologic treatments for opioid dependence: detoxification and maintenance options". Dialogues Clin Neurosci. 9 (4): 455–70. PMC 3202507. PMID 18286804.
- Kreek MJ, Borg L, Ducat E, Ray B (2010). "Pharmacotherapy in the treatment of addiction: methadone". J Addict Dis. 29 (2): 200–16. doi:10.1080/10550881003684798. PMC 2885886. PMID 20407977.
- Mazei-Robison MS, Nestler EJ (2012). "Opiate-induced molecular and cellular plasticity of ventral tegmental area and locus coeruleus catecholamine neurons". Cold Spring Harb Perspect Med. 2 (7): a012070. doi:10.1101/cshperspect.a012070. PMC 3385942. PMID 22762025.
- Kosten TR, George TP (2002). "The neurobiology of opioid dependence: implications for treatment". Sci Pract Perspect. 1 (1): 13–20. doi:10.1151/spp021113. PMC 2851054. PMID 18567959.
- Cao JL, Vialou VF, Lobo MK, Robison AJ, Neve RL, Cooper DC; et al. (2010). "Essential role of the cAMP-cAMP response-element binding protein pathway in opiate-induced homeostatic adaptations of locus coeruleus neurons". Proc Natl Acad Sci U S A. 107 (39): 17011–6. doi:10.1073/pnas.1010077107. PMC 2947876. PMID 20837544.
- Diagnostic and statistical manual of mental disorders : DSM-5. Arlington, VA Washington, D.C: American Psychiatric Association,American Psychiatric Association. 2013. ISBN 0-89042-555-8. OCLC 830807378.
- Diagnostic and statistical manual of mental disorders : DSM-5. Washington, D.C: American Psychiatric Association. 2013. ISBN 0890425558.
- Sites BD, Beach ML, Davis MA (2014). "Increases in the use of prescription opioid analgesics and the lack of improvement in disability metrics among users". Reg Anesth Pain Med. 39 (1): 6–12. doi:10.1097/AAP.0000000000000022. PMC 3955827. PMID 24310049.
- Volkow ND, McLellan AT (2016). "Opioid Abuse in Chronic Pain--Misconceptions and Mitigation Strategies". N Engl J Med. 374 (13): 1253–63. doi:10.1056/NEJMra1507771. PMID 27028915.
- Mattick RP, Breen C, Kimber J, Davoli M (2014). "Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence". Cochrane Database Syst Rev (2): CD002207. doi:10.1002/14651858.CD002207.pub4. PMID 24500948.
- Jarvis BP, Holtyn AF, Subramaniam S, Tompkins DA, Oga EA, Bigelow GE; et al. (2018). "Extended-release injectable naltrexone for opioid use disorder: a systematic review". Addiction. 113 (7): 1188–1209. doi:10.1111/add.14180. PMC 5993595. PMID 29396985.
- Burma NE, Kwok CH, Trang T (2017). "Therapies and mechanisms of opioid withdrawal". Pain Manag. 7 (6): 455–459. doi:10.2217/pmt-2017-0028. PMID 29125396.
- Wesson DR, Ling W (2003). "The Clinical Opiate Withdrawal Scale (COWS)". J Psychoactive Drugs. 35 (2): 253–9. doi:10.1080/02791072.2003.10400007. PMID 12924748.
- Vernon MK, Reinders S, Mannix S, Gullo K, Gorodetzky CW, Clinch T (2016). "Psychometric evaluation of the 10-item Short Opiate Withdrawal Scale-Gossop (SOWS-Gossop) in patients undergoing opioid detoxification". Addict Behav. 60: 109–16. doi:10.1016/j.addbeh.2016.03.028. PMID 27124502.
- Center for Substance Abuse Treatment (2006). "Detoxification and Substance Abuse Treatment". SAMHSA/CSAT Treatment Improvement Protocols. PMID 22514851.
- Doughty B, Morgenson D, Brooks T (2019). "Lofexidine: A Newly FDA-Approved, Nonopioid Treatment for Opioid Withdrawal". Ann Pharmacother. 53 (7): 746–753. doi:10.1177/1060028019828954. PMID 30724094.
- Gossop M (1990). "The development of a Short Opiate Withdrawal Scale (SOWS)". Addict Behav. 15 (5): 487–90. doi:10.1016/0306-4603(90)90036-w. PMID 2248123.
- Handelsman L, Cochrane KJ, Aronson MJ, Ness R, Rubinstein KJ, Kanof PD (1987). "Two new rating scales for opiate withdrawal". Am J Drug Alcohol Abuse. 13 (3): 293–308. doi:10.3109/00952998709001515. PMID 3687892.