Opioids are potent analgesics and euphoriants with the potential to cause sedation and respiratory depression. Respiratory depression may occur with high doses and can be managed with antidotes (eg, naloxone) in the case of an overdose. The threshold at which respiratory depression may occur differs across individuals as it is directly related to opioid tolerance levels. Opioid toxicity complicated by severe respiratory depression can be treated with naloxone and respiratory support when needed. Opioid withdrawal is primarily a clinical diagnosis and can be treated with withdrawal management and initiation of maintenance therapy.Opioids are potent analgesics and euphoriants with the potential to cause sedation and respiratory depression. Respiratory depression may occur with high doses and can be managed with antidotes (eg, naloxone) in the case of an overdose. The threshold at which respiratory depression may occur differs across individuals as it is directly related to opioid tolerance levels. Opioid toxicity complicated by severe respiratory depression can be treated with naloxone and respiratory support when needed. Opioid withdrawal is primarily a clinical diagnosis and can be treated with withdrawal management and initiation of maintenance therapy.
The term opioid is used to refer to natural substances (originally derived from the opium poppy) and their semisynthetic and synthetic analogs, which bind to opioid receptors. Opioids, which are potent analgesics, are common drugs of misuse and addiction because of their wide availability and euphoriant properties; see also Opioid Analgesics and Opioid Use Disorder and Rehabilitation.
Tolerance and physiologic dependence at opioid receptors build over time, and the degree of each is a function of the dose and duration of opioid use. If physiologic dependence is present and the opioid is suddenly stopped, opioid withdrawal symptoms occur. (See also Tolerance and Resistance.)
Withdrawal has both physiologic and psychological components and can overlap with withdrawal syndromes of other substances. Four signs are specific to opioid withdrawal:
Mydriasis
Piloerection
Lacrimation/rhinorrhea
Yawning
Opioid withdrawal is a clinical diagnosis; urine toxicology screens for opioids are helpful.
Withdrawal symptoms can be treated by substitution with a long-acting opioid (eg, methadone) or buprenorphine (a partial opioid agonist). In addition to agonist therapy, supportive medications such as clonidine, ondansetron, acetaminophen, loperamide, and anxiolytics can be used for symptomatic relief.Withdrawal symptoms can be treated by substitution with a long-acting opioid (eg, methadone) or buprenorphine (a partial opioid agonist). In addition to agonist therapy, supportive medications such as clonidine, ondansetron, acetaminophen, loperamide, and anxiolytics can be used for symptomatic relief.
Pathophysiology of Opioid Use and Tolerance
There are 3 main opioid receptors in the brain: delta, kappa, and mu. Opioid receptors are found throughout the central nervous system but particularly in areas and tracts associated with pain perception. Opioid receptors are also located on peripheral nerves, on mast cells, and in the gastrointestinal tract, where they help regulate gut motility (1). Each receptor subtype has a different distribution pattern in central vs peripheral tissues; for example, certain brain regions (caudate, nucleus accumbens, cerebellum) are highly enriched for mu opioid receptors (2), implicating mu receptors in the reward pathway and the neurobiology of addiction.
Opioid receptors are stimulated by endogenous endorphins, which produce analgesia and a sense of well-being. Exogenous opioids are used therapeutically, primarily as analgesics. Exogenous opioids vary in their receptor activity, and some (eg, buprenorphine) have combined agonist and antagonist actions. Compounds with pure antagonist activity (eg, naloxone, naltrexone) are used to reverse overdose and have a protective blocking effect on opioid receptors when bound.Opioid receptors are stimulated by endogenous endorphins, which produce analgesia and a sense of well-being. Exogenous opioids are used therapeutically, primarily as analgesics. Exogenous opioids vary in their receptor activity, and some (eg, buprenorphine) have combined agonist and antagonist actions. Compounds with pure antagonist activity (eg, naloxone, naltrexone) are used to reverse overdose and have a protective blocking effect on opioid receptors when bound.
Exogenous opioids can be taken by almost any route: orally, intravenously, subcutaneously, rectally, intranasally, or inhaled as smoke. Peak effects are reached approximately 10 minutes after IV injection, 10 to 15 minutes after nasal insufflation, and 90 to 120 minutes after oral ingestion, although time to peak effects and duration of effect vary considerably depending on the specific drug.
When exogenous opioids are used for a prolonged period of time without interruption, opioid tolerance via neuroadaptive changes occurs at the opioid receptors (3). The presence of opioid tolerance leads to opioid withdrawal symptoms when an exogenous opioid is removed. The severity of opioid withdrawal syndrome is correlated with an individual's degree of opioid tolerance. The hallmark symptoms of autonomic activation associated with acute opioid withdrawal (mydriasis, piloerection, rhinorrhea, lacrimation, yawning, diaphoresis, GI upset) are attributable to unopposed cAMP signaling pathway activity, which becomes upregulated with chronic mu opioid receptor activation.
Chronic effects
Opioid tolerance can develop quickly, often leading to escalating dose requirements to reach the same degree of pain relief or euphoria. Tolerance to the various effects of opioids frequently develops unevenly. People who use opioids chronically may become relatively tolerant to the drug’s euphoric and respiratory depression effects but continue to have constricted pupils and opioid-associated constipation.
A minor opioid withdrawal syndrome may occur after only several days' use. Severity of the syndrome increases with the daily opioid dose and the duration of dependence.
Long-term effects of the opioids themselves are minimal; even decades of methadone use appears to be well tolerated physiologically, although long-term opioid users can experience chronic constipation (sometimes complicated by bowel obstruction), nausea and vomiting, hyperhydrosis, opioid-induced hyperalgesia, pruritis, dizziness, fatigue, drowsiness, mood disturbance, and hypogonadism in males (Long-term effects of the opioids themselves are minimal; even decades of methadone use appears to be well tolerated physiologically, although long-term opioid users can experience chronic constipation (sometimes complicated by bowel obstruction), nausea and vomiting, hyperhydrosis, opioid-induced hyperalgesia, pruritis, dizziness, fatigue, drowsiness, mood disturbance, and hypogonadism in males (4, 5). Opioid users who inject opioids intravenously are at risk of adverse effects from contaminants (eg, talc) and adulterants (eg, xylazine, nonprescription stimulant drugs) and cardiac, pulmonary, and hepatic damage due to infections such as ). Opioid users who inject opioids intravenously are at risk of adverse effects from contaminants (eg, talc) and adulterants (eg, xylazine, nonprescription stimulant drugs) and cardiac, pulmonary, and hepatic damage due to infections such asHIV infection, endocarditis, and hepatitis B or C, which are spread by nonsterile injection techniques and shared needles (see Injection Drug Use).
Pregnancy
Use of opioids during pregnancy can result in opioid dependence in the fetus with subsequent neonatal abstinence syndrome (NAS) at birth. Treatment of pregnant people with opioid use disorder (OUD) using opioid agonists results in improvement in both neonatal and maternal outcomes (6). While both methadone and buprenorphine are effective for managing OUD during pregnancy, buprenorphine is associated with more favorable neonatal outcomes, including a lower incidence and severity of NAS (). While both methadone and buprenorphine are effective for managing OUD during pregnancy, buprenorphine is associated with more favorable neonatal outcomes, including a lower incidence and severity of NAS (7). However, methadone has been associated with higher treatment retention rates both during pregnancy and postpartum. Pregnancy can be a highly motivating time for expectant mothers to seek treatment. Pregnant people with OUD on maintenance treatment are overall less likely to discontinue treatment than their nonpregnant counterparts (). However, methadone has been associated with higher treatment retention rates both during pregnancy and postpartum. Pregnancy can be a highly motivating time for expectant mothers to seek treatment. Pregnant people with OUD on maintenance treatment are overall less likely to discontinue treatment than their nonpregnant counterparts (8, 9).
Laws vary by state in the legal ramifications of substance use in pregnancy and after birth, which has implications for how pregnant patients engage with health care professionals about ongoing substance use. Studies have shown that states that have punitive policies for substance use during pregnancy are associated with reduced access to medications for OUD and lower rates of prenatal and postpartum care (10, 11). (See also discussion of opioids in Social and Illicit Drugs During Pregnancy.)
Symptoms and Signs of Opioid Toxicity and Opioid Withdrawal
Acute effects of intoxication
Acute opioid intoxication is characterized by euphoria and drowsiness. Mast cell effects (eg, flushing, itching) are common, particularly with morphine. Gastrointestinal effects include nausea, vomiting, decreased bowel sounds, and constipation.Acute opioid intoxication is characterized by euphoria and drowsiness. Mast cell effects (eg, flushing, itching) are common, particularly with morphine. Gastrointestinal effects include nausea, vomiting, decreased bowel sounds, and constipation.
Toxicity or overdose
The main toxic effect in overdose is decreased respiratory rate and respiratory volume, which can progress to apnea. Other complications (eg, pulmonary edema, which usually develops within minutes to a few hours after opioid overdose) and death result primarily from hypoxia. Pupils are miotic in an overdose. Delirium, hypotension, bradycardia, decreased body temperature, and urinary retention may also occur.
Serotonin syndrome occasionally occurs when fentanyl, meperidine, tramadol, methadone, codeine, or oxycodone is taken concomitantly with a medication that has serotonergic effects (eg, selective serotonin reuptake inhibitors, monoamine oxidase inhibitors). Serotonin syndrome consists of 1 or more of the following:occasionally occurs when fentanyl, meperidine, tramadol, methadone, codeine, or oxycodone is taken concomitantly with a medication that has serotonergic effects (eg, selective serotonin reuptake inhibitors, monoamine oxidase inhibitors). Serotonin syndrome consists of 1 or more of the following:
Hypertonia
Tremor and hyperreflexia
Spontaneous, inducible, or ocular clonus
Diaphoresis and autonomic instability
Agitation
Temperature > 38°
Although, spongiform leukoencephalopathy has been reported after heroin use, primarily by the inhalation of heroin fumes ("chasing the dragon") but by other routes as well (1, 2). The symptoms depend on the timing of presentation and may show motor restlessness, apathy, ataxia, or paralysis. The symptoms may resolve, or can progress to autonomic dysregulation and death.
Withdrawal
The opioid withdrawal syndrome usually includes symptoms and signs of central nervous system hyperactivity. Onset and duration of the syndrome depend on the specific drug and its half-life. Symptoms may appear as early as 4 hours after the last dose of heroin, peak within 48 to 72 hours, and subside after about a week. Anxiety and a craving for the drug are followed by increased resting respiratory rate (> 16 breaths/minute), usually with diaphoresis, yawning, lacrimation, rhinorrhea, mydriasis, and stomach cramps. Later, piloerection (gooseflesh), tremors, muscle twitching, tachycardia, hypertension, fever and chills, anorexia, nausea, vomiting, and diarrhea may develop.
Withdrawal has both a physiologic and psychological component. Acute opioid withdrawal manifests initially as anxiety and drug craving—the psychological component of withdrawal—followed by physiologic signs such as increased respiratory rate, diaphoresis, yawning, lacrimation, rhinorrhea, mydriasis, piloerection, and stomach cramping. Later, tremors, muscle twitches, tachycardia, hypertension, fever, chills, anorexia, nausea, vomiting, and diarrhea can occur. Opioid withdrawal symptoms can overlap with withdrawal syndromes of other substances. However, 4 signs are specific to opioid withdrawal: mydriasis, piloerection, lacrimation/rhinorrhea, and yawning. Opioid withdrawal is a clinical diagnosis; urine toxicology screens for opioids are helpful.
Opioid withdrawal does not typically cause fever, seizures, or altered mental status, and the presence of these symptoms necessitates further diagnostic evaluation and clarification of comorbid substance use. Although it may be distressingly symptomatic, opioid withdrawal itself is not life threatening.
The withdrawal syndrome in people taking methadone (which has a long half-life when taken daily) develops more slowly and may be less acutely severe than heroin withdrawal, although users may describe it as worse. Even after the withdrawal syndrome remits, lethargy, malaise, anxiety, and disturbed sleep may persist for several weeks to several months. Drug craving may persist for years.The withdrawal syndrome in people taking methadone (which has a long half-life when taken daily) develops more slowly and may be less acutely severe than heroin withdrawal, although users may describe it as worse. Even after the withdrawal syndrome remits, lethargy, malaise, anxiety, and disturbed sleep may persist for several weeks to several months. Drug craving may persist for years.
Mydriasis can occur in one or both eyes during acute opioid withdrawal and often renders the pupil unresponsive to light.
Wirestock/stock.adobe.com
Piloerection frequently occurs during acute opioid withdrawal and gives rise to "goosebumps" or "gooseflesh."
Oleksii Sergieiev/stock.adobe.com
Diagnosis of Opioid Toxicity and Opioid Withdrawal
History and physical examination
Sometimes urine drug testing
Sometimes a validated withdrawal scale
Diagnosis of opioid use is usually made clinically and sometimes with urine drug testing; laboratory tests are performed as needed to identify drug-related complications. Drug levels are not usually measured.
Using the Clinical Opioid Withdrawal Scale (COWS) can be helpful in assessing the severity of opioid withdrawal using a numerical value and can guide management in health care settings.
Treatment of Opioid Toxicity and Opioid Withdrawal
Treatment differs depending on whether the patient requires management for overdose (toxicity) or withdrawal. Treatment for withdrawal also includes initiation of maintenance therapy.
Toxicity or overdose
Respiratory support as needed
NaloxoneNaloxone
Treatment to maintain the airway and ensure adequate ventilation is the first priority.
Patients with spontaneous respirations can be treated with an opioid antagonist, typically naloxone 0.4 mg to 2 mg IV given in increments of 0.4 mg every 2 to 3 minutes as needed (for children Patients with spontaneous respirations can be treated with an opioid antagonist, typically naloxone 0.4 mg to 2 mg IV given in increments of 0.4 mg every 2 to 3 minutes as needed (for children< 20 kg, 0.1 mg/kg); naloxone has no agonist activity and a has short half-life (see table 20 kg, 0.1 mg/kg); naloxone has no agonist activity and a has short half-life (see table). Naloxone rapidly reverses unconsciousness and apnea due to an opioid in most patients. If IV access is not immediately available, intramuscular, subcutaneous, or intranasal administration is also effective. Additional doses can be given if there is no response within 2 minutes. Overdose and intoxication with potent synthetic opioids such as the fentanyl derivatives may require higher doses of naloxone. ). Naloxone rapidly reverses unconsciousness and apnea due to an opioid in most patients. If IV access is not immediately available, intramuscular, subcutaneous, or intranasal administration is also effective. Additional doses can be given if there is no response within 2 minutes. Overdose and intoxication with potent synthetic opioids such as the fentanyl derivatives may require higher doses of naloxone.
Some patients become agitated, delirious, and combative as consciousness returns, and because naloxone precipitates acute withdrawal, management of agitation is at times required for patient and staff safety in health care settings. To ameliorate withdrawal in long-term users, some experts suggest titrating very small doses of naloxone (0.1 mg) when the clinical situation does not require emergency reversal of severe opioid toxicity.Some patients become agitated, delirious, and combative as consciousness returns, and because naloxone precipitates acute withdrawal, management of agitation is at times required for patient and staff safety in health care settings. To ameliorate withdrawal in long-term users, some experts suggest titrating very small doses of naloxone (0.1 mg) when the clinical situation does not require emergency reversal of severe opioid toxicity.
Apneic patients can initially be treated with naloxone 2 mg IV if it can be given without delay; note that the dose is higher than for patients who are only somnolent. In the United States and some other countries, naloxone is available without a prescription so apneic patients can be rescued by friends or family. When naloxone is available and given quickly, endotracheal intubation is rarely required. Apneic patients can initially be treated with naloxone 2 mg IV if it can be given without delay; note that the dose is higher than for patients who are only somnolent. In the United States and some other countries, naloxone is available without a prescription so apneic patients can be rescued by friends or family. When naloxone is available and given quickly, endotracheal intubation is rarely required.
Patients should be observed for several hours after they regain spontaneous respirations. Because the half-life of naloxone is shorter than that of some opioids, respiratory depression can recur within hours of an overdose from a long-acting opioid such as methadone, sustained-released oxycodone, or extended-release morphine. Thus, the duration of close observation and monitoring of vital signs should vary depending on the half-life of the opioid involved. Typically, patients who overdose on longer-acting opioids should be admitted to the hospital for observation; patients who overdose on short-acting opioids may be discharged after several hours. Patients should be observed for several hours after they regain spontaneous respirations. Because the half-life of naloxone is shorter than that of some opioids, respiratory depression can recur within hours of an overdose from a long-acting opioid such as methadone, sustained-released oxycodone, or extended-release morphine. Thus, the duration of close observation and monitoring of vital signs should vary depending on the half-life of the opioid involved. Typically, patients who overdose on longer-acting opioids should be admitted to the hospital for observation; patients who overdose on short-acting opioids may be discharged after several hours.
If respiratory depression recurs, naloxone should be readministered at an appropriate dose. The best dosing regimen is unclear. Many clinicians use repeat bolus doses of the same dose that was effective initially. Others recommend a continuous naloxone infusion, typically beginning with about two-thirds of the initially effective dose per hour. In theory, a continuous infusion should allow the dose to be titrated to maintain respiratory rate without precipitating or worsening withdrawal; however, in practice this can be difficult to do and there is the risk that respiratory depression will recur if the infusion is interrupted (eg, by losing IV access). Both regimens require close monitoring, typically in an intensive care unit. If respiratory depression recurs, naloxone should be readministered at an appropriate dose. The best dosing regimen is unclear. Many clinicians use repeat bolus doses of the same dose that was effective initially. Others recommend a continuous naloxone infusion, typically beginning with about two-thirds of the initially effective dose per hour. In theory, a continuous infusion should allow the dose to be titrated to maintain respiratory rate without precipitating or worsening withdrawal; however, in practice this can be difficult to do and there is the risk that respiratory depression will recur if the infusion is interrupted (eg, by losing IV access). Both regimens require close monitoring, typically in an intensive care unit.
Patients should be observed until no naloxone pharmacologic activity is present and they have no opioid-related symptoms. The serum half-life of naloxone is approximately 1 hour, so an observation period of 2 to 3 hours after use of naloxone should clarify disposition. The half-life of IV heroin is relatively short, and recurrent respiratory depression after naloxone reversal of IV heroin is rare.Patients should be observed until no naloxone pharmacologic activity is present and they have no opioid-related symptoms. The serum half-life of naloxone is approximately 1 hour, so an observation period of 2 to 3 hours after use of naloxone should clarify disposition. The half-life of IV heroin is relatively short, and recurrent respiratory depression after naloxone reversal of IV heroin is rare.
Additional respiratory support for apneic or hypopneic patients is provided as needed along with naloxone, or if naloxone is not available, including airway management, bag-mask ventilation, endotracheal intubation, and mechanical ventilation.Additional respiratory support for apneic or hypopneic patients is provided as needed along with naloxone, or if naloxone is not available, including airway management, bag-mask ventilation, endotracheal intubation, and mechanical ventilation.
Acute pulmonary edema is treated with supplemental oxygen and often noninvasive or invasive modalities of breathing support (eg, bilevel positive airway pressure [BiPAP], endotracheal intubation).
Withdrawal management and detoxification
Treatment may involve several strategies:
Substitution with buprenorphine or methadoneSubstitution with buprenorphine or methadone
Long-acting intramuscular naltrexoneLong-acting intramuscular naltrexone
Supportive adjuvant medications for symptoms
Psychosocial interventions and psychotherapeutic support
The opioid withdrawal syndrome is self-limited and, although severely uncomfortable, is not life threatening. Minor metabolic and physical withdrawal effects may persist for up to 6 months. Withdrawal can be managed in outpatient settings, unless patients require hospitalization for concurrent medical or behavioral problems.
Options for management of withdrawal include agonist therapy (with methadone or buprenorphine) along with adjuvant medications such as clonidine, acetaminophen, loperamide, and ondansetron to support the patient symptomatically. Using adjuvant medications alone (detoxification) without starting a maintenance medication for OUD is linked with high risk of fatal opioid overdose (Options for management of withdrawal include agonist therapy (with methadone or buprenorphine) along with adjuvant medications such as clonidine, acetaminophen, loperamide, and ondansetron to support the patient symptomatically. Using adjuvant medications alone (detoxification) without starting a maintenance medication for OUD is linked with high risk of fatal opioid overdose (1, 2).
BuprenorphineBuprenorphine, a partial opioid agonist usually given sublingually, has been successfully used in treatment of withdrawal. Sublingual doses of 8 to 24 mg/day are typically used. Low-dose induction protocols allow for buprenorphine to be started at low doses and gradually increased while a concomitant full agonist such as methadone is used to treat withdrawal symptoms (, a partial opioid agonist usually given sublingually, has been successfully used in treatment of withdrawal. Sublingual doses of 8 to 24 mg/day are typically used. Low-dose induction protocols allow for buprenorphine to be started at low doses and gradually increased while a concomitant full agonist such as methadone is used to treat withdrawal symptoms (3). The intent of the low-dose induction method is to avoid worsening opioid withdrawal by avoiding a component of precipitated withdrawal, which can occur if long-acting opioid agonists—-such as fentanyl—are replaced at the receptor level by buprenorphine too quickly. A high-dose induction method for buprenorphine also exists and is most likely to be successful when someone is already experiencing severe opioid withdrawal. Sublingual buprenorphine can serve as a bridge to long-acting injectable buprenorphine; these injections are repeated monthly if the person with OUD chooses to stay on maintenance treatment. ). The intent of the low-dose induction method is to avoid worsening opioid withdrawal by avoiding a component of precipitated withdrawal, which can occur if long-acting opioid agonists—-such as fentanyl—are replaced at the receptor level by buprenorphine too quickly. A high-dose induction method for buprenorphine also exists and is most likely to be successful when someone is already experiencing severe opioid withdrawal. Sublingual buprenorphine can serve as a bridge to long-acting injectable buprenorphine; these injections are repeated monthly if the person with OUD chooses to stay on maintenance treatment.
Sublingual naloxone in combination with buprenorphine is given to reduce misuse potential. Naloxone is inactive when the combination is taken sublingually but precipitates acute withdrawal if taken intravenously. Thus crushing the pill and injecting or snorting it can increase withdrawal symptoms and act as a deterrent.Sublingual naloxone in combination with buprenorphine is given to reduce misuse potential. Naloxone is inactive when the combination is taken sublingually but precipitates acute withdrawal if taken intravenously. Thus crushing the pill and injecting or snorting it can increase withdrawal symptoms and act as a deterrent.
The Substance Abuse and Mental Health Services Administration (SAMHSA) provides information on buprenorphine and the training required to prescribe the medication in the United States, as well as protocols (available for download) for using buprenorphine for detoxification or maintenance therapy. provides information on buprenorphine and the training required to prescribe the medication in the United States, as well as protocols (available for download) for using buprenorphine for detoxification or maintenance therapy.
MethadoneMethadone is an opioid agonist used for maintenance treatment of OUD. In the United States, the use of methadone for maintenance treatment of OUD must be supervised in a licensed Opioid Treatment Program (OTP). However, methadone can be used in acute care settings to treat acute opioid withdrawal, with some restrictions to the maximum dose that can be used. The typical initial dose range is 10 to 40 mg (10 to 20 mg for those with lower levels of opioid tolerance or conditions that may cause hypoxia; 20 to 40 mg for patients displaying signs of withdrawal). Titration should be individualized, using symptoms of withdrawal and craving as guides to dosing needed to achieve stability. The dose should be increased gradually, by no more than 10 to 20 mg per day in an inpatient setting. It is recommended to hold the dose steady for approximately 5 days after each dose increase to allow for methadone to achieve steady state. Once initial withdrawal is stabilized, a common daily dose is 60 to 120 mg per day, although some patients may require higher doses to achieve stability due to the pervasiveness of fentanyl in the United States today (is an opioid agonist used for maintenance treatment of OUD. In the United States, the use of methadone for maintenance treatment of OUD must be supervised in a licensed Opioid Treatment Program (OTP). However, methadone can be used in acute care settings to treat acute opioid withdrawal, with some restrictions to the maximum dose that can be used. The typical initial dose range is 10 to 40 mg (10 to 20 mg for those with lower levels of opioid tolerance or conditions that may cause hypoxia; 20 to 40 mg for patients displaying signs of withdrawal). Titration should be individualized, using symptoms of withdrawal and craving as guides to dosing needed to achieve stability. The dose should be increased gradually, by no more than 10 to 20 mg per day in an inpatient setting. It is recommended to hold the dose steady for approximately 5 days after each dose increase to allow for methadone to achieve steady state. Once initial withdrawal is stabilized, a common daily dose is 60 to 120 mg per day, although some patients may require higher doses to achieve stability due to the pervasiveness of fentanyl in the United States today (4).
Symptom scales are available for estimating the appropriate dose. Higher doses should be given when evidence of withdrawal is observed. After the appropriate dose has been established, it should be reduced progressively by 10 to 20% each day unless the patient is enrolled in a methadone program or planning to do so on discharge (Symptom scales are available for estimating the appropriate dose. Higher doses should be given when evidence of withdrawal is observed. After the appropriate dose has been established, it should be reduced progressively by 10 to 20% each day unless the patient is enrolled in a methadone program or planning to do so on discharge (methadone maintenance).
Methadone has been reported to be associated with QTc prolongation and serious arrhythmias, including torsades de pointes (see also Methadone has been reported to be associated with QTc prolongation and serious arrhythmias, including torsades de pointes (see alsoLong QT Syndrome and Torsades de Pointes). Thus, it should be used very carefully with appropriate patient evaluation and monitoring of EKGs during initiation and dose titration.
Naltrexone,Naltrexone, an opioid antagonist at the mu opioid receptor, blocks the effects of full agonist opioids. A monthly depot intramuscular formulation is available and is the preferred method of administration for OUD maintenance treatment. Because naltrexone is an opioid antagonist, it cannot be given within 7 days of last full agonist opioid administration to avoid precipitating acute withdrawal. Naltrexone may be useful for patients with less severe dependence, early-stage opioid dependence, and comorbid an opioid antagonist at the mu opioid receptor, blocks the effects of full agonist opioids. A monthly depot intramuscular formulation is available and is the preferred method of administration for OUD maintenance treatment. Because naltrexone is an opioid antagonist, it cannot be given within 7 days of last full agonist opioid administration to avoid precipitating acute withdrawal. Naltrexone may be useful for patients with less severe dependence, early-stage opioid dependence, and comorbidalcohol use disorder.
Clonidine,Clonidine, a centrally acting adrenergic medication, can suppress autonomic symptoms and signs of opioid withdrawal. Starting dosages are 0.1 mg orally every 4 to 6 hours and may be increased to 0.2 mg orally every 4 to 6 hours as tolerated. Clonidine can cause hypotension and drowsiness, and its abrupt discontinuation may precipitate restlessness, insomnia, irritability, tachycardia, and headache. a centrally acting adrenergic medication, can suppress autonomic symptoms and signs of opioid withdrawal. Starting dosages are 0.1 mg orally every 4 to 6 hours and may be increased to 0.2 mg orally every 4 to 6 hours as tolerated. Clonidine can cause hypotension and drowsiness, and its abrupt discontinuation may precipitate restlessness, insomnia, irritability, tachycardia, and headache.
Other adjuvant medications for symptomatic relief during opioid withdrawal include acetaminophen, clonidine, ibuprofen, loperamide, ondansetron, and benzodiazepines.Other adjuvant medications for symptomatic relief during opioid withdrawal include acetaminophen, clonidine, ibuprofen, loperamide, ondansetron, and benzodiazepines.
Rapid and ultrarapid protocols have been evaluated for managing withdrawal and detoxification. In rapid induction protocols, combinations of naloxone, nalmefene, and naltrexone are used to induce withdrawal, and clonidine and various adjuvant medications are used to suppress withdrawal symptoms (have been evaluated for managing withdrawal and detoxification. In rapid induction protocols, combinations of naloxone, nalmefene, and naltrexone are used to induce withdrawal, and clonidine and various adjuvant medications are used to suppress withdrawal symptoms (5, 6). Ultrarapid protocols used large boluses of naloxone and diuretics to enhance excretion of the opioids while patients were under general anesthesia; these ultrarapid protocols are currently not recommended because they have a high risk of complications and no substantial additional benefit (). Ultrarapid protocols used large boluses of naloxone and diuretics to enhance excretion of the opioids while patients were under general anesthesia; these ultrarapid protocols are currently not recommended because they have a high risk of complications and no substantial additional benefit (4).
Psychosocial interventions and psychotherapeutic supportare important components of therapy, regardless of which medication strategy is chosen for opioid withdrawal management. It is important to offer these options once the patient is feeling stable enough to engage with such services. Support from peers with lived experience can be particularly helpful in acute medical settings where patients may have developed mistrust after repeated experiences with stigmatized care. Involving peer recovery coaches in a patient's care during inpatient hospitalization for OUD has been shown to improve post-discharge involvement in OUD care and reduce frequency of patient-directed discharges from the hospital (7, 8).
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