Opioid use disorder is a chronic condition characterized by the regular and prolonged use of opioids, leading to significant impairment or distress in an individual’s life. In the United States, the number of people who use opioids on a regular basis is comparable to the combined number of individuals diagnosed with psoriatic arthritis, obsessive-compulsive disorder, and epilepsy. The diagnosis of opioid use disorder is based on the criteria outlined in the DSM-5.
One of the key features of this disorder is a strong and persistent desire to obtain and consume opioids, despite facing adverse professional and societal consequences. Opioids encompass a range of substances, including illicit drugs like heroin, as well as prescription medications like codeine, morphine, fentanyl, and synthetic opioids such as oxycodone. Individuals with opioid use disorder often experience an overwhelming craving for opioids, which leads to a progressively higher tolerance for the drug.
When attempts are made to discontinue or reduce opioid use, withdrawal syndrome manifests as physical and psychological symptoms. Opioid use disorder comprises addiction and dependence, with addiction indicating the most severe form. Dependence refers to the body’s adaptation to opioids, resulting in withdrawal symptoms upon cessation. In contrast, addiction involves the compulsive and uncontrollable use of opioids, despite negative consequences and a loss of control over drug-seeking behavior.
Epidemiology
Globally, over 16 million individuals are dependent on opioids and meet the criteria for opioid use disorder, with three million residing in the United States. This pervasive problem leads to a staggering number of deaths yearly, with over 120,000 deaths worldwide attributed to opioid use disorder. The opioid-related death toll in the U.S. represents the most lethal drug epidemic in history.
According to the CDC, the age-adjusted rate of drug poisoning deaths involving opioid analgesics rose to 7.0 per 100,000 in 2015. Substance abuse, methamphetamines, alcohol, and opioids are widespread, affecting more than 20 million people who suffer from substance use disorder. Disturbingly, nearly 10% of the U.S. population over 12 has engaged in illicit drug use within the past month.
Among the 20 million Americans grappling with substance abuse, two million individuals are dependent on prescription opioid pain medications, while 500,000 individuals use heroin. Although the recreational use of opioids peaked in 2010, there has been a gradual decline as the opioid epidemic has gained significant attention across the United States. Remarkably, up to 50% of patients receiving long-term opioid therapy meet the criteria for opioid use disorder. The prevalence of opioid use and dependency varies across age groups and genders.
Men exhibit higher rates of opioid use, develop a dependence on various opioids and account for most opioid-related overdoses. On the other hand, women have been prescribed opioids more frequently than men for pain management. Deaths resulting from opioid use tend to be more common among older individuals, with opioid overdoses peaking between the ages of 40 and 50. However, heroin overdoses are most prevalent among individuals aged 20 to 30.
The peak age for treatment of opioid use disorder falls within the range of 20 to 35 years old. Patients diagnosed with opioid use disorder who experience legal issues related to their drug use are often found to have previous criminal records and exhibit high impulsivity tendencies. It is crucial to understand the complexities of these circumstances in order to provide appropriate care and support to those affected by opioid use disorder.
Anatomy
Pathophysiology
The pathophysiology of opioid use disorder involves complex interactions between opioids and the brain’s reward and pain pathways. Opioids exert their effects primarily by binding to opioid receptors in various central nervous system regions, including the brain. When opioids bind to these receptors, they activate the reward pathway, which releases dopamine, a neurotransmitter associated with pleasure and reinforcement. This activation leads to a euphoric feeling and reinforces the desire to continue using opioids.
Over time, repeated opioid use can lead to neuroadaptations in the brain, altering the reward system’s functioning and contributing to addiction development. Chronic opioid use also affects other neurotransmitter systems, such as gamma-aminobutyric acid (GABA), glutamate, and norepinephrine, which regulate mood, anxiety, and stress responses. These alterations contribute to the dysregulation of emotional and motivational processes observed in individuals with opioid use disorder.
Additionally, opioids can cause physical dependence, where the body adapts to the presence of opioids and requires them to function normally. Prolonged use of opioids leads to the downregulation of opioid receptors and desensitization of the reward system. This results in the development of tolerance, where higher doses of opioids are needed to achieve the desired effects. Withdrawal symptoms occur when opioid use is abruptly discontinued or significantly reduced.
Etiology
Opioid use disorder has a multifaceted etiology influenced by biological, environmental, genetic, and psychosocial factors. Opioids, including prescription analgesics, are derived from the poppy plant and are commonly prescribed by clinicians to manage pain, suppress cough, or relieve diarrhea. Opioid use disorder can affect individuals from diverse educational and socioeconomic backgrounds. Biologically, addiction can have a foundation in certain deficiencies.
For example, patients may have neurotransmitter imbalances, such as low levels of dopamine, which can drive them to seek external sources of endorphins. This deficit can lead some individuals to turn to opioids for self-medication. Additionally, individuals with a family history of substance abuse disorders, particularly in first-degree relatives, are more susceptible to developing opioid use disorder. The estimated heritability of opioid use disorder is around 50%, suggesting a genetic component.
The environment in which a patient with opioid use disorder is exposed can also influence their likelihood of developing a substance abuse disorder. Environmental factors may include social influences, such as peer relationships, or exposure to opioids through previous legitimate prescriptions for injuries. Patients with a history of depression, post-traumatic stress disorder (PTSD), anxiety, childhood trauma and abuse are more prone to substance abuse.
Genetics play a role in the development of opioid use disorder as well. There are three primary types of opioid receptors: mu, delta, and kappa. The mu receptor, found in the brain, is involved in reducing the release of neurotransmitters. Genetic factors have been shown to influence the treatment of pain and opioid use disorder. However, specific pharmacogenomic dosing recommendations have not been established due to the lack of clear evidence linking genotype to drug effects, toxicity, or dependence.
Genetics
Prognostic Factors
The diagnosis of opioid use disorder is crucial for clinicians to make informed decisions about prescribing practices and to identify patients who are using opioids chronically. One important intervention clinicians should consider is offering naloxone to all patients with opioid use disorder. Naloxone is a mu-opioid receptor antagonist that can reverse the effects of opioid overdose and save lives.
Patients with opioid use disorder are at the highest risk of death within the first four weeks of starting opioid dependence treatment and the subsequent four weeks after treatment discontinuation. Therefore, clinicians need to maintain close contact with patients during and after tapering off medications like methadone. Discontinuing maintenance treatments without proper support and follow-up can significantly increase the risk of relapse to illicit drug use and potentially lead to fatal overdoses.
Compared to methadone, induction with buprenorphine has a lower risk of mortality. Both methadone and buprenorphine therapies can reduce morbidity and mortality associated with opioid use disorder. Opioid replacement therapies, such as these, have been shown to decrease the incidence of long-term opioid addiction, reduce illegal opiate use, and lower mortality rates.
Clinical History
Clinical History
When evaluating a patient who meets the criteria for an opioid use disorder, it is essential to conduct a comprehensive social history and mental health history. This information provides valuable insights into the patient’s background, lifestyle, and potential contributing factors to their opioid use. Additionally, recording the patient’s previous injury history is crucial as it can shed light on the initial exposure to opioids and the potential development of dependence.
Opioid use disorder is characterized by opioid use and the recurrence of two or more specific problems within 12 months. These problems, as outlined in the diagnostic criteria, encompass a range of issues. They include experiencing withdrawal symptoms when attempting to stop using opioids, sacrificing important life activities in favor of opioid use, and spending excessive amounts of time using opioids. Additionally, individuals with opioid use disorder exhibit significant impairment or distress as a direct consequence of their opioid use.
The severity of the condition is determined by the presence of six or more of these diagnostic criteria. There are several signs and symptoms associated with opioid use disorder. One notable symptom is drug-seeking behavior, where individuals persistently try to obtain opioids, often disregarding legal or social consequences. Another sign may be the acquisition of multiple opioid prescriptions from different clinicians, indicating attempts to procure more opioids.
Additionally, medical complications can arise due to opioid use, highlighting the potential adverse effects on health. These complications may include respiratory depression, infections, cardiovascular problems, and hormonal imbalances. Individuals with opioid use disorder commonly experience cravings for opioids, which can be intense and challenging to resist.
As the disorder progresses, tolerance to opioids develops, leading to increased usage over time as higher doses are required to achieve the desired effects. Moreover, if opioids are abruptly discontinued or significantly reduced, individuals with opioid use disorder may exhibit withdrawal symptoms. These symptoms can be physically and psychologically distressing, including restlessness, muscle aches, nausea, vomiting, diarrhea, and dysphoria.
Physical Examination
Physical Examination
Opioid withdrawal symptoms encompass a range of physical and psychological manifestations. These symptoms may include abdominal cramps, intense cravings for opioids, restlessness, agitation, diarrhea, dilated pupils, anxiety, elevated blood pressure, sneezing, excessive sweating, increased heart rate, tearing, tremors or shakiness, muscle pain, runny nose, goosebumps, and insomnia. These symptoms can be highly distressing and contribute to the cycle of opioid use and dependence.
Conversely, opioid intoxication is characterized by a distinct set of symptoms. These symptoms may include confusion, constricted pupils, excessive drowsiness or hypersomnia, nausea, feelings of euphoria, constipation, and a decreased perception of pain. These effects contribute to the pleasurable and sedating properties of opioids, which can reinforce the cycle of misuse and addiction.
In the case of a suspected opioid overdose, a physical examination may reveal specific indicators. Notably, pinpoint pupils (pupillary constriction) are often observed. The patient may exhibit hypothermia or bradycardia (abnormally low body temperature or slow heart rate). They may also display limited responsiveness or be unconscious, indicating a severe overdose state.
Age group
Associated comorbidity
Associated activity
Acuity of presentation
Differential Diagnoses
Differential Diagnoses
Substance Abuse Disorder
Laboratory Studies
Imaging Studies
Procedures
Histologic Findings
Staging
Treatment Paradigm
Rehabilitation for opioid use disorder typically employs a cognitive-behavioral approach similar to treating other chronic conditions. A comprehensive treatment plan includes maintenance programs that incorporate psychological support. Patients are encouraged to make positive changes through education, cooperative efforts, and the use of medications. The primary goal of therapy is to minimalize the risk of drug use relapse and promote long-term recovery.
Opioid replacement, maintenance, or substitution therapy involves substituting a longer-acting opioid with less euphoric and addictive properties for the problematic opioid. Commonly used medications include buprenorphine and methadone, which are prescribed and administered under medical supervision. The combination of buprenorphine and naloxone is widely utilized. Opioid maintenance medications help alleviate withdrawal symptoms, reduce cravings, and minimize the euphoric effects of opioids. With the assistance of these medications, nearly half of the patients can achieve abstinence from additional opioids while on replacement therapy.
The goals of maintenance therapy extend beyond drug cessation and focus on improving overall health and quality of life. This includes reducing the risks of infectious diseases such as HIV, hepatitis B, and hepatitis C. Additional objectives include enhancing interpersonal relationships, reducing cravings, and decreasing engagement in criminal activities often associated with funding illicit drug use. Methadone is a commonly used medication for opioid replacement therapy. It has been extensively studied and implemented worldwide, and methadone maintenance is a well-established approach.
Methadone treatment offers advantages such as blocking the euphoric effects of opioids, reducing cravings, and lowering the transmission of infectious diseases. Methadone maintenance is generally non-sedating and considered medically safe when used without concomitant prescription or illicit drugs. The maintenance phase typically begins approximately six weeks after initiating therapy and can last for years or even a lifetime. Reduction in methadone can be a gradual process that spans several weeks or months, depending on the individual’s level of opioid dependence.
As an adjunctive therapy, clonidine or lofexidine can address the signs and symptoms of opioid withdrawal. In certain countries, although not in the United States, individuals who are long-term injecting drug users and have not responded to methadone may receive pure injectable diamorphine as a treatment option. Dihydrocodeine, available in extended-release and immediate-release formulations, can be a viable alternative to methadone or buprenorphine for maintenance treatment.
Clonidine or tizanidine can be beneficial in reducing anxiety associated with opioid withdrawal and alleviating autonomic overactivity symptoms such as piloerection. Benzodiazepines or other sedating drugs are used to manage anxiety and insomnia related to opioid withdrawal. Loperamide is commonly used to treat nausea, diarrhea, and vomiting, while prochlorperazine, combined with sports drinks or intravenous fluids, can also provide relief. Nonsteroidal anti-inflammatory agents like naproxen are utilized for pain relief. Combination therapies have demonstrated superior efficacy to placebo in providing symptomatic relief during opioid withdrawal.
Sublocade
For the first two months, use 300 mg subcutaneously once per month; then, take 100 mg/month as a maintenance dosage.
If a 100-mg dosage is tolerated, but the patient does not show an acceptable clinical response, the maintenance dose can be increased to 300 mg monthly.
Brixadi
Indicated to be used after a single dose of transmucosal buprenorphine in people with moderate to severe OUD
Target dosage advised weekly: 24mg subcutaneously every seven days
Follow these titrations over the first week.
When objective indications of mild to moderate withdrawal occur, provide a test dose of 4 mg of transmucosal buprenorphine.
If the test dosage is tolerated without precipitating withdrawal, deliver the first 16 mg (Brixadi) subcutaneously.
To reach the suggested 24-mg dosage (weekly), give a second dose of 8 mg Brixadi within three days after the first dose.
Give an additional 8 mg dosage if necessary during the first week of therapy, waiting at least 24 hours after the initial injection for a total weekly dose of 32 mg.
32 mg is the maximum weekly dosage.
Brixadi weekly substitution for transmucosal buprenorphine
Administer every 7 days.
A weekly dosage may be given up to two days before or after the weekly time point to prevent missed doses.
≤6mg Sublingual-8mg subcutaneous
8 to 10mg Sublingual-16mg subcutaneous
12 to 16mg Sublingual-24mg subcutaneous
18 to 24mg Sublingual-32mg subcutaneous
Brixadi monthly substitution for transmucosal buprenorphine
To prevent missed doses, provide monthly dosage one week before or after the time point.
≤6mg Sublingual-N/A
8 to 10mg Sublingual-64mg subcutaneous
12 to 16mg Sublingual-96mg subcutaneous
18 to 24mg Sublingual-128mg subcutaneous
Brixadi's Change from Weekly to Monthly
16 mg/week Subcutaneous: Administer 64 mg subcutaneous monthly
24 mg/week Subcutaneous: Administer 96 mg subcutaneous monthly
32 mg/week Subcutaneous: Administer 128 mg subcutaneous monthly
Brixadi dosage changes
Depending on the patient's response to treatment, the maximum weekly
Brixadi dose is 32 mg, and the maximum monthly Brixadi dose is 128 mg.
Dose Adjustments
Renal impairment
Patients with impaired kidney function were excluded from the studies.
Hepatic impairment
Moderate to severe pre-existing condition
Due to these drugs' extended half-lives, dose modifications do not immediately affect plasma buprenorphine levels.
Patients with moderate-to-severe pre-existing hepatic impairment are unsuitable for treatment with buprenorphine because levels cannot be immediately adjusted.
Indicated for opioid withdrawal
initial dose: 0.18 mg of three tablets (i.e.,0.54 mg) orally four times a day, while in the peak time of withdrawal symptoms (like the 5-7 days following opioid use
it should not exceed 2.88 mg of total dose in a day (i.e.,16 tablets)
it should not exceed 0.72 mg of a single dose in a day (i.e.,4 tablets)
therapy can be continued for nearly 14 days with dosing guided by the symptoms
for people who show a higher sensitivity, the dose can be decreased, held, or also discontinued
when opioid withdrawal symptoms get subside, the decreased dose may be suitable
discontinue by slowly decreasing the dose for over a 2-4 day period to alleviate the lofexidine withdrawal symptoms (like decreasing by one tablet/dose every one-two day)
kratom is currently being investigated for its potential therapeutic effects in pain management, mood regulation, and opioid addiction treatment. Researchers are exploring its alkaloids' interactions with opioid receptors to better understand its mechanisms of action
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Opioid use disorder is a chronic condition characterized by the regular and prolonged use of opioids, leading to significant impairment or distress in an individual’s life. In the United States, the number of people who use opioids on a regular basis is comparable to the combined number of individuals diagnosed with psoriatic arthritis, obsessive-compulsive disorder, and epilepsy. The diagnosis of opioid use disorder is based on the criteria outlined in the DSM-5.
One of the key features of this disorder is a strong and persistent desire to obtain and consume opioids, despite facing adverse professional and societal consequences. Opioids encompass a range of substances, including illicit drugs like heroin, as well as prescription medications like codeine, morphine, fentanyl, and synthetic opioids such as oxycodone. Individuals with opioid use disorder often experience an overwhelming craving for opioids, which leads to a progressively higher tolerance for the drug.
When attempts are made to discontinue or reduce opioid use, withdrawal syndrome manifests as physical and psychological symptoms. Opioid use disorder comprises addiction and dependence, with addiction indicating the most severe form. Dependence refers to the body’s adaptation to opioids, resulting in withdrawal symptoms upon cessation. In contrast, addiction involves the compulsive and uncontrollable use of opioids, despite negative consequences and a loss of control over drug-seeking behavior.
Globally, over 16 million individuals are dependent on opioids and meet the criteria for opioid use disorder, with three million residing in the United States. This pervasive problem leads to a staggering number of deaths yearly, with over 120,000 deaths worldwide attributed to opioid use disorder. The opioid-related death toll in the U.S. represents the most lethal drug epidemic in history.
According to the CDC, the age-adjusted rate of drug poisoning deaths involving opioid analgesics rose to 7.0 per 100,000 in 2015. Substance abuse, methamphetamines, alcohol, and opioids are widespread, affecting more than 20 million people who suffer from substance use disorder. Disturbingly, nearly 10% of the U.S. population over 12 has engaged in illicit drug use within the past month.
Among the 20 million Americans grappling with substance abuse, two million individuals are dependent on prescription opioid pain medications, while 500,000 individuals use heroin. Although the recreational use of opioids peaked in 2010, there has been a gradual decline as the opioid epidemic has gained significant attention across the United States. Remarkably, up to 50% of patients receiving long-term opioid therapy meet the criteria for opioid use disorder. The prevalence of opioid use and dependency varies across age groups and genders.
Men exhibit higher rates of opioid use, develop a dependence on various opioids and account for most opioid-related overdoses. On the other hand, women have been prescribed opioids more frequently than men for pain management. Deaths resulting from opioid use tend to be more common among older individuals, with opioid overdoses peaking between the ages of 40 and 50. However, heroin overdoses are most prevalent among individuals aged 20 to 30.
The peak age for treatment of opioid use disorder falls within the range of 20 to 35 years old. Patients diagnosed with opioid use disorder who experience legal issues related to their drug use are often found to have previous criminal records and exhibit high impulsivity tendencies. It is crucial to understand the complexities of these circumstances in order to provide appropriate care and support to those affected by opioid use disorder.
The pathophysiology of opioid use disorder involves complex interactions between opioids and the brain’s reward and pain pathways. Opioids exert their effects primarily by binding to opioid receptors in various central nervous system regions, including the brain. When opioids bind to these receptors, they activate the reward pathway, which releases dopamine, a neurotransmitter associated with pleasure and reinforcement. This activation leads to a euphoric feeling and reinforces the desire to continue using opioids.
Over time, repeated opioid use can lead to neuroadaptations in the brain, altering the reward system’s functioning and contributing to addiction development. Chronic opioid use also affects other neurotransmitter systems, such as gamma-aminobutyric acid (GABA), glutamate, and norepinephrine, which regulate mood, anxiety, and stress responses. These alterations contribute to the dysregulation of emotional and motivational processes observed in individuals with opioid use disorder.
Additionally, opioids can cause physical dependence, where the body adapts to the presence of opioids and requires them to function normally. Prolonged use of opioids leads to the downregulation of opioid receptors and desensitization of the reward system. This results in the development of tolerance, where higher doses of opioids are needed to achieve the desired effects. Withdrawal symptoms occur when opioid use is abruptly discontinued or significantly reduced.
Opioid use disorder has a multifaceted etiology influenced by biological, environmental, genetic, and psychosocial factors. Opioids, including prescription analgesics, are derived from the poppy plant and are commonly prescribed by clinicians to manage pain, suppress cough, or relieve diarrhea. Opioid use disorder can affect individuals from diverse educational and socioeconomic backgrounds. Biologically, addiction can have a foundation in certain deficiencies.
For example, patients may have neurotransmitter imbalances, such as low levels of dopamine, which can drive them to seek external sources of endorphins. This deficit can lead some individuals to turn to opioids for self-medication. Additionally, individuals with a family history of substance abuse disorders, particularly in first-degree relatives, are more susceptible to developing opioid use disorder. The estimated heritability of opioid use disorder is around 50%, suggesting a genetic component.
The environment in which a patient with opioid use disorder is exposed can also influence their likelihood of developing a substance abuse disorder. Environmental factors may include social influences, such as peer relationships, or exposure to opioids through previous legitimate prescriptions for injuries. Patients with a history of depression, post-traumatic stress disorder (PTSD), anxiety, childhood trauma and abuse are more prone to substance abuse.
Genetics play a role in the development of opioid use disorder as well. There are three primary types of opioid receptors: mu, delta, and kappa. The mu receptor, found in the brain, is involved in reducing the release of neurotransmitters. Genetic factors have been shown to influence the treatment of pain and opioid use disorder. However, specific pharmacogenomic dosing recommendations have not been established due to the lack of clear evidence linking genotype to drug effects, toxicity, or dependence.
The diagnosis of opioid use disorder is crucial for clinicians to make informed decisions about prescribing practices and to identify patients who are using opioids chronically. One important intervention clinicians should consider is offering naloxone to all patients with opioid use disorder. Naloxone is a mu-opioid receptor antagonist that can reverse the effects of opioid overdose and save lives.
Patients with opioid use disorder are at the highest risk of death within the first four weeks of starting opioid dependence treatment and the subsequent four weeks after treatment discontinuation. Therefore, clinicians need to maintain close contact with patients during and after tapering off medications like methadone. Discontinuing maintenance treatments without proper support and follow-up can significantly increase the risk of relapse to illicit drug use and potentially lead to fatal overdoses.
Compared to methadone, induction with buprenorphine has a lower risk of mortality. Both methadone and buprenorphine therapies can reduce morbidity and mortality associated with opioid use disorder. Opioid replacement therapies, such as these, have been shown to decrease the incidence of long-term opioid addiction, reduce illegal opiate use, and lower mortality rates.
Clinical History
When evaluating a patient who meets the criteria for an opioid use disorder, it is essential to conduct a comprehensive social history and mental health history. This information provides valuable insights into the patient’s background, lifestyle, and potential contributing factors to their opioid use. Additionally, recording the patient’s previous injury history is crucial as it can shed light on the initial exposure to opioids and the potential development of dependence.
Opioid use disorder is characterized by opioid use and the recurrence of two or more specific problems within 12 months. These problems, as outlined in the diagnostic criteria, encompass a range of issues. They include experiencing withdrawal symptoms when attempting to stop using opioids, sacrificing important life activities in favor of opioid use, and spending excessive amounts of time using opioids. Additionally, individuals with opioid use disorder exhibit significant impairment or distress as a direct consequence of their opioid use.
The severity of the condition is determined by the presence of six or more of these diagnostic criteria. There are several signs and symptoms associated with opioid use disorder. One notable symptom is drug-seeking behavior, where individuals persistently try to obtain opioids, often disregarding legal or social consequences. Another sign may be the acquisition of multiple opioid prescriptions from different clinicians, indicating attempts to procure more opioids.
Additionally, medical complications can arise due to opioid use, highlighting the potential adverse effects on health. These complications may include respiratory depression, infections, cardiovascular problems, and hormonal imbalances. Individuals with opioid use disorder commonly experience cravings for opioids, which can be intense and challenging to resist.
As the disorder progresses, tolerance to opioids develops, leading to increased usage over time as higher doses are required to achieve the desired effects. Moreover, if opioids are abruptly discontinued or significantly reduced, individuals with opioid use disorder may exhibit withdrawal symptoms. These symptoms can be physically and psychologically distressing, including restlessness, muscle aches, nausea, vomiting, diarrhea, and dysphoria.
Physical Examination
Opioid withdrawal symptoms encompass a range of physical and psychological manifestations. These symptoms may include abdominal cramps, intense cravings for opioids, restlessness, agitation, diarrhea, dilated pupils, anxiety, elevated blood pressure, sneezing, excessive sweating, increased heart rate, tearing, tremors or shakiness, muscle pain, runny nose, goosebumps, and insomnia. These symptoms can be highly distressing and contribute to the cycle of opioid use and dependence.
Conversely, opioid intoxication is characterized by a distinct set of symptoms. These symptoms may include confusion, constricted pupils, excessive drowsiness or hypersomnia, nausea, feelings of euphoria, constipation, and a decreased perception of pain. These effects contribute to the pleasurable and sedating properties of opioids, which can reinforce the cycle of misuse and addiction.
In the case of a suspected opioid overdose, a physical examination may reveal specific indicators. Notably, pinpoint pupils (pupillary constriction) are often observed. The patient may exhibit hypothermia or bradycardia (abnormally low body temperature or slow heart rate). They may also display limited responsiveness or be unconscious, indicating a severe overdose state.
Differential Diagnoses
Substance Abuse Disorder
Rehabilitation for opioid use disorder typically employs a cognitive-behavioral approach similar to treating other chronic conditions. A comprehensive treatment plan includes maintenance programs that incorporate psychological support. Patients are encouraged to make positive changes through education, cooperative efforts, and the use of medications. The primary goal of therapy is to minimalize the risk of drug use relapse and promote long-term recovery.
Opioid replacement, maintenance, or substitution therapy involves substituting a longer-acting opioid with less euphoric and addictive properties for the problematic opioid. Commonly used medications include buprenorphine and methadone, which are prescribed and administered under medical supervision. The combination of buprenorphine and naloxone is widely utilized. Opioid maintenance medications help alleviate withdrawal symptoms, reduce cravings, and minimize the euphoric effects of opioids. With the assistance of these medications, nearly half of the patients can achieve abstinence from additional opioids while on replacement therapy.
The goals of maintenance therapy extend beyond drug cessation and focus on improving overall health and quality of life. This includes reducing the risks of infectious diseases such as HIV, hepatitis B, and hepatitis C. Additional objectives include enhancing interpersonal relationships, reducing cravings, and decreasing engagement in criminal activities often associated with funding illicit drug use. Methadone is a commonly used medication for opioid replacement therapy. It has been extensively studied and implemented worldwide, and methadone maintenance is a well-established approach.
Methadone treatment offers advantages such as blocking the euphoric effects of opioids, reducing cravings, and lowering the transmission of infectious diseases. Methadone maintenance is generally non-sedating and considered medically safe when used without concomitant prescription or illicit drugs. The maintenance phase typically begins approximately six weeks after initiating therapy and can last for years or even a lifetime. Reduction in methadone can be a gradual process that spans several weeks or months, depending on the individual’s level of opioid dependence.
As an adjunctive therapy, clonidine or lofexidine can address the signs and symptoms of opioid withdrawal. In certain countries, although not in the United States, individuals who are long-term injecting drug users and have not responded to methadone may receive pure injectable diamorphine as a treatment option. Dihydrocodeine, available in extended-release and immediate-release formulations, can be a viable alternative to methadone or buprenorphine for maintenance treatment.
Clonidine or tizanidine can be beneficial in reducing anxiety associated with opioid withdrawal and alleviating autonomic overactivity symptoms such as piloerection. Benzodiazepines or other sedating drugs are used to manage anxiety and insomnia related to opioid withdrawal. Loperamide is commonly used to treat nausea, diarrhea, and vomiting, while prochlorperazine, combined with sports drinks or intravenous fluids, can also provide relief. Nonsteroidal anti-inflammatory agents like naproxen are utilized for pain relief. Combination therapies have demonstrated superior efficacy to placebo in providing symptomatic relief during opioid withdrawal.
Sublocade
For the first two months, use 300 mg subcutaneously once per month; then, take 100 mg/month as a maintenance dosage.
If a 100-mg dosage is tolerated, but the patient does not show an acceptable clinical response, the maintenance dose can be increased to 300 mg monthly.
Brixadi
Indicated to be used after a single dose of transmucosal buprenorphine in people with moderate to severe OUD
Target dosage advised weekly: 24mg subcutaneously every seven days
Follow these titrations over the first week.
When objective indications of mild to moderate withdrawal occur, provide a test dose of 4 mg of transmucosal buprenorphine.
If the test dosage is tolerated without precipitating withdrawal, deliver the first 16 mg (Brixadi) subcutaneously.
To reach the suggested 24-mg dosage (weekly), give a second dose of 8 mg Brixadi within three days after the first dose.
Give an additional 8 mg dosage if necessary during the first week of therapy, waiting at least 24 hours after the initial injection for a total weekly dose of 32 mg.
32 mg is the maximum weekly dosage.
Brixadi weekly substitution for transmucosal buprenorphine
Administer every 7 days.
A weekly dosage may be given up to two days before or after the weekly time point to prevent missed doses.
≤6mg Sublingual-8mg subcutaneous
8 to 10mg Sublingual-16mg subcutaneous
12 to 16mg Sublingual-24mg subcutaneous
18 to 24mg Sublingual-32mg subcutaneous
Brixadi monthly substitution for transmucosal buprenorphine
To prevent missed doses, provide monthly dosage one week before or after the time point.
≤6mg Sublingual-N/A
8 to 10mg Sublingual-64mg subcutaneous
12 to 16mg Sublingual-96mg subcutaneous
18 to 24mg Sublingual-128mg subcutaneous
Brixadi's Change from Weekly to Monthly
16 mg/week Subcutaneous: Administer 64 mg subcutaneous monthly
24 mg/week Subcutaneous: Administer 96 mg subcutaneous monthly
32 mg/week Subcutaneous: Administer 128 mg subcutaneous monthly
Brixadi dosage changes
Depending on the patient's response to treatment, the maximum weekly
Brixadi dose is 32 mg, and the maximum monthly Brixadi dose is 128 mg.
Dose Adjustments
Renal impairment
Patients with impaired kidney function were excluded from the studies.
Hepatic impairment
Moderate to severe pre-existing condition
Due to these drugs' extended half-lives, dose modifications do not immediately affect plasma buprenorphine levels.
Patients with moderate-to-severe pre-existing hepatic impairment are unsuitable for treatment with buprenorphine because levels cannot be immediately adjusted.
Indicated for opioid withdrawal
initial dose: 0.18 mg of three tablets (i.e.,0.54 mg) orally four times a day, while in the peak time of withdrawal symptoms (like the 5-7 days following opioid use
it should not exceed 2.88 mg of total dose in a day (i.e.,16 tablets)
it should not exceed 0.72 mg of a single dose in a day (i.e.,4 tablets)
therapy can be continued for nearly 14 days with dosing guided by the symptoms
for people who show a higher sensitivity, the dose can be decreased, held, or also discontinued
when opioid withdrawal symptoms get subside, the decreased dose may be suitable
discontinue by slowly decreasing the dose for over a 2-4 day period to alleviate the lofexidine withdrawal symptoms (like decreasing by one tablet/dose every one-two day)
kratom is currently being investigated for its potential therapeutic effects in pain management, mood regulation, and opioid addiction treatment. Researchers are exploring its alkaloids' interactions with opioid receptors to better understand its mechanisms of action
medtigo
Opioid Use Disorder
Updated :
August 30, 2023
Opioid use disorder is a chronic condition characterized by the regular and prolonged use of opioids, leading to significant impairment or distress in an individual’s life. In the United States, the number of people who use opioids on a regular basis is comparable to the combined number of individuals diagnosed with psoriatic arthritis, obsessive-compulsive disorder, and epilepsy. The diagnosis of opioid use disorder is based on the criteria outlined in the DSM-5.
One of the key features of this disorder is a strong and persistent desire to obtain and consume opioids, despite facing adverse professional and societal consequences. Opioids encompass a range of substances, including illicit drugs like heroin, as well as prescription medications like codeine, morphine, fentanyl, and synthetic opioids such as oxycodone. Individuals with opioid use disorder often experience an overwhelming craving for opioids, which leads to a progressively higher tolerance for the drug.
When attempts are made to discontinue or reduce opioid use, withdrawal syndrome manifests as physical and psychological symptoms. Opioid use disorder comprises addiction and dependence, with addiction indicating the most severe form. Dependence refers to the body’s adaptation to opioids, resulting in withdrawal symptoms upon cessation. In contrast, addiction involves the compulsive and uncontrollable use of opioids, despite negative consequences and a loss of control over drug-seeking behavior.
Globally, over 16 million individuals are dependent on opioids and meet the criteria for opioid use disorder, with three million residing in the United States. This pervasive problem leads to a staggering number of deaths yearly, with over 120,000 deaths worldwide attributed to opioid use disorder. The opioid-related death toll in the U.S. represents the most lethal drug epidemic in history.
According to the CDC, the age-adjusted rate of drug poisoning deaths involving opioid analgesics rose to 7.0 per 100,000 in 2015. Substance abuse, methamphetamines, alcohol, and opioids are widespread, affecting more than 20 million people who suffer from substance use disorder. Disturbingly, nearly 10% of the U.S. population over 12 has engaged in illicit drug use within the past month.
Among the 20 million Americans grappling with substance abuse, two million individuals are dependent on prescription opioid pain medications, while 500,000 individuals use heroin. Although the recreational use of opioids peaked in 2010, there has been a gradual decline as the opioid epidemic has gained significant attention across the United States. Remarkably, up to 50% of patients receiving long-term opioid therapy meet the criteria for opioid use disorder. The prevalence of opioid use and dependency varies across age groups and genders.
Men exhibit higher rates of opioid use, develop a dependence on various opioids and account for most opioid-related overdoses. On the other hand, women have been prescribed opioids more frequently than men for pain management. Deaths resulting from opioid use tend to be more common among older individuals, with opioid overdoses peaking between the ages of 40 and 50. However, heroin overdoses are most prevalent among individuals aged 20 to 30.
The peak age for treatment of opioid use disorder falls within the range of 20 to 35 years old. Patients diagnosed with opioid use disorder who experience legal issues related to their drug use are often found to have previous criminal records and exhibit high impulsivity tendencies. It is crucial to understand the complexities of these circumstances in order to provide appropriate care and support to those affected by opioid use disorder.
The pathophysiology of opioid use disorder involves complex interactions between opioids and the brain’s reward and pain pathways. Opioids exert their effects primarily by binding to opioid receptors in various central nervous system regions, including the brain. When opioids bind to these receptors, they activate the reward pathway, which releases dopamine, a neurotransmitter associated with pleasure and reinforcement. This activation leads to a euphoric feeling and reinforces the desire to continue using opioids.
Over time, repeated opioid use can lead to neuroadaptations in the brain, altering the reward system’s functioning and contributing to addiction development. Chronic opioid use also affects other neurotransmitter systems, such as gamma-aminobutyric acid (GABA), glutamate, and norepinephrine, which regulate mood, anxiety, and stress responses. These alterations contribute to the dysregulation of emotional and motivational processes observed in individuals with opioid use disorder.
Additionally, opioids can cause physical dependence, where the body adapts to the presence of opioids and requires them to function normally. Prolonged use of opioids leads to the downregulation of opioid receptors and desensitization of the reward system. This results in the development of tolerance, where higher doses of opioids are needed to achieve the desired effects. Withdrawal symptoms occur when opioid use is abruptly discontinued or significantly reduced.
Opioid use disorder has a multifaceted etiology influenced by biological, environmental, genetic, and psychosocial factors. Opioids, including prescription analgesics, are derived from the poppy plant and are commonly prescribed by clinicians to manage pain, suppress cough, or relieve diarrhea. Opioid use disorder can affect individuals from diverse educational and socioeconomic backgrounds. Biologically, addiction can have a foundation in certain deficiencies.
For example, patients may have neurotransmitter imbalances, such as low levels of dopamine, which can drive them to seek external sources of endorphins. This deficit can lead some individuals to turn to opioids for self-medication. Additionally, individuals with a family history of substance abuse disorders, particularly in first-degree relatives, are more susceptible to developing opioid use disorder. The estimated heritability of opioid use disorder is around 50%, suggesting a genetic component.
The environment in which a patient with opioid use disorder is exposed can also influence their likelihood of developing a substance abuse disorder. Environmental factors may include social influences, such as peer relationships, or exposure to opioids through previous legitimate prescriptions for injuries. Patients with a history of depression, post-traumatic stress disorder (PTSD), anxiety, childhood trauma and abuse are more prone to substance abuse.
Genetics play a role in the development of opioid use disorder as well. There are three primary types of opioid receptors: mu, delta, and kappa. The mu receptor, found in the brain, is involved in reducing the release of neurotransmitters. Genetic factors have been shown to influence the treatment of pain and opioid use disorder. However, specific pharmacogenomic dosing recommendations have not been established due to the lack of clear evidence linking genotype to drug effects, toxicity, or dependence.
The diagnosis of opioid use disorder is crucial for clinicians to make informed decisions about prescribing practices and to identify patients who are using opioids chronically. One important intervention clinicians should consider is offering naloxone to all patients with opioid use disorder. Naloxone is a mu-opioid receptor antagonist that can reverse the effects of opioid overdose and save lives.
Patients with opioid use disorder are at the highest risk of death within the first four weeks of starting opioid dependence treatment and the subsequent four weeks after treatment discontinuation. Therefore, clinicians need to maintain close contact with patients during and after tapering off medications like methadone. Discontinuing maintenance treatments without proper support and follow-up can significantly increase the risk of relapse to illicit drug use and potentially lead to fatal overdoses.
Compared to methadone, induction with buprenorphine has a lower risk of mortality. Both methadone and buprenorphine therapies can reduce morbidity and mortality associated with opioid use disorder. Opioid replacement therapies, such as these, have been shown to decrease the incidence of long-term opioid addiction, reduce illegal opiate use, and lower mortality rates.
Clinical History
When evaluating a patient who meets the criteria for an opioid use disorder, it is essential to conduct a comprehensive social history and mental health history. This information provides valuable insights into the patient’s background, lifestyle, and potential contributing factors to their opioid use. Additionally, recording the patient’s previous injury history is crucial as it can shed light on the initial exposure to opioids and the potential development of dependence.
Opioid use disorder is characterized by opioid use and the recurrence of two or more specific problems within 12 months. These problems, as outlined in the diagnostic criteria, encompass a range of issues. They include experiencing withdrawal symptoms when attempting to stop using opioids, sacrificing important life activities in favor of opioid use, and spending excessive amounts of time using opioids. Additionally, individuals with opioid use disorder exhibit significant impairment or distress as a direct consequence of their opioid use.
The severity of the condition is determined by the presence of six or more of these diagnostic criteria. There are several signs and symptoms associated with opioid use disorder. One notable symptom is drug-seeking behavior, where individuals persistently try to obtain opioids, often disregarding legal or social consequences. Another sign may be the acquisition of multiple opioid prescriptions from different clinicians, indicating attempts to procure more opioids.
Additionally, medical complications can arise due to opioid use, highlighting the potential adverse effects on health. These complications may include respiratory depression, infections, cardiovascular problems, and hormonal imbalances. Individuals with opioid use disorder commonly experience cravings for opioids, which can be intense and challenging to resist.
As the disorder progresses, tolerance to opioids develops, leading to increased usage over time as higher doses are required to achieve the desired effects. Moreover, if opioids are abruptly discontinued or significantly reduced, individuals with opioid use disorder may exhibit withdrawal symptoms. These symptoms can be physically and psychologically distressing, including restlessness, muscle aches, nausea, vomiting, diarrhea, and dysphoria.
Physical Examination
Opioid withdrawal symptoms encompass a range of physical and psychological manifestations. These symptoms may include abdominal cramps, intense cravings for opioids, restlessness, agitation, diarrhea, dilated pupils, anxiety, elevated blood pressure, sneezing, excessive sweating, increased heart rate, tearing, tremors or shakiness, muscle pain, runny nose, goosebumps, and insomnia. These symptoms can be highly distressing and contribute to the cycle of opioid use and dependence.
Conversely, opioid intoxication is characterized by a distinct set of symptoms. These symptoms may include confusion, constricted pupils, excessive drowsiness or hypersomnia, nausea, feelings of euphoria, constipation, and a decreased perception of pain. These effects contribute to the pleasurable and sedating properties of opioids, which can reinforce the cycle of misuse and addiction.
In the case of a suspected opioid overdose, a physical examination may reveal specific indicators. Notably, pinpoint pupils (pupillary constriction) are often observed. The patient may exhibit hypothermia or bradycardia (abnormally low body temperature or slow heart rate). They may also display limited responsiveness or be unconscious, indicating a severe overdose state.
Differential Diagnoses
Substance Abuse Disorder
Rehabilitation for opioid use disorder typically employs a cognitive-behavioral approach similar to treating other chronic conditions. A comprehensive treatment plan includes maintenance programs that incorporate psychological support. Patients are encouraged to make positive changes through education, cooperative efforts, and the use of medications. The primary goal of therapy is to minimalize the risk of drug use relapse and promote long-term recovery.
Opioid replacement, maintenance, or substitution therapy involves substituting a longer-acting opioid with less euphoric and addictive properties for the problematic opioid. Commonly used medications include buprenorphine and methadone, which are prescribed and administered under medical supervision. The combination of buprenorphine and naloxone is widely utilized. Opioid maintenance medications help alleviate withdrawal symptoms, reduce cravings, and minimize the euphoric effects of opioids. With the assistance of these medications, nearly half of the patients can achieve abstinence from additional opioids while on replacement therapy.
The goals of maintenance therapy extend beyond drug cessation and focus on improving overall health and quality of life. This includes reducing the risks of infectious diseases such as HIV, hepatitis B, and hepatitis C. Additional objectives include enhancing interpersonal relationships, reducing cravings, and decreasing engagement in criminal activities often associated with funding illicit drug use. Methadone is a commonly used medication for opioid replacement therapy. It has been extensively studied and implemented worldwide, and methadone maintenance is a well-established approach.
Methadone treatment offers advantages such as blocking the euphoric effects of opioids, reducing cravings, and lowering the transmission of infectious diseases. Methadone maintenance is generally non-sedating and considered medically safe when used without concomitant prescription or illicit drugs. The maintenance phase typically begins approximately six weeks after initiating therapy and can last for years or even a lifetime. Reduction in methadone can be a gradual process that spans several weeks or months, depending on the individual’s level of opioid dependence.
As an adjunctive therapy, clonidine or lofexidine can address the signs and symptoms of opioid withdrawal. In certain countries, although not in the United States, individuals who are long-term injecting drug users and have not responded to methadone may receive pure injectable diamorphine as a treatment option. Dihydrocodeine, available in extended-release and immediate-release formulations, can be a viable alternative to methadone or buprenorphine for maintenance treatment.
Clonidine or tizanidine can be beneficial in reducing anxiety associated with opioid withdrawal and alleviating autonomic overactivity symptoms such as piloerection. Benzodiazepines or other sedating drugs are used to manage anxiety and insomnia related to opioid withdrawal. Loperamide is commonly used to treat nausea, diarrhea, and vomiting, while prochlorperazine, combined with sports drinks or intravenous fluids, can also provide relief. Nonsteroidal anti-inflammatory agents like naproxen are utilized for pain relief. Combination therapies have demonstrated superior efficacy to placebo in providing symptomatic relief during opioid withdrawal.
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