Opioids: addiction, symptoms and treatment

The use of opioids for medical purposes without supervision by health care professionals and any use for non-medical indications can lead to severe consequences with the development of dependence. It is characterized by an extremely strong urge to continue taking opioids, the development of tolerance, when an increase in the dose is necessary to achieve the initial effect, and physical dependence, the severity of which increases with increasing dosage and duration of use.

Opioid dependence is rapidly increasing. Heroin is the most commonly used substance, with opium use rare. Dependence on prescription opioid analgesics such as morphine and oxycodone is increasing, with some increase in the proportion of people using them for legitimate medical purposes. In addition, many people find that using opioids enables them to cope with what they consider intolerable life stress.

Physical dependence inevitably leads to continued use of the same opioid or a related drug to prevent withdrawal. Withdrawal from the drug or administration of an antagonist causes the development of a characteristic withdrawal syndrome.

A therapeutic dose taken regularly for 2-3 days may lead to some tolerance and dependence, and when the drug is stopped, a person may experience mild withdrawal symptoms that are barely noticeable or flu-like.

Patients with chronic pain requiring long-term use should not be considered addicts, although they may have some problems with tolerance and physical dependence. Opioids cause cross-tolerance, so patients may substitute one drug for another. People who have developed tolerance may have few symptoms of drug use, are able to function normally in everyday life, but have a persistent problem obtaining the drug. Tolerance to the different effects of these drugs often develops unevenly. For example, heroin users may be highly tolerant to the euphoric and lethal effects of heroin, but still have pinpoint pupils and constipation.

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Symptoms of Opioid Addiction

Acute intoxication (overdose) is characterized by euphoria, flush, itching (especially for morphine), miosis, drowsiness, decreased frequency and depth of breathing, hypotension, bradycardia, and decreased body temperature.

Physical dependence can be suspected if the patient injects opioids 3 or more times a day, has fresh injection marks, has withdrawal symptoms and signs, or has morphine glucuronide in the urine (heroin is biotransformed into morphine, conjugated with glucuronide, and excreted). Since heroin is often inhaled, the nasal septum may be perforated.

Withdrawal symptoms typically include symptoms and signs of CNS hyperactivity. The severity of the syndrome increases with increasing opioid dose and duration of dependence. Withdrawal symptoms begin 4 hours after drug administration and peak at 72 hours for heroin. Anxiety associated with drug craving is followed by increased respiratory rate at rest (>16 breaths per minute), usually with yawning, sweating, lacrimation, and rhinorrhea. Other symptoms include mydriasis, piloerection (goose bumps), tremors, muscle twitching, hot and cold flashes, muscle pain, and anorexia. Withdrawal in patients taking methadone (which has a longer half-life) develops more slowly and is less severe in appearance than heroin withdrawal, although patients may describe it as more severe.

Complications of heroin addiction

Complications of heroin addiction are related to unsanitary administration of the drug, the characteristic features of the drug, overdose, or behavior in a state of drug intoxication. The main complications concern the pulmonary, skeletal, and nervous systems; hepatitis and immunological changes are possible.

Aspiration pneumonitis, pneumonia, lung abscess, septic pulmonary embolism, and atelectasis may occur. Pulmonary fibrosis due to talc granulomatosis may develop if opioid analgesics are injected in tablet form. Chronic heroin addiction results in decreased vital capacity and a mild to moderate decrease in diffusion capacity. These effects are distinct from the pulmonary edema that may occur with heroin injection. Many patients who use heroin smoke one or more packs of cigarettes per day, making them particularly susceptible to a variety of pulmonary infections.

Viral hepatitis A, B, C may occur. The combination of viral hepatitis and often significant alcohol consumption may play a role in the high incidence of liver dysfunction.

The most common musculoskeletal complication is osteomyelitis (especially of the lumbar spine), possibly due to hematogenous spread of organisms from unsterile injections. Infectious spondylitis and sacrolithiasis may occur. In myositis ossificans (injection of a drug into the cubital veins), the brachialis muscle is damaged by improper needle manipulation, followed by replacement of the muscle ligaments by calcific mass (extraosseous metaplasia).

Hypergammaglobulinemia, both IgG and IgM, is observed in about 90% of addicts. The reasons for this are unclear but probably reflect repeated antigenic stimulation from infections and daily parenteral administration of foreign substances. Hypergammaglobulinemia is reduced by methadone maintenance therapy. Patients who use heroin and other intravenous drugs have an extremely high risk of HIV infection and AIDS. In communities where needles and syringes are shared, the spread of AIDS is alarming.

Neurological disorders in patients using heroin are usually non-infectious complications of coma and cerebral anoxia. Toxic amblyopia (probably due to the substitution of quinine for heroin for adulteration), transverse myelitis, various mononeuropathies and polyneuropathies, and Julian-Barré syndrome may be observed. Cerebral complications also include those secondary to bacterial endocarditis (bacterial meningitis, mycotic aneurysm, brain abscess, subdural and epidural abscess), viral hepatitis or tetanus, and acute cerebral falciparum malaria. Some neurological complications may be associated with allergic reactions to a mixture of heroin and adulterants.

Superficial skin abscesses, cellulitis, lymphangitis, lymphadenitis, and phlebitis due to contaminated needles may occur. Many heroin users begin by injecting subcutaneously and may return to this route when severe scarring makes the veins inaccessible. When addicts reach a point of desperation, skin ulcers may develop in unusual locations. Contaminated needles and drug may cause bacterial endocarditis, hepatitis, and HIV infection. These complications accompany frequent injections. As heroin potency increases, more people are snorting and smoking heroin, which may reduce the problems associated with microbial contamination.

Complications associated with heroin use are often transmitted to the fetus from heroin-using mothers. Because heroin and methadone readily cross the placenta, the fetus quickly becomes physically dependent. Mothers infected with HIV or hepatitis B can transmit the infection to the fetus. Pregnant women who are diagnosed early should be offered methadone maintenance therapy. Abstinence is undoubtedly better for the fetus, but such mothers often return to heroin use and refuse prenatal care. Late withdrawal of heroin or methadone in pregnant women can cause preterm labor, so pregnant women at late stages of pregnancy are better stabilized with methadone than to risk opioid withdrawal. Mothers on methadone maintenance therapy can breastfeed their infants without noticeable clinical problems in the infant, since drug concentrations in milk are minimal.

Infants born to mothers addicted to opioids may experience tremors, loud crying, shaking, seizures (rarely), and tachypnea.

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Opioid Addiction Treatment

Acute use. Overdose is usually treated with the opioid antagonist naloxone (0.4 to 2 mg intravenously) because it has no respiratory depression properties. It rapidly reverses opioid-induced unconsciousness. Because some patients become agitated and aggressive after emerging from a comatose state, physical restraint may be necessary before antagonists are used. All patients with overdose should be hospitalized and observed for at least 24 hours because naloxone has a relatively short duration of action. Respiratory depression may also recur within a few hours, especially with methadone, requiring repeat methadone administration at an appropriate dose for that period. Severe pulmonary edema, which can lead to death due to hypoxia, is usually not treated with naloxone and its relationship to overdose is unclear.

Chronic use. Clinical treatment of heroin addicts is extremely difficult. The AIDS epidemic has spurred the harm reduction movement, the search for appropriate ways to reduce the harm caused by drugs without stopping drug use. For example, providing clean needles and syringes for injections can reduce the spread of HIV. Despite this evidence for harm reduction, federal funding in the United States does not provide needles and syringes to intravenous drug users. Other harm reduction strategies, such as easy access to methadone or buprenorphine substitution programs, alternative maintenance strategies, and reduced restrictions on prescriptions for psychoactive substances, are more common in some European countries than in the United States, where these programs are seen as encouraging drug use.

The physician must be fully aware of federal, state, and local laws. Treatment is complicated by the need to cope with societal attitudes toward the treatment of addicted patients (including the attitudes of law enforcement, other physicians, and health care workers). In most cases, the physician should refer the patient to a specialized treatment center rather than attempt to treat the patient himself.

For opioid medications to be legally used to treat addiction, a physician must be convinced that physical dependence on opioids exists. However, many patients seeking help use low-grade heroin, which may not be physically addictive. Dependence on low-grade heroin (which may occur in people who have been taking opioid analgesics for a long time) can be treated by slowly tapering the dose, substituting weak opioids (such as propoxyphene), or using benzodiazepines (which do not cross-tolerate with opioids) in decreasing doses.

Withdrawal is self-limiting and, although extremely unpleasant, is not life-threatening. Minor metabolic and physical withdrawal effects may persist for up to 6 months. Whether such prolonged withdrawal contributes to relapse is unclear. Drug-seeking behavior usually begins with the first withdrawal symptoms, and hospital staff should be alert to drug-seeking behavior. Visitors should be limited. Many patients with withdrawal symptoms have underlying medical problems that need to be diagnosed and treated.

Methadone substitution is the preferred method of opioid withdrawal in severely dependent patients because of methadone's long half-life and less pronounced sedation and euphoria. Methadone is given orally in minimal amounts (usually 15-40 mg once daily), which prevents severe withdrawal symptoms, but not necessarily all of them. Higher doses are given if there is evidence of withdrawal. Doses of 25 mg or more may cause unconsciousness unless the patient has developed tolerance. Once an appropriate dose has been established, it should be progressively reduced by no more than 20% per day. Patients typically become irritable and request additional doses. Withdrawal from methadone is similar to that of heroin, but the onset is more gradual and delayed, 36-72 hours after cessation of use. Acute withdrawal symptoms usually subside within 10 days, but patients often report deep muscle aches. Weakness, insomnia, and generalized anxiety are common for several months. Withdrawal from methadone in addicts on methadone maintenance therapy can be particularly difficult, as the methadone dose can be as high as 100 mg/day. In general, detoxification should begin with a reduction in the dose to 60 mg once daily for several weeks before attempting full detoxification.

The central adrenergic drug clonidine can reverse virtually all signs of opioid withdrawal. It probably reduces central adrenergic turnover secondary to central receptor stimulation (clonidine lowers blood pressure by a similar mechanism). However, clonidine can cause hypotension and drowsiness, and its withdrawal may result in anxiety, insomnia, irritability, tachycardia, and headache. Clonidine may help patients with heroin or methadone withdrawal before they begin oral naltrexone treatment. The mixed opioid agonist-antagonist buprenorphine may also be used successfully in withdrawal.

Maintenance treatment for opioid addiction

There is no consensus on long-term treatment for opioid-dependent patients. In the United States, thousands of opioid-dependent patients are in methadone maintenance programs, which are designed to control the patients’ problem-solving by providing them with large doses of oral methadone, enabling them to be socially productive. Methadone blocks the effects of injectable heroin and relieves cravings for the drug. For many patients, the program works. However, the widespread use of methadone has provoked social and political unrest, and many people question the usefulness of the treatment.

Buprenorphine, an agonist-antagonist, is available for maintenance treatment of opioid-dependent patients and is becoming a preferred choice over methadone. It blocks receptors, thereby discouraging the illicit use of heroin or other opioid analgesics. Buprenorphine can be prescribed by specially trained physicians certified by the federal government. The usual dose is 8 or 16 mg tablet once daily. For many opioid addicts, this option is preferable to a methadone program because it eliminates the need to attend a methadone maintenance clinic.

Levomethadyl acetate (LAAM) is a long-acting opioid closely related to methadone. Some patients taking LAAM have been found to have abnormal QT intervals. Therefore, its use is not approved, and patients receiving it are best transitioned to methadone maintenance therapy. LAAM is administered three times per week, reducing the cost and hassle of daily client visits or taking medication at home. A dose of 100 mg three times per week is comparable to methadone at a dose of 80 mg once per day.

Naltrexone, an orally bioavailable opioid antagonist, blocks the effects of heroin. It has weak agonist properties, and most opioid-dependent patients do not voluntarily take it. The usual dose is 50 mg once daily or 350 mg/week, divided into 2 or 3 doses.

The therapeutic community concept, pioneered by Daytop Village and Phoenix House, involves drug-free residential treatment in community centers where drug users are educated and reoriented, enabling them to build new lives. Residential stays typically last 15 months. These communities help, even transform, some patients. However, the initial dropout rate is very high. How well these communities work, how many should be opened, and how much the community should subsidize them, remains unclear.