Description

Methadone, sold under the brand name Dolophine among others, is an opioid used for opioid maintenance therapy in opioid dependence and for chronic pain management. Detoxification using methadone can be accomplished in less than a month, or it may be done gradually over as long as six months. While a single dose has a rapid effect, maximum effect can take up to five days of use. The pain-relieving effects last about six hours after a single dose. After long-term use, in people with normal liver function, effects last 8 to 36 hours. Methadone is usually taken by mouth and rarely by injection into a muscle or vein.

Side effects are similar to those of other opioids. These frequently include dizziness, sleepiness, vomiting, and sweating. Serious risks include opioid abuse and a decreased effort to breathe. Abnormal heart rhythms may also occur due to a prolonged QT interval. The number of deaths in the United States involving methadone poisoning declined from 4,418 in 2011 to 3,300 in 2015. Risks are greater with higher doses. Methadone is made by chemical synthesis and acts on opioid receptors.

Methadone was developed in Germany around 1937 to 1939 by Gustav Ehrhart and Max Bockmühl. It was approved for use in the United States in 1947. It is on the World Health Organization’s List of Essential Medicines, the safest and most effective medicines needed in a health system. In 2013, about 41,400 kilograms were manufactured globally. It is regulated similarly to other narcotic drugs. It is not particularly expensive in the United States

Medical uses

Methadone maintenance

Methadone is used for the treatment of opioid use disorder. It may be used as maintenance therapy or in shorter periods for detoxification to manage opioid withdrawal symptoms.

A 2009 Cochrane review found methadone was effective in retaining people in treatment and in the reduction or cessation of heroin use as measured by self-report and urine/hair analysis but did not affect criminal activity or risk of death.

Treatment of opioid-dependent persons with methadone follows one of two routes: maintenance or detoxification. Methadone maintenance therapy (MMT) usually takes place in outpatient settings. It is usually prescribed as a single daily dose medication for those who wish to abstain from illicit opioid use. Treatment models for MMT differ. It is not uncommon for treatment recipients to be administered methadone in a specialist clinic, where they are observed for around 15–20 minutes post-dosing, to reduce the risk of diversion of medication.

The duration of methadone treatment programs ranges from a few months to several years. Given opioid dependence is characteristically a chronic relapsing/remitting disorder, MMT may be lifelong. The length of time a person remains in treatment depends on a number of factors. While starting doses may be adjusted based on the number of opioids reportedly used, most clinical guidelines suggest doses start low (e.g. at doses not exceeding 40 mg daily) and are incremented gradually.

Methadone maintenance has been shown to reduce the transmission of bloodborne viruses associated with opioid injection, such as hepatitis B and C, and/or HIV. The principal goals of methadone maintenance are to relieve opioid cravings, suppress the abstinence syndrome, and block the euphoric effects associated with opioids.

Chronic methadone dosing will eventually lead to neuroadaptation, characterized by a syndrome of tolerance and withdrawal (dependence). However, when used correctly in treatment, maintenance therapy has been found to be medically safe, non-sedating, and can provide a slow recovery from opioid addiction. Methadone has been widely used for pregnant women addicted to opioids.

Opioid detoxification[edit]

Methadone is approved in the US, and many other parts of the world, for the treatment of opioid addiction. Its use for the treatment of addiction is usually strictly regulated. In the US, outpatient treatment programs must be certified by the federal Substance Abuse and Mental Health Services Administration (SAMHSA) and registered by the Drug Enforcement Administration (DEA) in order to prescribe methadone for opioid addiction.

Pain

Methadone is used as an analgesic in chronic pain, often in rotation with other opioids.[21][22] Due to its activity at the NMDA receptor, it may be more effective against neuropathic pain; for the same reason, tolerance to the analgesic effects may be less than that of other opioids

Adverse effects

  • Adverse effects of methadone include:
  • Sedation
  • Diarrhea or constipation
  • Flushing
  • Perspiration and sweating
  • Heat intolerance
  • Dizziness or fainting
  • Weakness
  • Chronic fatigue, sleepiness, and exhaustion
  • Sleep problems such as drowsiness, trouble falling asleep (Insomnia), and trouble staying asleep
  • Constricted pupils
  • Dry mouth
  • Nausea and vomiting
  • Low blood pressure
  • Hallucinations or confusion
  • Headache
  • Heart problems such as chest pain or fast/pounding heartbeat
  • Abnormal heart rhythms
  • Respiratory problems such as trouble breathing, slow or shallow breathing (hypoventilation), light-headedness, or fainting
  • Loss of appetite, and in extreme cases anorexia
  • Weight loss or weight gain
  • Memory loss
  • Stomach pains
  • Itching
  • Difficulty urinating
  • Swelling of the hands, arms, feet, and legs
  • Feeling restless or agitated
  • Mood changes, euphoria, disorientation
  • Nervousness or anxiety
  • Blurred vision
  • Decreased libido, missed menstrual periods, difficulty in reaching orgasm, or impotence
  • Skin rash
  • Seizures
  • Central sleep apnea

Withdrawal symptoms

Physical symptoms

  • Lightheadedness
  • Tearing of the eyes
  • Mydriasis (dilated pupils)
  • Photophobia (sensitivity to light)
  • Hyperventilation syndrome (breathing that is too fast/deep)
  • Runny nose
  • Yawning
  • Sneezing
  • Nausea, vomiting, and diarrhea
  • Fever
  • Sweating
  • Chills
  • Tremors
  • Akathisia (restlessness)
  • Tachycardia (fast heartbeat)
  • Aches and pains, often in the joints or legs
  • Elevated pain sensitivity
  • Blood pressure that is too high (hypertension, may cause stroke)

Cognitive symptoms

  • Suicidal ideation
  • Susceptibility to cravings
  • Depression
  • Spontaneous orgasm
  • Prolonged insomnia
  • Delirium
  • Auditory hallucinations
  • Visual hallucinations
  • Increased perception of odors (olfaction), real or imagined
  • Marked decrease or increase in sex drive
  • Agitation
  • Anxiety
  • Panic disorder
  • Nervousness
  • Paranoia
  • Delusions
  • Apathy
  • Anorexia (symptom)

Methadone withdrawal symptoms are reported as being significantly more protracted than withdrawal from opioids with shorter half-lives.

Methadone is sometimes administered as an oral liquid. Methadone has been implicated in contributing to significant tooth decay. Methadone causes dry mouth, reducing the protective role of saliva in preventing decay. Other putative mechanisms of methadone-related tooth decay include craving for carbohydrates related to opioids, poor dental care, and a general decrease in personal hygiene. These factors, combined with sedation, have been linked to the causation of extensive dental damage