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Methadone Misuse: Overdose, Dependence and Treatment

Claire Wilcox, MD profile image
By Claire Wilcox, MD • Updated Aug 23, 2023

Methadone is a medication prescribed for the treatment of opioid use disorder and pain. It is an agonist at the opioid receptor, meaning it activates the receptor like morphine and heroin.

Methadone is usually safe if taken as prescribed under the supervision of a doctor. 

If misused, methadone is dangerous because it stays in the blood for a long time and carries a significant risk of overdose. 

From 1999 to 2006, overdose deaths from methadone rose more quickly than those involving other opioid pain pills or heroin.[1] Methadone was also involved in 30% of opioid-related deaths in 2010 and 40% of single-drug opioid-related deaths, according to data from a study involving 13 states.

What Is Methadone?

Methadone is a long-acting opioid agonist taken by mouth as a liquid or pill. It is a Schedule II drug, which means it has a high potential for abuse, and its dispensing is closely monitored and regulated by the Drug Enforcement Agency. 

Like all opioids, it can cause respiratory depression and death if blood levels get high enough. This is especially concerning since it stays in the blood for almost three days.

Concurrent benzodiazepine use increases the risk of overdose even further in patients taking methadone for opioid use disorder treatment or for chronic pain.[2]

Methadone has two primary therapeutic purposes: for opioid use disorder (OUD) treatment and for pain management. 

Methadone for OUD Treatment

Methadone is dispensed by SAMHSA-certified Opioid Treatment Programs (OTP) as one of the Medication for Addiction Treatment (MAT) options.

When used for OUD treatment, methadone reduces death rates and improves functioning compared to people who do not get any medication. It also helps them avoid using illicit opioids.[3] 

Although effective, methadone carries a higher risk of overdose than the other options for OUD treatment like buprenorphine or naltrexone. The highest risk period of overdose on methadone is during the initiation phase.[4]

Methadone for Pain Treatment

Methadone is also prescribed for chronic pain by pain-management clinics and primary care settings.[5] Compared to most other opioid medications, methadone carries a higher risk of death due to overdose, even if taken as prescribed.[5] 

Taking higher doses than prescribed or taking another opioid or sedative on top of methadone is also highly dangerous. 

Methadone Misuse

Medication misuse means taking the medication for any other reason than what it was prescribed for or taking it in higher doses than prescribed. Misuse is the first step in the downward spiral leading to loss of control and OUD.

Any opioid can be misused, and methadone is no exception. For example, if it is used to “get high,” relax or sleep.

Up to a third of patients prescribed opioids for chronic pain misuse them, around 10% develop an opioid use disorder, and 6% of those go on to use heroin.

Methadone misuse and its most dangerous consequence – overdose are on the rise.

  • Between 1999 and 2006, deaths from other opioids increased from 2,757 to over 7,035. Deaths related to methadone increased from 786 to 5,416, a much more significant rise.
  • The American Association of Poison Control Centers reports that the number of methadone exposures that resulted in a death increased from 26 in 2000 to 103 in 2008.
  • Methadone accounted for 46 out of the 254 total deaths due to unintentional prescription (18.1%) in a San Diego medical examiner study – 100% of this methadone was prescribed by primary care specialists, highlighting the high risks of overdose when used for chronic pain, rather than OUD treatment.[6]

The Dangers Associated with Methadone Misuse

Due to its long half-life, methadone misuse is particularly dangerous because it can easily cause an overdose. It also has a high potential for interactions with other drugs like antibiotics, antidepressants and benzodiazepines, and other sedatives. 

Methadone Overdose

Overdose deaths involving any prescription opioids have been on the rise since the 1990s. The number of overdose deaths in the US from opioids in 2020 was almost twice that from motor vehicle fatalities

In the San Diego sample, methadone was the most common drug present in single-drug overdose patients, highlighting its particularly high level of dangerousness. [6]

Of particular importance is the potential for dangerous effects and higher overdose risk when patients take benzodiazepines or use alcohol concurrently. The combination raises the risk of sedation, respiratory suppression, and, subsequently, death. 

Unfortunately, the use of benzodiazepines in people on methadone for OUD is not uncommon. 

Methadone also interacts with many antidepressants, antibiotics, and other medicines, affecting the blood levels of one another because they are both metabolized by the same enzymes in the liver.

When people misuse methadone, they might experience an unanticipated interaction which could lead to high blood levels of methadone and an accidental overdose. 

Methadone Dependence 

As is seen with any opioid, people who misuse methadone are at risk of losing control and developing cravings and tolerance. If they stop using methadone, they will likely experience withdrawal symptoms or continue using, even though it is highly dangerous and causes negative consequences.

These are the characteristics common to an opioid use disorder (OUD) or more colloquially known as addiction or dependence.

Like with any other abusable drug, the onset of a use disorder can be insidious. If a person is taking methadone for chronic pain, it might start with the person taking one or two extra doses in a day to get better pain control.

This might lead them to run out of their prescription early, causing them to go through withdrawal and develop cravings. This pattern reoccurs month after month until their use spins out of control. 

Getting Treatment for Methadone Dependence

The first step towards recovering from an opioid use disorder is admitting that there is a problem and seeking help for it. Attending 12-step meetings and engaging in group and individual therapy can be useful.

However, the cornerstone of treatment for an OUD is Medication for Addiction Treatment MAT

MAT significantly reduces mortality from OUD compared to psychosocial treatment alone. There are three medication classes utilized for the treatment of OUD: 

  • Methadone
  • Buprenorphine
  • Naltrexone

If dispensed under the structured protocols of OTPs, often with daily observed dosing at the licensed clinics, methadone reduces death from opioids and helps people get back to their lives. 

Therefore, if methadone is given in a structured, closely observed manner, it can promote recovery from its own use disorder.

Buprenorphine-containing medications like Suboxone are another great option and safer than methadone in terms of overdose risk. Buprenorphine is more accessible since more providers can prescribe it, and the patient does not have to travel to a clinic on a daily basis for observed dosing. 

Several days of abstinence from methadone may be needed before buprenorphine is safe to start, which can make initiation a bit challenging.

A third option is naltrexone or Vivitrol — an opioid blocker that confers virtually no risk of overdose. However, it is difficult to initiate, even more so than buprenorphine because it blocks opioid receptors. 

If someone has opioids in their system, naltrexone can trigger an uncomfortable withdrawal syndrome. In the case of methadone use disorder, someone would need to be opioid-free for 7 to 10 days before starting naltrexone, which is a long time to wait if cravings are high.

How Bicycle Health Can Help with Methadone Dependence 

If you or someone you know is struggling to overcome a methadone dependence problem, reach out to Bicycle Health to find out more about telemedicine treatment options. Call us at (844)943-2514 or schedule an appointment here.

By Claire Wilcox, MD

Claire Wilcox, MD, is a general and addiction psychiatrist in private practice and an associate professor of translational neuroscience at the Mind Research Network in New Mexico; and has completed an addictions fellowship, psychiatry residency, and internal ... Read More


1. Warner M, Chen LH, Makuc DM. Increase in Fatal Poisonings Involving Opioid Analgesics in the United States. NCHS Data Brief. 2009; No 22. 

2. Caplehorn JR, Drummer OH. Fatal methadone toxicity: signs and circumstances, and the role of benzodiazepines. Aust N Z J Public Health 2002; 26:358.

3. Mattick RP, Breen C, Kimber J, Davoli M. Methadone maintenance therapy versus no opioid replacement therapy for opioid dependence. Cochrane Database Syst Rev 2009 :CD002209.

4. Zador DA, Sunjic SD. Methadone-related deaths and mortality rate during induction into methadone maintenance, New South Wales. Drug Alcohol Rev 2002 Jun;21(2):131-6.  doi: 10.1080/09595230220139028. 

5. Ray WA, Chung CP, Murray KT, Hal K, Stein CB. Prescription of Long-Acting Opioids and Mortality in Patients with Chronic Noncancer Pain. JAMA. 2016 June 14; 315(22): 2415–2423. doi:10.1001/jama.2016.7789.

6. Lev SP, Lee A, Lee O, Lucas J, Castillo EM, Egnatios J, Vilke G.  Methadone related deaths compared to all prescription related deaths.  2015 Dec;257:347-352. doi: 10.1016/j.forsciint.2015.09.021. Epub 2015 Oct 22.

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