Methadone Side Effects: Complications in Treatment

Author: Jessica Eiseman, M.S.

Methadone is a Schedule II controlled substance and a long-acting, synthetic opioid prescribed to treat opioid use disorder (OUD) or for pain management. It blocks the effects of opioid use and reduces withdrawal effects or cravings. However, there are potentially severe methadone side effects, even if it is taken as prescribed. Methadone treatment should be administered as prescribed and with professional supervision.¹

In this article:

• Common Side Effects of Methadone
• Dangerous Methadone Side Effects
• Methadone Treatment

Common Side Effects of Methadone

As with most medications, there are well-documented methadone side effects. If you are unsure what you are experiencing is a common side effect of methadone or the side effects do not go away, contact your doctor immediately. During normal use, the most common side effects of methadone include:^{1, 2}

• Vomiting or nausea
• Restlessness
• Slowed or depressed breathing
• Irritated or itchy skin
• Drowsiness
• Heavy sweating
• Decreased libido
• Sexual dysfunction
• Missed menstruation cycles
• Constipation
• Weight gain
• Edema, or swelling in arms or legs

Several factors can contribute to whether you experience the side effects of methadone. These include other drugs or supplements you are taking and your medical history. Side effects can occur when you start taking methadone, if you increase the dose of methadone, or if you stop taking methadone suddenly.

Dangerous Methadone Side Effects

Methadone side effects on the body can be severe and should be taken seriously. You may be experiencing an allergic reaction, or the methadone could be interacting with another substance you have taken.

Methadone’s side effects on the body include the central nervous system (CNS), the gastrointestinal system (stomach), and the circulatory and respiratory systems. CNS methadone side effects include drowsiness, fatigue, confusion, or disorientation. Methadone side effects on the stomach include stomach muscle spasms, constipation, nausea, and vomiting, among others. Side effects of methadone on the bloodstream and circulatory and respiratory systems can cause major breathing and heart-related problems.

If you are experiencing any side effects of methadone, contact your doctor immediately. Potentially dangerous side effects include:^{1, 8}

• Difficulty breathing or shallow breathing
• Feeling lightheaded, dizzy, or faint
• Hives or a rash
• Swelling of the face, lips, tongue, or throat
• Chest pain
• A fast or pounding heartbeat
• Hallucinations or confusion
• A dramatic change in mood
• Constricted pupils
• Stomach upsets (e.g. constipation, nausea, vomiting)
• Lowered blood pressure or weak pulse
• Confusion or disorientation
• Drowsiness or fatigue
• Slurred speech
• Weakness
• Muscle twitches
• Coma
• Cold, clammy skin or blue fingernails or lips
• Limp body
• Difficulty waking
• Life-threatening arrythmia or respiratory issues

It is vital to know the side effects of methadone, especially in the first two weeks of taking it. The risk of overdosing during this period is highest. Additionally, you should let your provider know if you feel high or sedated within the first four hours of taking methadone.²

The Effects of Stopping Methadone Treatment Suddenly

It is not recommended to stop methadone treatment suddenly. Doing so may cause methadone withdrawal. Methadone withdrawal can occur in as little as 24 hours after you took your last dose.³ Methadone stays in the body longer due to its long half-life and its slow release of its tissue binding sites, including to your brain and nervous system. The long-term side effects of methadone can last for as little as a few weeks to up to six months.

Stopping methadone treatment suddenly, you may feel flu-like symptoms, turning into more common or severe side effects. Because the effects of stopping methadone treatment suddenly can be so adverse, it is recommended to detox off of methadone in a medical treatment setting. Stopping methadone treatment suddenly increases your risk of having more severe side effects of methadone.

Taking More Methadone than Prescribed

It is possible to overdose on methadone, especially if you take more methadone than the prescribed dose. You also increase your risk of experiencing methadone side effects. Furthermore, prescribing the right amount of methadone varies between each person and leaves room for errors that could lead to an overdose of methadone. Absorption and metabolism vary depending on the person.³ Methadone can last long after taking it in the body, due to its slow release into the brain and nervous system.⁴

If it seems like the methadone amount prescribed does not seem to be working, talk to your doctor. Due to the half-life of methadone in the body, taking higher or more frequent doses of methadone can lead to a methadone overdose. It is crucial to be monitored carefully by your doctor while taking methadone, as dependence and overdose can develop.

Methadone Treatment

Like any medication, methadone can be a safe, effective treatment when taken as prescribed and with the right dosage.⁵ Comparative research has been done on other treatments, and methadone is considered one of the most efficacious and widely used treatments for OUD at this time, despite some safety concerns.⁶

There are several forms of methadone administration. These include liquid concentration—the most common form used in treatment programs—tablets, and powder.^{1, 2} Methadone should be given at the lowest dose possible and then increased gradually to reduce methadone side effects or the risk of accidental overdose. Because of this, you may not feel the effects of methadone for at least the first four days of treatment. Typically methadone is administered by a medical professional in either an inpatient or outpatient setting. Over time, your provider may give you treatments to give yourself in between program visits.⁵

Having an OUD diagnosis does not necessarily qualify you for methadone treatment, especially if you have a mild OUD diagnosis. Typically, you also need to have had an opioid addiction for at least 12 months and be able to give voluntary informed consent. People with methadone allergies, asthma, high CO₂ levels, or paralytic ileus should not take methadone. Mixing alcohol or benzos with methadone or buprenorphine, which is common in OUD, increases the risk of respiratory depression.²

Risk Factors for Methadone Side Effects

The following factors increase your risk of experiencing side effects of methadone:⁷

• Long-term methadone use
• Rotating several different kinds of opioids
• Previous methadone overdose
• Increased tolerance to methadone
• The need for pain relief while struggling with a co-occurring substance use disorder
• A history of opioid use disorder or opioid misuse
• If you are an older adult or have any debilitating disorder
• Taking other medications that also cause heart arrhythmia

Who Should Not Have Methadone Treatment?

Some medical conditions can complicate methadone treatment. Therefore, methadone should be prescribed with caution or not at all if you have any of the following diagnoses:^{9, 10}

• Respiratory conditions such as asthma
• Diabetes mellitus
• Hypothyroidism
• Urethral stricture
• Hypopituitarism
• Adrenocortical insufficiency
• Prostatic hypertrophy
• Lung diseases such as chronic obstructive pulmonary disease (COPD), chronic bronchitis, or emphysema
• Head injury
• Brain tumor or any condition that has increased the amount of pressure in your brain
• Malnourishment resulting from disease
• Severe liver disease (methadone may precipitate hepatic encephalopathy)
• Intolerance of methadone or ingredients in methadone formulations

Many of the above conditions contraindicate methadone use. Some  methadone side effects exacerbate preexisting conditions, such as impeded breathing.¹⁰

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Pregnancy and Methadone Treatment

If you are seeking or engaged in methadone treatment and are or will soon become pregnant, discuss ongoing treatment with your primary care physician. When treating pregnant people with opioid use disorders, methadone is considered the highest standard of care among medication-assisted treatment options. However, it can be detected in cord blood, newborn urine, amniotic fluid, and it crosses the placenta. Nevertheless, newborns whose parents use methadone while pregnant have improved fetal outcomes when compared to withdrawal or continued opioid misuse. Because methadone leaves the body faster when pregnant, you may need to discuss increasing your dose with your doctor.¹¹

Methadone maintenance treatment (MMT) while breastfeeding is safe if your infant is tolerant of the medication. Your physician will assist you in determining when you can breastfeed. When breastfeeding, methadone can be passed to the nursing child at a concentration that is about 2% to 3% of the breastfeeding parent’s dosage and appears in the milk only 4 to 5 hours after ingestion of an oral dose. Physicians may recommend that you monitor your infant after feeding to check for slowed breathing or complete sedation.¹¹

Seeking Treatment or Information on Methadone Side Effects

When you talk to your provider, ensure you are honest about your medical and mental health history. This can help them rule out any concerns which may increase your risk factors for methadone side effects.

To speak to a treatment specialist about methadone side effects or treatment, call 800-994-1867Who Answers?. They will direct you to the appropriate program for treatment and offer helpful information.

Resources

1. Substance Abuse and Mental Health Services Administration. (2022). Methadone.
2. Center for Substance Abuse Treatment. (2018). Chapter 3B: Methadone. In Medications for opioid use disorder: For healthcare and addiction professionals, policymakers, patients, and families. Treatment Improvement Protocol (TIP) Series, No. 63. Rockville (MD): Substance Abuse and Mental Health Services Administration (US).
3. Grissinger, M. (2011). Keeping patients safe from methadone overdoses. P & T: a peer-reviewed journal for formulary management, 36(8), 462-466.
4. Faul, M., Bohm, M., & Alexander, C. (2017). Methadone prescribing and overdose and the association with Medicaid preferred drug list policies — United States, 2007–2014. Morbidity and Mortality Weekly Report, 66(12), 320-323.
5. U. S. Department of Health & Human Services. (2019). Follow Directions: How to Use Methadone Safely. Substance Abuse and Mental Health Services Administration. Food and Drug Administration.
6. Ali, S., Tahir, B., Jabeen, S., & Malik, M. (2017). Methadone Treatment of Opiate Addiction: A Systematic Review of Comparative Studies. Innovations in Clinical Neuroscience, 14(7-8), 8–19.
7. Substance Abuse and Mental Health Services Administration. (2018). SAMHSA Opioid Overdose Prevention Toolkit.
8. National Library of Medicine. (2021). Methadone Hydrochloride concentrate label. Hikma Pharmaceuticals (USA).
9. National Center for Biotechnology. (2009). Chapter 6: Methadone maintenance treatment. In World Health Organization’s Clinical Guidelines for Withdrawal Management and Treatment of Drug Dependence in Closed Settings.
10. National Library of Medicine. (2022). Methadone.
11. Centers for Disease Control and Prevention. (2021). Treatment for Opioid Use Disorder Before, During, and After Pregnancy.