Does Methadone Interact With Antidepressants?

Medically Reviewed by Johnelle Smith, M.D. on December 29, 2021

People that take methadone may experience negative effects when it is taken with some antidepressants. These drug interactions may lead to dangerous conditions including respiratory arrest and death.

Does Methadone Interact With Antidepressants?

Methadone is known to interact with many kinds of antidepressants. In general, these drugs will either enhance or inhibit a person’s ability to metabolize methadone.

Because methadone regimens are dose-dependent, any variation to the drug’s efficacy can result in people experiencing withdrawal symptoms if their normal dose doesn’t work as usual.

Learn more about negative drug interactions with methadone

Methadone And Antidepressant Drug Interactions

Some people will intentionally take antidepressants as a way to increase the effects of methadone.

It is considered a sign of abuse when other drugs are taken to increase the effects of methadone taken to treat opioid dependence.

Methadone And Benzodiazepines

Benzodiazepines taken with methadone can enhance sedative effects felt from methadone intake. When taken to excess, this can lead to respiratory depression and potential death.

Benzodiazepine antidepressants include diazepam (Valium), clonazepam (Klonopin), lorazepam (Ativan), and alprazolam (Xanax).

Methadone And MAOIs

Both methadone and monoamine oxidase inhibitors (MAOIs) interact with serotonin neurotransmitters.

When these drugs are taken together, it increases the risk of serotonin syndrome.

Serotonin syndrome symptoms include:

  • rapid heart rate
  • high blood pressure
  • agitation and confusion
  • diarrhea
  • dilated pupils
  • sweating
  • muscle rigidity
  • headache
  • goosebumps

Life-threatening symptoms of severe serotonin syndrome can include:

  • irregular heartbeat
  • high fever
  • unconsciousness
  • seizures

MAOIs that may cause adverse reactions with methadone include:

  • methylene blue
  • tranylcypromine (Parnate)
  • isocarboxazid (Marplan)
  • linezolid (Zyvox)
  • phenelzine (Nardil)
  • selegiline (Eldepryl, Emsam, Zelapar)
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Methadone And SSRIs

The selective serotonin reuptake inhibitors (SSRIs) like sertraline (Zoloft) and fluoxetine (Prozac) work to inhibit methadone metabolism.

This results in increased methadone bioavailability and stronger effects from methadone.

Because methadone and SSRIs both work on serotonin pathways, a person taking both at the same time may experience serotonin syndrome.

Methadone And Tricyclic Antidepressants

Some tricyclic antidepressants may increase the risk of irregular heartbeat that may be life-threatening.

Although this drug interaction is not common, it is serious enough that people taking these prescription medications should avoid mixing these drugs.

Some tricyclic antidepressants that may interact poorly with methadone include:

  • amitriptyline
  • doxepin
  • imipramine
  • trimipramine

Managing Depression When On Methadone

Many people feel more “themselves” when they have safe access to their antidepressants.

Because methadone interacts poorly with many antidepressants, it’s important to work towards a treatment plan that is effective for treating both depression and opioid use disorder.

Dual diagnosis programs encourage people with depression that are taking methadone to embrace behavioral therapy in recovery and stick to the appropriate tapering schedule.

In some inpatient programs, a daily structure that includes therapy and regular exercise has been found to help depression.

Getting Help For Opioid Abuse

Managing co-occurring mental health conditions and substance use disorders can be difficult. If you or a loved one is struggling with opioid abuse, inpatient and outpatient rehab can help.

Talk to an addiction specialist today to learn more about the best treatment options for your needs. It’s the best investment you can make in your future.

This page does not provide medical advice. See more

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These include peer-reviewed journals, government entities and academic institutions, and leaders in addiction healthcare and advocacy. Learn more about how we safeguard our content by viewing our editorial policy.

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Medically Reviewed by
Johnelle Smith, M.D. on December 29, 2021

Canton, Massachusetts

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Plymouth, Massachusetts

Ohio Recovery Center


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Payment Options: Insurance Accepted, Self Pay

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