Methadone Interactions: How Drugs & Alcohol Interact with Methadone

For more than 50 years, scientists have studied how methadone interacts with other substances. Many medications can be taken without issue while on methadone. However, some combinations increase the risk of respiratory depression, overdose and other serious side effects. 

Patients should always be honest with doctors about medications and medical conditions and tell their methadone clinic when they start new medications, even if there is no known interaction.

Alcohol Benzodiazepines  | Opioids Gabapentin Antidepressants Antipsychotics Other InteractionsAsk Your Question

Mixing Methadone and Alcohol

Mixing methadone and alcohol can be dangerous and even life-threatening. 

Combining these substances has a synergistic effect (the combined effects are greater than the sum of their individual effects), which increases the risk of:

Recommendations for Alcohol When Taking Methadone

Patients that drink heavily before starting methadone are recommended to go to an inpatient detox or hospital to overcome the physical withdrawals from alcohol before starting methadone. Methadone can even be started at inpatient treatment and continued at an outpatient clinic after discharge, which is usually in 3-10 days.

Patients that start drinking heavily after already stabilized on methadone maintenance are also recommended to stay for 3-10 days in an inpatient facility for alcohol detox. Methadone can be continued during this stay, especially in a hospital setting.

Patients that drink occasionally while taking methadone should understand that this is dangerous. People are not typically able to recognize their slowed breathing to be able to seek help. And, a high percentage of methadone patients struggle with alcohol addiction. Alcohol addiction is just as life-destroying as opioid addiction and has its own painful and actually deadly withdrawal symptoms. Please consider following the recommendation to not drink alcohol while taking methadone. 

Mixing Methadone and Benzodiazepines

Taking benzodiazepines (“benzos”) with methadone has been shown to dramatically increase the likelihood of fatal overdoseThis is because both medications are “downers” and can slow down breathing to the point of death. It is especially dangerous to take these medications without a doctor’s oversight.

Methadone Should Not Be Mixed With Other Depressant Drugs

Methadone should not be mixed with alcohol, benzos or opioids

Benzodiazepines are also addictive. Patients that struggle with opioid use disorder are likely to become both physically dependent and mentally addicted to benzodiazepines too, which:

Recommendations for Benzodiazepines When Taking Methadone

Benzodiazepines should not be started while on methadone. Antidepressants are usually ideal alternatives to benzodiazepines and are generally safer and equally effective in treating anxiety and anxiety-related insomnia. Therapy and stopping illicit drug use also help with anxiety.

For those already taking benzodiazepines, methadone can still be started under medical supervision. Benzodiazepine requires a taper and stopping cold turkey can be life-threatening.

Methadone and Opioids

Methadone is a long-acting opioid. So, adding other opioids in addition to methadone increases the risk of opioid overdose, which is often fatal.

See also: Methadone Overdose

Using opioids also impacts your methadone treatment because:

Suboxone and Methadone

Suboxone is a partial opioid but also contains Naloxone, an opioid blocker. Taking methadone with Suboxone will cause intense opioid withdrawal symptoms within an hour after taking the Suboxone.

See also: Switching from Methadone to Suboxone

Anesthesia and Methadone

Opioids are commonly used as anesthesia, though there are non-opioid options. Patients should always disclose methadone use to the anesthesiologists.

For most procedures, patients continue their normal methadone dose. For bigger procedures (ie. a hip replacement), the methadone dose may be lowered to allow more opioid receptors in the brain to open up for anesthesia pain blocking. It isn’t always necessary to alter the methadone dosing, so always check with the anesthesiologist.

Recommendations for Opioids When Taking Methadone

Taking additional opioids while taking methadone is not recommended.

If chronic pain is not well-controlled with methadone, talk to your methadone provider. Increased doses and other medications (like Gabapentin) may help, along with physical and mental therapies.

Methadone used to stop the use of other opioids.

Methadone and Gabapentin

Gabapentin has been studied in combination with methadone in the hope to improve treatment results. But, the data is not conclusive.

Gabapentin is an anticonvulsant but has depressive properties. It can increase the risk of slow or shallow breathing when mixed with a depressant like methadone.

In addition, gabapentin is addictive and causes physical dependence, meaning distressing withdrawal symptoms if stopped abruptly. Adding a gabapentin addiction on top of an opioid addiction can be a setback.

Recommendations for Gabapentin When Taking Methadone

Gabapentin should only be used with methadone as prescribed by the doctor. The medication is sometimes prescribed to methadone patients for anxiety or unmanaged pain or withdrawal symptoms.

Methadone and Antidepressants

Depressive symptoms have been shown to decrease in severity over the first eight months of methadone treatment. But, as high as 50% of methadone patients struggle with depression.

Generally, combining antidepressants with methadone is common and does not pose serious interactions.

However, there are many types of antidepressants that interact differently with the brain, and therefore, with methadone. 

For example:

Recommendations for Antidepressants When Taking Methadone

If depressive symptoms persist after stabilizing on methadone, SSRI medications are usually the first choice for depression treatment. Sertraline (Zoloft) or citalopram (Celexa) can be good options for those taking methadone. SNRI antidepressants like bupropion (Wellbutrin) have also been shown to be helpful for those taking methadone.

Antidepressants can be considered when tapering off methadone too.

Depression should also be treated with therapy — including Cognitive Behavioral Therapies (CBT), Mindfulness-Based Therapies and, if needed, trauma therapies. The cycle of addiction is unlikely to be successful without diagnosing and adequately treating underlying issues like depression.

Also, antidepressant medications should always be disclosed to a methadone provider since some antidepressants can impact dosing.

Methadone and Antipsychotics

While methadone has been shown to reduce the need for antipsychotics, the use of both methadone and antipsychotics can be helpful for some patients.
However, typical antipsychotics aren’t always as effective for substance use patients and some antipsychotics have shown to be risky when used with methadone.

Olanzapine (Zyprexa) is an antipsychotic that is commonly misused by those with opioid addiction, usually for sleep or anxiety. Without the oversight of a doctor, the risk of overdose from Olanzapine combined with opioids (including methadone) is high and life-threatening. There are safer ways to treat anxiety and sleep issues while on methadone.

The data on Quetiapine (Seroquel) use with methadone is inconclusive, though certainly indicates the potential of a dangerous interaction that has proven fatal.

Low doses of antipsychotics, such as chlorpromazine, fluphenazine and haloperidol may be a better consideration for patients on methadone continuing to experience psychotic symptoms.

Recommendations for Antipsychotics When Taking Methadone

Delaying the start of antipsychotic medications until a steady state has been reached with methadone is ideal when possible.
The doses of antipsychotic medications may be lower for those on methadone. And, the methadone dose may need to be higher, especially when psychotic symptoms are severe or chronic.

If your methadone clinic is not able to properly treat your mental health issues, seek outside psychiatric services instead of “living with it” or self-medicating!

Methadone and Other Interactions

Like most medications, drug interactions are possible with methadone.  To stay safe, disclose methadone use to all doctors and inform the methadone clinic of any changes to medication. 

Barbiturates are depressants that come with the same risks and recommendations as other depressants like alcohol or benzodiazepine — avoid mixing with methadone.

Mixing two depressants can slow body processes, including breathing, to the point the body cannot function.
Barbiturates aren’t prescribed very commonly. If a patient requires the medication for seizure, the methadone clinic can help assess and provide safe dosages.

If using barbiturates illicitly for sleep, your methadone clinic should be able to provide you with something safer that works better. For example, Mirtazapine is an antidepressant that has been shown to help methadone patients with sleep issues.

For more sleep tips, see: Withdrawal Insomnia

Stimulants like Adderall can be safe to use under doctor supervision, though aren’t recommended unless necessary.

Taking excessive Adderall and methadone can lead to a rare condition called serotonin syndrome. Symptoms of serotonin syndrome include excessive sweating, shaking, blurred vision, muscle spasm or stiffness, cramps or vomiting and can result in coma. It can also increase the risk of side effects like dizziness, drowsiness and difficulty breathing. Adderall is also addictive and causes physical dependence /withdrawals.

Because of these risks, methadone patients should never take Adderall without a prescription.

Methadone has been shown to help patients adhere to their HIV treatment, which helps the virus become undetectable. The two medications can be taken together safer, though there are known interactions that impact dosing. 

Impact on Methadone
Efavirenz (Sustiva / Stocrin), for example, was shown to require a methadone dose increase of 52% on average. Nevirapine (Viramune) required a 20% increase in methadone.
While methadone dosing should not increase unless symptoms of opioid withdrawal occur, an increased dose can cause serious issues if the HIV medication is missed or decreased. Stopping the HIV medication abruptly while maintaining the methadone dose could even cause opioid toxicity. It is important to keep the methadone clinic updated with any changes to HIV medications.

There are also HIV medications that don’t seem to require increased methadone dosing including etravirine (Intelence), atazanavir (Reyataz) and ritonavir (Norvir) combined with indinavir (Crixivan), saquinavir (Invirase) or fosamprenavir (Lexiva).

Impact on HIV Medication
Methadone has been shown to decrease the absorption of stavudine (Zerit), resulting in less effective HIV treatment that can lead to virus resistant to antiviral medications.
The interaction of methadone with zidovudine can cause symptoms that are easily confused with opioid withdrawal but are actually HIV medication toxicity.

Both physicians should be aware of all specific medications a patient takes. Certain HIV medications have been shown to require additional methadone. Other HIV medications may need an increased or decreased dosage if used with methadone. There are also HIV medication options that have not shown to interact with methadone that can be considered.

Some patients find the juice methadone is typically mixed with too acidic on an empty stomach. But, methadone can be taken with or without food.

Methadone and Vitamins
While studies have looked into the link between methadone patients and vitamins, there is no known interaction between vitamins and methadone. Those struggling with addiction tend to have low vitamin levels and taking a supplement may help overall health.

Methadone and Grapefruit
Grapefruit has been shown to modestly increase the response to methadone making the effects feel stronger. While it is not expected to cause issues, patients can consider avoiding grapefruit and grapefruit juice while on methadone.

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