What is the best antidepressant to take with Suboxone? A guide to safe combinations

October 10, 2025 •

4 min read

According to research, upwards of 60% of people undergoing treatment for a substance use disorder also have a co-occurring mental health issue, like depression. For individuals on Medication-Assisted Treatment (MAT) for opioid use disorder (OUD), the question of what is the best antidepressant to take with Suboxone is a common and important one that requires careful medical consideration.

Quick Summary

The ideal antidepressant to use with Suboxone varies by patient, but SSRIs and SNRIs are generally common and considered safe under medical supervision. Key considerations include the risk of serotonin syndrome and increased sedation, necessitating careful doctor monitoring. An individualized approach addresses both opioid use disorder and depression for better overall treatment outcomes.

Key Points

No Single 'Best' Antidepressant: There is no one-size-fits-all answer; the ideal antidepressant depends on individual patient factors and requires a doctor's evaluation.
SSRIs and SNRIs are Common and Generally Safe: Selective Serotonin Reuptake Inhibitors (SSRIs) and Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs) are frequently prescribed and safe to take with Suboxone under monitoring.
Watch for Serotonin Syndrome: While rare, combining Suboxone with serotonergic antidepressants can lead to serotonin syndrome, which requires immediate medical attention.
Avoid CNS Depressants: Combining Suboxone with other central nervous system (CNS) depressants, especially benzodiazepines and alcohol, significantly increases the risk of dangerous respiratory depression.
Professional Guidance is Essential: A personalized treatment plan and close medical monitoring by a healthcare provider are necessary to safely combine Suboxone and an antidepressant.
Integrated Treatment Improves Outcomes: Treating both opioid use disorder and depression concurrently is more effective for long-term recovery than treating either condition alone.
MAOIs Should be Avoided: Older antidepressants known as Monoamine Oxidase Inhibitors (MAOIs) pose a higher risk of interaction and are not typically recommended with Suboxone.

The Importance of Treating Co-Occurring Conditions

Many individuals with opioid use disorder (OUD) also struggle with depression or other mental health conditions. For these co-occurring disorders, addressing both conditions simultaneously is crucial for the best chance of successful, long-term recovery. Untreated depression can significantly undermine an individual's recovery efforts, increasing the risk of relapse. Conversely, effectively managing depressive symptoms alongside OUD can lead to improved treatment adherence and better overall well-being.

Suboxone (buprenorphine/naloxone) helps manage opioid cravings and withdrawal symptoms, but it does not treat depression directly, even though buprenorphine itself may have some mood-lifting properties. For this reason, a comprehensive treatment plan often involves combining Suboxone with an antidepressant.

Choosing an Antidepressant While on Suboxone

There is no single “best” antidepressant for everyone taking Suboxone. The most suitable medication depends on a variety of factors unique to the patient, including:

The severity of depression symptoms.
Potential side effects.
Other medical conditions.
The risk of drug interactions.
Individual patient tolerability.

For these reasons, the selection of an antidepressant must be made in close consultation with a healthcare provider who can carefully weigh the benefits and risks.

Common and Safe Antidepressant Classes with Suboxone

Several classes of antidepressants are commonly prescribed alongside Suboxone and are generally considered safe when taken under careful medical supervision. Your doctor will monitor you for any potential interactions or side effects, particularly when starting a new medication or adjusting a dosage.

Selective Serotonin Reuptake Inhibitors (SSRIs)

SSRIs are often the first-line treatment for depression due to their effectiveness and generally favorable side-effect profile. Examples of SSRIs include:

Sertraline (Zoloft)
Fluoxetine (Prozac)
Escitalopram (Lexapro)
Citalopram (Celexa)

SSRIs work by increasing serotonin levels in the brain, a neurotransmitter that influences mood. Suboxone also has serotonergic effects, meaning it can boost serotonin. While the combination is typically safe at standard doses, a key risk is serotonin syndrome, which requires close monitoring.

Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs)

SNRIs are another common and safe class of antidepressants to use with Suboxone. They work by increasing both serotonin and norepinephrine levels in the brain. Examples of SNRIs include:

Venlafaxine (Effexor)
Duloxetine (Cymbalta)
Desvenlafaxine (Pristiq)

Similar to SSRIs, SNRIs also carry a small risk of serotonin syndrome, particularly with very high doses. However, many SNRIs are not sedating, which is an advantage when combined with Suboxone, which can cause drowsiness.

Tricyclic Antidepressants (TCAs)

TCAs are an older class of antidepressants that can be effective but typically have more side effects than SSRIs or SNRIs. While they can be used with Suboxone, they are associated with an increased risk of sedation. Examples include:

Amitriptyline (Elavil)
Nortriptyline (Pamelor)

Norepinephrine-Dopamine Reuptake Inhibitors (NDRIs)

Bupropion (Wellbutrin) is a common NDRI that affects norepinephrine and dopamine, rather than serotonin. This different mechanism of action can be an advantage for some patients, particularly those who experience sexual side effects from SSRIs or SNRIs. It is generally considered safe to combine with Suboxone.

Potential Drug Interactions and Risks

While combining Suboxone and antidepressants can be safe and highly beneficial, it is essential to be aware of potential drug interactions and risks.

Serotonin Syndrome

Both buprenorphine (a component of Suboxone) and many antidepressants increase serotonin levels. When combined, there is a risk, albeit rare, of serotonin syndrome. This potentially life-threatening condition occurs when serotonin levels become too high. Symptoms include:

Restlessness and agitation
Rapid heart rate and high blood pressure
Confusion
Muscle stiffness
Sweating and shivering
Dilated pupils

It is vital to report any of these symptoms to your doctor immediately. The risk is highest with older antidepressants like Monoamine Oxidase Inhibitors (MAOIs), which are generally avoided with Suboxone.

Increased Sedation and Respiratory Depression

Suboxone can cause drowsiness. Combining it with other CNS depressants greatly increases the risk of sedation and dangerous respiratory depression (slowed breathing). This risk is particularly high with benzodiazepines (e.g., Xanax, Klonopin) and alcohol. Some antidepressants, like TCAs, can also have sedating effects. Close monitoring is necessary if you are taking any of these medications.

Antidepressant Options Comparison Table


Antidepressant Class	Example Drugs	Safety with Suboxone (Monitored)	Risk of Serotonin Syndrome	Risk of Increased Sedation
SSRIs	Sertraline (Zoloft), Fluoxetine (Prozac)	High	Low to Moderate (dose-dependent)	Low
SNRIs	Venlafaxine (Effexor), Duloxetine (Cymbalta)	High	Low to Moderate (dose-dependent)	Low
TCAs	Amitriptyline (Elavil), Nortriptyline (Pamelor)	Moderate	Moderate	High
NDRIs	Bupropion (Wellbutrin)	High	Very Low (different mechanism)	Low
MAOIs	Phenelzine (Nardil)	Very Low	High (generally contraindicated)	Varies

The Role of the Prescribing Physician

Given the complexities of treating co-occurring disorders, open and honest communication with your healthcare provider is paramount. Always inform your doctor of all medications, supplements, and substances you are taking. A doctor will carefully evaluate your medical history and specific needs to create a safe and effective treatment plan. A comprehensive approach, often including behavioral therapies, counseling, and peer support alongside medication, provides the most robust support for both OUD and depression.

Conclusion

While there is no single "best" antidepressant to take with Suboxone, many options within the SSRI and SNRI classes are safe and effective under professional medical guidance. The right choice is a personalized one, made in collaboration with your doctor, who will carefully monitor for potential risks like serotonin syndrome and increased sedation. Addressing both OUD and depression with an integrated treatment plan significantly improves the chances of achieving and maintaining long-term recovery and well-being.

For more in-depth information on managing substance use disorder and co-occurring mental health issues, the Substance Abuse and Mental Health Services Administration (SAMHSA) is an excellent resource.

Frequently Asked Questions

Yes, it is often safe to take antidepressants with Suboxone under the supervision of a healthcare provider. Many people with co-occurring depression and opioid use disorder successfully combine these medications as part of an integrated treatment plan.

The biggest risk is serotonin syndrome, a rare but serious condition that can occur when serotonin levels become too high. This risk is primarily associated with SSRIs and SNRIs, and close medical monitoring is necessary to prevent it.

Prozac, an SSRI, is one of the antidepressants that can be combined with Suboxone. However, this must be done under a doctor's supervision to monitor for side effects and the potential, though rare, risk of serotonin syndrome.

If you experience any unusual symptoms or side effects like increased restlessness, confusion, or a fast heart rate, you should contact your healthcare provider immediately. They may need to adjust your dosage or switch your medication.

Older antidepressants called Monoamine Oxidase Inhibitors (MAOIs) are generally not safe to take with Suboxone and should be avoided due to the high risk of serious interactions.

Your doctor will consider your medical history, current symptoms, other medications you take, potential side effects, and any past responses to medication. They will work with you to find a personalized and safe treatment approach.

Yes, it is very common. An estimated 60% of people in treatment for substance use disorders have a concurrent mental health condition, with depression and anxiety being particularly prevalent.