Does Diazepam interact with Fluoxetine? (+1 interaction)

In this article, we will answer the question “Does Diazepam interact with Fluoxetine?”. We will discuss the potential interaction between Diazepam and Fluoxetine, the mechanism behind the interaction and what research has to say in this regard. We will also discuss what are the risk factors affecting the interaction of Diazepam and Fluoxetine, the factors influencing the interaction and how to manage the concomitant use of both medications to minimize interactions.

Does Diazepam interact with Fluoxetine?

Yes, Diazepam and Fluoxetine can interact with each other when used simultaneously. However, not all individuals will experience extensive side effects related to this interaction. Some individuals may experience side effects while others may not.

Diazepam (also known as Valium), is an anxiolytic benzodiazepine. This medication is approved by the FDA for the treatment of anxiety disorders, short-term anxiety relief, managing side effects of acute alcohol withdrawal, relieving skeletal muscle spasms and as an adjunct in seizures (1,2).

Diazepam has also been used ‘off-label’ for sedation and the short-term treatment of muscle stiffness in children suffering from cerebral palsy (1).

Fluoxetine (also known as Prozac), is an antidepressant belonging to the class of selective serotonin reuptake inhibitors (SSRIs), approved by the FDA for the treatment of major depressive disorder (MDD), obsessive-compulsive disorder (OCD), bulimia nervosa and panic disorder (PD) with or without agoraphobia (3).

Diazepam and Fluoxetine tend to interact with each other and can cause an array of complications and side effects. If you are taking both medications and experiencing anything out of the ordinary, make sure to inform your healthcare provider.

How does Diazepam interact with Fluoxetine?

The inhibition of Diazepam metabolism is the major interaction caused by Fluoxetine when both medications are taken simultaneously. This can be beneficial as well as harmful for the individual taking the combination.

Diazepam is majorly metabolized by two cytochrome P450 enzymes, namely CYP3A4 and CYP2C19. Fluoxetine is the inhibitor of both these enzymes. If the combination of these medications is given, the concentration of Diazepam may increase in the blood. This can cause an increase in therapeutic effects as well as side effects of Diazepam.

If Diazepam stays for a longer duration in the blood it may help in a better management of the condition being treated. It can also cause excessive sedation or drowsiness. You should monitor your symptoms and report anything unusual to your healthcare provider.

What does research suggest?

A few studies have been published discussing the effect of a combination of Diazepam and Fluoxetine on the individual receiving treatment. They are as follows:

A case study was published, assessing the consequences of a Diazepam-Fluoxetine interaction in an elderly man who was prescribed these medications along with warfarin. The patient developed delirium-like symptoms due to the excessive Diazepam circulating in the body (4).

Another research study assessing the effects of Fluoxetine on the pharmacokinetics of Diazepam administered both medications in normal, healthy volunteers. The results showed that individuals when given the combination showed longer half-life and lower plasma clearance in individuals when they took the combination (5).

What are the side effects of the Diazepam and Fluoxetine interaction?

When both medications are used simultaneously, there may be a risk of increase in the following side effects:

  • Levels of Diazepam, causing increased side effects
  • Sedation
  • Tremors
  • Drowsiness
  • Dizziness
  • Confusion
  • Delirium
  • Incidence of suicidal thoughts

What factors influence the interaction of Diazepam and Fluoxetine?

Various factors can influence the interaction between Diazepam and Fluoxetine. Some of them are as follows:


High doses of both medications can increase the impact and intensity of the interaction because of the higher levels of both drugs circulating in the system.

Duration of use

If you use this combination for a longer duration of time, there can be an increased risk of interaction and side effects.

Individual characteristics

Each individual reacts differently to different medications. So the response of patients receiving the combination of Diazepam and Fluoxetine may vary from person to person. Some may see immediate side effects while some may be able to tolerate the combination.

Pre-existing medical conditions

Pre-existing medical conditions may influence the risk of the interaction occurring between Diazepam and Fluoxetine. Any other medications that you may be taking to help you with these conditions may also affect the combination and cause extensive side effects.

How to ensure the safe use of Diazepam and Fluoxetine?

To ensure safe usage of the combination of Diazepam and Fluoxetine the following recommendations should be considered:

Effective communication

You should have open and effective communication with your healthcare provider. Make sure to inform your doctor about any side effects you experience.

Medical supervision

You should always consult your healthcare provider before starting or stopping any medication. All medications should be prescribed to you under proper medical supervision. Adverse events can increase if you use Diazepam or Fluoxetine unnecessarily. Your healthcare provider will examine your condition and symptoms and guide you if this combination is safe or not.

Regular monitoring

If you are prescribed the combination of Diazepam and Fluoxetine after the assessment of the risks and benefits of combination therapy, your doctor will conduct regular follow-ups and closely monitor you for the occurrence of any interactions or side effects.

Dosage adjustment

Sometimes your healthcare provider may adjust the dosage of one or both medications to minimise the occurrence of side effects and interactions.

To the best of my knowledge and according to research, Diazepam and Fluoxetine interact with each other to produce an array of side effects. However, some individuals may also tolerate this combination exceptionally well.

Adjustment of doses can reduce the occurrence of side effects. But if you still experience discomfort or your symptoms get worse you should inform your healthcare provider and seek immediate medical attention.

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Dhaliwal JS, Rosani A, Saadabadi A. Diazepam. [Updated 2023 Aug 28]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from:


The Food and Drug Administration (FDA). HIGHLIGHTS OF PRESCRIBING INFORMATION. VALIUM® (diazepam) tablets for Oral Use. Available from: 


The Food and Drug Administration (FDA). HIGHLIGHTS OF PRESCRIBING INFORMATION. PROZAC® (fluoxetine capsules) for oral use. Available from: 


Dent LA, Orrock MW. Warfarin‐fluoxetine and diazepam‐fluoxetine interaction. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy. 1997 Jan 2;17(1):170-2.


Lemberger L, Rowe H, Bosomworth JC, Tenbarge JB, Bergstrom RF. The effect of fluoxetine on the pharmacokinetics and psychomotor responses of diazepam. Clinical Pharmacology & Therapeutics. 1988 Apr;43(4):412-9.

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