Can I Take Diazepam with Amitriptyline? Understanding the Risks

October 10, 2025 •

4 min read

A 2024 study on Central Nervous System (CNS) polypharmacy found that among patients taking multiple CNS-active drugs, 56.1% involved the co-use of an antidepressant and a benzodiazepine [1.6.2]. This highlights why asking, 'Can I take diazepam with amitriptyline?' is a critical safety question.

Quick Summary

Combining diazepam (a benzodiazepine) and amitriptyline (a tricyclic antidepressant) is generally not recommended without strict medical supervision due to a high risk of additive side effects, including severe drowsiness, impaired coordination, and respiratory depression [1.2.1, 1.2.2].

Key Points

Additive CNS Depression: Combining diazepam and amitriptyline significantly increases the risk of central nervous system (CNS) depression, leading to severe drowsiness and sedation [1.2.1].
Impaired Function: The interaction can cause dizziness, confusion, and difficulty concentrating, impairing motor coordination and judgment [1.2.2].
Medical Supervision is Essential: These medications should only be taken together under the strict guidance of a doctor, who will monitor for adverse effects [1.2.1].
Avoid Hazardous Activities: Patients using both drugs should avoid driving or operating machinery until they know how the combination affects them [1.2.2].
Increased Drug Levels: Diazepam may increase the concentration and duration of amitriptyline in the body, intensifying its side effects [1.2.5].
Safer Alternatives Exist: SSRIs and SNRIs are generally preferred as first-line treatments for co-occurring anxiety and depression due to a better safety profile [1.8.1, 1.8.3].

Understanding Diazepam and Amitriptyline

Before exploring the interaction, it's essential to understand each medication individually. Both drugs act on the central nervous system (CNS), but they belong to different classes and have distinct primary uses [1.4.2, 1.5.1]. Consulting a healthcare professional before combining any prescription medication is paramount.

What is Diazepam (Valium)?

Diazepam, commonly known by the brand name Valium, is a long-acting benzodiazepine [1.4.1]. It is prescribed for a range of conditions, including:

Anxiety disorders [1.4.2]
Muscle spasms [1.4.2]
Seizures, including status epilepticus [1.4.2]
Symptoms of alcohol withdrawal [1.4.2]

Mechanism of Action: Diazepam works by enhancing the effects of a neurotransmitter called gamma-aminobutyric acid (GABA) [1.4.2]. GABA is an inhibitory neurotransmitter, meaning it has a calming effect on the brain. By boosting GABA's activity, diazepam slows down the central nervous system, leading to sedation, muscle relaxation, and reduced anxiety [1.4.1, 1.4.2].

What is Amitriptyline (Elavil)?

Amitriptyline is a tricyclic antidepressant (TCA) [1.5.1]. While it was originally developed to treat major depression, its applications have expanded over time. Today, it's often prescribed for:

Major Depressive Disorder [1.5.1]
Neuropathic (nerve) pain [1.5.2]
Migraine prevention [1.5.4]
Fibromyalgia [1.5.2]

Mechanism of Action: Amitriptyline primarily works by blocking the reuptake of two neurotransmitters, serotonin and norepinephrine, in the brain [1.5.1, 1.5.4]. This action increases the concentration of these chemicals in the synapse, which helps improve mood and block pain signals. It also affects other receptors, contributing to both its therapeutic effects and its side effects [1.5.1].

The Interaction: Why Combining Diazepam and Amitriptyline is Risky

The primary concern with taking diazepam and amitriptyline together is the potential for additive or synergistic depressant effects on the central nervous system [1.2.1]. Both medications slow down brain activity, and when taken concurrently, this effect can become dangerously amplified.

Key Risks of a Combined Use

The combination may increase the severity and likelihood of several side effects [1.2.2, 1.3.2]:

Excessive Drowsiness and Sedation: This is the most common interaction effect. The combined sedation can be profound, significantly impairing daily function [1.2.2].
Impaired Cognitive Function: Patients may experience significant difficulty with concentration, confusion, and impaired judgment [1.2.2].
Poor Motor Coordination (Ataxia): The risk of dizziness, unsteadiness, and falls increases substantially, which is a particular concern for the elderly [1.2.2, 1.3.1].
Respiratory Depression: In severe cases, the combination can lead to slowed or difficult breathing. This risk is a serious medical concern and is heightened when alcohol or other CNS depressants are also consumed [1.2.1, 1.3.4].
Increased Drug Concentration: Some studies suggest that diazepam can interfere with the metabolism of amitriptyline, potentially leading to higher levels of amitriptyline in the bloodstream and a longer half-life, which can intensify its effects and side effects [1.2.5].

Due to these risks, patients taking this combination should be strongly counseled to avoid activities that require mental alertness, such as driving or operating heavy machinery [1.2.1, 1.2.2].

Comparison of Diazepam and Amitriptyline


Feature	Diazepam	Amitriptyline
Drug Class	Benzodiazepine [1.4.1]	Tricyclic Antidepressant (TCA) [1.5.1]
Primary Uses	Anxiety, seizures, muscle spasms, alcohol withdrawal [1.4.2]	Depression, nerve pain, migraine prevention [1.5.4]
Mechanism	Enhances the effect of GABA (inhibitory neurotransmitter) [1.4.2]	Blocks reuptake of serotonin and norepinephrine [1.5.4]
Common Side Effects	Drowsiness, dizziness, muscle weakness, confusion [1.9.1]	Dry mouth, constipation, blurred vision, weight gain, drowsiness [1.10.1, 1.10.3]
Onset of Action	Fast-acting (oral peak in 1-1.5 hours) [1.4.3]	Slower onset for antidepressant effects (weeks) [1.5.1]
Addiction Potential	High risk of dependence and abuse [1.9.3]	Low risk of dependence, but can cause withdrawal [1.10.4]

Safe Use and Medical Supervision

There are specific clinical situations where a doctor might prescribe both medications, but this requires careful management. A physician may initiate treatment with very low doses and titrate cautiously while monitoring the patient for excessive CNS and respiratory depression [1.2.1]. It is crucial to inform your doctor about all medications you are taking, including over-the-counter drugs, vitamins, and herbal supplements [1.2.2]. Never adjust your dosage or stop taking either medication without first talking to your doctor [1.2.2].

Alternatives for Anxiety and Depression

If you have co-occurring anxiety and depression, safer first-line treatments are often preferred over combining a benzodiazepine and a TCA [1.8.1, 1.8.3].

Selective Serotonin Reuptake Inhibitors (SSRIs): Drugs like escitalopram (Lexapro) and sertraline (Zoloft) are considered first-line treatments for both anxiety and depression due to their effectiveness and better tolerability [1.8.1, 1.8.5].
Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs): Medications such as venlafaxine (Effexor XR) and duloxetine (Cymbalta) are also effective for both conditions and are a standard treatment choice [1.8.1, 1.8.5].
Buspirone: This is a non-sedating anti-anxiety medication that has a lower risk of dependence compared to benzodiazepines [1.8.3, 1.8.5].
Psychotherapy: Cognitive Behavioral Therapy (CBT) is a highly effective, non-pharmacological approach for managing both anxiety and depression [1.8.1].

Conclusion: Prioritize Safety and Communication

So, can you take diazepam with amitriptyline? While it is possible under strict medical supervision, it is a combination that carries significant risks of enhanced sedation, cognitive impairment, and other serious side effects [1.2.1, 1.2.2]. The interaction between these two CNS depressants requires extreme caution. Always have an open dialogue with your healthcare provider about your symptoms and all medications you are taking to ensure a safe and effective treatment plan. For many patients, alternative medications like SSRIs or SNRIs offer a safer profile for treating concurrent anxiety and depression [1.8.1].

For more information on drug interactions, you can visit the U.S. Food and Drug Administration's website: https://www.fda.gov/drugs [1.3.4]

Frequently Asked Questions

The most common side effects include increased dizziness, severe drowsiness, confusion, and difficulty concentrating. Impairment in thinking, judgment, and motor coordination is also common, especially in the elderly [1.2.2].

No. You should avoid or limit the use of alcohol. Alcohol is also a central nervous system depressant and can significantly worsen side effects like drowsiness, dizziness, and respiratory depression when combined with these medications [1.2.2, 1.3.4].

While both medications have sedative properties, combining them specifically for sleep increases the risk of excessive CNS depression and other side effects. A doctor might prescribe it for bedtime use to mitigate daytime drowsiness, but this must be done with caution [1.2.4, 1.10.2].

Avoid any activities that require mental alertness, like driving. Monitor yourself for excessive drowsiness or dizziness. If you have any concerns or experience prolonged or severe side effects, contact your doctor or pharmacist for guidance [1.2.1, 1.2.3].

Yes, first-line treatments for co-occurring anxiety and depression are typically SSRIs (like escitalopram, sertraline) or SNRIs (like venlafaxine, duloxetine). These classes of antidepressants are generally considered to have a better safety profile than combining a benzodiazepine with a TCA [1.8.1, 1.8.3].

Yes, elderly patients are particularly vulnerable to the additive effects of these drugs. They may experience more pronounced impairment in thinking, judgment, and motor coordination, which increases the risk of falls and injury [1.2.1, 1.3.1].

Signs of an overdose can include extreme drowsiness leading to unresponsiveness or coma, slowed or stopped breathing, low blood pressure, confusion, and heart rhythm problems. An overdose is a medical emergency and requires immediate attention by calling 911 [1.7.2, 1.7.3, 1.10.4].