Can You Take Amitriptyline with Diazepam? A Guide to a Risky Combination

October 10, 2025 •

4 min read

Studies show that between 3% and 5% of all in-hospital medication errors are due to drug-drug interactions [1.6.7]. A particularly concerning combination is whether can you take amitriptyline with diazePAM, as both drugs depress the central nervous system, creating additive risks [1.3.1].

Quick Summary

Combining amitriptyline, a tricyclic antidepressant, and diazepam, a benzodiazepine, poses significant health risks, primarily through additive central nervous system (CNS) and respiratory depression [1.2.3, 1.3.1].

Key Points

Major Interaction: Combining amitriptyline and diazepam can cause additively or synergistically increased central nervous system (CNS) and respiratory depression [1.2.3, 1.3.1].
Significant Risks: The combination increases side effects like severe drowsiness, dizziness, confusion, and impaired motor coordination [1.2.1].
Medical Supervision is Essential: This drug combination should only be used under the strict supervision of a doctor, who may adjust doses to ensure safety [1.2.1, 1.3.1].
Avoid Other Depressants: Alcohol and other CNS depressants must be avoided as they can exacerbate the dangerous side effects of the combination [1.3.2].
Elderly at Higher Risk: Elderly or debilitated patients are particularly susceptible to the impairing effects on thinking, judgment, and motor skills [1.2.1, 1.3.1].
Performance Impairment: Studies show the combination impairs performance on tasks requiring vigilance and attention more than either drug alone [1.2.5, 1.2.7].
Alternative Treatments: Safer alternatives for anxiety and depression, such as SSRIs or SNRIs, are often preferred to avoid the risks of combining TCAs and benzodiazepines [1.7.1, 1.7.6].

Understanding Amitriptyline and Diazepam

Amitriptyline and diazepam are two distinct medications that act on the central nervous system (CNS) [1.2.2]. While they may be prescribed for overlapping conditions like anxiety, their mechanisms and primary uses differ significantly. Understanding each drug individually is the first step in recognizing the dangers of their combined use.

What is Amitriptyline (Elavil)?

Amitriptyline is a tricyclic antidepressant (TCA) primarily used to treat major depression [1.4.1]. It works by blocking the reuptake of neurotransmitters like serotonin and norepinephrine in the brain, which helps to elevate mood [1.4.1, 1.4.5]. Beyond depression, it's also prescribed off-label for conditions such as neuropathic pain, fibromyalgia, and migraine prevention [1.4.2, 1.4.5]. Amitriptyline is known for its sedative properties and a wide range of side effects, including dry mouth, dizziness, constipation, and potential cardiac issues, which has led it to be labeled a "dirty drug" due to its action on multiple receptor types [1.4.1, 1.4.6].

What is Diazepam (Valium)?

Diazepam, best known by its brand name Valium, is a benzodiazepine [1.5.2]. It is used for its anxiolytic (anti-anxiety), sedative, muscle relaxant, and anticonvulsant properties [1.5.1]. Diazepam works by enhancing the effect of a neurotransmitter called gamma-aminobutyric acid (GABA), which is the body's primary inhibitory or "calming" chemical [1.5.2]. This action slows down brain activity, making it effective for treating anxiety disorders, muscle spasms, seizures, and symptoms of alcohol withdrawal [1.5.1, 1.5.2]. Due to its potential for dependence and misuse, it is typically recommended for short-term use [1.5.2].

The Core Risk: Can You Take Amitriptyline with Diazepam?

The simple answer is that this combination should be avoided unless explicitly prescribed and closely monitored by a healthcare professional [1.2.1, 1.3.2]. The primary and most dangerous interaction is the additive effect on the central nervous system [1.3.1]. Both medications are CNS depressants, and when taken together, their effects are not just added but can be synergistically increased [1.3.1].

This potentiation leads to a higher risk of:

Severe Drowsiness and Sedation: This can impair your ability to perform tasks that require mental alertness, such as driving or operating machinery [1.2.1, 1.3.2].
Impaired Judgment and Coordination: The combination can cause significant dizziness, confusion, and difficulty with motor control, increasing the risk of falls and accidents, especially in the elderly [1.2.1].
Respiratory Depression: This is a particularly dangerous risk where breathing can become slow and shallow. In severe cases, it can be life-threatening [1.3.1, 1.3.6].
Cognitive Impairment: Patients may experience difficulty concentrating, thinking clearly, and memory problems [1.2.1, 1.3.5].

Clinical studies have confirmed these risks. One study noted that when diazepam was added to amitriptyline treatment, the impairment on performance tasks increased [1.2.5]. Another found that the deterioration in vigilance caused by amitriptyline was potentiated by the addition of diazepam [1.2.7].

Comparison Table: Amitriptyline vs. Diazepam


Feature	Amitriptyline (Elavil)	Diazepam (Valium)
Drug Class	Tricyclic Antidepressant (TCA) [1.4.1]	Benzodiazepine [1.5.1]
Primary Mechanism	Blocks reuptake of serotonin and norepinephrine [1.4.5]	Enhances the effect of GABA [1.5.2]
Primary Uses	Depression, neuropathic pain, migraine prevention [1.4.2, 1.4.5]	Anxiety, muscle spasms, seizures, alcohol withdrawal [1.5.1]
Common Side Effects	Dry mouth, drowsiness, constipation, blurred vision, weight gain [1.4.5]	Drowsiness, fatigue, muscle weakness, impaired coordination [1.5.2, 1.5.3]
Key Interaction Risk	Additive CNS depression, sedation, anticholinergic effects [1.3.1, 1.3.6]	Additive CNS and respiratory depression, sedation [1.3.1, 1.3.6]

Medical Guidance and Safe Practices

If a doctor prescribes both amitriptyline and diazepam, it is typically done with extreme caution, often for specific, severe conditions and under strict supervision [1.3.1]. In such cases, the prescriber will likely start with the lowest possible doses and titrate carefully while monitoring for adverse effects [1.3.1].

Patients should adhere to the following safety measures:

Inform Your Doctor: Always tell your doctor about all medications you are taking, including over-the-counter drugs, vitamins, and herbal supplements [1.2.1].
Avoid Alcohol: Alcohol is also a CNS depressant and will significantly increase the sedative and respiratory-depressant effects of this drug combination [1.2.1, 1.3.2].
Do Not Drive: Avoid any activities that require mental alertness until you know how this combination affects you [1.3.2].
Recognize Warning Signs: Be aware of the symptoms of excessive CNS depression, such as extreme drowsiness, confusion, difficulty breathing, or severe impairment, and seek medical help if they occur [1.3.2].
Do Not Self-Medicate: Never take these medications together without a doctor's explicit instruction. Do not adjust your doses on your own [1.2.1].

Conclusion

Combining amitriptyline and diazepam is a high-risk activity due to the potential for severe, additive central nervous system and respiratory depression [1.3.1, 1.3.6]. The interaction can significantly impair cognitive and motor functions, making daily activities like driving dangerous [1.2.1]. While a doctor may prescribe this combination in rare and specific circumstances with careful monitoring, patients should never take these two drugs together without direct medical supervision. The risks of this interaction generally outweigh the potential benefits [1.2.3].

For more detailed information on this specific interaction, you can visit a comprehensive drug database:

Authoritative Link: Amitriptyline and diazepam Interactions - Drugs.com

Frequently Asked Questions

Taking them together significantly increases side effects like dizziness, severe drowsiness, confusion, and difficulty concentrating. It can also lead to dangerous respiratory depression, where breathing becomes slow and shallow [1.2.1, 1.3.1].

It is generally not considered safe and should be avoided. A doctor might prescribe them together in special circumstances, but only with very careful dose management and close monitoring due to the high risk of interaction [1.2.3, 1.3.1].

The most dangerous signs are prolonged or excessive CNS and respiratory depression. This can manifest as extreme sleepiness, profound confusion, unresponsiveness, and very slow or shallow breathing, which can be life-threatening [1.3.1, 1.3.6].

No. You should avoid or limit the use of alcohol. Alcohol is also a CNS depressant and will amplify the sedative effects of the medications, increasing the risk of severe side effects [1.2.1, 1.3.2].

Elderly patients are often more sensitive to the effects of CNS depressants. They may experience more severe impairment in thinking, judgment, and motor coordination, which significantly increases the risk of falls and other accidents [1.2.1, 1.3.1].

CNS depression is a slowing down of brain activity. It results in decreased wakefulness and can cause drowsiness, poor coordination, confusion, and slowed breathing. Both amitriptyline and diazepam cause CNS depression [1.3.1].

Yes. For anxiety and depression, doctors often prefer medications like SSRIs (e.g., escitalopram, fluoxetine) or SNRIs (e.g., duloxetine, venlafaxine) as first-line treatments because they generally have a safer side effect profile and fewer risky interactions than combining TCAs and benzodiazepines [1.7.1, 1.7.6].