Tramadol and Diazepam: Can They Be Taken Together?

What is Tramadol?

Tramadol is an opioid analgesic, which means that it binds to opioid receptors in the brain and can be used for pain management in adults. Opioids are generally used for moderate to severe pain, in contrast to over-the-counter drugs like Ibuprofen, but have a higher risk of physical dependence, also known as addiction.

Chemistry of Tramadol

Tramadol is a synthetic, or lab-made, centrally acting weak μ-opioid receptor analgesic and is a racemic mixture of (+)-tramadol and (-)-tramadol enantiomers. The (+)-tramadol has a higher affinity (higher likelihood of finding) for μ-opioid receptor and provides additional prevention of 5- hydroxy tryptamine reuptake, while the (-)-tramadol is a successful noradrenaline reuptake inhibitor and intensifies its release by activating the noradrenaline autoreceptor.

Tramadol is a unique analgesic medication that is available in various formulations. It has both monoaminergic reuptake inhibitory and opioid receptor agonist activity. It is a prodrug metabolized by the cytochrome P450 (CYP) enzymes CYP2D6 and CYP3A4 to its more potent opioid analgesic metabolites, mainly the O-demethylation product M1.

Tramadol's simultaneous opioid agonist action and serotonin (5-HT) and norepinephrine reuptake inhibitory effects result in a unique side effect profile and significant drug interactions that must be considered. Abrupt cessation of tramadol increases the risk for both opioid and serotonin-norepinephrine reuptake inhibitor withdrawal syndromes.

What is Diazepam?

Diazepam, also known by the brand name Valium, is a benzodiazepine medication. Like other benzodiazepines, it can alleviate symptoms of anxiety, promote sleep or sedation, prevent seizures, and relax muscles [1, 2]. DIazepam has a quick onset latency of about 2-10 minutes. This means it is beneficial in acute cases like status epilepticus—a seizure lasting more than 5 minutes [3]. 

Diazepam works by increasing inhibition in the brain and reducing neuronal activity by enhancing the effect of a neurotransmitter called gamma-aminobutyric acid (GABA) throughout the central nervous system. 

Diazepam is also commonly prescribed for the management of severe alcohol withdrawal symptoms. It can prevent some of the severe physiological symptoms of alcohol withdrawal, which include anxiety, seizures, muscle spasms, or delirium [2].

The adult dosage can depend on the condition but ranges from 2-10mg. Although diazepam is effective and safe to use if you have been prescribed diazepam, it can lead to mild to moderate side effects. These include impaired motor coordination, dizziness, mood changes, and/or slurred speech, meaning one should not drive after taking diazepam. It is also easy to become dependent on diazepam as your brain adapts to increased levels of GABA stimulation, and this consequently increases the risks of overdose [4].

Tramadol and Diazepam

Tramadol and Diazepam are both potent medications that can have significantly different effects on the body. Tramadol is an opioid analgesic used to treat moderate to severe pain, while diazepam is a benzodiazepine used to treat mental health conditions such as anxiety, seizures, and muscle spasms. When taken together, these drugs can interact in ways that alter their effects and potentially increase the risk of adverse reactions.

Research has shown that the combination of tramadol and diazepam does not increase the risk of fatality compared to tramadol alone. However, it does alter the toxicity pattern of tramadol. The combination of these two drugs has been found to enhance sedation and respiratory depression, which can be dangerous [5].

The interaction between Tramadol and Diazepam is mainly pharmacodynamic, meaning it affects how the drugs work in the body. However, Tramadol does increase the risk of seizures, which is essential to consider if you are taking Diazepam for epilepsy or seizures. Furthermore, taking Tramadol and Diazepam increased the risk of respiratory depression and sedation compared to taking the opioid analgesic alone [5]. This indicates that taking Diazepam and Tramadol together could exacerbate the side effects of diazepam.

Additionally, taking Tramadol with diazepam may affect its metabolism. This can increase the duration of time Tramadol stays in your system, increasing the risks of side effects [5].

Tramadol and Diazepam: A Summary

To summarise, while Tramadol and Diazepam can be taken together, it is crucial to do so under the close supervision of a healthcare provider due to the increased risk of enhanced sedation and respiratory depression. Never drive after taking Diazepam, as your attention and reaction times will be impaired.