Does trazodone interact with clonazepam? (5+ factors)

In this article, we’ll discuss whether trazodone and clonazepam interact with each other or not. Furthermore, we will explore the potential interactions between them, what research suggests on this, the benefits and possible side effects of taking these two in combination and the precautionary guidelines for their safe co-administration.

Does trazodone interact with clonazepam?

Yes, trazodone may interact with clonazepam. Both of these medications can increase the risk of central nervous system depression individually and so the effect is exacerbated when taken in combination. This leads to enhanced sedation and drowsiness. (1)

Trazodone, an antidepressant, is FDA-approved for the treatment of major depressive disorders. It is classified as a serotonin modulator which exerts its effects by increasing the levels of serotonin in the brain. Serotonin is a crucial neurotransmitter which helps in mood regulation and boosts motivation in a person, thereby reducing feelings of depression and anxiety. (1)

Clonazepam, on the other hand, is widely used as an anxiolytic (anxiety-reducing) medication and is also used for anticonvulsive purposes. It is classified as a benzodiazepine, which works by enhancing the effects of an inhibitory neurotransmitter called GABA (gamma-aminobutyric acid). This neurotransmitter in turn produces inhibitory effects on the central nervous system which produces a sense of calmness and sedation. (2)

If you’re considering or are currently taking trazodone and clonazepam together and have concerns about the interactions or experience troublesome side effects, it’s advisable to consult with your healthcare provider. 

What are the potential interactions between trazodone and clonazepam?

Trazodone and clonazepam can interact with each other based on their mechanisms of action. Trazodone works by balancing the levels of serotonin and clonazepam works by stimulating the activity of GABA. Both of these drugs produce sedative effects by increasing the depression of the central nervous system. When given concurrently the risk of CNS depression is increased which leads to enhanced sedation and drowsiness. (1,2)

The combination of these two medications, especially when taken at higher doses may cause respiratory depression, particularly in individuals who already have some pre-existing respiratory condition. This combination may also lead to cognitive impairment which may include memory-related issues and difficulty in concentrating or focusing. (2)

It’s important to remember that everyone is unique in terms of brain chemistry and how they respond to certain medications. Some people may be more sensitive to the combined effects of trazodone and clonazepam while others may tolerate the combination well. 

What does research suggest?

According to a research study, researchers performed a clinical trial on 112 patients suffering from Parkinson’s disease and sleep issues to determine the safety and efficacy of trazodone along with clonazepam. They randomly split the patients into 3 groups and each group was given a different treatment protocol for 4 weeks with melatonin at 3mg per day for group 1, clonazepam at 1mg per day for group 2 and trazodone at 50mg per day for group 3. (3)

The results showed that out of 112 participants, only 93 completed the study and all of them experienced better sleep quality after 4 weeks with each drug treatment. However, they concluded that combining these medications could exacerbate the sedative and drowsy effect of medications making a person feel more sleepy throughout the day. (3)

It’s better to take these medications separately or if your doctor has prescribed them together then the dose and timings must be adjusted to avoid interactions and risk of side effects and monitoring is required.

What factors may increase the risk of trazodone and clonazepam interaction? 

Several factors may contribute to the risk of increased interaction between trazodone and clonazepam. Some of them are discussed below: (4,5)

Central nervous system (CNS) depressants: 

Both trazodone and clonazepam have CNS depressant effects and taking them in combination with other substances with similar effects on CNS like alcohol or other sedatives can lead to an additive sedative effect and increase the risk of drowsiness, impaired coordination and respiratory depression. 

Individual variability in metabolism: 

The variations in the metabolism of an individual, such as how fast or slow they can absorb and process the medications and their elimination from the body significantly influence drug interaction. Genetic factors, age and a person’s overall health can contribute to these differences. 

Liver and kidney function: 

Both trazodone and clonazepam are metabolized (broken down) in the liver and if the liver is not functioning properly it can affect the metabolism of these drugs, potentially leading to increased concentration in the bloodstream and an elevated risk of interaction. Similarly, kidney dysfunction may influence a drug’s clearance from the body.


Older people are generally more sensitive and at increased risk of drug interactions as their metabolism and renal or hepatic function is reduced with age and they might be taking multiple medications at once for different conditions.

Dosage levels: 

Higher doses of trazodone and clonazepam may increase the chances of interaction compared to lower doses. 

Underlying health conditions: 

If a person has pre-existing health conditions especially related to the central nervous system, respiratory system or cardiovascular system, the person is thought to be more susceptible to drug interactions and enhanced side effects. 

What are the potential side effects of trazodone and clonazepam combination?

Using trazodone and clonazepam in combination can increase the risk of side effects due to the additive effects of these medications. Some potential side effects may include: (1,5)

  • Increased sedation and drowsiness
  • Impaired coordination
  • Respiratory depression
  • Cognitive impairment (memory-related issues, reduced mental clarity etc)
  • Increased risk of fall
  • Dizziness or lightheadedness
  • Hypotension (low blood pressure)
  • Increased risk of overdose
  • Increased risk of serotonin syndrome (characterised by symptoms such as hallucinations, agitation, rapid heartbeat, fever, confusion, tremors etc)
  • Withdrawal symptoms
  • Mood changes
  • Erectile dysfunction (with high doses of clonazepam or trazodone)

If you experience any of the aforementioned side effects from the use of these medications, it’s advisable to inform your healthcare provider without wasting time. 

How to safely use trazodone and clonazepam together?

Using trazodone and clonazepam together must be done under the supervision and regular monitoring of a healthcare provider. Before starting or adjusting any medication’s dosage regimen talk to your doctor. Inform them about your complete medical history including any allergies and health conditions, and the medications you might have been taking including all prescription and over-the-counter drugs and herbal supplements. (4,5)

Your doctor will assess your specific health condition and make a suitable treatment plan based on your above-mentioned data and current symptoms. Do not change the dose of your medication, such as increasing or decreasing it on your own and neither stop taking it abruptly otherwise, you’ll face consequential withdrawal side effects. In case, your doctor wants to stop it, they may gradually taper it off. 

Always stick to the recommended dosage guidelines and other specific instructions given by your doctor. Schedule time-to-time follow-up visits to keep your symptoms and side effects monitored. 

Try to incorporate healthy lifestyle habits into your daily routine. Avoid overconsumption of alcohol and other substances that cause central nervous system depression and exacerbate side effects. If you’re pregnant, planning to conceive or breastfeeding, first consult your doctor before starting these medications to ensure the safety profile of the fetus. (5)

As a pharmacist, I would suggest not completely relying on antidepressants and sleeping pills for better mood and improved sleep quality.

Instead of taking these two medications in combination, try to ask your doctor to choose any of them that best suits your health condition and suggest some lifestyle and dietary considerations that positively complement your treatment plan like regular exercise including running and cardio or practising certain stress-reducing techniques like yoga or meditation and eat a diet rich in essential nutrients. 

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