From the Guidelines
Taking trazodone and oxycodone together requires cautious consideration and monitoring due to potential risks of serotonin syndrome and increased central nervous system depression. The combination of these medications can lead to excessive sedation, confusion, respiratory depression, and impaired coordination, increasing the risk of falls, accidents, and potentially fatal respiratory suppression [ 1 ]. According to the CDC clinical practice guideline for prescribing opioids for pain, clinicians should exercise caution when prescribing opioids, especially extended-release/long-acting (ER/LA) opioids like oxycodone, due to the higher risk of overdose and the potential for increased total average daily opioid dosage compared to intermittent, as-needed opioid use [ 1 ].
Key considerations for the safe use of this combination include:
- Monitoring for signs of serotonin syndrome, such as extreme drowsiness, confusion, agitation, rapid heart rate, fever, muscle rigidity, or difficulty breathing
- Avoiding alcohol and other CNS depressants
- Disclosing all medications to healthcare providers to prevent dangerous interactions
- Following the prescribed dosages and timing strictly, without adjustments on your own
- Regular follow-up with your healthcare provider to assess the benefits and risks of continuing this combination
It's essential to note that the FDA has modified the labeling for ER/LA opioid pain medications, recommending that they be reserved for management of pain severe enough to require daily, around-the-clock, long-term opioid treatment when alternative treatment options are ineffective, not tolerated, or would be otherwise inadequate [ 1 ]. Clinicians should not initiate opioid treatment for subacute or chronic pain with ER/LA opioids and should not prescribe ER/LA opioids for intermittent use [ 1 ]. If you are prescribed both trazodone and oxycodone, your healthcare provider has likely weighed the potential benefits against the risks for your specific situation, and it's crucial to adhere to their guidance and monitoring recommendations.
From the Research
Safety of Concomitant Use of Trazodone and Oxycodone
- The safety of taking trazodone (an antidepressant) and oxycodone (an opioid analgesic) together is a concern due to potential drug-drug interactions 2.
- There is no direct evidence in the provided studies that specifically addresses the safety of concomitant use of trazodone and oxycodone.
- However, studies suggest that trazodone can be safely combined with other medications, but monitoring and counseling patients are prudent when starting a new serotonergic agent or when doses are increased 3.
- The risk of serotonin syndrome, a potentially fatal complication, is a concern when combining serotonergic agents, including trazodone, with other medications 4, 5.
- A study on the combination of trazodone with citalopram and fluoxetine found no significant impact on trazodone serum levels, suggesting no metabolic interaction between these medications 6.
- Another study reported a fatal drug interaction between oxycodone and clonazepam, highlighting the potential risks of combining opioids with other central nervous system depressants 2.
Potential Risks and Interactions
- Serotonin syndrome is a potential risk when combining trazodone with other serotonergic agents 3, 4, 5.
- The combination of oxycodone with other central nervous system depressants, such as clonazepam, can increase the risk of fatal drug interactions 2.
- Monitoring and counseling patients are essential when starting a new serotonergic agent or when doses are increased 3.
- Age, sex, and body weight can influence the pharmacokinetic pattern of trazodone, causing higher concentrations in females and older patients 6.