From the Guidelines
Combining sertraline and trazodone can be safe for most patients when done under medical supervision, with careful monitoring for symptoms of serotonin syndrome, and gradual dosage adjustments as needed. When prescribing these medications together, it is essential to start the second non-MAOI serotonergic drug, in this case, trazodone, at a low dose and increase it slowly, while monitoring for symptoms, especially in the first 24 to 48 hours after dosage changes 1. Sertraline, an SSRI antidepressant, and trazodone, often prescribed at lower doses for sleep, can be taken together, but patients should be aware of the potential increased risk of serotonin syndrome, a rare but serious condition.
Some key considerations when combining these medications include:
- Starting with a low dose of trazodone and gradually increasing it as needed and tolerated
- Monitoring patients closely for symptoms of serotonin syndrome, such as agitation, confusion, rapid heart rate, and muscle rigidity
- Being aware of potential side effects like dizziness, drowsiness, or sexual dysfunction, which may be more pronounced when taking both medications
- Adjusting dosages based on individual response and tolerance, under the guidance of a healthcare provider
It is crucial for patients to report any unusual symptoms immediately and never adjust dosages or stop either medication without consulting their healthcare provider. Medical education, training, and experience are necessary to safely and effectively prescribe antidepressant medications, including combinations like sertraline and trazodone 1.
From the FDA Drug Label
The development of a potentially life-threatening serotonin syndrome has been reported with SNRIs and SSRIs, including sertraline, alone but particularly with concomitant use of other serotonergic drugs (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, and St John’s Wort) and with drugs that impair metabolism of serotonin (in particular, MAOIs, both those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue). Serotonin-norepinephrine reuptake inhibitors (SNRIs) and SSRIs, including Trazodone Hydrochloride Tablets, can precipitate serotonin syndrome, a potentially life-threatening condition. The risk is increased with concomitant use of other serotonergic drugs (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptan, buspirone, and St. John’s Wort) and with drugs that impair metabolism of serotonin, i. e., MAOIs
Key Considerations:
- Serotonin Syndrome Risk: The concomitant use of sertraline and trazodone may increase the risk of serotonin syndrome, a potentially life-threatening condition.
- Serotonergic Drugs: Both sertraline and trazodone are serotonergic drugs, which can increase the risk of serotonin syndrome when used together.
- Monitoring Required: Patients should be monitored for the emergence of serotonin syndrome when taking sertraline and trazodone concomitantly.
It is not safe for patients who take sertraline to take trazodone without careful consideration and monitoring by a healthcare provider due to the increased risk of serotonin syndrome 2 3.
From the Research
Safety of Combining Sertraline and Trazodone
- The combination of sertraline and trazodone may increase the risk of serotonin syndrome, a potentially life-threatening condition caused by a toxic excess of serotonin 4.
- Serotonin syndrome can cause symptoms such as neuromuscular excitation, autonomic instability, and altered mental status, and can be fatal if left unrecognized and untreated 4.
- A case report described a patient who developed serotonin syndrome after taking sertraline and trazodone, highlighting the importance of monitoring patients for signs of serotonin syndrome when combining these medications 4.
Risk Factors for Serotonin Syndrome
- The risk of serotonin syndrome may be increased in patients taking higher doses of sertraline and trazodone, as well as in patients taking other medications that increase serotonin levels 5.
- Older adults may also be at increased risk of serotonin syndrome due to age-related changes in drug metabolism and increased sensitivity to serotonin 5.
- Concomitant use of potent cytochrome P450 2D6 inhibitors may also increase the risk of serotonin syndrome in patients taking sertraline and trazodone 5.
Alternative Treatments for Insomnia
- Trazodone is sometimes used off-label to treat insomnia, but its efficacy and safety for this indication are not well established 6, 7.
- Melatonin may be a safer alternative to trazodone for treating insomnia, as it has a lower risk of serotonin syndrome and other adverse effects 6.
- Selective serotonin reuptake inhibitors (SSRIs) such as sertraline may also be used to treat insomnia, but their efficacy and safety for this indication are uncertain 7.