From the Guidelines
Skelaxin (metaxalone) may interact with Zoloft (sertraline) and Elavil (amitriptyline), increasing the risk of central nervous system depression and serotonin syndrome. When taking Skelaxin with Zoloft or Elavil, there is a potential for increased central nervous system depression, which could cause symptoms like excessive drowsiness, dizziness, impaired coordination, and slowed reflexes. This interaction occurs because both medications can affect brain function - Skelaxin is a muscle relaxant that works on the central nervous system, while Zoloft is an SSRI antidepressant and Elavil is a tricyclic antidepressant that affects serotonin levels in the brain 1.
According to the study published in the Journal of Crohn's and Colitis 1, serotonergic/adrenergic drugs such as sertraline and amitriptyline can cause serious adverse reactions, including hypertensive crisis, when used with other medications that may inhibit monoamine oxidase (MAO). Although this study does not specifically mention metaxalone, it highlights the potential risks of combining serotonergic medications with other central nervous system depressants.
Another study published in the Mayo Clinic Proceedings 1 discusses the potential risks of combining triptans with SSRIs or SNRIs, which are similar to the potential risks of combining Skelaxin with Zoloft or Elavil. The study notes that the risk of serotonin syndrome with combining these medications is low, but it is still a theoretical concern.
If you are prescribed Skelaxin with Zoloft or Elavil, take them exactly as directed by your healthcare provider, who has likely considered this potential interaction when prescribing. Do not adjust dosages on your own, and avoid activities requiring mental alertness until you know how these medications affect you. Also, avoid alcohol while taking this combination, as it can further increase CNS depression. Contact your doctor immediately if you experience severe drowsiness, confusion, or difficulty breathing.
Key points to consider:
- Skelaxin can increase the risk of central nervous system depression when combined with Zoloft or Elavil
- The combination of these medications can cause symptoms like excessive drowsiness, dizziness, impaired coordination, and slowed reflexes
- There is a theoretical risk of serotonin syndrome when combining serotonergic medications with other central nervous system depressants
- Avoid alcohol and activities requiring mental alertness when taking this combination
- Contact your doctor immediately if you experience severe side effects.
From the FDA Drug Label
The sedative effects of metaxalone tablets and other CNS depressants (e.g., alcohol, benzodiazepines, opioids, tricyclic antidepressants) may be additive.
- Metaxalone may interact with Amitriptyline (Elavil), a tricyclic antidepressant, as the sedative effects of these two drugs may be additive.
- There is no direct information in the drug label about an interaction between Metaxalone and Sertraline (Zoloft), which is an SSRI antidepressant. 2
From the Research
Interaction between Metaxalone and Amitriptyline or Sertraline
- There are no direct studies on the interaction between Metaxalone (Skelaxin) and Amitriptyline (Elavil) or Sertraline (Zoloft) in the provided evidence.
- However, the studies suggest that serotonin syndrome is a potential risk when combining certain medications that enhance serotonin activity, such as selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs) 3, 4, 5, 6.
- Metaxalone is a muscle relaxant, and its interaction with Amitriptyline (a TCA) or Sertraline (an SSRI) is not explicitly mentioned in the provided studies.
- A study on the association of coprescription of triptan antimigraine drugs and selective serotonin reuptake inhibitor or selective norepinephrine reuptake inhibitor antidepressants with serotonin syndrome found that the risk of serotonin syndrome was low 5.
- Another study reviewed the clinical use of sertraline in mood and anxiety disorders and found it to be safe and well-tolerated, but did not discuss its interaction with metaxalone 7.
- A case report of serotonin syndrome from sertraline monotherapy highlights the importance of monitoring for serotonin syndrome even when patients are taking SSRIs at therapeutic doses 6.