Drug Interaction and Serotonin Toxicity with Opioid Use: Another Reason to Avoid Opioids in Headache and Migraine Treatment

Abstract

Treatment of headache, specifically migraine attacks, has always been a challenging subject, especially for neurologist and pain specialists. Triptans are generally underutilized, despite being the gold standard abortive medication for migraine attacks. On the other hand, opioid analgesics are overused as a treatment for headache. One reason for this could be physician unfamiliarity with drug interactions between opioids and other medications, especially the possibility of serotonin toxicity. The general awareness of potential serotonin toxicity with using opioid analgesics is low. In this review, we will conduct a theoretic and evidence-based review of the potential for developing serotonin syndrome in patients who are using opioids analgesics, especially in combination with antidepressants, a common co-prescribed combination. We also review the current diagnostic criteria for serotonin syndrome and identify possible shortcomings of those criteria. Our aim is to increase the awareness of health care providers about potential drug interaction of opioid analgesics with other classes of medication. We place particular emphasis on tramadol since this drug is one of the most commonly used opioid analgesics for headache. The potential for developing serotonin syndrome is relatively high in the patients who are using opioid for pain control. The use of opioids in migraine headache is already discouraged due to the high risk of medication overuse headache and also an increase in headache-related disability (Katsarava et al. Neurology 62:788-790, 2004; Bigal and Lipton. Neurology 71:1821-8, 2008; Casucci and Cevoli. Neurol Sci. 34 Suppl 1:S125-8, 2013). This is another reason that physicians and health care providers should avoid using this class of medication for pain, specifically headache and migraine treatment.

Serotonin Syndrome after Initiation of Pregabalin on a Stable Regimen of Antidepressant Medication

“…Combining serotonergic agents like antidepressants or opioids can cause excessive stimulation of the 5HT1a and 5HT2a receptors [15].…”

Drug–drug interactions involving antidepressants: focus on desvenlafaxine

“… 62 However, there are debatable concerns regarding the safety and PD interactions of this coprescription. 63 – 65 Pharmacologically, triptans demonstrate only weak affinity for 5-hydroxytryptamine 1 (5HT 1 ) receptors and no activity at 5HT 2 receptors, 66 which are believed to be mechanistically implicated in the development of serotonin syndrome. 65 However in 2010, the US Food and Drug Administration recommended that patients treated concomitantly with a triptan and SSRI/SNRI be informed of the possibility of serotonin syndrome.…”

“…A higher occurrence of serotonin syndrome has been found when opioids, particularly tramadol, are coadministered with an SSRI or SNRI. 63 , 89 This is because tramadol also has a possible SNRI effect. 90 Consequently, there is a potential for PD interaction, as both desvenlafaxine and tramadol are serotonergic drugs.…”

The Basic Pharmacology of Opioids Informs the Opioid Discourse about Misuse and Abuse: A Review

“…For example, opioids are not very effective and might be better avoided in the treatment of headaches, such as cluster headaches and migraines [63]. The long-term use of opioids for chronic noncancer pain remains controversial [64–67].…”