By Marcello Cherchi, MD PhD
For patients
Serotonin-specific reuptake inhibitors (SSRIs) are drugs you can take by mouth. They are sometimes used for problems with mood (like depression or anxiety), but some doctors also prescribe them to protect against migraine.
For clinicians
Overview
Serotonin-specific reuptake inhibitors (SSRIs) are sometimes used in otoneurology for migraine prophylaxis, though evidence in support of this application is modest.
Introduction
Serotonin-specific reuptake inhibitors (SSRIs) were originally developed and approved for the treatment of various mood disorders. Over the years they have found a number of off-label uses, including migraine prophylaxis. As of this writing many SSRIs had been FDA approved, including citalopram, escitalopram, fluoxetine, fluvoxamine, olanzapine, paroxetine and sertraline.
Pharmacology
Many drugs influence serotonin metabolism, such a tricyclic compounds. Serotonin-specific reuptake inhibitors, as their name suggests, have an effect that more narrowly targets serotonin reuptake.
Cautions and contraindications
As with any drugs that have serotonergic activity, SSRIs post the risk of inducing serotonin syndrome. The risk of serotonin syndrome is very small, but becomes non-trivial if these drugs are used in high doses, especially if used simultaneously with other serotonergic medications.
SSRIs should not be taken during pregnancy and lactation.
Relevance in otoneurology
Probably the main application of SNRIs in otoneurology is in the management of migraine with migraine associated vertigo (MAV).
There is very little literature regarding citalopram (Rampello et al. 2004) and escitalopram for migraine prophylaxis (Tarlaci 2009).
Fluoxetine was studied in several randomized, placebo-controlled trials, and found to be superior to placebo for migraine prophylaxis (d’Amato et al. 1999; Steiner et al. 1998).
A single study reported that fluvoxamine had comparable efficacy to amitriptyline but was better tolerated for migraine prophylaxis (Bank 1994).
A single retrospective study of olanzapine suggested possible efficacy for migraine prophylaxis (Silberstein et al. 2002).
Several early studies suggested that paroxetine has efficacy for migraine prophylaxis (Black and Sheline 1995; Hays 1997) independently of any effect on mood (Park et al. 2006).
An early study of sertraline showed no superiority over placebo for migraine prophylaxis (Landy et al. 1999).
A Cochrane review of SSRIs concluded that there is insufficient evidence of efficacy for migraine (Banzi et al. 2015), though some investigators have reached different conclusions (Wang et al. 2020).
Other notes
We prefer using SNRIs (specifically venlafaxine) for migraine prophylaxis. However, if a patient’s psychiatrist has reason to manage a mood disorder with an SSRI, then the literature suggests that fluoxetine, fluvoxamine and paroxetine would be reasonable options.
References
Bank J (1994) A comparative study of amitriptyline and fluvoxamine in migraine prophylaxis. Headache 34: 476-8. doi: 10.1111/j.1526-4610.1994.hed3408476.x
Banzi R, Cusi C, Randazzo C, Sterzi R, Tedesco D, Moja L (2015) Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) for the prevention of migraine in adults. Cochrane Database Syst Rev 4: CD002919. doi: 10.1002/14651858.CD002919.pub3
Black KJ, Sheline YI (1995) Paroxetine as migraine prophylaxis. J Clin Psychiatry 56: 330-1.
d’Amato CC, Pizza V, Marmolo T, Giordano E, Alfano V, Nasta A (1999) Fluoxetine for migraine prophylaxis: a double-blind trial. Headache 39: 716-9.
Hays P (1997) Paroxetine prevents migraines. J Clin Psychiatry 58: 30-1.
Landy S, McGinnis J, Curlin D, Laizure SC (1999) Selective serotonin reuptake inhibitors for migraine prophylaxis. Headache 39: 28-32. doi: 10.1046/j.1526-4610.1999.3901028.x
Park HJ, Lee ST, Shim JY, Kim B, Hwang SH, Kim SH, Park JE, Park JH, Jung SH, Ahn JY, Chu K, Kim M (2006) The Effect of Paroxetine on the Reduction of Migraine Frequency is Independent of Its Anxiolytic Effect. J Clin Neurol 2: 246-51. doi: 10.3988/jcn.2006.2.4.246
Rampello L, Alvano A, Chiechio S, Malaguarnera M, Raffaele R, Vecchio I, Nicoletti F (2004) Evaluation of the prophylactic efficacy of amitriptyline and citalopram, alone or in combination, in patients with comorbidity of depression, migraine, and tension-type headache. Neuropsychobiology 50: 322-8. doi: 10.1159/000080960
Silberstein SD, Peres MF, Hopkins MM, Shechter AL, Young WB, Rozen TD (2002) Olanzapine in the treatment of refractory migraine and chronic daily headache. Headache 42: 515-8. doi: 10.1046/j.1526-4610.2002.02126.x
Steiner TJ, Ahmed F, Findley LJ, MacGregor EA, Wilkinson M (1998) S-fluoxetine in the prophylaxis of migraine: a phase II double-blind randomized placebo-controlled study. Cephalalgia 18: 283-6.
Tarlaci S (2009) Escitalopram and venlafaxine for the prophylaxis of migraine headache without mood disorders. Clin Neuropharmacol 32: 254-8. doi: 10.1097/WNF.0b013e3181a8c84f
Wang F, Wang J, Cao Y, Xu Z (2020) Serotonin-norepinephrine reuptake inhibitors for the prevention of migraine and vestibular migraine: a systematic review and meta-analysis. Reg Anesth Pain Med 45: 323-330. doi: 10.1136/rapm-2019-101207
