Case report 301

Migraine headache prophylaxis and treatment with low-dose

mirtazapine

Emmanuelle Le

´

vy and Howard C. Margolese

Other than amitriptyline, few antidepressants have shown

consistent effic acy in migraine treatment prophylaxis. Only

one other case supporting the use of mirtazapine for

migraine prophylaxis has been reported. T o our knowledge,

there are no reports suggesting dose dependence in

mirtazapine effectiveness for migraine treatment, nor

proposals to explain the mechanism of this effect. A 25-

year-old patient was followed in our outpatient department

for DS M-IV treatment-resistant recurr ent major depression.

Multiple antidepressants were used and discontinued

because of migraine exacerbation. Mirtazapine was then

initiated for residual depressive symptoms. Decreased

frequency and intensity of migraines were observed with

low-dose mirt azapine, which reoccurred with higher doses.

Migraine treatment with mirtazapine can be explained

through two possible mechanisms. First, mirt azapine

prevents migraine initiation through hist amine and 5-HT

2

receptor family inhibition. Second, it treats migraines

through 5-HT

1

receptor family activation. However , at

higher doses, histamine activation may explain reoccur-

rence of migraines. Int Clin Psychopharmacol 18:3 01–303

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2003 Lippincott Williams & Wilkins.

International Clinical Psychopharmacology 2003, 18: 3 01–303

Keywords: mirtazapine, migraine, heada che, serotonin, depression

Clinical Ps ychopharmacology Unit, McGill University Health Centre and

Department of Psychiatry, McGill University, Montreal, Quebec, Canada.

Correspondence and requests for reprints to Dr H. C. Margolese, Clinical

Psychopharmacology Unit, Allan Memor ial Institute, McGill Univers ity Health

Centre, 1025 Pine Avenue W est, Montreal, Quebec H3A 1A1, Canada.

T el: + 1 514 843 16 72; fax: + 1 514 9 82 6620;

e-mail: psychopharm.unit@mcgill.ca

Received 5 May 2003 Accepted 8 May 2003

Introduction

Migraine headaches occur in 18% of women and 6% of

men (Silberstein, 2000). Comorbidity between major

depression and m igraine headaches has been establ ished

in epidemiological studies. F or example, patients with

severe migraine headaches have a three-fold higher

lifetime prevalence of major depression compared to

those with no history of headaches (Breslau et al. , 2000).

The only antidepr essant showing co nsistent efficacy in

randomized-placebo -controlled trials for mig raine pro -

phylaxis is amitriptyline (Gomersall and Stuart, 1973;

Couch and Hassanein, 197 9; Zegl er et al. , 1987). One

study even reported a 40% reduction in migraine

frequency (Gomer sall and Stuart, 1973) . T wo placebo -

controlled studies on the use of fluoxetine use in

migraine prophylaxis produced paradoxical results (Adly

et al. , 1992; Saper et al. , 1994). One reveale d superiority of

fluoxetine over pla cebo in the prevention of migrai ne

(Saper et al. , 1994), wherea s the other failed to duplicate

this finding (Adly et al. , 1992). However , a recent

randomized-placebo -controlled study with fluoxetine

found a sign ifican tly reduced pain index after 3 months

of treatment (d’A mato et al. , 1999).

A previous report has postulated a link betwee n

mirtazapine and the treatment of migraine headaches

(Brannon et al. , 2000). This report corroborates the

treatment effectiveness of mirtazapine for migraines.

Similar to the previ ous rep ort, mirtazapine relieved

migraines at low doses. However , ours is the first report

showing dissipation of treatmen t effectiveness at higher

doses, thus su ggesting an inverse dose relationshi p

between mir tazapine and migraine treatment. F urther-

more, we provide a hypothesis supporting the effective-

ness of mirtazapine for migraine headach e treatment and

prophylaxis based on its unique receptor pharm acology .

Case report

The patient was a 25-y ear-old woman with recurren t

DSM-IV (Amer ican Psychiatric Association, 2001) treat-

ment-resistant major depressive disorder and obsessiv e–

compulsive disorder . Her medical history included

fibromyalgia, endom etriosis and migrai nes. Her medica-

tion history revealed numero us adverse reactions to

psychotropics, includ ing cutaneous vasculitis with parox-

etine (Ma rgolese et al. , 2001), intolerab le gastroin testinal

side-effects with venlafax ine and nef azodone , and rash

with valproic acid (which disappeared after anticonvul-

sant discontinuation). F urthermore, she experienced

migraine exacerbation with both fluoxetine and fluvox-

amine.

In January 2002, mirtazapine was introduced at 15 mg/day

to alleviate residual depr essive symptom s. At that time,

her other medications included buprop rion SR 400 mg/

day , amitriptyline 10 mg/day (discontinued 10 days after

mirtazapine initiation), lamotrigine 125 mg/ day , pancreli-

pase enzymes and narat riptan 2.5 mg/d ay p.r .n.

0268-1315

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2003 Lippincott Williams & Wilkins DOI: 10.1097 /01.yic.0000080803.87368.01

Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.