Psychiatry and Clinical Neurosciences 2011; 65: 296298
Short Communication
Effectiveness of aripiprazole for medication overuse
headache: A case report pcn_2194
Kazuo Yamada, MD, PhD,1* Yasuyuki Makihara, DDS, PhD2 and Yoshiki Imamura, DDS, PhD2
1
Department of Psychiatry, Tokyo Womens Medical University, Medical Center East, and 2Department of Oral Diagnosis,
Nihon University School of Dentistry, Tokyo, Japan
Aripiprazole, a dopamine D2 receptor partial agonist,
has been used to treat schizophrenia and might be
effective for alcohol dependence and craving. We
treated a 53-year-old woman with refractory medica-
tion overuse headache, which was successfully
treated with aripiprazole. Our experience suggests
EDICATION OVERUSE HEADACHE (MOH)1 is
M the result of excessive use of a therapeutic agent
in a susceptible patient, and leads to considerable
disability prior to treatment.2 The recommended
treatment for MOH is abrupt drug withdrawal in an
outpatient or inpatient setting.3 Most patients
improve after discontinuing regular drug intake.
However, some patients with MOH cannot discon-
tinue analgesics.
Aripiprazole is a dopamine D2 receptor partial
agonist, a serotonin 5-HT1A receptor partial agonist
and 5-HT2 receptor antagonist.4 It is used to treat
schizophrenia and mania, and to prevent the relapse
of mood episode in bipolar disorder. Recently,
several studies suggested that aripiprazole might also
be effective for alcohol dependence and craving.57
In this case report, we describe a patient with
refractory MOH who was successfully treated with
aripiprazole in an outpatient setting.
CASE REPORT
A 53-year-old woman had experienced right upper
jaw pain since receiving dental treatment in 2003,
*Correspondence: Kazuo Yamada, MD, PhD, Department of
Psychiatry, Tokyo Womens Medical University, Medical Center East,
2-1-10 Nishi-ogu, Arakawa-ku, Tokyo 116-8567, Japan. Email:
yamadaps@dnh.twmu.ac.jp
Received 1 September 2010; revised 5 November 2010; accepted
12 January 2011.
296
Psychiatry and Clinical Neurosciences 2011 Japanese Society of Psychiatry and Neurology
doi:10.1111/j.1440-1819.2011.02194.
296..298
that aripiprazole may be effective for patients with
medication overuse headache.
Key words: aripiprazole, craving, medication overuse
headache, over-the-counter analgesic.
and she subsequently began to take an over-the-
counter analgesic named Naron-Ace, which includes
ibuprofen, bromvalerylurea, ethenzamide and caf-
feine, for her face pain. In 2004, she was taking
Naron-Ace more than ten times a day. This overuse of
an analgesic aggravated her face pain further, so she
attended a pain clinic where the diagnosis of MOH
was made, and she was advised to discontinue anal-
gesics. After the discontinuation of Naron-Ace, her
face pain decreased. However, she restarted Naron-
Ace again, because her face pain did not disappear
completely. Her face pain soon worsened consider-
ably. As no organic disease was observed, a presump-
tive diagnosis of somatoform pain disorder was
made, and she was referred to our clinic in July 2006.
We considered the diagnosis to be somatoform
pain disorder, and prescribed amitriptyline.
Although we advised her not to take analgesics, she
could not discontinue Naron-Ace. After we increased
amitriptyline to 100 mg/day in September 2006, her
face pain improved markedly. However, sporadic
pain attacks under stressor persisted, and she contin-
ued to take Naron-Ace two or three times a day on
average. Two months later, her face pain worsened
and it was thought that MOH might be the cause of
exacerbation. Despite our warning, she could not dis-
continue taking Naron-Ace. Therefore, we increased
amitriptyline to 150 mg/day. However, her analgesia-
taking behavior did not change. Valproate (up to
800 mg/day) and risperidone (up to 2 mg/day) also
2011 The Authors
Psychiatry and Clinical Neurosciences 2011; 65: 296298
did not change her behavior. In July 2008, she was
taking Naron-Ace more than ten times a day. She said
that she was unable to stop taking Naron-Ace by
herself, although she understood that she should dis-
continue analgesics. A vicious spiral of medication
overuse and increasing pain progressed, and we
considered that she had lapsed into a craving for
Naron-Ace.
After obtaining written informed consent from the
patient, we prescribed aripiprazole at a daily dose of
6 mg, in September 2008. Four weeks after the com-
mencement of aripiprazole, her use of Naron-Ace had
decreased, although her face pain persisted. Subse-
quently, aripiprazole was increased to 12 mg/day.
One month later, she was able to completely discon-
tinue taking Naron-Ace, and her face pain had disap-
peared. Although amitriptyline was decreased to
100 mg/day in November 2008, her pain did not
recur. However, when aripiprazole was decreased to
6 mg/day in December 2008, the craving for Naron-
Ace restarted and her face pain appeared again. Sub-
sequently, aripiprazole was increased to 12 mg/day
in January 2009, and her craving promptly disap-
peared within a few days, and her pain also disap-
peared within a month. Aripiprazole was decreased
to 6 mg/day in May 2010 and discontinued in June
2010, and afterward her craving and facial pain did
not recur. No adverse event occurred with aripipra-
zole administration.
DISCUSSION
We treated a patient with refractory MOH, which
was successfully treated with aripiprazole. There has
been no previous report on the use of aripiprazole or
other atypical antipsychotics for treatment of MOH,
although there was a case report in which migraine
was successfully treated with aripiprazole.8 Therefore
our report is the first case in the world. The patient
showed craving for an over-the-counter analgesic,
and it was felt that aripiprazole improved her craving
and MOH without adverse events. Amitriptyline,
valproate and risperidone were not effective in our
patient. For patients who fail to withdraw in an
outpatient setting, inpatient withdrawal is recom-
mended.3 However, our patient was able to withdraw
in an outpatient setting under treatment with arip-
iprazole. Although the findings of recent studies
suggest that patients are at greatest risk of relapse
within the first 12 months,9 our patient has not
relapsed for 12 months after treatment.
Psychiatry and Clinical Neurosciences 2011 Japanese Society of Psychiatry and Neurology
Aripiprazole for medication overuse headache 297
Aripiprazole is a dopamine D2 receptor partial
agonist4 and probably a dopamine D3 receptor
partial agonist.10 No data concerning the effectiveness
of aripiprazole for pain has been reported. However,
the efficacy of aripiprazole for alcohol dependence
and craving has been reported by several studies.57
Aripiprazole has also been effective for craving of
cocaine or other substances.1113 In a previous
report,14 it was suggested that MOH was associated
with behaviors of substance dependence. Stimulation
of the dopamine system is likely to be a key factor in
the craving and reward aspect.7 Our patient might
have been able to discontinue taking the over-the-
counter analgesic due to aripiprazole stimulating her
dopamine system and relieving her craving.
The effective dosage of aripiprazole for our patient
was 12 mg/day. In three previous reports on alcohol
dependence,57 the dosage of aripiprazole was 515,
15 and 230 mg/day, respectively. The appropriate
dosage of aripiprazole for MOH remains to be
determined.
In conclusion, our experience demonstrated arip-
iprazole to be safe and effective for patients with
MOH, who tend to crave medication. To confirm the
effectiveness and safety of aripiprazole for MOH,
a larger, well-controlled double-blind study is
warranted.
REFERENCES
1. Headache Classification Subcommittee of the Interna-
tional Headache Society. The International Classification
of Headache Disorders, 2nd edn. Cephalalgia 2004; 24
(Suppl. 1): 1160.
2. Grazzi L, Andrasik F, Usai S, Bussone G. Headache with
medication overuse: treatment strategies and proposals of
relapse prevention. Neurol. Sci. 2008; 29: 9398.
3. Katsarava Z, Holle D, Diener H-C. Medication overuse
headache. Curr. Neurol. Neurosci. Rep. 2009; 9: 115
119.
4. DeLeon A, Patel NC, Crismon ML. Aripiprazole: a com-
prehensive review of its pharmacology, clinical efficacy,
and tolerability. Clin. Ther. 2004; 26: 649666.
5. Janiri L, Martinotti G, DiNicola M. Aripiprazole for relapse
prevention and craving in alcohol-dependent subjects:
results from a pilot study. J. Clin. Psychopharmacol. 2007;
27: 519520.
6. Voronin K, Randall P, Myrick H, Anton R. Aripiprazole
effects on alcohol consumption and subjective reports in a
clinical laboratory paradigm: possible influence of self-
control. Alcohol. Clin. Exp. Res. 2008; 32: 19541961.
7. Anton RF, Kranzler H, Breder C, Marcus RN, Carson WH,
Han J. A randomized, multicenter, double-blind, placebo-
2011 The Authors
298 K. Yamada et al.
controlled study of the efficacy and safety of aripiprazole
for the treatment of alcohol dependence. J. Clin. Psychop-
harmacol. 2008; 28: 512.
8. LaPorta LD. Relief from migraine headache with aripipra-
zole treatment. Headache 2007; 47: 922926.
9. Andrasik F, Grazzi L, Usai S, DAmico D, Kass S, Bussone
G. Disability in chronic migraine with medication
overuse: treatment effect at 3 years. Headache 2007; 47:
12771281.
10. Tadori Y, Forbes RA, McQuade RD, Kikuchi T. Character-
ization of aripiprazole partial agonist activity at human
dopamine D3 receptors. Eur. J. Pharmacol. 2008; 597:
2233.
11. Brown ES, Jeffress J, Liggin JDM, Garza M, Beard L. Switch-
ing outpatients with bipolar or schizoaffective disorders
2011 The Authors
Psychiatry and Clinical Neurosciences 2011 Japanese Society of Psychiatry and Neurology
Psychiatry and Clinical Neurosciences 2011; 65: 296298
and substance abuse from their current antipsychotic to
aripiprazole. J. Clin. Psychiatry 2005; 66: 756760.
12. Beresford TP, Clapp L, Martin B, Wiberg JL, Alfers J, Beres-
ford HF. Aripiprazole in schizophrenia with cocaine
dependence: a pilot study. J. Clin. Psychopharmacol. 2005;
25: 363366.
13. Vorspan F, Bellais L, Keijzer L, Lepine J-P. An open-label
study of aripiprazole in nonschizophrenic crack-
dependent patients. J. Clin. Psychopharmacol. 2008; 28:
570572.
14. Fuha J-L, Wanga S-J, Lub S-R, Juang K-D. Does medication
overuse headache represent a behavior of dependence?
Pain 2005; 119: 4955.