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Keywords:

  • aripiprazole;
  • craving;
  • medication overuse headache;
  • over-the-counter analgesic

Abstract

  1. Top of page
  2. Abstract
  3. CASE REPORT
  4. DISCUSSION
  5. REFERENCES

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 medication overuse headache, which was successfully treated with aripiprazole. Our experience suggests that aripiprazole may be effective for patients with medication overuse headache.

MEDICATION OVERUSE HEADACHE (MOH)1 is 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 discontinue 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.5–7

In this case report, we describe a patient with refractory MOH who was successfully treated with aripiprazole in an outpatient setting.

CASE REPORT

  1. Top of page
  2. Abstract
  3. CASE REPORT
  4. DISCUSSION
  5. REFERENCES

A 53-year-old woman had experienced right upper jaw pain since receiving dental treatment in 2003, and she subsequently began to take an over-the-counter analgesic named ‘Naron-Ace’, which includes ibuprofen, bromvalerylurea, ethenzamide and caffeine, 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 analgesics. 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 considerably. As no organic disease was observed, a presumptive 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 continued 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 discontinue 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 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 discontinue 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 commencement of aripiprazole, her use of Naron-Ace had decreased, although her face pain persisted. Subsequently, aripiprazole was increased to 12 mg/day. One month later, she was able to completely discontinue taking Naron-Ace, and her face pain had disappeared. 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. Subsequently, aripiprazole was increased to 12 mg/day in January 2009, and her craving promptly disappeared within a few days, and her pain also disappeared 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 aripiprazole administration.

DISCUSSION

  1. Top of page
  2. Abstract
  3. CASE REPORT
  4. DISCUSSION
  5. REFERENCES

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 recommended.3 However, our patient was able to withdraw in an outpatient setting under treatment with aripiprazole. 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.

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.5–7 Aripiprazole has also been effective for craving of cocaine or other substances.11–13 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,5–7 the dosage of aripiprazole was 5–15, 15 and 2–30 mg/day, respectively. The appropriate dosage of aripiprazole for MOH remains to be determined.

In conclusion, our experience demonstrated aripiprazole 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. Top of page
  2. Abstract
  3. CASE REPORT
  4. DISCUSSION
  5. REFERENCES