Long-Acting Opioids for Refractory Chronic Migraine
Many patients with chronic migraine (CM) are refractory to our usual therapies.1 Medication choices for the refractory chronic migraineur are limited and include polypharmacy with several preventives, monamine oxidase inhibitors, botulinum toxin type A and opioids, among others.2 Each of these pharmacologic approaches helps a limited number of patients.
There have been a number of studies on long-acting opioids (LAO) as a treatment for refractory chronic daily headache.3-5 Earlier studies focused on the use of low doses of methadone and a small minority of patients who did well long-term. Several studies reported better success rates with other opioids, such as oxycodone CR or long-acting morphine preparations.6 This suggested that, for the difficult-to-treat patient, this approach may be worthwhile, despite the difficulties in prescribing daily opioids.
The current study evaluated long-acting opioids for those who had done well with short-acting opioids (SAOs) for an extended period. These patients had been prescribed SAOs for significant periods in the past. Certain comorbidities were evaluated to assess if they could have predictive value as to who would do well with the opioid and who would fail. These comorbidities were also used to assess risk for abuse.
This retrospective study was conducted at a single U.S. headache clinic. Data was collected via chart review, patient diary and patient interview. Patients who had been prescribed long-acting opioids during the six-year period 2002-2007 were assessed.
Patients kept a headache diary and used a 10-point visual analog scale to measure severity. Functional status was assessed with each visit. If adequate functioning was not maintained, the patient was usually withdrawn from the opioid. During each visit, the following were assessed in addition to functioning:
- pain level,
- brief physical exam,
- side effects of the opioid, and
- overuse/abuse behaviors.
For the study 115 patients were evaluated (87 female, 28 male, age range 23-77). All patients had been diagnosed as having refractory chronic migraine.7 They had longstanding daily headaches that caused significant functional impairment or decreased quality of life. Each patient had failed multiple trials of preventive medicines. In addition, they had little or no relief from abortive medications (triptans, NSAIDs, DHE, etc.) While attempts were made to minimize medication overuse headache, patients with this condition were not excluded from using the long-acting opioids. Virtually every one of these patients would qualify as refractory chronic migraine utilizing the 2008 proposed criteria for definition of refractory migraine and refractory chronic migraine.7
Long-time patients at the treating headache clinic with a diagnosis of refractory chronic migraine were included. Chronic migraine was defined according to the International Headache Society criteria.8 All patients had been prescribed long-acting opioids, including metha-done, long-acting forms of morphine or oxycodone, or the fentanyl patch during the years 2002-2007. All patients had previously shown improved functioning and quality of life on short-acting opioids. The minimum period of use of the SAOs was one year. Thirty two (28%) of the patients had abused the SAOs to some degree.
Primary Outcome Measure: Efficacy
The primary outcome measure was efficacy of the opioid. Efficacy was determined to be positive (+) if the patient continued on the long-acting opioid for at least nine months and the patient consistently reported a 30% or greater improvement in headache frequency and/or severity over baseline. The base-line of comparison was the 3-month period prior to initiation of the long-acting opioid.
Secondary Outcome Measures: Definitions and Criteria
Opioid Abuse. The term ‘opioid abuse’ is not well defined in the literature and is rather imprecise. However, we use this term for the study because it encompasses not only true addiction but lesser forms of overuse as well—such as chemical coping.9 In our current study, patients were labeled as abusers if certain behaviors were severe, persistent, or pervasive. Some of the criteria were felt to be more significant than others. The criteria that we used included: early refill requests; dose escalations; insistence on increasing doses; abusive treatment of the staff regarding refills; false reports of stolen or lost medications; utilizing the opioid for depression or anxiety; using the opioid for other pains not discussed with the physician; receiving similar medication from other physicians; unexpected or abnormal urine screening test results; using illicit drugs or alcohol; repeatedly missing, canceling, or refusing appointments; selling the drugs; obtaining opioids from non-medical arenas; frequent ER visits for opioids; hoarding, forging or altering scripts; borrowing or stealing similar medications from family and friends; physical signs of overuse or addiction; and calls to the physician from family members with concerns about patient overuse.10,11
Anxiety. Patients with anxiety disorders included those with generalized anxiety disorder, panic disorder, and obsessive compulsive disorder. Anxiety was assessed via patient interviews, histories, and the initial anxiety and psychiatric assessment forms. DSM-IV criteria were utilized.12
Depression. Unipolar depression and dysthymia were evaluated according to DSM-IV criteria. Patient interviews, histories, psychiatric assessment forms, Beck Depression Inventory, and the PHQ-9 (Patient Health Questionnaire Depression Module) were utilized.12
The Bipolar Spectrum. Evaluation was accomplished by the following: (1) chart review, (2) Mood Disorder Questionnaire, (3) PHQ-9 (Patient Health Questionnaire Depression Module), and (4) interviews with patients and families.
The lifetime prevalence of bipolar, including the milder end of the spectrum, was assessed. Bipolar illness was defined according to the criteria established by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV).12 In addition, the modifications to DSM-IV by Akiskal were utilized in defining bipolar disorders.13,14
Personality Disorders (PD). The diag-nosis of PD was done in accordance with DSM-IV criteria.12 Patients with severe personality disorders were not placed on the opioids. Only patients deemed moderate-to-severe with PD psychopathology were included.15
The PD characteristics were pervasive, longstanding, and influential in social and work functioning. The purpose of this was twofold: to identify patients at risk to themselves and their healthcare providers, and to exclude those with marginal PD diagnoses. Cluster A, B and C personality disorders were included. The most prevalent were borderline, avoidant, dependent, and obsessive-compulsive.