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Selected Strategies for Refractory Chronic Daily Headache
DESIGN AND METHODS
Retrospective evaluation was completed on 59 patients with chronic daily headache who had been on a daily dose of a triptan medication (sumatriptan or naratriptan) for a minimum of 6 months. The age of the patients ranged from 22 to 63; the median age was 48. The mean age of headache onset was 19.Fifty-five of 59 patients had either chronic tension-type headache or transformed migraine. Four patients had chronic cluster headache. Fifty-two of the 55 patients with chronic daily headache experienced migraine headache as well. These patients had all been refractory to multiple preventive and abortive medications. They felt that the severity and/or frequency of the headaches was at least 50% improved on the daily triptan. The patients in this study had all self-selected daily triptans; they realized, after years of cdh, on a daily dose of a triptan they experienced much less headache.
Fifty-nine percent of the patients utilized sumatriptan alone (tablets or nasal spray). Twenty-nine of these 35 patients utilized sumatriptan tablets alone, with the majority (72%) maintained on 50 mg. daily. Twenty patients utilized sumatriptan alternating with naratriptan, or naratriptan alone. Tolerance was noted in 25% of patients. Four of these patients had increased the dose; three other patients changed from sumatriptan to naratriptan. Thirty-nine percent of the patients had been on triptans for six to twelve months, whereas 61% had utilized the triptans for more than one year. Twenty-two percent were on daily triptans for at least three years. All patients (except one) had been on three or more preventive medications; the most commonly utilized of these were antidepressants, ß-blockers, sodium valproate, calcium channel blockers, and nsaids. Sixty-nine percent of the patients were concurrently on preventive medications with the daily triptans. Seventy-six percent of the patients used abortive medications in addition to the daily triptans; however, analgesic overuse was no longer present in these patients. Previous overuse of abortive medications was identified in 66% of patients.
Side effects were minimal in this patient population. Seven reported fatigue, 3 patients experienced paresthesias, 3 reported mild chest or throat pressure, and there were no cases of new cardiac symptoms during the course of treatment. However, this patient population had self-selected the use of daily triptans. The patients who had reported significant side effects did not continue on the medications for six months. Routine blood tests were normal in 47 of 59 patients.Of the twelve abnormal blood test results, none were felt to be due to the triptans. EKG was done in 23 of 59 patients. Nineteen were normal; the four abnormal results were not felt to be related to the triptans. Echocardiography was done on five patients; all were normal.
Rebound to triptans was not encountered in this study. The patients who had demonstrated sensitivity to rebound had discontinued daily triptan use prior to six months. The most commonly seen associated medication problems were irritable bowel syndrome, ulcer, gastritis, hypertension, asthma, and arthritis. Sixty-eight percent of patients were diagnosed as having an anxiety disorder (usually mild). Fifty-four percent had chronic depression and 47% were diagnosed as having insomnia.
ADVANTAGES AND DISADVANTAGES OF DAILY TRIPTANS
Advantages include: lack of weight gain or sedation, minimal short-term side effects.
Disadvantages include: cost, and long-term safety is not known.
DESIGN AND METHODS
Patients received one of three forms of long-acting opioids for severe, refractory, chronic daily headache. Patients were interviewed after six months of opioid therapy. Sixty-seven patients were given sustained-release (SR) morphine sulfate, 66 patients were placed on methadone, and 52 were treated with controlled-release (CR) oxycodone. This was a prospective, non-blinded study. Efficacy was judged via a visual analog scale. The patients kept a daily headache calendar.
By the end of six months, 46% of the patients had discontinued morphine, 48% had discontinued methadone, while 63% had discontinued CR oxycodone. Low doses of these medications were utilized, with average doses of SR morphine 40 mg., methadone 10 mg., or CR oxycodone 32 mg. daily.
After six months, 51% of the SR morphine patients, as well as 51% of those on methadone, reported moderate or excellent relief. After six months, 36% of those on CR oxycodone reported moderate or excellent relief. Constipation, somnolence, and nausea were commonly reported by those on SR morphine, as well as those on CR oxycodone. Fatigue, dizziness, and constipation were the most frequently encountered side effects with methadone.
Quality of life, both at work and at home, was improved in those who continued on the methadone and CR oxycodone. This was not measured in the SR morphine group. Work performance and relationships greatly improved in the patients who remained on the opioids.
Addictive behavior toward the drug was observed in 6% of the SR morphine patients, in 3% of those on methadone, and with 13% of the CR oxycodone patients. Previous prescription opiate abuse did not translate into overuse of the long-acting opioids. Of the patients on SR morphine, 33% previously overused prescription opioids, and the majority of those patients (64%), had moderate or excellent relief at six months, without overuse of the medication. Only one of the sixteen patients who had previously overused opioids abused the methadone. Seven of these sixteen patients (44%) did well on maintenance methadone.
Tolerance was observed in 56% of patients of those who continued on SR morphine, in 35% of those on methadone, and in 63% of the CR oxycodone patients. Every effort was made not to accelerate doses. Withdrawal symptoms were more severe with methadone than with the other opioids.
ADVANTAGES AND DISADVANTAGES OF LONG-ACTING OPIOIDS
Advantages include: Efficacy, no cardiovascular effects, once or twice daily dosing. Opioids may also help those with other chronic pains.
Disadvantages include: Addiction potential, constipation and sedation, regulatory and malpractice concerns, inconvenient to prescribe, withdrawal may be difficult, frequent tolerance.
Stimulants can be an effective adjunctive third-line therapy for selected patients with refractory headaches; they are also utilized for severe refractory depression. Stimulants may help to offset the sedation and weight gain that so often accompanies headache preventive medications.
DESIGN AND METHODS
This was a retrospective study of 94 refractory cdh patients. These were all long-term patients at the Robbins Headache Clinic. They were assessed, by chart review and interview with the treating neurologist, after 6 months of therapy with the medication. Relief was assessed via a visual analog scale (vas), and was judged to be none, mild, moderate, or excellent. While the primary reason for adding a stimulant was to help the headaches, many of these refractory cdh patients were also placed on the stimulants due to excessive fatigue, and/or because of excessive weight gain. Patients with anxiety that was more than mild, or those with moderate to severe insomnia, were usually not given these medications.
The number of patients who continued on the medication for at least 6 months, and achieved moderate or excellent relief was as follows:
Methylphenidate: 14/34 (41%) Average dose = 25 mg. daily
Dextroamphetamine:9/21 (43%) Average dose = 15 mg. daily
Adderall:10/20 (50%) Average dose = 20 mg. daily
Phentermine:6/19 (32%) Average dose = 30 mg. daily
Overall, 39/94 (41%) did well for at least 6 months.
32/94 (34%) of patients discontinued the stimulants because of lack of efficacy (efficacy was either none or mild). Prior to the 6 months, 23/94 (24%) of patients discontinued the medication primarily due to adverse events. The most common side effects were anxiety and insomnia.
ADVANTAGES AND DISADVANTAGES OF STIMULANTS
Advantages include:Lack of sedation or weight gain (these medications can partially offset those problems), and these are compatible with many of the other headache preventives. Stimulants may help to offset the sedation of the long-acting opioids. They may also help for those with severe depression, and for the headache patients with attention deficit disorder.
Disadvantages include: Insomnia, anxiety, addiction potential, regulatory or malpractice concerns. Withdrawal and tolerance may present problems. The more restricted stimulants are inconvenient to prescribe.
DESIGN AND METHODS
Forty-two patients with refractory chronic daily headache were entered into an open label study at the Robbins Headache Clinic. They kept a headache calendar, with severity assessed on a 1 to 10 visual analog scale. The patients charted on the calendar for 1 month prior to and 6 weeks post-treatment. A member of the Robbins Headache Clinic staff called the patient on day 2 after the intravenous dhe to evaluate the response. Return vists were scheduled at 3, 6, and 10 weeks. The patients had been refractory to the usual preventive medications, and an attempt was made to not change any daily preventive medications over the 6-week studyperiod.Of the 42 patients enrolled, 36 were female and 6 were male.Ages ranged from 20-53. The IV DHE was given according to the following protocol:
Repetitive IV Dihydroergotamine Outpatient Protocol
Therapeutic Response Scale
DESIGN AND METHODS
This was an open label, non-randomized non-blinded study. Eighty-seven participants, aged 23-67, were enrolled in the study, and 79 patients completed the study. Each patient had the diagnosis of moderate or severe chronic daily headache, refractory to the usual preventive medications. The patients recorded headache severity utilizing a visual analog scale for one month prior to treatment, and three months following treatment.
Each patient received low dose botulinum toxin A (BTA) injections, 12 injections of 2 units BTA each. The symmetrical injections, 6 on each side, were done frontally and temporally.
Thirty-six of 79 patients (46%) did not respond to the injections (response = at least a 2 point decrease on a 10 point vas). Forty-three of 79 (54%) were considered positive responders. Among the positive responders, 44% had a mild response (2 to 3 point decrease on the vas). Forty-seven percent had a moderate response (4 to 5 point decrease on the vas), while 9% had an excellent response (more than 5 point decrease on the vas).
Among the mild responders (19 of 43 = 44% of responders), in the second month, 16% declined to no response, 63% continued to have a mild response, while 10.5% of these mild responders had a moderate response and 10.5% reported an excellent response. During the 3rd month with these mild responders, 68% now had no response, 10.5% had a mild response, 10.5% had a moderate response, and 10.5% reported an excellent response.
For the moderate responders (20 of 43 = 47% of total responders), during the 2nd month 15% had no response, 15% had only a mild response, while 70% continued with a moderate response. During the 3rd month, 50% declined to no response, 10% continued with a mild response, while 40% continued with a moderate response.
For the excellent responders, which were only 4 of 43 responders in total, during the 2nd month all 4 remained excellent. During the 3rd month 2 of the 4 declined to a mild response, 1 had a moderate response and 1 of the 4 patients continued with an excellent response.
Adverse events were generally mild, with 6 patients reporting mild ptosis, 2 with bilateral edema of the eyelids, and 2 reported a dramatic increase in headache.
ADVANTAGES AND DISADVANTAGES OF BOTULINUM TOXIN INJECTIONS
Advantages include: Relatively safe, may be long-lasting, few adverse events.
Disadvantages include: Expensive, inconvenient, efficacy unproven. While probably safe, long-term effects of repeated injections is not known.
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