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Long-Term Success Of Preventative Medications
For Chronic Daily Headache
Lawrence Robbins, M.D. & Joseph F. Maides,
Jr., D.O.
Posted September 2003

Abstract and Key Words

To evaluate long-term continuation rates of daily preventative medications for chronic daily headache (CDH).

Many medications have been utilized in an effort to decrease severity/frequency of CDH. Short-term (less than 6 months) studies often demonstrate success at preventing CDH. However, the long-term success of these medications for CDH has not been demonstrated.

This retrospective study evaluated continuation rates (at least 6 months) for different classes of CDH preventatives. 646 moderate or severe CDH patients were evaluated. Among those who discontinued the medications, a determination was made as to whether the medication was stopped due to a lack of efficacy, versus the presence of adverse events.

Of those 646 patients, only 46% stated that they remained on a preventative for 6 months or longer. 36% of the patients continued (more than 6 months) on selective serotonin reuptake inhibitors (SSRIís). 35% continued long-term on sodium valproate (Depakote), while 31% continued on tricyclic antidepressants. Only 22% of patients remained on B-blockers long-term. Lack of efficacy was cited as the primary reason for discontinuation. Approximately 1/5 of patients discontinued the preventative primarily due to adverse events.

The majority (54%) of patients do not obtain adequate long-term relief from CDH preventative medications. SSRIís and sodium valproate were the most successful medications for preventing CDH.

Key Words:
Chronic Daily Headache, Preventative Medications

CDH - Chronic Daily Headache, SSRI Ė Selective Serotonin Reuptake Inhibitor, NSAID Ė Nonsteroidal Anti-Inflammatory Drug


Chronic daily headache (CDH) is a common problem, affecting approximately 3 to 4% of the population.(1) CDH poses a significant therapeutic challenge to both physician and patient. For those patients with moderate or severe CDH, preventative medications are often utilized in an effort to both limit analgesics and decrease headache frequency and/or severity. The primary first-line preventatives include antidepressants (primarily selective serotonin reuptake inhibitors (SSRIís) and tricyclics) and sodium valproate.(2) Antidepressants have been an attractive choice in those with comorbid depression and anxiety. Tricyclic antidepressants have been noted to have enhanced efficacy over SSRIís, but are not as well tolerated. The anticonvulsant sodium valproate has emerged as an effective drug for use in CDH.(3) It can be particularly useful for patients with comorbid seizure disorders, bipolar disorder, and even anxiety. Other medications that have shown some benefit in CDH prophylaxis include B-blockers, calcium channel blockers, NSAIDís, gabapentin, and muscle relaxants.(2) Unfortunately, due to a lack of efficacy, and/or the presence of side effects, the preventative medications are not always a useful long-term solution. The failure of the preventatives often frustrates physicians and patients. The purpose of this paper was to retrospectively evaluate preventative medications in a large number of chronic daily headache patients.

Materials and Methods

Primary Objective and End Point:
This study was a retrospective investigation of the continuation rates for different classes of headache preventative medications. Overall headache relief, defined as at least 50% improvement in headache frequency and/or severity, served as the primary end point.

Inclusion Criteria:
Men or women, at least 17 years of age, diagnosis of CDH or transformed migraine (TM) according to the criteria established by Silberstein et al,(4) moderate or severe intensity of the CDH, and current or past use of at least two classes of daily preventative medications for at least six months.

Exclusion Criteria:
Continuous analgesic rebound headache that had not been resolved, non-compliance with the daily preventative medications, evidence of renal insufficiency or impaired liver function upon routine laboratory evaluations, or the presence of any medical condition that could interfere with the absorption, metabolism, and excretion of any of the preventative medications.

Six hundred forty six moderate or severe chronic daily headache patients, ages 17 to 74, were evaluated. They were all long-term patients at the Robbins Headache Clinic, a private clinic with both physician and self-referred patients. Evaluation was accomplished via chart review and patient interviews conducted by the treating neurologist. Four main classes of preventative medications were evaluated: SSRIís sodium valproate, tricyclic antidepressants, and B-blockers. Patients included in the study were assessed to determine which preventative medications they remained on long-term. A determination was also made as to which preventative medications were discontinued due to a lack of efficacy, versus the presence of side effects. Statistical Analysis Ė Patient data was tabulated and analyzed suing SPSS Sigma Stat 2.03. Chi-square analysis was performed on the tabulated data. To assure accuracy, a power analysis of the Chi-square was utilized, using an alpha value of 0.05.