Prophylactic pharmacological treatment of chronic daily headache

Objective.—To review all the prophylactic pharmacological treatments for chronic daily headache from the past decade.
Background.—Chronic daily headache is among the most common diagnoses seen in specialized headache centers. Prior to 1988, there were no criteria for the diagnosis of chronic tension-type headache and chronic daily headache. An expanded chronic daily headache classification has been proposed.
Methods.—A MEDLINE search was performed using the following key words: chronic daily headache, intractable headache, transformed migraine, chronic tension headache, and chronic tension-type headache. We limited our review to those studies published in English in the last decade, including published abstracts and letters to the editor. Double-blind studies carried out prior to 1988 were also included.
Results.—Pharmacological treatments for chronic daily headache include antidepressants (tricyclics, tetracyclics, monoamine oxidase inhibitors, selective serotonin reuptake inhibitors), anticonvulsants, muscle relaxants, 5-HT₁ agonists, ergots, 5-HT₂ antagonists, antianxiety agents, and miscellaneous drugs. Many of these reports are anecdotal, and most are open rather than double-blind studies.
Conclusions.—There is a great variety of pharmacological treatments available for chronic daily headache. Only the antidepressants have been extensively studied. Other medications may be used if these fail. Recommendations based on our experience at the Headache Unit of the Montefiore Medical Center are outlined here.     

Chronic daily headache in children and adolescents presenting to tertiary headache clinics

BACKGROUND: Adults with chronic daily headache often describe a transformation from episodic migraine and partial retention of migrainous features. Although chronic daily headache has not been investigated as carefully in the pediatric population, one study showed a predominance of coexisting daily headache and episodic migraine, without a clear history of transformation. OBJECTIVE: To identify the clinical features of chronic daily headache in children and adolescents, to evaluate the efficacy of current headache classification criteria, and to compare the features of coexistent daily and episodic headaches so as to determine whether they represent separate syndromes or different stages in the "transformation" process. DESIGN: We surveyed 189 consecutive patients, 18 years of age or younger, who presented for initial evaluation of daily or near daily headache at one of 9 tertiary headache clinics. Data were collected in semistructured interviews employing a standard questionnaire and analyzed using Statistical Analysis Systems and Stata statistical software computer programs. RESULTS: Of the patients enrolled, 70% were female and 87% were white. Mean age was 13.0 +/- 3.1 years. Male gender was associated with a higher degree of reported disability. A family history of headache (typically migraine) was described in 79%. Use of nonsteroidal anti-inflammatory drugs 5 days per week or more was reported by 44% of patients. The International Headache Society (IHS) criteria failed to classify 64% of patients and criteria proposed by Silberstein et al failed to classify 31% of patients. Participating physicians misclassified patients according to criteria of the IHS and Silberstein et al in one third of cases. Nearly one quarter of patients reported two separate headache types with distinguishing characteristics. "Baseline" headache was present 27.3 +/- 4.1 days per month with a mean pain intensity of 5.9 +/- 2.1 on a 10-point scale. Superimposed episodic headache occurred 4.7 +/- 3.8 days per month with a mean pain intensity of 8.4 +/- 1.4, and was more often accompanied by other migrainous symptoms. After logistic regression to control for pain intensity, the only statistically significant difference between the two headache types was a lower prevalence of tension-type head pain with the superimposed headache. CONCLUSIONS: Our data suggest that rather than having two coexistent headache types, children and adolescents with chronic daily headache have a single syndrome that, in many cases, will paroxysmally worsen and gather migrainous features.     

Repetitive intravenous prochlorperazine treatment of patients with refractory chronic daily headache

OBJECTIVES: To investigate the efficacy and long-term outcome of intravenous prochlorperazine for the treatment of refractory chronic daily headache. BACKGROUND: Unlike dihydroergotamine, the treatment results of intravenous neuroleptics as first-line agents for refractory chronic daily headache have rarely been reported. METHODS: We retrospectively analyzed the data of inpatients with refractory chronic daily headache who received intravenous repetitive prochlorperazine treatment from November 1996 to March 1999. A semistructured telephone follow-up interview was done in September 1999. RESULTS: A total of 135 patients (44 men, 91 women) were recruited, including 95 (70%) with analgesic overuse. After intravenous prochlorperazine treatment, 121 (90%) achieved a 50% or greater reduction of headache intensity, including 85 (63%) who became headache-free. The mean hospital stay was 6.2 +/- 2.7 days, and mean total prochlorperazine used was 98 +/- 48 mg. Acute extrapyramidal symptoms occurred in 21 patients (16%). One hundred twenty-four patients (92%) were successfully followed up, with a mean duration of 14.3 +/- 7.5 months. Compared with pretreatment status, 93 patients (75%) considered their headache intensity decreased, and 86 patients (69%) considered their headache frequency decreased, although 40 (32%) still had a daily headache. Of the 87 patients with analgesic overuse who could be followed, 61 (70%) no longer overused analgesics. Poor response to prochlorperazine treatment (relative risk, 1.8) and presence of major depression (relative risk, 1.8) were predictors of persistent chronic daily headache at follow-up. CONCLUSIONS: Prochlorperazine was effective and safe in the treatment of patients with refractory chronic daily headache with or without analgesic overuse. Compared with dihydroergotamine, prochlorperazine seemed less effective at achieving "freedom from headache" during hospitalization, but had a similar outcome at follow-up.     

Comorbidity of depressive and anxiety disorders in chronic daily headache and its subtypes

OBJECTIVE: To investigate the frequency of depressive and anxiety disorders in patients with chronic daily headache. BACKGROUND: There is a lack of data in the literature on the extent of psychiatric comorbidity in patients with different subtypes of chronic daily headache. METHODS: We recruited consecutive patients with chronic daily headache seen in a headache clinic from November 1998 to December 1999. The subtypes of chronic daily headache were classified according to the criteria proposed by Silberstein et al. A psychiatrist evaluated the patients according to the structured Mini-International Neuropsychiatric Interview to assess the comorbidity of depressive and anxiety disorders. RESULTS: Two hundred sixty-one patients with chronic daily headache were recruited. The mean age was 46 years, and 80% were women. Transformed migraine was diagnosed in 152 patients (58%) and chronic tension-type headache in 92 patients (35%). Seventy-eight percent of patients with transformed migraine had psychiatric comorbidity, including major depression (57%), dysthymia (11%), panic disorder (30%), and generalized anxiety disorder (8%). Sixty-four percent of patients with chronic tension-type headache had psychiatric diagnoses, including major depression (51%), dysthymia (8%), panic disorder (22%), and generalized anxiety disorder (1%). The frequency of anxiety disorders was significantly higher in patients with transformed migraine after controlling for age and sex (P =.02). Both depressive and anxiety disorders were significantly more frequent in women. CONCLUSION: Psychiatric comorbidity, especially major depression and panic disorders, was highly prevalent in patients with chronic daily headache seen in a headache clinic. These results demonstrate that women and patients with transformed migraine are at higher risk of psychiatric comorbidity.     

Prevalence and clinical characteristics of headache in a rural community in Oman

OBJECTIVES: To perform a prospective epidemiological study of headache in a rural community in Oman, assessing prevalence, symptom profile, and health care utilization pattern. METHODS: Using a door-to-door survey prevalence estimates were based on a detailed structured headache assessment questionnaire performed in 1158 subjects. Migraine and tension-type headache were diagnosed according to the International Headache Society criteria. RESULTS: The crude lifetime and last-year prevalence of headache were 83.6% and 78.8%, respectively, with a female preponderance. The last-year prevalence of migraine and tension headache was 10.1% and 11.2%, respectively. There was no significant gender difference in migraine prevalence (4.5% in male and 5.6% in female), but tension-type headache was 2.6 times more common in females (3.1% in male and 8.1% in female). Last-year prevalence of frequent headaches was 5.4%. Forty eight percent of respondents sought medical assistance for their headaches and 79% were using medication, 40% of them used self-medication. CONCLUSIONS: This prospective study shows that headache is also highly prevalent in this community. Migraine and tension-type headache have the same prevalence, but the sex distribution for migraine is different from that observed in the Western world. Tension-type headache prevalence was substantially lower than that observed in other parts of the world. Frequent headaches were as common as in other population-based studies worldwide. Analgesic use/overuse probably also coexisted with headache, because self-medication was quite common.     

Chronic daily headaches in children and adolescents: a study of clinical characteristics

The clinical characteristics of chronic daily headache were studied in 40 children and adolescents, as well as the associated factors responsible for maintenance of the continuous headache pattern. The study of the clinical headache characteristics, showed a female preponderance (75%), mean age of 11 years old at the first consultation, and onset of headache symptomatology at a mean age of 8.5 years old. The average time interval for the evolution of sporadic headache into chronic daily headache was 1.4 years, and psychosocial stressors were present, acutely or chronically, during the period of headache-frequency increase in 47% of the children. Headaches were classified as transformed migraine (65%), mixed pattern (17.5%) and chronic tension-type headache (17.5%). Sixty per cent of patients had mothers with migraine. Data regarding common analgesic use showed an average intake of 11.2 days/month.     

Evaluation of chronic daily headache—comparison to criteria for chronic tension-type headache

The purpose of this study was to evaluate the adequacy of the International Headache Society (IHS) criteria for chronic tension-type headache and, if appropriate, suggest modifications of the IHS classification. We evaluated 100 consecutive patients with chronic daily headache. Approximately two-thirds of our patients fulfilled the criteria for chronic tension-type headache. Most of the patients who failed to meet the criteria did so because they had more than one migrainous feature. Approximately 50% of patients took excessive amounts of analgesic medication. We conclude that the IHS criteria should be modified to include chronic daily headache evolving from migraine; subtypes with and without medication overuse should be distinguished.     

Chronic daily headache in Taipei, Taiwan: prevalence, follow-up and outcome predictors

We conducted a two-stage population-based headache survey among subjects aged > or = 15 in Taipei, Taiwan. Subjects with chronic daily headache (CDH) in the past year were identified, interviewed and followed-up. CDH was defined as a headache frequency > 15 days/month, with a duration > 4 h/day. Of the 3377 participants, 108 (3.2%) fulfilled the criteria for CDH, with a higher prevalence in women (4.3%) than men (1.9%). TM was the most common subtype (55%), followed by CTTH (44%). Thirty-four per cent of the CDH subjects overused analgesics. At the 2-year follow-up, 35% of the CDH subjects still had CDH. The significant predictors for persistent CDH at follow-up included: older age ( > or = 40 years) (RR = 2.4), CDH onset after 32 years (RR = 1.8), CDH duration > or = 6 years (RR = 2.0), medication overuse (RR = 1.8), and "daily" headache (RR = 2.1). We found that CDH is not uncommon in the community and its prevalence is similar among different populations. Older subjects and those with medication overuse may have a more protracted course of illness.     

From migraine to chronic daily headache: the biological basis of headache transformation

Migraine headache carries the potential of transforming into chronic daily headache (CDH) over a period of time. Although several risk factors for migraine progression to CDH have been identified, the biological basis of this transformation is unknown. In this review, the consequences of stressful life events and medication overuse, 2 risk factors associated with the development of CDH, on brain processes involved in headache are examined. The extensive overlap in both neural circuitry and cellular events that occur with stress, medication overuse, and migraine provide insight into potential mechanisms that may lead to CDH. Particular attention is devoted to the effect of stress and medication overuse on peripheral and central neuroimmune interactions that can facilitate pain signaling. These interactions include the degranulation of mast cells in the dura, causing the sensitization of primary afferent neurons, as well as the activation of glial cells in the brain that can lead to central sensitization. It is hypothesized that the biological processes involved in migraine headache are directly impacted by stress, medication overuse, and other risk factors, resulting in a reduced threshold for induction of headache and transformation of episodic migraine to CDH.     

Major life changes before and after the onset of chronic daily headache: a population-based study

Chronic daily headache (CDH), when defined as ≥ 15 headache days per month, affects 3–5% of the adult population. Major life changes are putative precipitating events for onset of chronic pain, including chronic headache. This study compared the occurrence of specific life events between CDH cases and episodic headache controls in a community sample. CDH cases (180+ headache days per year: n  = 206) and episodic headache controls (2–104 headache days per year: n  = 507) were identified from a randomly selected adult US population. Subjects were interviewed about the occurrence of certain major life changes or events (change of residence, employment status, marital status, related to their children, deaths of relatives or close friends, and 'extremely stressful' ongoing situations) occurring in a defined time period. Events that occurred during the same year or year before frequent headache onset in cases or in an equivalent time period in controls were considered to be antecedent events. Those that occurred after this time were considered subsequent events. Compared with episodic headache controls, CDH cases had more major life changes in the year before or same year as CDH onset. After adjusting for age, gender, headache type and year of event, the odds of CDH increased additionally with each antecedent event [odds ratio (OR) 1.20 (1.1, 1.3), P  < 0.001], but not with subsequent events [OR 0.94 (0.8, 1.1), P  < 0.4]. In secondary analyses, the association between antecedent events and CDH was significant only for the approximately half of CDH cases who were aged ≥ 40 years [OR 1.33 (1.2, 1.50) vs. OR 1.04 (0.9, 1.2), P  < 0.05 for interaction by age]. These results suggest that major life changes are associated with the onset of chronic daily headache, particularly in middle age.     

A retrospective, comparative study on the frequency of abuse in migraine and chronic daily headache

OBJECTIVE: To assess and contrast the relative frequency of a past history of physical and/or sexual abuse in patients with chronic daily headache (CDH) versus migraine. BACKGROUND: A number of risk factors have been identified as risk factors for chronification of headache disorders. Limited data exist regarding the influence of physical and/or sexual abuse on primary headache disorders. METHODS: This was a retrospective chart review of 183 consecutive new headache patients seen from December 2004 through August 2005 at an outpatient tertiary-care center. Patients were included in the study if they had chronic daily headache (with criteria for medication over-use headache or chronic migraine), or migraine with or without aura. A history of physical and/or sexual abuse was systematically asked of all headache patients at their first visit in the clinic. This information was then transferred to a semi-standardized form and the relative frequency of abuse in both groups contrasted. RESULTS: Of the 161 patients included in the study, 90.1% were female with a mean age of 36.4 +/- 12.0. A total of 59.0% of the patients were diagnosed with CDH and 41.0% were diagnosed with migraine. Overall, 34.8% of all patients, 40.0% of CDH patients, and 27.3% of migraine patients had a history of physical and/or sexual abuse. The relative frequency of a history of physical and/or sexual abuse was higher in the CDH group as compared to the migraine group (P = .048). CONCLUSION: The relative frequency of abuse is higher in CDH sufferers than migraineurs, suggesting that physical and sexual abuse may be risk factors for chronification.     

Migraine and chronic daily headache management: a qualitative study of patients' perceptions

AIM: The aim of the study was to gain insight into the patients' perceptions of migraine and chronic daily headache (CDH) management. METHODS: Thirteen, semi-structured and individual interviews with seven migraine and five CDH patients were carried out and analysed in QSR NUD*IST5, using a grounded theory methodology. RESULTS: The participants described using five areas of management: 1) health care use; 2) medication use; 3) alternative therapies; 4) social support; and 5) lifestyle and self-help. The participants described their expectations, preferences, worries and (dis)satisfaction in relation to these five areas of management. The participants adapted headache management to suit their needs and preferences, making migraine and CDH management highly individual and giving the headache patient a central role within their own care. CONCLUSION: Health care is changing towards a greater involvement of the patients in their own care. Therefore, it is important to increase understanding of the patients' perspective of chronic diseases, including migraine and CDH. The results from this study inform health care professionals of the range of their patients' needs and preferences. This knowledge can be used to shape clinical practice, to develop patient education programmes and to further research efforts into issues that are important to the headache patient.     

Kaplan Award 1998. Epidemiology of chronic daily headache in the general population

Background and Objectives.—Although chronic daily headache, mainly transformed migraine, is an important reason for consultation in headache clinics, its actual prevalence is unknown. This study analyzes the prevalence of the different types of chronic daily headache in an unselected population.
Methods.—A questionnaire exploring headache frequency was distributed to 2252 unselected subjects. Those having headache 10 or more days per month were given a headache diary and were seen by a neurologist who classified their headaches. The varieties of chronic daily headache were classified according to the second revision of IHS criteria proposed by Silberstein et al published in Neurology 1996;47:871.
Results.—The questionnaire was returned by 1883 subjects (83.5%). One hundred thirty-five admitted to headache 10 or more days per month. Chronic daily headache criteria were fulfilled by 89 individuals (4.7%). Eighty were women. Forty-two (47.2% of subjects with chronic daily headache and 2.2% of all subjects) had chronic tension-type headache. Analgesic overuse was found in 8 (17%). Transformed migraine was diagnosed in 45 (50.6% of subjects with chronic daily headache and 2.4% of all subjects). Fourteen (31.1%) individuals with this form of chronic daily headache overused ergots or analgesics. The remaining 2 cases in this series met the criteria of new daily persistent headache. No one was diagnosed as having hemicrania continua.
Conclusions.—Almost 5% of the general population (9% of women) suffers from chronic daily headache, the proportion of chronic tension-type headache and transformed migraine being quite similar. Less than one third overuse analgesics. The prevalence of chronic daily headache subtypes shown here differs from data obtained from headache clinics, emphasizing that caution is needed in extrapolating data from specialized units to the general population.     

Chronic daily headache: a time perspective

OBJECTIVE: To determine the development and outcome of chronic daily headache in 258 headache practice patients, consisting of 50 men and 208 women. Chronic daily headache was defined as headaches occurring on at least 5 days per week for at least 1 year. METHODS: Two hundred fifty-eight patients with headache were interviewed and evaluated. Ninety-one patients were contacted by telephone for follow-up. RESULTS: Twenty-two percent of the patients had daily headaches from the onset, and 78% initially experienced intermittent headaches. Of the patients with initially intermittent headaches, 19% experienced an abrupt transition into daily headaches and 81%, a gradual one. In the patients with gradual transition, the transition of the initial, intermittent headaches into daily headaches took an average of 10.7 years. The initial headaches were mild in 33% of the patients and severe in 67%. The severe headaches were associated with nausea and vomiting significantly more often than the mild ones. However, the daily headaches that these patients ultimately developed were the same, regardless of whether the initial headaches were mild or severe. The patients who gradually developed daily headaches from initially intermittent headaches were contacted to determine the outcome of their headaches. Of these patients, 33% continued to have daily headaches and 67% again experienced intermittent headaches. Of the latter group, 88% of the patients who now had migraine also had migraine initially.     

Chronic daily headache prophylaxis with tizanidine: a double-blind,placebo-controlled,multicenter outcome study

OBJECTIVE: To assess the efficacy of tizanidine hydrochloride versus placebo as adjunctive prophylactic therapy for chronic daily headache (chronic migraine, migrainous headache, or tension-type headache). BACKGROUND: Tizanidine is an alpha2-adrenergic agonist that inhibits the release of norepinephrine at both the spinal cord and brain, with antinociceptive effects that are independent of the endogenous opioid system. Previous open-label studies have suggested the drug may be effective for treatment of chronic daily headache. METHODS: Two hundred patients completed a 4-week, single-blind, placebo baseline period, with 134 fulfilling selection criteria and then randomized to tizanidine or placebo. Ninety-two patients completed at least 8 weeks of treatment (tizanidine, n = 45; placebo, n = 47), and 85 patients completed 12 weeks of treatment (tizanidine, n = 44; placebo, n = 41). Most patients (77%) met the diagnostic criteria for migraine of the International Headache Society; 23% had either chronic migrainous headache or chronic tension-type headache. Tizanidine was slowly titrated over 4 weeks to 24 mg or the maximum dose tolerated (mean, 18 mg; SD, 6.4; median, 20.0; range, 2 to 24), divided equally over three dose intervals per day. Overall headache index ([headache days x average intensity x duration in hours]/28 days) was the primary end point. RESULTS: Tizanidine was shown to be superior to placebo in reducing the overall headache index (P =.0025), as well as mean headache days per week (P =.0193), severe headache days per week (P =.0211), average headache intensity (P =.0108), peak headache intensity (P =.0020), and mean headache duration (P =.0127). The mean percentage improvement during the last 4 weeks of treatment with tizanidine versus placebo was 54% versus 19% for the headache index (P =.0144), 55% versus 21% for severe headache days (P =.0331), 35% versus 19% for headache duration (P =.0142), 35% versus 20% for peak headache intensity (P =.0106), 33% versus 20% for average headache intensity (P =.0281), and 30% versus 22% for total headache days (P =.0593). Patients receiving tizanidine also scored higher ratings of overall headache improvement on a visual analog scale (P =.0069). There was no statistically significant difference in outcome for patients with chronic migraine versus those with only migrainous or tension-type headache. Adverse effects reported by more than 10% of the patients included somnolence (47%), dizziness (24%), dry mouth (23%), and asthenia (19%). Dropouts due to adverse events did not differ significantly between tizanidine and placebo. CONCLUSIONS: The results support tizanidine as an effective prophylactic adjunct for chronic daily headache, including migraine, migrainous headache, and tension-type headache. These results also suggest the possible importance of an alpha2-adrenergic mechanism underlying the pathophysiology of this spectrum of headache disorders.     

Chronic daily headache in children and adolescents: a clinic based study from India

Chronic Daily Headache (CDH) is uncommon in Indian children compared to their adult counterpart. This is a retrospective study looking at the headache phenomenology of CDH in Indian children and adolescents. The validity of the case definitions of subtypes of chronic primary headaches mentioned in the IHS 2004 classification have been evaluated. 22 children (age range 8-15 years; M : F-16 : 6) diagnosed as having primary CDH using a modified definition seen between 2002 and 2003 have been studied. CDH has been defined as daily or near daily headaches > 15d/month for > 6 weeks. The rationale for this modified definition has been discussed. Majority of children (15/22) had a more or loss specified time of onset of regular headache spells resembling New Daily Persistent Headache (NDPH) but did not fulfil totally the diagnostic criteria of NDPH as laid down by IHS 2004. In all cases headache phenomenology included a significant vascular component. Headache phenomenology closely resembled Chronic Tension Type Headache (CTTH) in 4 patients and Chronic Migraine in 3 patients. However, in no patient in these groups, a history of evolution from the episodic forms of the diseases could be elicited. Heightened level of anxiety mostly related to academic stress and achievement was noted in the majority (19/22). Only a minority of patients (3/22) had anxiety and depression related to interpersonal relationships in the family. Medication overuse was not implicated in any patient. CDH in children in India is very much different from CDH in adults with the vast majority of patients exhibiting overlapping features of migraine and tension-type headache. There is need for a modified diagnostic criteria and terminology for chronic primary headaches in children.     

Predictors of response to botulinum toxin type A (BoNTA) in chronic daily headache

OBJECTIVE: To evaluate predictors of response to botulinum toxin type A (BoNTA; BOTOX, Allergan Inc., Irvine, CA, USA) in patients with chronic daily headache (CDH). BACKGROUND: Chronic migraine (CM) and chronic tension-type headache (CTTH) form the majority of CDH disorders. Controlled trials indicate that BoNTAis effective in reducing the frequency of headache and number of headache days in patients with CDH disorders. A recent migraine study found that patients with imploding or ocular types of headaches were responders to BoNTA, whereas those with exploding headaches were not. To date, there are no data on factors that might predict response to BoNTA in patients with CDH. METHODS: A total of 71 patients with CM and 11 patients with CTTH were treated with 100 units BoNTA. Every patient received at least 2 sets of injections at intervals of 12-15 weeks; fixed sites, fixed dose, and "follow-the-pain" approaches were used for the injections. A detailed medical history was taken for each patient in addition to recording Migraine Disability Assessment Scale (MIDAS) scores at baseline and every 3 months after each set of injections. Headache frequency was assessed throughout the study from baseline to weeks 24-27. Patients recorded the frequency, severity, and duration of headaches in Headache Diaries. Patients were divided into responders (> or = 50% reduction in both headache frequency and MIDAS scores compared with baseline) and nonresponders (< 50% reduction in either of the above variables). Variables analyzed for predictors of response include headache that is predominantly unilateral or bilateral in location, presence of cutaneous allodynia (scalp allodynia), and presence of pericranial muscle tenderness (also referred to as muscle allodynia). Chi-square analysis was used for parallel-group comparisons (proportion of CM responders vs proportion of CM nonresponders and proportion of CTTH responders vs proportion of CTTH nonresponders). RESULTS: In the CM group, 76.1% (54 /71) of patients were responders to BoNTA, of which 68.5% (37/54) had headache that was predominantly unilateral in location and the remaining 31.5% (17/54) had headache that was predominantly bilateral in location (both P < .01 vs CM nonresponders). Of the 23.9% (17/71) CM nonresponders, 76.5% (13/17) reported predominantly bilateral headache and in the remaining 23.5% (4/17) the headache was unilateral. In the CM responders group, 81.5% (44/54) had clinically detectable scalp allodynia, while pericranial muscle tenderness was present in 61.1% (33/54) (both P < .01 vs CM nonresponders). The presence of scalp allodynia and pericranial muscle tenderness in the CM nonresponders was 11.8% (2/17) and 17.6% (3/17), respectively. In the CTTH group where all patients (100%, 11/11) had bilateral headache, 36.4% (4/11) of patients were responders to BoNTA. All of those CTTH responders (100%, 4/4) had pericranial muscle tenderness (P < .05 vs CTTH nonresponders). None of the CTTH nonresponders had pericranial muscle tenderness. No clinically significant serious adverse events (AEs) were reported. Mild AEs, eg, injection-site pain that persisted for 1-9 days, were reported in 11 patients. One patient had transient brow ptosis. CONCLUSIONS: A greater percentage of patients with CM responded to BoNTA than patients with CTTH. Headaches that were predominantly unilateral in location, presence of scalp allodynia, and pericranial muscle tenderness appear to be predictors of response to BoNTA in CM, whereas in CTTH, pericranial muscle tenderness may be a predictor of response.