Amitriptyline and dexamethasone combined treatment in drug-induced headache

Frequent or regular intake of antimigraine drugs, including analgesics, constitutes a common cause of chronic daily headache. Discontinuation. of symptomatic medication can produce an increase in head pain accompanied by withdrawal symptoms. We report the favourable outcome of treating a group of outpatients with the combination of amitriptyline, dexamethasone and sumatriptan. Dexamethasone (4 mg/day) was given intramuscularlv for 2 weeks, amitriptyline orally at night (50 mg/day) for at least 6 months, and sumatriptan subcutaneously to treat acute headache attacks. Eighteen out of 20 patients abstained from drug abuse. Eleven of these 18 patients showed a marked reduction in headache frequency (at least 75% in relation to the basal value), and were considered "very good responders". The other seven patients experienced at least 50%, reduction in headache frequency compared to baseline. This preliminary report suggests that drug-induced headache can be treated effectively in outpatients using dexamethasone, amitriptyline and sumatriptan in combination with significant benefit in everyday life conditions.     

Amitriptyline Is Effective in Chronic But Not in Episodic Tension-Type Headache: Pathogenetic Implications

The tricyclic antidepressant amitriptyline, is an effective drug for the treatment of chronic tension-type headache and for other chronic pain syndromes, but it is also effective in the prophylaxis of an episodic type of headache such as migraine. However, its efficacy in episodic tension-type headache has not yet been clarified. We compared the efficacy of amitriptyline (25 mg/day) in 82 nondepressed patients with either chronic or episodic tension-type headache in an open-label study. Amitriptyline significantly reduced ( P <0.05) frequency and duration of headache as well as analgesic consumption in chronic, but not in episodic, tension-type headache. Further placebo-controlled trials, possibly with higher doses of amitriptyline, might confirm if the different pattern of response to amitriptyline can be explained in terms of different involvement of central nociception and of peripheral myofascial factors in the chronic and in the episodic forms of tension-type headache.     

Treating chronic tension-type headache not responding to amitriptyline hydrochloride with paroxetine hydrochloride: a pilot evaluation

CONTEXT: In some individuals, chronic tension-type headache fails to respond to tricyclic antidepressant medications that often serve as first-line therapy. OBJECTIVE: To evaluate the clinical efficacy of paroxetine hydrochloride for chronic tension-type headache not responding to amitriptyline hydrochloride. DESIGN AND SETTING: Open-label trial of paroxetine conducted at 2 outpatient sites in Ohio. PARTICIPANTS AND INTERVENTION: Thirty-one adults (mean age, 37 years; 20 women) with chronic tension-type headache (mean, 25 headache days per month) who had failed to respond (less than 30% improvement) to treatment with either amitriptyline (n = 13) or matched placebo (n = 18). All participants were treated with paroxetine (up to 40 mg per day) in a 9-month protocol. OUTCOME MEASURES: Monthly headache index calculated as the mean of pain ratings (0 to 10 scale) recorded by participants in a diary 4 times per day, number of days per month with at least moderate pain (pain rating of 5 or greater), and analgesic medication use. RESULTS: In patients who had not responded to amitriptyline, paroxetine failed to reduce chronic tension-type headaches or analgesic medication use. In patients who had not responded to placebo, paroxetine produced modest reductions in chronic tension-type headaches and analgesic use. CONCLUSIONS: We found no evidence that chronic tension-type headaches that failed to respond to tricyclic antidepressant therapy with amitriptyline improved when subsequently treated with paroxetine. More support was found for the efficacy of paroxetine in patients with chronic tension-type headaches who had failed to respond to placebo.     

Low-dose tizanidine with nonsteroidal anti-inflammatory drugs for detoxification from analgesic rebound headache

OBJECTIVE: To describe an outpatient regimen for analgesic detoxification and resolution of analgesic rebound headache. BACKGROUND: Frequent analgesic use is believed to promote the transformation of episodic migraine into a chronic, pervasive headache syndrome. Management of pain precipitated by analgesic withdrawal is crucial to treatment success. Outpatient treatment protocols designed to achieve successful withdrawal will reduce costs and potentially lead to more widespread implementation of therapy. METHODS: Patients with appropriate histories were managed on an outpatient basis for detoxification by discontinuation of the offending analgesic and initiation of treatment with tizanidine and a long-acting nonsteroidal anti-inflammatory drug. Patients kept diaries of pain and medication use. Results were evaluated at 6 and 12 weeks. Patients able to tolerate no or trivial analgesic use (ie, 4 or fewer doses in each 2-week period) were considered responders. RESULTS: At 6 weeks, 36 patients (65%) were responders. At 12 weeks, 38 patients (69%) were responders. The chronic daily headache pattern had resolved at 12 weeks in 34 patients (62%). CONCLUSIONS: This treatment protocol was well tolerated and yielded a high degree of efficacy, demonstrating that outpatient management can be effective for achieving analgesic withdrawal and resolution of analgesic rebound headache.     

Cellular adaptation in migraineurs with chronic daily headache

Ergotamine and analgesic misuse are now recognized as causes of chronic daily headache and the condition responds well to drug withdrawal with reduced headache frequency. In this study, we have investigated whether medication misuse is associated with an alteration in membrane transduction which is sensitive to drug withdrawal. This was carried out by assay of the thrombin-stimulated generation of inositol phosphates in platelets from 12 migraine patients with chronic daily headache and analgesic misuse, 7 migraine patients with chronic daily headache and ergotamine misuse and 7 control subjects. After drug withdrawal, a significant decrease in headache frequency was seen at one month in both patient groups. Withdrawal of analgesics produced a significant decrease in thrombin-stimulated inositol phosphate production at one month; this was further decreased a month later with a reduction in B_max of 60% and no significant change in K_D. A similar pattern was obtained in ergot misuse patients, with the K_D value decreasing by 56% one month after drug withdrawal. These results provide evidence of an adaptation in transduction with misuse of analgesics and ergotamine which correlates with headache frequency.     

Drug-induced headache: long-term results of stationary versus ambulatory withdrawal therapy

Drug-induced headache is a well-known complication of the treatment of primary headache disorders, and its successful management is only possible by withdrawal therapy. However, it is unknown whether ambulatory or stationary withdrawal is the therapy preferred. We conducted a prospective study on the outcome of stationary versus ambulatory withdrawal therapy in patients with drug-induced headache according to the International Headache Society criteria. Out of 257 patients with the diagnosis of drug-induced headache during the study period, 101 patients (41 after ambulatory and 60 after stationary withdrawal therapy) could be followed up for 5.9 +/- 4.0 years. The total relapse rate after successful withdrawal therapy was 20.8% (14.6% after ambulatory and 25.0% after stationary withdrawal therapy, p < 0.2). The main risk factors for a relapse were male sex (OR = 3.9, CI = 1.3-11.6), intake of combined analgesic drugs (OR = 3.8, CI = 1.4-10.3), administration of naturopathy (OR = 6.0, CI = 1.2-29.3), and a trend to tension-type headache as the primary headache disorder (OR = 1.9, CI = 0.6-53.0). Our data suggest that neither the method of withdrawal therapy nor the kind of analgesic and other antimigraine drugs has a major impact on the long-term result after successful withdrawal therapy. Patients with risk factors according to our findings should be informed and monitored regularly, and combined drugs should be avoided. Furthermore, our data suggest that there is a need for research on individual psychological and behavioral risk factors for relapse after successful withdrawal therapy in drug-induced headache.     

Topiramate in the treatment of chronic migraine

The purpose of this study was to evaluate the efficacy of topiramate in the treatment of chronic migraine. This was a double-blind, randomized, placebo controlled, parallel-group study. Patients suffering from chronic migraine with analgesic overuse were randomly assigned in a 1 : 1 ratio to receive topiramate or placebo. Following a baseline phase of eight weeks, the study drug was titrated in 25-mg increments over one week to 50 mg daily. Titration phase was followed by a 8-week maintenance phase. Number of days with headache during a 28-day period was the efficacy variable. At baseline, there was no difference in the number of days with headache between patients treated with topiramate and those treated with placebo (mean +/- SD: 20.9 +/- 3.2 and 20.8 +/- 3.2, respectively). During the last 4 week-maintenance phase, topiramate-treated patients experienced a significantly lower 28-day headache frequency in comparison to those treated with placebo (mean number of days with headache +/- SD: 8.1 +/- 8.1 vs. 20.6 +/- 3.4, P < 0.0007). Topiramate at low doses proved to be an effective therapeutic approach to reduce headache frequency in patients with chronic migraine and analgesic overuse.     

Are there predictive factors for long-term outcome after withdrawal in drug-induced chronic daily headache?

OBJECTIVES: To investigate prognostic factors for long-term outcome of patients after inpatient withdrawal because of drug-induced chronic daily headache. PROCEDURES: Fifty-five patients (36 females) were re-examined by means of a standardized interview after inpatient withdrawal. The mean observation period was 9.28 +/- 2.85 years (mean +/- SD; median 8.58; range 5.00-13.50). RESULTS: Five years after withdrawal, one-third of the patients (34.6%) had an overall favourable outcome, one-third (32.7%) had no recurrent drug overuse and reported a clear-cut improvement of headache, and one-third (32.7%) developed recurrent drug overuse. Most relapses occurred within 2 years, and a small percentage within 5 years. No predictors for long-term outcome after inpatient withdrawal were found. CONCLUSIONS: All patients with drug-induced chronic daily headache should be considered as good candidates for inpatient withdrawal, and no patient should be excluded from that therapy.     

Amitriptyline reduces myofascial tenderness in patients with chronic tension-type headache

The tricyclic anti-depressant amitriptyline is widely used in the treatment of chronic tension-type headache. The aim of the present study was to investigate whether the analgesic effect is caused by a reduction of muscle pain or by a general reduction of pain sensitivity. Thirty-three non-depressed patients with chronic tension-type headache were treated with amitriptyline 75 mg/day and with the highly selective serotonin reuptake inhibitor citalopram 20 mg/day in a 32-week, double-blind, placebo-controlled, three-way crossover study. At the end of each treatment period, actual headache intensity and pericranial myofascial tenderness were recorded, pressure pain detection and tolerance thresholds were measured in the finger and in the temporal region and the electrical pain threshold was measured at the labial commissure. Amitriptyline reduced tenderness and headache intensity significantly more than placebo (P=0.01 and P=0.04, respectively). The reduction in tenderness could be ascribed solely to the group of patients who responded to amitriptyline treatment by at least 30% reduction in headache while tenderness was unchanged in non-responders. Amitriptyline did not affect pressure or electrical pain thresholds at any of the examined locations. Citalopram had no significant effect on any of the examined parameters. These findings indicate that amitriptyline elicits its analgesic effect in chronic myofascial pain by reducing the transmission of painful stimuli from myofascial tissues rather than by reducing overall pain sensitivity. We suggest that this effect is caused by a segmental reduction of central sensitization in combination with a peripheral anti-nociceptive action.     

MEDICATION OVERUSE HEADACHE AND OTHER CHRONIC DAILY HEADACHES

The purpose of this study was to evaluate the efficacy of topiramate in the treatment of chronic migraine. This was a double-blind, randomized, placebo controlled, parallel-group study. Patients suffering from chronic migraine with analgesic overuse were randomly assigned in a 1:1 ratio to receive topiramate or placebo. Following a baseline phase of eight weeks, the study drug was titrated in 25-mg increments over one week to 50 mg daily. Titration phase was followed by a 8-week maintenance phase. Number of days with headache during a 28-day period was the efficacy variable. At baseline, there was no difference in the number of days with headache between patients treated with topiramate and those treated with placebo (mean ± SD: 20.9 ± 3.2 and 20.8 ± 3.2, respectively). During the last 4 week-maintenance phase, topiramate-treated patients experienced a significantly lower 28-day headache frequency in comparison to those treated with placebo (mean number of days with headache ± SD: 8.1 ± 8.1 vs. 20.6 ± 3.4, P < 0.0007). Topiramate at low doses proved to be an effective therapeutic approach to reduce headache frequency in patients with chronic migraine and analgesic overuse.
Comment: This is a fascinating study for a number of reasons. Topiramate (TPM) received a Food and Drug Administration (FDA) approvable letter for an indication for migraine in late 2003. In the large, randomized, controlled studies for episodic migraine, 100 mg was superior to 50 mg and placebo, and 200 mg was not significantly different from 100 mg, but had more adverse events associated with use. See the following :     

The prophylactic treatment of chronic daily headache

Chronic daily headache (CDH), a heterogeneous group of headache disorders occurring on at least 15 days per month, affects up to 4% to 5% of the general population. CDH disorders include transformed (or chronic) migraine, chronic tension-type headache, new daily persistent headache, and hemicrania continua. Patients with CDH have greater disability and lower quality of life than episodic migraine patients and often overuse headache pain medications. To date, only topiramate, gabapentin, tizanidine, fluoxetine, amitriptyline, and botulinum toxin type A (BoNTA) have been evaluated as prophylactic treatment of CDH in randomized, double-blind, placebo-controlled, or active comparator-controlled trials. The evidence supporting the use of BoNTA as prophylaxis of CDH is composed of larger and longer trials, as over 1000 patients were evaluated for up to 11 months duration. Compared with placebo BoNTA has significantly reduced the frequency of headache episodes, a recommended efficacy measure for headache trials and has been demonstrated to be safe and very well tolerated with few discontinuations due to adverse events. Side effects are generally transient, mild to moderate, and nonsystemic. The results of clinical trials using traditional oral pharmacotherapy, while supportive of their use as prophylactic treatment of CDH, are limited by several factors, including small numbers of patients, the choice of efficacy measures, and short treatment periods. The use of oral agents was associated with systemic side effects, which may limit their effectiveness as prophylactic treatment of CDH.     

Amitriptyline versus amitriptyline combined with fluoxetine in the preventative treatment of transformed migraine: a double-blind study

BACKGROUND AND OBJECTIVES: Antidepressants are often used to treat chronic daily headache disorders such as transformed migraine, in part because of the high prevalence of associated mood disorder. We conducted this study to evaluate the efficacy and tolerability of combined treatment with amitriptyline and fluoxetine compared with amitriptyline alone for chronic daily headache due to transformed migraine. PATIENTS AND METHODS: Thirty-nine patients, 26 women and 13 men, aged 20 to 69 years (mean, 36.4; SD, 2.5) who fulfilled criteria for transformed migraine proposed by Silberstein et al were studied prospectively. Amitriptyline was dosed as follows: 8 mg/day for 6 days, 8 mg twice a day for 6 days, 20 mg/day for 6 days, and 20 mg twice a day for 45 days. In the group receiving combination therapy, fluoxetine was dosed and administered identically. The initial and end of the study (9 weeks) headache indices (frequency x intensity) were compared between groups. RESULTS: Twenty-seven patients completed the study, 13 in the amitriptyline-alone group (group 1) and 14 in the combination-therapy group (group 2). The most frequent adverse event in both groups was dry mouth, and there was no significant difference in the occurrence of this or other adverse events between the two groups. Initial headache indices were similar for groups 1 and 2. The mean difference between the initial and final headache index for group 1 was 513.5 (P<.0005) and 893 (P<.0017) for group 2. The difference between the final headache index for the two groups was not significant (P>.207). CONCLUSIONS: We were unable to demonstrate any significant benefit from amitriptyline plus fluoxetine over amitriptyline alone in the treatment of chronic daily headache/transformed migraine. Because of the small number of subjects involved and the short duration of our study, a type II error cannot be excluded.     

Withdrawal therapy improves chronic daily headache associated with long-term misuse of headache medication: a retrospective study

Chronic daily headache (CDH) associated with long-term misuse of headache medication is a common clinical problem which is refractory to most treatments. The present study is a retrospective analysis of the effect of drug withdrawal therapy in patients with CDH and frequent long-term use of headache symptomatic medication. One hundred and one adult patients (74 women and 27 men, aged between 16 and 72 years, mean age 43 years) were evaluated 1-3 months after drug withdrawal therapy had been initiated. The mean headache frequency at baseline was 26.9+/-4.0 days per month. Fifty-seven (56%) patients were significantly improved (defined as at least 50% reduction in number of headache days) after a period of drug withdrawal therapy. Based on the outcome of the drug withdrawal therapy, the patients were divided into three categories: group I, those who had between 0 and 10 headache days per month (n = 41), group II, those who had 11-20 days (n = 37), and group III, those who had 21-30 days (n = 23). The mean headache frequencies in groups I, II and III were 5.6+/-2.8 days, 15.7+/-2.5 days and 28.7+/-2.4 days, respectively. Treatment with amitriptyline was offered to patients in whom no improvement had been achieved. Ten of those 22 patients (36%) experienced a significant (> or = 50%) reduction of headache days. It is concluded that out-patient drug withdrawal therapy is the treatment of choice in patients with CDH and frequent long-term use of headache symptomatic medication, and that about one quarter of these CDH patients do not respond to drug withdrawal therapy only.     

Medication overuse headache: clinical features predicting treatment outcome at 1-year follow-up

We present a prospective study of 240 patients with medication overuse headache (MOH) treated with drug withdrawal and prophylactic medications. At 1-year follow-up, 137 (57.1%) patients were without chronic headache and without medication overuse, eight (3.3%) patients did not improve after withdrawal and 95 (39.6%) relapsed developing recurrent overuse. Age at time of MOH diagnosis, regular use of benzodiazepines, frequency and Migraine Disability Assessment (MIDAS) score of chronic headache, age at onset of primary headache, frequency and MIDAS score of primary headache, ergotamine compound overuse and daily drug intake were significantly different between successfully and unsuccessfully treated patients. Multivariate analysis determined the frequency of primary headache disorder, ergotamine overuse and disability of chronic headache estimated by MIDAS as independent predictors of treatment efficacy at 1-year follow-up.     

Similarities and differences between chronic migraine and episodic migraine

OBJECTIVE: To quantify and characterize the similarities and the differences between chronic migraine (CM) patients with medication overuse and episodic migraine (EM) patients with only occasional analgesic use. BACKGROUND: Population-level epidemiology, characteristics, mechanisms of chronic daily headache, and medication-overuse headache have been widely studied but patient characteristics have received less attention. Methods.-We compared sociodemographic data, family history, physiological and medical history, health services utilized, drugs taken/prescribed, and outcome of 2 groups of subjects: 150 patients, suffering from CM, complicated by probable medication-overuse headache (CM group), consecutively admitted during 2005 to the inpatients' ward of the Headache Centre of the University Hospital of Modena and Reggio Emilia, Italy, to undergo withdrawal from their overused medications; 100 patients suffering from EM, uncomplicated by medication overuse (EM group), consecutively referred to the outpatients' ward of the Headache Centre during November and December 2005. RESULTS: All sociodemographic characteristics were significantly different between the 2 groups. As a whole, the CM group began to suffer from migraine earlier than the EM group. Drug and/or alcohol abuse was significantly higher among first-degree relatives of CM (19%) than of EM (6%) patients. The most frequent comorbid disorders were psychiatric (67%) and gastrointestinal diseases (43%) in the CM group, and allergies in the EM group (31%). Seventy percent of CM patients and 42% of EM patients were taking daily at least another drug, besides those for headache treatment. Most overused medications in the CM group were triptans (43%); the EM group used above all single NSAIDs (56%). At 3-month follow-up, prophylactic treatments reduced, by at least 50%, the frequency of headache in about three-fourths of patients of both the groups; however, headache remained significantly more frequent in the CM than in EM group: only a minority (15%) of CM patients reverted to a headache frequency comparable to that of the EM group. CONCLUSIONS: CM patients present more multiple comorbid disorders, polypharmacy, and social impediments than EM patients. These associated conditions complicate CM clinical management. Even after withdrawal from medication overuse, CM could not be completely reverted by current prophylactic treatments.     

Long-term follow-up of patients treated for chronic headache with analgesic overuse

The study aim is to describe the long-term clinical outcome of 102 chronic headache patients with analgesic daily use. They were assessed for daily drug intake (DDI), headache index (HI) and quality of life (QoL) and compared with a parallel group of patients with active chronic daily headache but no analgesic overuse. For the primary study group, baseline 1995 DDI was 1.80 +/- 1.87 and did not differ significantly in 1999. Patients who daily continued to use analgesics had a higher 1995 baseline DDI (t = 2.275, P = 0.025), a longer drug abuse history (t = 2.282, P = 0.025) and a higher DDI (t = 4.042, P < 0.001) 4 years later. At 4 years of follow-up, only one-third of patients initially treated for chronic daily headache and analgesic overuse are successful in refraining from chronic overuse. Those subjects appear to have a persistence for combination analgesic agents; however, their QoL is slightly better than that of patients who revert to episodic headache or continue with chronic daily headache but do not overuse analgesic agents. Persistent analgesic overuse seems to be linked to the length of abuse and to the number of drugs ingested.     

Headache and other types of chronic pain

OBJECTIVE: To compare pain severity, disability, psychological distress, and quality of life between patients with headache and nonheadache treatment-seeking chronic pain patients. METHODS: Six hundred forty-three patients seeking treatment at a university pain clinic were divided into 3 categories based on primary pain complaint and the presence of focal or diffuse pain complaints: headache, nonheadache focal (pain involving <50% of the body), and nonheadache diffuse (pain involving >/=50% of the body). Patients completed questionnaires to identify pain severity, disability, depression, anxiety, and quality of life. RESULTS: Patients with headache differed from nonheadache patients for all evaluated parameters. Average pain severity on a 0 to 10 point severity scale was 5.55 for headache, 6.93 for nonheadache focal, and 8.05 for nonheadache diffuse. Pain occurred an additional 1.51 to 1.71 days per week for patients without headache. Compared to patients with headache, patients without headache reported greater frequency of reduced daily activities and complete disability related to pain. In addition, patients without headache and with diffuse pain reported more depression (78.2% vs. 45.8%) and anxiety (70.0% vs. 39.1%) than patients with headache. Quality of life measures were significantly reduced in patients with either nonheadache focal or diffuse conditions compared to patients with headache. CONCLUSIONS: Even when considering patients with focal rather than diffuse chronic pain complaints, patients with headache are dissimilar from other patients with chronic pain. Pain severity, frequency, disability, psychological distress, and quality of life are significantly more prominent or impaired in patients with chronic pain without headache compared to patients with headache.     

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.     

Longterm Prognosis of Analgesic Withdrawal in Patients with Drug-Induced Headaches

We studied long-term prognosis and prognostic variables for therapeutic outcome of analgesic withdrawal in 54 patients with drug-induced headaches. The duration of headache history was 21.9 +/- 12.8 years. Each patient took an average of 38.8 +/- 22.8 tablets or suppositories a week and an average of 2.5 distinct drugs. Most patients used drugs containing several components. Caffeine was contained in at least one drug in all cases, ergotamine in 80.0% and pyrazolone in 77.1%. All patients were admitted to the hospital for two weeks. The analgesics were discontinued abruptly and the withdrawal symptoms were alleviated by neuroleptics and neurotropics. During the second week of hospital stay we started a basic therapy with calcium antagonists or beta blockers in patients suffering from migraine initially and with tricyclic antidepressants, physical therapy or biofeedback in patients suffering from tension type headaches initially. At the end of the study (mean follow-up period = 16.8 +/- 13.6 months) 38 patients (70.1%) were evaluated. 76.3% of these patients had significantly reduced their analgesic intake, 60.5% had experienced a significant relief of headache both in intensity and frequency, and 23.7% were therapeutic failures. Analysis of the time course of relapse revealed the first six months after hospital discharge as the critical period determining long-term success. The variables tested for prognostic relevance (age, sex, duration of headache history, number of tablets or suppositories taken a week, organic mental syndrome, and type of initial headaches) were not statistically significant.