MMPI and Critical Flicker Frequency (CFF) Analysis in Headache Patients With and Without Drug Abuse

Sixty-three headache patients (migraine: n = 28; tension-type headache: n = 35) who fulfilled the IHS criteria of 'drug abuse' were investigated by means of the Minnesota Multiphasic Personality Inventory (MMPI) and the Critical Flicker Frequency (CFF) analysis. The results were compared to those of 63 headache patients without drug abuse (matched-pair case-control study).
With respect to the MMPI results, no statistically significant differences between patients with drug abuse and patients without drug abuse were found. However, patients with drug abuse showed significantly decreased CFF values compared to patients without drug abuse. This was true both for patients with migraine and for patients with tension-type headache.
Thus, CFF analysis may serve as a useful method to differentiate between headache patients with drug abuse and those without drug abuse.     

Long-term outcome of patients with headache and drug abuse after inpatient withdrawal: five-year follow-up

Thirty-eight patients with "chronic daily" headache and ergotamine and/or analgesics abuse according to the criteria proposed by the international Headache Society were re-investigated 5 years after inpatient drug withdrawal. At the end of the observation period, 19 patients (50.0%) had their headaches on only 8 days per month or less, 18 patients (47.4%) were free of symptoms or had only mild headaches. A close correlation was found between the frequency of headache and the duration of drug abuse, as well as between the intensity of headache and the number of tablets taken per month. Frequency and intensity of headache had changed within the first 2 years after withdrawal, but remained stable afterwards. Fifteen patients (39.5%) reported on recurrent drug abuse. Patients with migraine showed a tendency towards a better prognosis compared to patients with tension-type headache or with combined migraine and tension-type headache. The results of this study highlight the long-term efficacy of inpatient drug withdrawal in patients with headache and ergotamine and/or analgesics abuse.     

Ergotamine abuse: Results of ergotamine discontinuation, with special reference to the plasma concentrations

Twenty-three patients suffering from continuous headache linked with habitual daily use of ergotamine tartrate were studied. Their headaches were classified clinically, and possible side effects of ergotamine medication, plasma levels of ergotamine, and occurrence of withdrawal symptoms after discontinuation of drug abuse were recorded. Seventeen of the patients were clinically diagnosed as suffering from "ergotamine headache", and seven of them complained of coldness in the extremities. Plasma ergotamine levels were measured by using a radioimmunoassay. In almost half of the patients the 1 h plasma levels after the daily dose were below the detection limit of the procedure (0.12 ng/ml). The duration and severity of the withdrawal symptoms did not correlate with the doses and plasma levels of ergotamine. In only 4 of the 21 patients who were followed up for 3 to 6 months did headache symptoms not improve after ergotamine withdrawal. The results indicate that even small (0.5–1.0 mg/day) doses of ergotamine tartrate taken regularly may cause continuous headache symptoms and withdrawal symptoms after discontinuation.     

Controversy over the Classification of Medication-Overuse Headache

Medication-overuse headache (MOH) is a relatively common and impactful disorder, affecting 1% to 2% of the population, characterized by daily or near-daily headache aggravated by chronic acute medication intake. Primary headache patients do not necessarily develop MOH after acute medication overuse, although a pre-existing primary headache is inevitably present. Likewise, headache patients may deteriorate in terms of frequency without medication overuse, or suffer from chronic headache in the presence of drug abuse without any causal relationship. To classify and define diagnostic criteria for MOH in the absence of objective biomarkers is a difficult task that is presently based on clinical grounds and is limited in part by the relative lack of research in this field. The present criteria are less restrictive but also less precise than the previous versions because they allow the diagnosis without the previously required MOH confirmation after medication withdrawal. MOH should remain as a distinct secondary disorder based on the available clinical and pathophysiological evidence.     

Headache Caused by a Sphenoid Mucocele but Presenting as an Ergotamine-Induced Headache

In a 65-year-old woman, symptomatic headache caused by a mucocele of the sphenoid sinus led to ergotamine abuse and subsequent ergotamine-induced headache. Since there were no neurological symptoms initially and the patient previously suffered from migraine, the mucocele was not recognized. Only after unsuccessful drug withdrawal therapy and an MRI, was the correct diagnosis made. Surgical removal of the mucocele led to complete relief of headache within 3 weeks. We conclude that ergotamine-induced headache can develop on the basis of symptomatic headache. In spite of the effectiveness of ergotamine tartrate, an MRI should be performed if focal neurological symptoms occur.     

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.     

Discontinuation of medication overuse in headache patients: recovery of therapeutic responsiveness

It is generally accepted that ongoing medication overuse nullifies the effect of prophylactic treatment, although few data support this contention. We set out to describe the treatment outcome in patients withdrawn from medication overuse and relate any improvement to a renewed effect of prophylaxis. For patients with probable medication-overuse headache (pMOH), treated and dismissed from the Danish Headache Centre in 2002 and 2003, we assed, from prospective headache diaries, the headache frequency before and after withdrawal of offending drugs and compared these frequencies with the headache frequency at dismissal. Among 1326 patients, 337 had pMOH. Eligible were 175, mean age 49 years, male/female ratio 1 : 2.7. Overall, there was a 46% decrease in headache frequency from the first visit to dismissal (P < 0.0001). Patients with no improvement 2 months after complete drug withdrawal (N = 88) subsequently responded to pharmacological and/or non-pharmacological prophylaxis with a 26% decrease in headache frequency as measured from the end of withdrawal to dismissal (P < 0.0001). At dismissal, 47% were on prophylaxis. Former non-responders to medical prophylaxis had a 49% decrease in headache frequency from first visit to dismissal (P < 0.0001), whereas those who had never received prophylaxis had a 56% reduction (P < 0.0001). This difference was not statistically significant (P = 0.22). Almost all MOH patients benefit from drug withdrawal, either just from the withdrawal or by transformation from therapeutic non-responsiveness to responsiveness. According to the International Classification of Headache Disorders, 2nd edn, the MOH diagnosis requires improvement after drug withdrawal. Our data suggest that these diagnostic criteria are too strict.     

Medication overuse headache: predictors and rates of relapse in migraine patients with low medical needs. A 1-year prospective study

The aim of this study was to evaluate the rates and predictors of relapse, after successful drug withdrawal, in migraine patients with medication overuse headache (MOH) and low medical needs. The study population, study design, inclusion criteria and short-term effectiveness of the medication withdrawal strategies have been described elsewhere (Rossi et al., Cephalalgia 2006; 26:1097). Relapsers were defined as those patients fulfilling, at follow-up, the new International Classification of Headache Disorders, 2nd edn, appendix criteria for MOH. Complete datasets were available for 83 patients. At 1 year's follow up, the relapse rate was 20.5%. Univariate analysis showed that patients who relapsed had a longer duration of migraine with more than eight headache days/month, a longer duration of drug overuse, had tried a greater number of preventive treatments in the past, had a lower reduction of headache frequency after withdrawal, and had previously consulted a greater number of specialists. Binary logistic regression analysis was performed, and three variables emerged as significant predictors of relapse: duration of migraine with more than eight headache days/month [odds ratio (OR) 1.57, P = 0.01], a higher frequency of migraine after drug withdrawal (OR 1.48, P = 0.04) and a greater number of previous preventive treatments (OR 1.54, P = 0.01). In patients with migraine plus MOH and low medical needs, relapse seems to depend on a greater severity of baseline migraine.     

Medication overuse headache and applicability of the ICHD-II diagnostic criteria: 1-year follow-up study (CARE I protocol)

Medication overuse headache (MOH) is a growing problem worldwide and a challenge for clinicians and investigators. This study aims to contribute to the ongoing debate surrounding the classification of MOH. Applying the revised diagnostic criteria for MOH contained in the updated International Classification of Headache Disorders (ICHD-II), we enrolled 140 probable MOH (p-MOH) patients. They were submitted to an in-patient detoxification protocol and re-examined 2, 6 and 12 months later to confirm, or otherwise, the diagnosis of MOH and to observe the evolution of their headache. MOH diagnosis was confirmed 2 months after detoxification in 71% of patients, who reverted to an episodic headache pattern and stopped their drug overuse The overall clinical situation at 2 months closely reflected the 1-year trend. The 2-month period after drug withdrawal should be retained as a diagnostic criterion in the ICHD-II because it is useful not only as a diagnostic parameter, but also as predictor of a good outcome of 1-year drug withdrawal. In addition, the present findings point to the need for a more objective criterion to quantify headache frequency after drug withdrawal.     

Needle acupuncture in tension-type headache: a randomized, placebo-controlled study

A study with needle acupuncture was performed in tension-type headache employing a new placebo acupuncture METHOD: Sixty-nine patients (mean age 48.1 years, SD = 14.1) fulfilling the International Headache Society criteria for tension-type headache were randomly assigned to verum or placebo condition. No significant differences between placebo and verum with respect to visual analogue scale and frequency of headache attacks could be observed immediately, 6 weeks and 5 months after the end of treatment. There was a significant but weak improvement in quality of life parameters (clinical global impressions, Nottingham Health Profile) after verum treatment. In decision tree analyses, the changes in clinical global impressions and headache frequency depended significantly on primary headache frequency with a limit value of 24.5 days headache per month. High values in the von Zerssen Depression Score resulted in high mean visual analogue scale values.     

Headache in the Use and Withdrawal of Opiates and Other Associated Substances of Abuse

The incidence and character of headache were retrospectively studied in 40 opiate addicts and 40 control subjects. The relationships between headache and use and withdrawal of opiates or other associated substances of abuse were investigated. In the opiate-dependent patients, the effects of opiate intake and withdrawal on headache were also investigated during detoxification treatment. A higher (p less than 0.001) incidence of headache was found in the opiate addicts (60%), particularly those with a longer history of addiction, than in the control subjects. A history of different types of headache (tension type headache, migraine-like headaches), which seemed respectively to be associated with the use of certain types of heroin, cocaine intake, and opiate withdrawal, was reported by the addicts who suffered from headache. Out of the 24 patients who completed the detoxification therapy, a migraine-like headache occurred in 37.5% of the subjects after opiate withdrawal.     

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.     

5HT in migraine patients with medication-induced headache

Whole blood 5HT levels were measured in seven female migraine sufferers with chronic daily headache due to medication abuse, before and after abrupt medication withdrawal. A statistically significant increase in 5HT levels, from mean 4.89 mmol/1 to mean 6.59 mmol/l ( p < 0.05, Wilcoxon signed rank test), as well as a significant improvement in the number of headache-free days ( p < 0.05, Wilcoxon signed rank test), occurred after 4 weeks of withdrawal. We conclude from this pilot study that 5HT may be important in the physiopathogenesis of chronic daily headache. Alternatively, reduced 5HT may be the result of chronic daily headache or else an epiphenomenon.     

Amitriptyline treatment in chronic drug-induced headache: a double-blind comparative pilot study

OBJECTIVE: To assess the effects of amitriptyline and sudden analgesic withdrawal on headache frequency and quality of life in patients suffering from chronic daily headache related to analgesics abuse. METHODS: Seventeen nondepressed patients with chronic drug-induced headache were included in a 9-week, parallel-group, randomized, double-blind, placebo-controlled study. After abrupt analgesic withdrawal, amitriptyline or an active placebo (trihexyphenidyl) was started. The primary efficacy variable was headache frequency recorded on a headache diary in the last 4 weeks of each treatment. The secondary efficacy variable was quality of life (Nottingham Health Profile). RESULTS: Headache frequency decreased by 45% in the amitriptyline group and by 28% in the trihexyphenidyl group. Amitriptyline enhanced all the dimensions of quality of life and significantly improved emotional reaction and social isolation. CONCLUSION: This pilot study suggests a beneficial effect of amitriptyline on headache frequency and quality of life for patients with chronic drug-induced headache.     

Prophylaxis of hemicrania continua: two new cases effectively treated with topiramate

Hemicrania continua (HC) is an uncommon and under-recognized primary headache disorder characterized by a strictly unilateral continuous headache of moderate intensity with possible exacerbations and associated with ipsilateral autonomic features. HC has generally a prompt and enduring response to indomethacin although 25% to 50% of treated patients develop gastrointestinal side effects. These cases pose a difficult management challenge as no other drug is consistently effective in HC. Recently 2 HC patients responsive to topiramate treatment have been reported. Here we describe 2 more patients effectively treated with topiramate. Neither reported any side effects and one had persisting response for 6 months after drug withdrawal.     

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.     

Reduced serotonin vascular sensitivity in ergotamine abusers

The action of ergotamine on the 5-hydroxytryptamine (5-HT) venous sensitivity was studied in ergotamine abuser and non-abuser migraine patients. Ergotamine abusers showed reduced 5-HT hand vein contraction during abuse, compared to seven days after ergotamine withdrawal. In non-ergotamine users, the 5-HT venoconstriction was not significantly modified 12 h after a single intramuscular ergotamine (0.25 mg) administration. Even the administration of ergotamine locally into the vein did not change the venospasm of 5-HT given acutely in the same vein. Therefore, it seems that the 5-HT antagonism does not contribute to the therapeutic effect of ergotamine during the migraine attack. Moreover, the reduced 5-HT responsiveness during ergotamine abuse may possibly be compatible with the chronic headache present in some abusers, the withdrawal headache attacks and the abuse itself.     

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.     

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.