Zaza Katsarava

Features of medication overuse headache following overuse of different acute headache drugs

ObjectiveTo investigate pharmacologic features such as mean critical duration until onset of medication-overuse headache (MOH) (MCDO), mean critical monthly intake frequencies (MCMIF), and mean critical monthly dosages (MCMD) as well as specific clinical features of MOH after overuse of different acute headache drugs, with a focus on newly approved triptans. Methods In a prospective study 98 patients with MOH according to International Headache Society (IHS) criteria underwent standardized inpatient withdrawal from their medication. Patient diaries and structured interviews were used to calculate the MCDO, MCMIF, and MCMD for each substance group. Results The MCDO was shortest for triptans (1.7 years), longer for ergots (2.7 years), and longest for analgesics (4.8 years). The MCMIF was lowest for triptans (18 single doses per month), higher for ergots (37), and highest for analgesics (114). Although patients overusing ergots and analgesics typically had a daily tension-type headache, patients with triptan-induced MOH were more likely to describe a (daily) migrainelike headache or an increase in migraine frequency. Conclusion Overuse of triptans leads to MOH faster and with lower dosages compared with ergots and analgesics. Clinical features of MOH depend on the type of overused headache medication. Pharmacologic and clinical characteristics of triptan-induced MOH call for the renewal of the current IHS classification.

Incidence and predictors for chronicity of headache in patients with episodic migraine

The authors followed 532 consecutive patients with episodic migraine (<15 days/month) for 1 year. Sixty-four patients (14%) developed chronic headache (≥15 days/month). The odds ratios for developing CH were 20.1 (95% CI 5.7 to 71.5) comparing patients with a “critical” (10 to 14 days/month) vs “low” (0 to 4 days/month) and 6.2 (95% CI 1.7 to 26.6) in patients with an “intermediate” (6 to 9 days/month) vs “low” headache frequency and 19.4 (95% CI 8.7 to 43.2) comparing patients with and without medication overuse.

The cost of headache disorders in Europe: the Eurolight project.

Background and purpose:  Headache disorders are very common, but their monetary costs in Europe are unknown. We performed the first comprehensive estimation of how economic resources are lost to headache in Europe.

Medication-overuse headache.

PURPOSE OF REVIEW Medication-overuse headache (MOH) is a well described clinical entity. There is a growing body of knowledge on the epidemiology of MOH, risk factors, and treatment strategies. RECENT FINDINGS The International Headache Society updated the classification criteria for MOH. Population-based studies provided an insight into the prevalence and peculiarities of MOH patients in eastern Europe and Asia. Large-scaled population-based longitudinal studies made it possible to analyze risk factors leading to the development of MOH. Imaging studies helped to better understand the pathophysiology of headache chronicity. New treatment strategies have been suggested. SUMMARY MOH is a common headache disorder and a serious public health problem all over the world. Although the treatment regimen for MOH patients is straightforward and the outcomes are favorable, it is time now to move forward and establish a predictive model for early recognition of patients at high risk, to intervene early and avoid development of chronic headache.

Clinical features of withdrawal headache following overuse of triptans and other headache drugs

Background: Complete withdrawal from headache medication is the treatment of choice for medication-overuse headache. Discontinuation of the overused headache medication, however, results in the development of withdrawal headache, often associated with nausea, vomiting, and sleep disturbances. Method: In a prospective study of 95 patients, the authors investigated the duration and severity of withdrawal headache after overuse of various headache drugs, including single and combination analgesics, ergots, and triptans. All patients underwent standard inpatient withdrawal therapy for 14 days. Results: The duration of withdrawal headache was shorter in patients overusing triptans (4.1 days) than in patients overusing ergots (6.7 days) or analgesics (9.5 days; p < 0.002). The mean headache intensity on the first day of withdrawal did not differ between the groups (p = 0.821). By day 14, however, it was lower in patients overusing triptans (0.08) than in patients overusing ergots (0.4) or analgesics (0.9; p < 0.005). Rescue medication was requested less by patients undergoing triptan withdrawal (0.25 requests) than by patients undergoing ergot withdrawal (1.25) or analgesic withdrawal (1.85; p < 0.05). Similar to findings in the entire patient population, withdrawal headache was shorter and less severe in migraineurs overusing triptans than in those overusing ergots or analgesics. Because only patients with migraine, but no patient with tension-type headache, overused triptans, withdrawal headache was shorter in the group of patients with migraine alone (6.7 days versus 9.6 days for patients with tension-type headache and 8.5 days for patients with combination headache, p < 0.02). Conclusion: The duration and severity of withdrawal clearly depend on the type of overused headache drug only.

Medication overuse headache: rates and predictors for relapse in a 4‐year prospective study

We present a prospective 4-year follow-up study of 96 patients with medication overuse headache following withdrawal. Complete datasets were available from 85 patients (89%) 6 months, from 79 patients (82%) 1 year and from 75 patients (78%) 4 years after withdrawal. Twenty-six patients (31%) relapsed within the first 6 months after withdrawal. The number of relapses increased to 32 (41%) 1 year and to 34 (45%) 4 years after withdrawal. The 4-year relapse rate was lower in migraine than in tension-type headache (32% vs. 91%, P ≤ 0.001) and combination of migraine and tension-type headache (32% vs. 70%, P ≤ 0.027) and also lower in patients overusing triptans than analgesics (21% vs. 71%, P ≤ 0.001). The study suggests that the majority of relapses occur within the first year after withdrawal and that the long-term success of withdrawal depends on the type of primary headache and the type of overused medication.

Lamotrigine reduces migraine aura and migraine attacks in patients with migraine with aura

This study examined the efficacy of lamotrigine in the prevention of migraine aura. Fifty nine patients suffering from migraine with aura received lamotrigine in a controlled three year prospective open study. Treatment response was defined as a reduction of aura frequency each month by at least 50%. Primary endpoint was reached by three quarters of the patients. Lamotrigine significantly reduced both frequency of migraine aura (mean, 1.5 (SD, 0.6) each month before v 0.4 (0.7) after treatment; p < 0.001) and aura duration (mean, 27 (SD, 11) minutes before v 8 (14) after treatment; p < 0.001). Furthermore, more than three quarters of those patients with a reduction of aura symptoms experienced a significant reduction of frequency of migraine attacks (mean, 2.1 (SD, 1.0) each month before v 1.2 (1.1) after treatment; p < 0.001). Lamotrigine was highly effective in reducing migraine aura and migraine attacks. The strong correlation between reduction of aura symptoms and migraine attacks stresses the potential role of aura-like events and possibly cortical spreading depression as a trigger for trigeminal vascular activation, and subsequently the development of migraine headaches.

Repair Capacity for Platinum-DNA Adducts Determines the Severity of Cisplatin-Induced Peripheral Neuropathy

The pronounced neurotoxicity of the potent antitumor drug cisplatin frequently results in the onset of peripheral polyneuropathy (PNP), which is assumed to be initially triggered by platination products in the nuclear DNA of affected tissues. To further elucidate the molecular mechanisms, we analyzed in a mouse model the formation and processing of the main cisplatin-induced DNA adduct (guanine–guanine intrastrand cross-link) in distinct neuronal cell types by adduct-specific monoclonal antibodies. Comparison of the adduct kinetics in cisplatin-injected mice either proficient or deficient for nucleotide excision repair (NER) functions revealed the essential role of this DNA repair pathway in protecting differentiated cells of the nervous system from excessive formation of such lesions. Hence, chronic exposure to cisplatin resulted in an accelerated accumulation of unrepaired intrastrand cross-links in neuronal cells of mice with dysfunctional NER. The augmented adduct levels in dorsal root ganglion (DRG) cells of those animals coincided with an earlier onset of PNP-like functional disturbance of their sensory nervous system. Independently from the respective repair phenotype, the amount of persisting DNA cross-links in DRG neurons at a given cumulative dose was significantly correlated to the degree of sensory impairment as measured by electroneurography. Collectively, these findings suggest a new model for the processing of cisplatin adducts in primary neuronal cells and accentuate the crucial role of effectual DNA repair capacity in the target cells for the individual risk of therapy-induced PNP.

Central sensitization of the trigeminal and somatic nociceptive systems in medication overuse headache mainly involves cerebral supraspinal structures.

Trigeminal and somatic nociceptive systems were studied in controls (n = 15), episodic migraine (n = 16), analgesics (n = 14) and triptan-induced medication overuse headache (MOH) (n = 15) before and after withdrawal. Patients with MOH and comorbid depressive symptoms and depression without headache were studied to investigate the influence of depression. Trigeminal nociception was studied by simultaneous registration of pain-related cortical potentials (PREP) and nociceptive blink reflex (nBR) following nociceptive-specific electrical stimulation of the forehead. Somatic nociception was evaluated using PREP of upper limbs. We found facilitation of both trigeminal and somatic PREP but not of nBR in MOH, which normalized after withdrawal. No differences were found comparing analgesics vs. triptan MOH. No differences were observed between controls and patients with episodic migraine and depression without headache. A transient facilitation was found of trigeminal and somatic nociceptive systems in MOH, which was more pronounced on a supraspinal level.

Primary headache disorders in the Republic of Georgia: Prevalence and risk factors

Objective: To estimate the 1-year prevalences of migraine and tension-type headache (TTH), and identify their principal risk factors, in the general population of the Republic of Georgia. Methods: In a community-based door-to-door survey, 4 medical residents interviewed all biologically unrelated adult members (≥16 years) of 500 adjacent households in Tbilisi, the capital city, and 300 in rural Kakheti in eastern Georgia, using a previously validated questionnaire based on International Headache Society diagnostic criteria. Results: The target population included 1,145 respondents, 690 (60%) women, mean age 45.4 ± 12.0 years. The 1-year prevalences were as follows: migraine 6.5% (95% confidence interval 5.0–7.9), probable migraine 9.2% (7.5–10.8), all migraine 15.6% (13.5%–17.7%), TTH 10.0% (8.2–11.7), probable TTH 27.3% (24.8–29.9), all TTH 37.3% (34.5%–40.1%). Female gender and low socioeconomic status were risk factors for migraine but not for TTH. Headache on ≥15 days/month was reported by 87 respondents, a prevalence of 7.6% (6.1–9.1). Female gender, low socioeconomic status, and frequent use (≥10 days/month) of acute headache drugs were risk factors. The likely prevalence of medication overuse headache was 0.9% (0.3–1.4), of chronic migraine 1.4% (0.7–2.1), and of chronic TTH 3.3% (2.3–4.4), but caution is needed in interpreting these estimates. Conclusions: While the prevalences of migraine and tension-type headache are comparable with those in Europe and the United States, a remarkably high percentage of the population of Georgia have headache on ≥15 days/month. This study demonstrates the importance of socioeconomic factors in a developing country and unmasks the unmet needs of people with headache disorders.