Does medication overuse headache represent a behavior of dependence?

Medication overuse is relatively common in patients with frequent headache. To explore the prevalence of patients who meet the criteria for substance dependence in Diagnostic and Statistical Manual of Mental Disorders, Edition IV (DSM-IV), and to identify variables of substance dependence among patients with chronic daily headache, we recruited consecutive patients with chronic daily headache at a headache clinic from November 1999 to June 2004. Each patient completed a headache intake form, a dependence questionnaire modified from DSM-IV, and the Hospital Anxiety and Depression Scale (HADS). The presence of probable medication overuse headache (pMOH) was defined on the basis of the International Classification of Headache Disorders, 2nd edition, 2004. A total of 1,861 patients with chronic daily headache (1,369 women, 492 men; mean age, 49.6+/-15.4 years) were recruited. Almost half (895/1,861, 48%) met criteria of pMOH, and 606 of these patients (606/895, 68%) met three of five DSM-IV substance dependence criteria. In contrast, only 191 of 968 patients without pMOH (20%) met the DSM-IV criteria (OR=8.6, [7.0-10.6], chi-square test, P<0.001). Patients who fulfilled DSM-IV criteria of dependence had higher numbers of physician appointments in the past year. Multivariate logistic regression analyses revealed that migraine headache, frequent physician consultation, intensity of headache, and presence of a higher anxiety score were significant independent variables for substance dependence. Among patients with chronic daily headache, pMOH was associated with behaviors of substance dependence.     

Chronic migraine plus medication overuse headache: two entities or not?

Chronic migraine (CM) represents migraine natural evolution from its episodic form. It is realized through a chronicization phase that may require months or years and varies from patient to patient. The transition to more frequent attacks pattern is influenced by lifestyle, life events, comorbid conditions and personal genetic terrain, and it often leads to acute drugs overuse. Medication overuse headache (MOH) may complicate every type of headache and all the drugs employed for headache treatment can cause MOH. The first step in the management of CM complicated by medication overuse must be the withdrawal of the overused drugs and a detoxification treatment. The goal is not only to detoxify the patient and stop the chronic headache but also to improve responsiveness to acute or prophylactic drugs. Different methods have been suggested: gradual or abrupt withdrawal; home treatment, hospitalization, or a day-hospital setting; re-prophylaxes performed immediately or at the end of the wash-out period. Up to now, only topiramate and local injection of onabotulinumtoxinA have shown efficacy as therapeutic agents for re-prophylaxis after detoxification in patients with CM with and without medication overuse. Although the two treatments showed similar efficacy, onabotulinumtoxinA is associated with a better adverse events profile. Recently, the Phase III Research Evaluating Migraine Prophylaxis Therapy (PREEMPT) clinical program proved that patients with CM, even those with MOH, are the ones most likely to benefit from onabotulinumtoxinA treatment. Furthermore, it provided an injection paradigm that can be used as a guide for a correct administration of onabotulinumtoxinA.     

A CARE pathway in medication–overuse headache: the experience of the Headache Centre in Pavia

Medication–overuse headache (MOH) is one of the headache forms that most frequently prompts patients to consult a specialist headache centre. The prevaence of this form in the general population is approximately 1–2%. Around 40% of patients seen at headache centres present with a chronic form of headache and 80% of this chronic headache patients make excessive use of symptomatic drugs. MOH shows a clinical improvement, accompained by a reduction in the consumption of analgesic drugs, if patients are submitted to detoxification therapy. But detoxification is only the first stage in a long and complex course of care and global approach demands adequate follow–up visit to prevent early relapses. At the Headache Centre of the C. Mondino Institute of Neurologt in Pavia, a course of care (CARE) has been developed for the complente management of patients with MOH both during Hospitalization and durimg the subsequent follow–up period. CARE IS designed to trace the clinical, psychopathological and pharmacological profile of MOH in the short–, medium– and long–term; to look for factors possibility predictive of relapse; to assess the direct costs linked to overuse–headache in the year leading up to and following detoxification; and to evaluate disability, in terms of working days lost, before and after detoxification.     

What do the patients with medication overuse headache expect from treatment and what are the preferred sources of information?

Lack of knowledge on patients’ expectations to treatment may lead to misunderstandings and prevent successful outcome. Presently, treatment of medication overuse headache (MOH) leads to improvement in up to 75% of patients, but the relapse rate may exceed 40%. This study aimed to evaluate the preferences on information and expectations to treatment in patients entering a treatment programme for MOH. A questionnaire on patients’ needs and preferences on information and expectations was distributed to 65 MOH patients from specialized headache clinics in Italy, Germany and Denmark. A total of 75% selected personal verbal information as their primary need, significantly higher than the percentage of patients who selected leaflets and website information 35 and 35%, respectively (p < 0.001). Telephone and E-mail consultation was requested by 59 and 48%, respectively. The information source preferred was again personal verbal information (82%), significantly higher than all other information sources (p < 0.001). In decreasing order, patients preferred telephone consultation (48%), E-mail consultation (44%), website information (41%), and leaflets (33%). 51% expected their headache to be cured, 71 and 57% requested effective prevention and fast relief of the headache episodes. 80 and 75%, respectively expected reduction in frequency and intensity. A total of 64% expected information about self-management and 52% expected to receive education on their headaches. The study demonstrates that patients in specialized headache centres prefer personal information, that expectations are very high, and that education and information are important. Providing the right information and thus give patients realistic expectations might enhance compliance and improve outcome.     

Chronic daily headache in the absence of medication overuse: Is daily or continuous pain more treatment-resistant than chronic daily headache with pain-free days?

To our patients, their families, and treatment providers who may not be headache specialists, chronic daily headache (CDH) would appear to refer to headache disorders marked by the presence of daily pain over an extended period of time. To the headache specialist, in contrast, CDH represents a family of headache disorders in which pain occurs from 15 to 30 days each month [1], now reflected in the International Headache Society (IHS) criteria for chronic migraine (CM) or chronic tension-type headache [2]. The IHS classification does not distinguish between daily CM and intermittent CM marked by at least some pain-free days [3]. Research studies and clinical reports of the diagnostic entities subsumed under CDH often include patients with pain-free days and those with true daily pain.     

Should we treat all the diseases of the elderly?

The coexistence of several diseases, the loss of autonomy and certain social and behavioural factors lead to polymedication. It is important to reduce the number of drugs prescribed to prevent drug-drug interactions or interactions between drugs and a system weakened by age and comorbiditiy. Because of the limited number of therapeutic trials performed in individuals aged >75 years, clinical consideration based on the consensus of experts is the primary way of establishing priorities and making rational choices.     

What do we know about the state of chronic pain?

Chronic pain syndromes are characterized by altered neuronal excitability in the pain matrix. The ability to rapidly acquire and store memory of aversive events is one of the basic principles of nervous systems throughout the animal kingdom. These neuroplastic changes take place e. g. in the spinal cord, in thalamic nuclei and cortical and subcortical (limbic) areas integrating pain threshold, intensity and affective components. Chronic inflammation or injury of peripheral nerves evokes the reorganisation of cortical sensory maps. Neurons conveying nociceptive information are controlled by various sets of inhibitory interneurons. The discharge activity of these interneurons counteracts long-term changes in the pain matrix following nociceptor activation, i. e. it prevents the transition of acute pain signaling to chronic pain states. Our most recent research suggests that pain states may be sensitive to novel families of agents and therapeutic measures not predicted by traditional preclinical pain models as well as human pain states. The endogenous cannabinoid system plays a central role in the extinction of aversive memories. We propose that endocannabinoids facilitate extinction of aversive memories via their selective inhibitory effects on GABAergic networks in the amygdala.     

What do we know about the genetics of aspirin intolerance?

Although acetylsalicylic acid is prescribed for a broad range of diseases, it can induce a wide array of clinically recognized hypersensitivity reactions, including aspirin-intolerant asthma (AIA) with rhinitis and aspirin-intolerant urticaria (AIU) with anaphylaxis. Altered eicosanoid metabolism is the generally accepted mechanism of aspirin intolerance; the overproduction of cysteinyl leucotrienes has been suggested to play a causative role in both AIA and AIU. Genetic markers suggested for AIA include HLA-DPBI*0301, leucotriene C4 synthase (LTC4S), ALOX5, CYSLT, PGE2, TBXA2R and TBX21. Similarly, HLA-DB1*0609, ALOX5, FCER1A and HNMT have been identified as possible genetic markers for AIU. An additional low-risk genetic marker for AIA is MS4A2, which encodes the beta-chain of FCER1. Other single and sets of two or more interacting genetic markers are currently being investigated. Analyses of the genetic backgrounds of patients with AIA and AIU will promote the development of early diagnostic and therapeutic interventions, which may reduce the incidence of AIA and AIU.     

Should we consider the infusion of lipid emulsion in the resuscitation of poisoned patients?

The use of intravenous lipid emulsions (ILEs) as antidote in local anaesthetic systemic toxicity has gained widespread support following convincing data from animal models, and successful case reports in humans. Proposed beneficial mechanisms of action for ILEs include intravascular sequestration of intoxicant and subsequent enhanced redistribution to biologically inert tissues, augmentation of fatty acid utilisation for ATP synthesis in the context of metabolic poisoning, and direct cardiotonic and ion channel effects. The evidence base for use of ILEs in acute drug intoxication is evolving. The present evidence supports use of ILEs only in local anaesthetic systemic toxicity and in lipophilic cardiotoxin intoxication when there is an immediate threat to life, and other therapies have proven ineffective.