Paolo Martelletti

Psychiatric comorbidity in patients with chronic daily headache and migraine: a selective overview including personality traits and suicide risk

Studies on the prevalence and impact of psychiatric disorders among headache patients have yielded findings that have clarified the relationship between migraine and major affective disorders, anxiety, illicit drug abuse, nicotine dependence, and suicide attempts. Studies in both clinical and community-based settings have demonstrated an association between migraine and a number of specific psychiatric disorders. In large-scale population-based studies, persons with migraine are from 2.2 to 4.0 times more likely to have depression. In longitudinal studies, the evidence supports a bidirectional relationship between migraine and depression, with each disorder increasing the risk of the other disorder. Although a strong association has been demonstrated consistently for migraine and major depression, especially for migraine with aura, there has been less systematic research on the links between migraine and bipolar disorder. This review will focus on the way in which psychiatric disorders decrease the quality of life and result in a worse prognosis, chronicity of the disease, and a worse response to treatment. Short-term pharmaceutical care intervention improves the patients’ mental health, but it does not significantly change the number and severity of headaches. The increase in self-efficacy and mental health associated with pharmaceutical care may be instrumental in improving the long-term pharmacotherapy of patients with migraine and headache.

Neuromodulation of chronic headaches: position statement from the European Headache Federation

The medical treatment of patients with chronic primary headache syndromes (chronic migraine, chronic tension-type headache, chronic cluster headache, hemicrania continua) is challenging as serious side effects frequently complicate the course of medical treatment and some patients may be even medically intractable. When a definitive lack of responsiveness to conservative treatments is ascertained and medication overuse headache is excluded, neuromodulation options can be considered in selected cases.Here, the various invasive and non-invasive approaches, such as hypothalamic deep brain stimulation, occipital nerve stimulation, stimulation of sphenopalatine ganglion, cervical spinal cord stimulation, vagus nerve stimulation, transcranial direct current stimulation, repetitive transcranial magnetic stimulation, and transcutaneous electrical nerve stimulation are extensively published although proper RCT-based evidence is limited. The European Headache Federation herewith provides a consensus statement on the clinical use of neuromodulation in headache, based on theoretical background, clinical data, and side effect of each method. This international consensus further gives recommendations for future studies on these new approaches.In spite of a growing field of stimulation devices in headaches treatment, further controlled studies to validate, strengthen and disseminate the use of neurostimulation are clearly warranted. Consequently, until these data are available any neurostimulation device should only be used in patients with medically intractable syndromes from tertiary headache centers either as part of a valid study or have shown to be effective in such controlled studies with an acceptable side effect profile.

'Ictal epileptic headache' : Recent concepts for new classifications criteria

Dear Sir, More frequently associated than expected on the basis of coincidence, headache and epilepsy are both characterized by transient paroxysmal episodes of altered brain function with clinical, pathophysiological and therapeutic overlap. Cortical spreading depression (CSD) is probably the connection point between these two conditions. In fact, CSD and an epileptic focus are able to facilitate each other (1–3), and in the central nervous system there is a hierarchical organization based on ‘neuronal networks’ (cortical and subcortical) which may be more or less prone to CSD (migraine) and/or an epileptic focal discharge (i.e. seizures). Hyperexcitation occurs in epilepsy, in migraine hypoexcitation followed by hyperexcitation, as rebound phenomenon (spreading depression) (1–3). Moreover, a disexcitability condition (hyperand hypoexcitation in the same patient at different points in time) has even been demonstrated (1–3). The International Classification of Headache Disorders (ICHD-2) committee recognizes three nosographic entities concerning the relationship between epilepsy and headache (Table 1). The International League Against Epilepsy (ILAE) classification fully

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.

Psychiatric comorbidity and suicide risk in patients with chronic migraine.

The aim of this study was to explore the impact of mental illness among patients with migraine. We performed MedLine and PsycINFO searches from 1980 to 2008. Research has systematically documented a strong bidirectional association between migraine and psychiatric disorders. The relationship between migraine and psychopathology has often been clinically discussed rather than systematically studied. Future research should include sound methodologically-based studies focusing on the interplay of factors behind the relationship between migraine, suicide risk, and mental illness.

Tumor necrosis factor gene polymorphism in migraine

Objective.—To better define the involvement of human leukocyte antigen region (HLA) genes in migraine via an association study of the tumor necrosis factor (TNF) genes, located in the HLA class III region, with migraine with and without aura.

Emerging treatment for chronic migraine and refractory chronic migraine

Introduction: Chronic migraine (CM), the suffering of 15 or more headache days with at least 8 of these migraine days, afflicts 1.3% - 5.1% of the global population. CM is the most common disorder faced by experts in tertiary headache centers. When resistant to conventional medical treatment and prophylactic medication this condition is known as refractory chronic migraine (RCM). RCM is one of the greatest challenges in headache medicine. Areas covered: State-of-the-art and future medical treatments of chronic migraine include: OnabotulinumtoxinA, antiepileptic drugs (Levetiracetam, Magnesium valproate hydrate, Lacosamide, BGG-492), 5-HT agonists (Lasmiditan, NXN-188, novel delivery systems of Sumatriptan, a well-established drug treatment for acute migraine), CGRP receptor antagonists (BMS-927711), ML-1 agonists (Ramelteon), orexin receptor antagonist (MK-6096), plant-derived compound (LLL-2011) and other multitarget drugs such as Tezampanel, Tonabersat, intranasal carbon dioxide and BOL-148. The role for neuromodulation, the application of targeted electrical stimulation, will be examined. Expert opinion: Medication overuse headache (MOH) is now recognized to be a major factor in many cases of both chronic and refractory chronic migraine. MOH must be addressed prior to evaluating the effectiveness of new preventative and prophylactic treatment approaches. Innovative new drugs and electrical neuromodulation are promising CM treatments. Future studies must carefully screen patients and acquire data that can lead to personalized, tailored treatment strategies.

Lifting The Burden: the first 7 years

In September 2003, the World Health Organization (WHO) signed a Memorandum of Understanding that brought into being the Global Campaign against Headache (GC), known as Lifting The Burden.

Refractory chronic migraine: a Consensus Statement on clinical definition from the European Headache Federation

The debate on the clinical definition of refractory Chronic Migraine (rCM) is still far to be concluded. The importance to create a clinical framing of these rCM patients resides in the complete disability they show, in the high risk of serious adverse events from acute and preventative drugs and in the uncontrolled application of therapeutic techniques not yet validated.The European Headache Federation Expert Group on rCM presents hereby the updated definition criteria for this harmful subset of headache disorders. This attempt wants to be the first impulse towards the correct identification of these patients, the correct application of innovative therapeutic techniques and lastly aim to be acknowledged as clinical entity in the next definitive version of the International Classification of Headache Disorders 3 (ICHD-3 beta).

A six year retrospective review of occipital nerve stimulation practice - controversies and challenges of an emerging technique for treating refractory headache syndromes

BackgroundA retrospective review of patients treated with Occipital Nerve Stimulation (ONS) at two large tertiary referral centres has been audited in order to optimise future treatment pathways.MethodsPatient’s medical records were retrospectively reviewed, and each patient was contacted by a trained headache expert to confirm clinical diagnosis and system efficacy. Results were compared to reported outcomes in current literature on ONS for primary headaches.ResultsTwenty-five patients underwent a trial of ONS between January 2007 and December 2012, and 23 patients went on to have permanent implantation of ONS. All 23 patients reached one-year follow/up, and 14 of them (61%) exceeded two years of follow-up. Seventeen of the 23 had refractory chronic migraine (rCM), and 3 refractory occipital neuralgia (ON). 11 of the 19 rCM patients had been referred with an incorrect headache diagnosis. Nine of the rCM patients (53%) reported 50% or more reduction in headache pain intensity and or frequency at long term follow-up (11–77 months). All 3 ON patients reported more than 50% reduction in pain intensity and/or frequency at 28–31 months. Ten (43%) subjects underwent surgical revision after an average of 11 ± 7 months from permanent implantation - in 90% of cases due to lead problems. Seven patients attended a specifically designed, multi-disciplinary, two-week pre-implant programme and showed improved scores across all measured psychological and functional parameters independent of response to subsequent ONS.ConclusionsOur retrospective review: 1) confirms the long-term ONS success rate in refractory chronic headaches, consistent with previously published studies; 2) suggests that some headaches types may respond better to ONS than others (ON vs CM); 3) calls into question the role of trial stimulation in ONS; 4) confirms the high rate of complications related to the equipment not originally designed for ONS; 5) emphasises the need for specialist multidisciplinary care in these patients.