Nocebo is the enemy, not placebo. A meta-analysis of reported side effects after placebo treatment in headaches

Cephalalgia ◽  
2011 ◽  
Vol 31 (5) ◽  
pp. 550-561 ◽  
Author(s):  
Dimos D Mitsikostas ◽  
Leonidas I Mantonakis ◽  
Nikolaos G Chalarakis
Keyword(s):  
Clinical Trials ◽  
Cluster Headache ◽  
Meta Analysis ◽  
Preventive Treatment ◽  
Primary Headache ◽  
Symptomatic Treatment ◽  
Adverse Side Effect ◽  
Primary Headaches ◽  
Nocebo Effect ◽  
Primary Headache Disorders

The aim was to determine the magnitude of the nocebo (adverse effects following placebo administration) in clinical trials for primary headache disorders. We reviewed randomized, placebo-controlled studies for migraine, tension-type headache (TTH), and cluster headache treatments published between 1998 and 2009. The frequency of nocebo was estimated by the percentage of placebo-treated patients reporting at least one adverse side effect. The dropout frequency was estimated by the percentage of placebo-treated patients who discontinued the treatment due to intolerance. In studies of symptomatic treatment for migraine, the nocebo and dropout frequencies were 18.45% and 0.33%, but rose to 42.78% and 4.75% in preventative treatment studies. In trials for prevention of TTH, nocebo and dropout frequencies were 23.99% and 5.44%. For symptomatic treatment of cluster headache, the nocebo frequency was 18.67%. Nocebo is prevalent in clinical trials for primary headaches, particularly in preventive treatment studies. Dropouts due to nocebo effect may confound the interpretation of many clinical trials.

scholarly journals Comorbidities of primary headache disorders: a literature review with meta-analysis

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Valeria Caponnetto ◽  
Manuela Deodato ◽  
Micaela Robotti ◽  
Maria Koutsokera ◽  
Valeria Pozzilli ◽  
...  
Keyword(s):  
Back Pain ◽  
Depressive Disorders ◽  
Population Studies ◽  
Meta Analysis ◽  
Primary Headache ◽  
Global Burden ◽  
Primary Headaches ◽  
Headache Disorders ◽  
Primary Headache Disorders ◽  
The Impact

Abstract Background Primary headache disorders are common and burdensome conditions. They are associated to several comorbidities, such as cardiovascular or psychiatric ones, which, in turn, contribute to the global burden of headache. The aim of this study is to provide a comprehensive description of the pooled prevalence of comorbidities of primary headache disorders using a meta-analytical approach based on studies published between 2000 and 2020. Methods Scopus was searched for primary research (clinical and population studies) in which medical comorbidities were described in adults with primary headache disorders. Comorbidities were extracted using a taxonomy derived from the Global Burden of Disease (GBD) study. We compared prevalence of comorbidities among headache sufferers against general population using GBD-2019 estimates, and compared comorbidities’ proportions in clinical vs. population studies, and by age and gender. Results A total of 139 studies reporting information on 4.19 million subjects with primary headaches were included: in total 2.75 million comorbidities were reported (median per subject 0.64, interquartile range 0.32–1.07). The most frequently addressed comorbidities were: depressive disorders, addressed in 51 studies (pooled proportion 23 %, 95 % CI 20–26 %); hypertension, addressed in 48 studies (pooled proportion 24 %, 95 % CI 22–26 %); anxiety disorders addressed in 40 studies (pooled proportion 25 %, 95 % CI 22–28 %). For conditions such as anxiety, depression and back pain, prevalence among headache sufferers was higher than in GBD-2109 estimates. Associations with average age and female prevalence within studies showed that hypertension was more frequent in studies with higher age and less females, whereas fibromyalgia, restless leg syndrome, and depressive disorders were more frequent in studies with younger age and more female. Conclusions Some of the most relevant comorbidities of primary headache disorders – back pain, anxiety and depression, diabetes, ischemic heart disease and stroke – are among the most burdensome conditions, together with headache themselves, according to the GBD study. A joint treatment of headaches and of these comorbidities may positively impact on headache sufferers’ health status and contribute to reduce the impact of a group of highly burdensome diseases.

scholarly journals Primary headache disorders

2019 ◽  
Vol 9 (3) ◽  
pp. 233-240 ◽  
Author(s):  
Peter J. Goadsby
Keyword(s):  
Cluster Headache ◽  
Nerve Stimulation ◽  
Controlled Trial ◽  
Preventive Treatment ◽  
Primary Headache ◽  
Migraine Treatment ◽  
Headache Disorders ◽  
Primary Headache Disorders ◽  
Trigeminal Nerve Stimulation ◽  
Episodic Cluster Headache

Purpose of reviewTo review 5 new areas in primary headache disorders, especially migraine and cluster headache.Recent findingsCalcitonin gene-related peptide (CGRP) receptor antagonists (gepants—rimegepant and ubrogepant) and serotonin 5-HT1F receptor agonists (ditans—lasmiditan) have completed phase 3 clinical trials and will soon offer novel, effective, well-tolerated nonvasoconstrictor options to treat acute migraine. CGRP preventive treatment is being revolutionized after the licensing of 3 monoclonal antibodies (MABs), erenumab, fremanezumab, and galcanezumab, with eptinezumab to follow, especially designed for migraine; they are effective and well tolerated. For patients seeking a nondrug therapy, neuromodulation approaches, single-pulse transcranial magnetic stimulation, noninvasive vagus nerve stimulation (nVNS), and external trigeminal nerve stimulation, represent licensed, well-tolerated approaches to migraine treatment. For the acute treatment of episodic cluster headache, nVNS is effective, well tolerated, and licensed; nVNS is effective and well tolerated in preventive treatment of cluster headache. The CGRP MAB galcanezumab was effective and well tolerated in a placebo-controlled trial in the preventive treatment of episodic cluster headache. Sphenopalatine ganglion stimulation has been shown to be effective and well tolerated in 2 randomized sham-controlled studies on chronic cluster headache. Understanding the premonitory (prodromal) phase of migraine during which patients experience symptoms such as yawning, tiredness, cognitive dysfunction, and food cravings may help explain apparent migraine triggers in some patients, thus offering better self-management.SummaryHeadache medicine has made remarkable strides, particularly in understanding migraine and cluster headache in the past 5 years. For the most common reason to visit a neurologist, therapeutic advances offer patients reduced disability and neurologists a rewarding, key role in improving the lives of those with migraine and cluster headache.

scholarly journals Osmophobia in primary headache patients: associated symptoms and response to preventive treatments

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Marianna Delussi ◽  
Anna Laporta ◽  
Ilaria Fraccalvieri ◽  
Marina de Tommaso
Keyword(s):  
Cluster Headache ◽  
Rating Scale ◽  
Preventive Treatment ◽  
Primary Headache ◽  
Tension Type Headache ◽  
Primary Headaches ◽  
Self Rating ◽  
Type Headache ◽  
Headache Center ◽  
Headache Patients

Abstract Background Osmophobia, is common among primary headaches, with prevalence of migraine. The study aimed to evaluate prevalence and clinical characteristics of patients with osmophobia in a cohort of primary headache patients selected at a tertiary headache center. The second aim was to verify the possible predicting role of osmophobia in preventive treatment response in a sub cohort of migraine patients. Methods This was an observational retrospective cohort study based on data collected in a tertiary headache center. We selected patients aged 18–65 years, diagnosed as migraine without aura (MO), migraine with aura (MA) or Chronic Migraine (CM), Tension-Type Headache (TTH); and Cluster Headache (CH). We also selected a sub-cohort of migraine patients who were prescribed preventive treatment, according to Italian Guidelines, visited after 3 months follow up. Patients were considered osmophobic, if reported this symptom in at least the 20% of headache episodes. Other considered variables were: headache frequeny, the migraine disability assessment (MIDAS), Allodynia Symptom Checklist, Self-rating Depression scale, Self-rating Anxiety scale, Pain intensity evaluated by Numerical Rating Scale-NRS- form 0 to 10. Results The 37,9% of patients reported osmophobia (444 patients with osmophobia, 726 without osmophobia). Osmophobia prevailed in patients with the different migraine subtypes, and was absent in patients with episodic tension type headache and cluster headache (chi square 68.7 DF 7 p < 0.0001). Headache patients with osmophobia, presented with longer hedache duration (F 4.91 p 0.027; more severe anxiety (F 7.56 0.007), depression (F 5.3 p 0.019), allodynia (F 6 p 0.014), headache intensity (F 8.67 p 0.003). Tension type headache patients with osmophobia (n° 21), presented with more frequent headache and anxiety. A total of 711 migraine patients was visited after 3 months treatment. The change of main migraine features was similar between patients with and without osmophobia. Conclusions While the present study confirmed prevalence of osmophobia in migraine patients, it also indicated its presence among chronic tension type headache cases, marking those with chronic headache and anxiety. Osmophobia was associated to symptoms of central sensitization, as allodynia. It was not relevant to predict migraine evolution after first line preventive approach.

Headache

2018 ◽  
Author(s):  
Benjamin W Friedman
Keyword(s):  
Differential Diagnosis ◽  
Clinical Characteristics ◽  
Sinus Thrombosis ◽  
International Headache Society ◽  
Primary Headache ◽  
Primary Headaches ◽  
Key Words Migraine ◽  
Secondary Headaches ◽  
Primary Headache Disorders ◽  
Greater Occipital Nerve

Headaches are one of the most common complaints of patients seen by emergency physicians. They can be classified as primary headaches, which have no identifiable underlying cause, and secondary headaches, which are classified according to their cause. The majority of headaches are benign in origin, and most patients with headache can be treated successfully in the emergency department and discharged home; however, some have potentially life-threatening causes, and consideration of a broad differential diagnosis for all patients is essential. This review covers the primary headache disorders, pathophysiology, stabilization and assessment, diagnosis and treatment, and disposition and outcomes. The figure shows areas of the brain sensitive to pain. Tables review differential diagnosis of headache, International Headache Society primary headache criteria, clinical characteristics of secondary headaches, high-risk clinical characteristics among patients with a headache peaking in intensity within 1 hour, drugs associated with headache, and parenteral treatment of acute migraine. This review contains 1 figure, 9 tables, and 58 references. Key words: migraine, calcitonin gene related peptide, greater occipital nerve block, venous sinus thrombosis, reversible cerebral vasoconstriction syndrome, Ottawa, subarachnoid, cluster headache, trigeminal autonomic cephalalgias, post-traumatic headache

The need for preventive therapy in primary headaches

2011 ◽  
pp. 46-49
Author(s):  
Mario Fernando Prieto Peres ◽  
Daniel Krempel Amado ◽  
André Leite Gonçalves ◽  
Reinaldo Ribeiro ◽  
Jorge Roberto Pagura ◽  
...  
Keyword(s):  
Preventive Treatment ◽  
Primary Headache ◽  
Preventive Therapy ◽  
Tension Type Headache ◽  
Primary Headaches ◽  
Correct Treatment ◽  
Treatment Type ◽  
Geographical Regions ◽  
Probable Migraine ◽  
Type Headache

Introduction: Primary headaches are common conditions. In Brazil, the prevalence of migraine is 15.2%, tension-type headache 13% and chronic daily headache (CDH) 6.9%. Although frequent disorders a proportion of patients are undertreated. Patients patterns of headache care can trend toward acute medication only and those in need of prevention may not receive it. Objective: To estimate the rates of preventive treatment in primary headache sufferers. Methods: A telephone interview containing questions about headache and socio-demographic characteristics was applied to 3,848 people from 27 States of Brazil, in its five geographical regions. We considered MIDAS > 10 points as a marker for the need of preventive treatment. Patients were asked if they were taking any medication on a daily basis or any treatment to prevent headaches from happening. Subjects were divided into: 1. Those who responded positively for the question regarding preventive treatment regardless of the treatment type. 2. Those who responded positively for the question, but only medications or treatments studied for migraine prevention, labeled as "Correct treatment" 3. Those who responded positively for the question, but only medications or treatments from the prevention consensus (Brazilian Headache Society), labeled as "Consensus treatment" Results: In total, 12.8% of primary headache sufferers had MIDAS higher than 10, meeting criteria for prophylactic treatment, but only 8.4% of them reported it, 3.9% were using a right preventive treatment. The percentage of patients in need for prevention was 24.7% in migraine, 15.6 % in probable migraine, 5 % for tension-type headache (TTH) and 4% for probable TTH. Only 2.6% of migraineurs, 7.5% of probable migraine patients, 4.3% of tension-type headache and 0% of probable TTH received proper preventive treatment Conclusion: Primary headaches are common, debilitating conditions but a substantial proportion of those who might need prevention do not receive it. Patient education, public health initiatives in order to deliver migraine and other primary headaches treatment for the general population should be considered not only in Brazil, but worldwide.

Headaches

2021 ◽  
pp. 329-342
Author(s):  
Andrew D. Hershey
Keyword(s):  
Early Recognition ◽  
Primary Headache ◽  
Primary Care Providers ◽  
School Nurses ◽  
Primary Headaches ◽  
Care Providers ◽  
Primary Headache Disorders ◽  
Tension Type Headaches ◽  
The Impact

This chapter discusses recurrent headaches, especially when episodic, which are much more likely to represent primary headache disorders. Primary headaches are intrinsic to the nervous system and are the disease itself. Early recognition of the primary headaches in patients should result in improved response and outcome, minimizing the impact of the primary headaches and disability. Primary headaches can be grouped into migraine, tension-type headaches, and trigeminal autonomic cephalalgia, and an additional grouping of rarer headaches without a secondary cause. The primary headache that has the greatest impact on a child’s quality of life and disability is migraine, and subsequently is the most frequent primary headache brought to the attention of parents, primary care providers, and school nurses.

Brain structure and function related to headache: Brainstem structure and function in headache

Cephalalgia ◽  
2018 ◽  
Vol 39 (13) ◽  
pp. 1635-1660 ◽  
Author(s):  
Marta Vila-Pueyo ◽  
Jan Hoffmann ◽  
Marcela Romero-Reyes ◽  
Simon Akerman
Keyword(s):  
Primary Headache ◽  
Structure And Function ◽  
Affective Processing ◽  
Primary Headaches ◽  
Headache Disorders ◽  
Primary Headache Disorders ◽  
Brain Structure And Function ◽  
And Function ◽  
The Brain

Objective To review and discuss the literature relevant to the role of brainstem structure and function in headache. Background Primary headache disorders, such as migraine and cluster headache, are considered disorders of the brain. As well as head-related pain, these headache disorders are also associated with other neurological symptoms, such as those related to sensory, homeostatic, autonomic, cognitive and affective processing that can all occur before, during or even after headache has ceased. Many imaging studies demonstrate activation in brainstem areas that appear specifically associated with headache disorders, especially migraine, which may be related to the mechanisms of many of these symptoms. This is further supported by preclinical studies, which demonstrate that modulation of specific brainstem nuclei alters sensory processing relevant to these symptoms, including headache, cranial autonomic responses and homeostatic mechanisms. Review focus This review will specifically focus on the role of brainstem structures relevant to primary headaches, including medullary, pontine, and midbrain, and describe their functional role and how they relate to mechanisms of primary headaches, especially migraine.

Primary headache and migraine in headache specialists – does personal history of doctors matter?

Cephalalgia ◽  
2019 ◽  
Vol 40 (1) ◽  
pp. 96-106 ◽  
Author(s):  
Stefan Evers ◽  
Nicole Brockmann ◽  
Oliver Summ ◽  
Ingo W Husstedt ◽  
Achim Frese
Keyword(s):  
Cluster Headache ◽  
General Practitioners ◽  
Primary Headache ◽  
Treatment Recommendations ◽  
Personal History ◽  
Self Report ◽  
Primary Headache Disorders ◽  
History Of ◽  
The Impact ◽  
Age And Sex

Objective Migraine is a common disorder affecting more than 10% of the population. The prevalence of migraine among physicians and, in particular, among headache specialists is widely unknown as is the impact of suffering from migraine on the attitudes towards migraine and on treatment recommendations of physicians. We designed a survey among headache specialists and neurologists and compared the results to general pain specialists and general practitioners. Methods A standardized interview in randomly selected samples of these four groups of physicians was performed. The interview included data on the prevalence of migraine and other primary headache disorders in the physician groups, self-report on their own treatment, attitudes towards migraine, and treatment recommendations for migraine. The prevalence rates were also compared to an age- and sex-matched German general population sample. Results The lifetime prevalence of migraine was higher in headache specialists (53.0%) than in general neurologists (43.0%), pain specialists (21.7%), general practitioners (19.3%), and in the general age- and sex-matched population (16.8%). Cluster headache prevalence was high in neurologists (1.9%) and in headache specialists (1.3%); episodic tension-type headache prevalence was significantly lower in general practitioners (19.5%). One reason, among others, was that being a migraine (or cluster headache) patient more often prompted the sufferers to become a specialist in neurology. Physicians with migraine rated the biopsychosocial concept of lower importance for migraine than did physicians without migraine. The self-treatment of migraine in physicians differs from the treatment recommendations to the patients. For example, only 36.4% of the headache specialists with migraine take triptans whereas 94.4% recommend triptans to their patients. Conclusions We conclude that being a headache specialist or a neurologist is associated with an increased migraine or cluster headache prevalence. This personal history of migraine leads to a more somatic view of migraine as a disorder and to different treatment recommendations as compared to self-treatment.

Pharmacotherapy Options for the Management of Cluster Headache

2013 ◽  
Vol 5 ◽  
pp. CMT.S10251 ◽  
Author(s):  
Jared L. Pomeroy ◽  
Michael J. Marmura
Keyword(s):  
Adverse Events ◽  
Cluster Headache ◽  
Preventive Treatment ◽  
Primary Headache ◽  
Good Evidence ◽  
Unilateral Headache ◽  
Acute Medication ◽  
Subcutaneous Sumatriptan ◽  
Zolmitriptan Nasal Spray ◽  
Effective Medication

Cluster headache is a primary headache syndrome characterized by attacks of severe unilateral headache typically lasting 30 to 180 minutes without treatment and prominent autonomic symptoms on the affected side. Often attacks occur in cycles lasting weeks to months with up to 8 attacks per day, and a minority of individuals continue to experience attacks throughout the year. Persons with cluster headache usually require both acute medication for attacks and preventive treatment to keep the headaches from occurring. Subcutaneous sumatriptan is the most effective medication for acute cluster attacks, but other triptans such as zolmitriptan nasal spray are also effective. inhaling 100% oxygen is also effective and is a useful treatment for those with frequent attacks or contraindications to triptans. Corticosteroids are among the most effective transitional treatments, typically used at the start of a cycle. Dihydroergotamine is an effective treatment for refractory or severe cluster headache with multiple attacks requiring large triptan doses. Verapamil and lithium are among the most effective preventive medications with good evidence of effectiveness, but other studies support the use of gabapentin, topiramate, diavalproex sodium, and methysergide, to name a few. Each of these medications requires monitoring for adverse events and can be discontinued within a few weeks of a cluster headache cycle.

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