Symptomatic pharmacotherapy of migraine.

This review summarizes data on the effectiveness of various symptomatic migraine pharmacotherapies and makes recommendations for treatment. A wide variety of agents are available for the symptomatic treatment of migraine headache, including over-the-counter analgesics, nonsteroidal anti-inflammatory drugs (NSAIDs), combination products, opiates, ergot alkaloids, corticosteroids, dopamine antagonists, and triptans. In the stepped-care approach, simple analgesics and NSAIDs are the recommended first step for the treatment of mild-to-moderate migraine headaches. Patients who do not respond to first-step treatments may be given ergots, combination products, dopamine antagonists, or triptans as the second step. Corticosteroids or opiates may be used as rescue treatment in patients who do not respond to second-step treatment. A stratified approach to care individualizes treatment based on the severity of the headache and other patient-specific factors. In a stratified approach, dihydroergotamine or triptans may be the first-step treatment for patients who present with a history of severe migraines that have responded poorly to previous treatments. Sumatriptan was the first triptan approved for the symptomatic treatment of migraine headache; newer triptans include zolmitriptan, naratriptan, and rizatriptan. Since sumatriptan is rapidly absorbed by the subcutaneous route, its time to onset of effect is shortest. Among triptan drugs that are administered orally, the relative time to onset may be shorter with rizatriptan than sumatriptan. Naratriptan has a longer time to onset but is associated with a lower rate of migraine recurrence than other triptans. graine headache, ergot alkaloids, triptans,     

Drug-induced refractory headache

Two hundred patients who were taking daily symptomatic or immediate relief medications, often in excessive quantities, yet suffering from daily or near daily severe headaches were studied. One hundred and sixteen (58%) of them were also taking concomitant prophylactic medications and they were ineffective. Low-tyramine, low-caffeine dietary instructions and biofeedback training were given to all patients. The effect of continuing symptomatic medications, discontinuing symptomatic medications, and adding or changing prophylactic medications were studied in the various treatment groups. It is concluded that: (1) daily use of symptomatic or immediate relief medications results in chronic daily headache; (2) discontinuing daily symptomatic medication itself results in improvement of headache; (3) concomitant use of symptomatic medications nullifies the effect of prophylactic medications; (4) discontinuing daily symptomatic medications enhances the beneficial effect of prophylactic medications.     

Pharmacological treatment of attacks in juvenile migraine

Although migraine is a common complaint in childhood and adolescence, there is a lack of controlled clinical studies regarding treatment. In the young patient, the pharmacological approach should be preceded by setting up non-pharmacological measures which include behavioural intervention. The sole use of symptomatic therapies should be limited to patients who complain of up to four partially or totally disabling attacks, or those who suffer from headache for more than 4 days per month. The therapeutic armamentarium includes non-specific symptomatic drugs, such as analgesics and non-steroidal anti-inflammatory drugs (NSAIDs), as well as anti-emetics and specific drugs, such as the triptans. Analgesics and NSAIDs are the most frequently used drugs in childhood and adolescence for the symptomatic treatment of migraine attacks of slight or moderate intensity. The first-choice drug for those under 12 years of age is acetaminophen. Among NSAIDs, two double-blind, randomized, placebo-controlled studies were conducted for ibuprofen, supporting its efficacy. In the past, ergot derivatives played an important role in the treatment of spontaneous migraine attacks, particularly in adults, but after the triptan revolution their role was strongly confined to a small number of patients. Although they are considered first-choice drugs for moderate and severe migraine attacks in adults, triptans are still under study in migraine patients under 18 years of age. The Health Ministry rules do not approve their use in patients under 18 years. They can only be given legally if the therapeutic plan for their use is previously approved by the Ethics Committee and after informed consent from the patient/parents. Promising results have been obtained, particularly for sumatriptan in nasal spray formulation as well as for zolmitriptan and rizatriptan, showing a high tolerability and safety profile.     

Combined pharmacological and short-term psychodynamic psychotherapy for probable medication overuse headache: a pilot study

We studied the effects of short-term psychodynamic psychotherapy (STPP) and pharmacological therapy in 26 consecutive patients with probable medication overuse headache (pMOH). Patients underwent a standard in-patient detoxification protocol, lasting a mean of 7 days. Eleven patients overused non-steroidal anti-inflammatory drugs (NSAIDs), five a combination of NSAIDs and triptans, four triptans, four a combination of NSAIDs, and three triptans and ergot derivates. Preventive therapy was initiated during detoxification. The STPP protocol comprised the Brief Psychodynamic Investigation (BPI) and psychoanalysis-inspired psychotherapy. All patients (groups A and B) underwent the BPI and pharmacological therapy. Half of the patients (group B) also not randomly underwent psychoanalysis-inspired psychotherapy. We found a significant interaction between time and group for headache frequency and medication intake. At 12-month follow-up, a statistically greater decrease in headache frequency and medication intake was observed in group B than in group A ( P  = 0.0108 and P  = 0.0097, respectively). The relapse rate was much lower in group B patients at both 6 and 12 months [15.3%, odds ratio (OR) 0.11, P  = 0.016, and 23%, OR 0.18, P  = 0.047, respectively] than in group A. The risk of developing chronic migraine (CM) during follow-up was higher in group A than in group B at 6 (OR 2.0, P  = 0.047) and 12 months (OR 2.75, P  = 0.005). Our study suggests that STPP in conjunction with drug withdrawal and prophylactic pharmacotherapy relieves headache symptoms in pMOH, reducing both long-term relapses and the burden of CM.     

Drug Induced Refractory Headache - Clinical Features and Management

Two hundred patients who were taking daily symptomatic or immediate relief medications, often in excessive quantities, yet suffering from daily or near daily severe headaches were studied. One hundred and sixteen (58%) of them were also taking concomitant prophylactic medications and they were ineffective. Low tyramine, low caffeine dietary instructions and biofeedback training were given to all patients. The effect of continuing symptomatic medications, discontinuing symptomatic medications, and adding or changing prophylactic medications were studied in the various treatment groups. It is concluded that; 1.) Daily use of symptomatic or immediate relief medications result in chronic daily headache. 2.) Discontinuing daily symptomatic medications itself result in improvement of headache. 3.) Concomitant use of symptomatic medications nullifies the effect of prophylactic medications. 4.) Discontinuing daily symptomatic medications enhances the beneficial effect of prophylactic medications.     

Acute Migraine Treatment in Adults

There are many options for acute migraine attack treatment, but none is ideal for all patients. This study aims to review current medical office‐based acute migraine therapy in adults and provides readers with an organized approach to this important facet of migraine treatment. A general literature review includes a review of several recent published guidelines. Acetaminophen, 4 nonsteroidal anti‐inflammatory drugs (NSAIDs) (ibuprofen, acetylsalicylic acid [ASA], naproxen sodium, and diclofenac potassium), and 7 triptans (almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan, and zolmitriptan) have good evidence for efficacy and form the core of acute migraine treatment. NSAID–triptan combinations, dihydroergotamine, non‐opioid combination analgesics (acetaminophen, ASA, and caffeine), and several anti‐emetics (metoclopramide, domperidone, and prochlorperazine) are additional evidence‐based options. Opioid containing combination analgesics may be helpful in specific patients, but should not be used routinely. Clinical features to be considered when choosing an acute migraine medication include usual headache intensity, usual rapidity of pain intensity increase, nausea, vomiting, degree of disability, patient response to previously used medications, history of headache recurrence with previous attacks, and the presence of contraindications to specific acute medications. Available acute medications can be organized into 4 treatment strategies, including a strategy for attacks of mild to moderate severity (strategy one: acetaminophen and/or NSAIDs), a triptan strategy for patients with severe attacks and for attacks not responding to strategy one, a refractory attack strategy, and a strategy for patients with contraindications to vasoconstricting drugs. Acute treatment of migraine attacks during pregnancy, lactation, and for patients with chronic migraine is also discussed. In chronic migraine, it is particularly important that medication overuse is eliminated or avoided. Migraine treatment is complex, and treatment must be individualized and tailored to the patient's clinical features. Clinicians should make full use of available medications and formulations in an organized approach.     

Management of the acute migraine headache

As many as 30 million Americans have migraine headaches. The impact on patients and their families can be tremendous, and treatment of migraines can present diagnostic and therapeutic challenges for family physicians. Abortive treatment options include nonspecific and migraine-specific therapy. Nonspecific therapies include analgesics (aspirin, nonsteroidal anti-inflammatory drugs, and opiates), adjunctive therapies (antiemetics and sedatives), and other nonspecific medications (intranasal lidocaine or steroids). Migraine-specific abortive therapies include ergotamine and its derivatives, and triptans. Complementary and alternative therapies can also be used to abort the headache or enhance the efficacy of another therapeutic modality. Treatment choices for acute migraine should be based on headache severity, migraine frequency, associated symptoms, and comorbidities.     

Acute treatment of headache

Effective acute treatment of headache begins with making an accurate diagnosis and ruling out secondary causes of headache. Once a primary headache is diagnosed, it is important to choose the right combination of behavioural therapy and acute care (abortive and symptomatic) therapy for each patient. Some patients may need preventive medication on a daily basis. If patients overuse acute medications and develop medication overuse headache (previously called analgesic rebound headache), they often seek medical attention due to the chronicity and/or intensity of their pain and resultant disability. For acute care of migraine, physicians should choose a triptan they know and expect to work. They should prescribe the dose and route of administration that will provide the most rapid and complete response to all the associated symptoms of migraine, in addition to the pain. The effectiveness of the 7 available triptans in early, double-blind, controlled trials is more similar than different. How and when to give them will be discussed. Treatment of cluster headache will be presented briefly.     

Overview of diagnosis and management of paediatric headache. Part II: therapeutic management

A thorough evaluation of headache in children and adolescents is necessary to make the correct diagnosis and initiate treatment. In part 1 of this article (Özge et al. in J Headache Pain, 2010), we reviewed the diagnosis of headache in children and adolescents. In the present part, we will discuss therapeutic management of primary headaches. An appropriate management requires an individually tailored strategy giving due consideration to both non-pharmacological and pharmacological measures. Non-pharmacological treatments include relaxation training, biofeedback training, cognitive-behavioural therapy, different psychotherapeutic approaches or combinations of these treatments. The data supporting the effectiveness of these therapies are less clear-cut in children than in adults, but that is also true for the data supporting medical treatment. Management of migraine and TTH should include strategies relating to daily living activities, family relationships, school, friends and leisure time activities. In the pharmacological treatment age and gender of children, headache diagnosis, comorbidities and side effects of medication must be considered. The goal of symptomatic treatment should be a quick response with return to normal activity and without relapse. The drug should be taken as early as possible and in the appropriate dosage. Supplementary measures such as rest in a quiet, darkened room is recommended. Pharmaco-prophylaxis is only indicated if lifestyle modification and non-pharmacological prophylaxis alone are not effective. Although many prophylactic medications have been tried in paediatric migraine, there are only a few medications that have been studied in controlled trials. Multidisciplinary treatment is an effective strategy for children and adolescents with improvement of multiple outcome variants including frequency and severity of headache and school days missed because of headache. As a growing problem both children and families should be informed about medication overuse and the children’s drug-taking should be checked.     

Acute migraine medications and evolution from episodic to chronic migraine: a longitudinal population-based study

Background.— Though symptomatic medication overuse is believed to play a major role in progression from episodic to chronic or transformed migraine (TM), population‐based longitudinal data on these agents are limited. Objectives.— To assess the role of specific classes of acute medications in the development of TM in episodic migraine (EM) sufferers after adjusting for other risk factors for headache progression. Methods.— As a part of the American Migraine Prevalence and Prevention study (AMPP), we initially surveyed a population sample of 120,000 individuals to identify a sample of migraineurs to be followed annually over 5 years. Using logistic and linear regression, we modeled the probability of transition from EM in 2005 to TM in 2006 in relation to medication use status at baseline. Adjustments were made for gender, headache frequency and severity, and prevention medication use. Results.— Of 8219 individuals with EM in 2005, 209 (2.5%) had developed TM by 2006. Baseline headache frequency was a risk factor for TM. Using acetaminophen user as the reference group, individuals who used medications containing barbiturates (OR = 2.06, 95%CI = 1.3‐3.1) or opiates (OR = 1.98, 95%CI = 1.4‐2.2) were at increased risk of TM. A dose–response relationship was found for use of barbiturates. Use of triptans (OR = 1.25, 95%CI = 0.9‐1.7) at baseline was not associated with prospective risk of TM. Overall, NSAIDs (OR = 0.85, 95%CI = 0.63‐1.17) were not associated with TM. Indeed, NSAIDs were protective against transition to TM at low to moderate monthly headache days, but were associated with increased risk of transition to TM at high levels of monthly headache days. Conclusion.— EM sufferers develop TM at the rate of 2.5% per year. Any use of barbiturates and opiates was associated with increased risk of TM after adjusting for covariates, while triptans were not. NSAIDs were protective or inducers depending on the headache frequency.     

Chronic daily headache in a primary care population: prevalence and headache impact test scores

BACKGROUND: Population-based surveys estimate the prevalence of chronic daily headache (CDH) in the general community to be approximately 4%. The prevalence of CDH among patients seen in the primary care setting in the United States, however, is unknown. PURPOSE: To estimate the prevalence and associated burden of suffering of CDH in a primary care patient population. METHODS: Cross-sectional survey of a randomly selected sample of 1500 adult patients in an academic Family Medicine Center was done. Outcome measures include self-reported headache frequency and Headache Impact Test scores. RESULTS: Completed questionnaires were returned by 853 (57%) patients. The mean age of respondents was 49 years (SD = 16), with a range of 18 to 94 years. Two hundred ninety-six (58%) patients reported having had 1 or more severe headaches in the past month. Seventy-four (9%) patients reported a frequency of headache consistent with CDH, defined as the occurrence of headache 15 or more days in the past month. Twenty-four patients (32%) with CDH either believed that none of their doctors know that they experienced headaches or were not sure if their doctors were aware of their headaches, and 21 (28%) reported that they have not needed a doctor's care for their headaches. CONCLUSIONS: The prevalence of CDH is greater among a primary care patient population compared to the general community. A substantial proportion of patients with CDH do not bring their headaches to the attention of their health-care providers. In light of the advances in the development of effective medications for migraines and the growing body of evidence implicating medications as a contributing cause of CDH, it may be appropriate to encourage patients to inform their health-care providers about their headaches and to encourage providers to identify patients with frequent headaches.     

Characteristics,impact and treatment of 6000 headache attacks: The PAMINA study

The aim of this study was to prospectively evaluate the characteristics of headache attacks, their impact on daily activities as well as the type and efficacy of acute medication in patients with migraine. We included 281 patients with episodic migraine (87% females, aged 41.2±12.1). All patients kept a headache diary for 3 months covering headache characteristics, therapy and questions adopted from the Headache Impact Test (HIT‐6) for rating the impact of each single headache attack (HIT‐6 s). For evaluating the efficacy of acute medication we compared triptans with other compounds using headache duration as outcome parameter. Of 6051 headache attacks 52.8% fulfilled the ICHD‐II criteria of migraine. The HIT‐6 s score was 2.4±2.2 (range 0–6). It was lowest in untreated headaches (2.0±2.1) and highest in those treated with a combination of triptans and other compounds (4.1±2.0, p <0.001). Patients used triptans on 8.0% of all headache days, other compounds on 33.1%, a combination of both on 1.5% and no medication on 57.3% of the headache days. Migraine attacks of moderate or severe intensity treated with triptans alone lasted significantly shorter than those treated with other compounds (5.1±3.6 vs. 6.9±5.3 h, p <0.001). In conclusion, almost 50% of the headaches occurring in patients with migraine do not fulfill migraine criteria. Use of triptans is associated with a shorter duration of moderate and severe migraine attacks compared to use of other compounds.     

Transformed or Evolutive Migraine

SYNOPSIS
630 (39%) of 1600 patients seen in a Headache Clinic over a three year period had chronic daily headaches (CDH). In 78% of these CDH patients, the daily headaches evolved out of a prior history of episodic migraine; these patients we designate as having "transformed" or "evolutive" migraine. The other 12% had migraine headaches which were daily from the start.
Patients with transformed migraine, in contrast to those with daily headaches from the start, have a significantly higher incidence of positive family history of migraine, menstrual aggravation of migraine, identifiable trigger factors, associated G.I. and neurological symptoms, and early morning awakening with headache.
The CDH group in general over-used symptomatic medication and exhibited abnormalities on behavioral scale testing. Withdrawal of daily symptomatic medication, institution of a low tyramine low caffeine diet, initiation of prophylactic anti-migraine therapy, and biofeedback and behavioral therapy, gave worthwhile improvement in 76% of chronic daily headache patients.
Factors which promote "evolution" of migraine from intermittent to chronic daily occurrence are not well-defined but may include medication abuse, medication withdrawal, and psychiatric disturbances.     

Managing chronic headaches in the clinic

Chronic daily headache (CDH), which is often linked to a history of migraine, tension-type headache and the abuse of headache medications, and cluster headache are the best known of the chronic headaches. These headaches may not be well recognised or well treated in primary care. This article outlines the development of management algorithms for these headache subtypes, designed for use by the primary care physician with an interest in headache. Principles of care for chronic headaches include implementation of screening procedures, differential diagnosis, tailoring of management to the individual's needs, proactive follow-up and a team approach to care. These principles can be customised to the headache subtype by the selection of appropriate therapies. The optimal treatments for CDH include physical therapy to the neck if there is any stiffness there, withdrawal of abused medications and treatment of any subsequent withdrawal symptoms and headache prophylaxis, together with the provision of acute medications as rescue therapy. Optimal treatments for cluster headache include short- and long-term prophylaxis to prevent the headaches developing and acute medications for use as rescue. If treatment is ineffective, alternative medications can be provided at follow-up, with the possibility of referral for refractory patients.     

Headache induced by chronic substance use: analysis of medication overused and minimum dose required to induce headache

BACKGROUND: The International Headache Society has defined the diagnostic criteria for headache induced by substance use. Recently, a revision to these criteria has been proposed. OBJECTIVE: To consider whether the International Headache Society criteria for headache induced by substance use and the proposed revisions for the classification of daily and near-daily headache with medication abuse permit classification of patients commonly seen in a headache center. METHODS: One hundred fourteen consecutive patients (96 women [84.2%] and 18 men [15.8%]; mean age, 54.2 years [SD, 14]) with headache and chronic overuse of medications, admitted for detoxification to the inpatient unit of a headache center, participated in the study. The initial headache, medications and doses used, duration of daily medication use, and means of medication administration were studied. RESULTS: Eighty-one patients (71%) had an initial headache of migraine without aura, 13 patients (11.4%) had migraine without aura and coexistent tension-type headache, 11 (9.7%) patients had migraine with and without aura, and 9 patients (7.9%) had episodic tension-type headache. Medications overused by patients included analgesics combined with barbiturates or other nonnarcotic substances in 39.5%, simple analgesics in 38.6%, triptans in 11.4%, and ergotamine in 10.5%. Using the International Headache Society diagnostic criteria, we were able to classify only 28.1% of our patients; the proposed revised criteria for daily and near-daily headaches with medication abuse permitted the classification of 46.4% of patients. CONCLUSION: The minimum dose of medication required to induce chronic headache should be revised because a high proportion of patients are not classifiable using either the International Headache Society diagnostic criteria or the revised criteria recently proposed. A more comprehensive definition for the required minimum dose might be used. Triptan abuse can cause chronic headache and should be included in the International Headache Society classification.     

The role of triptans and analgesics for primary headache treatment

Primary headache especially migraine is very common disorder. The mainstay in the acute treatment of migraine is triptans (sumatriptan, zolmitriptan, eletriptan, naratriptan) and analgesics or NSAIDs. However, it is still unclear the appropriate usage of triptans and analgesics or NSAIDs for migraine treatment. Mild attacks may be managed with analgesics or NSAIDs while severe disabling ones usually respond better to specific antimigraine drugs, triptans. Analgesics or NSAIDs administration is always plagued with the potential of subsequent drug induced headache phenomenon. Therefore usage of analgesics or NSAIDs should be restricted only for young and typical type patients with migraine. As triptan medication method corresponding to various life style, in addition to tablet formulation, there are subcutaneous injector and nasal spray formulation in sumatriptan, rapid melt tablet formulation in zolmitriptan (rapimelt) and naratriptan (rapidisk). These different type of formulation are valuable for patient's needs.     

Epidemiology of chronic daily headache

Daily or near-daily headache is a widespread problem in clinical practice. The general term of chronic daily headache (CDH) encompasses those primary headaches presenting more than 15 days per month and lasting more than 4 hours per day. CDH includes transformed migraine (TM), chronic tension-type headache (CTTH), new daily persistent headache (NDPH), and hemicrania continua (HC). Around 40% of patients attending a specialized headache clinic meet CDH diagnostic criteria, of which 80% are women. In these clinics about 60% of patients suffer from TM, 20% from CTTH, and 20% meet NDPH criteria. Most, some 80%, overuse symptomatic medications. One should be very cautious on extrapolating these numbers to the general population. CDH prevalence in the general population seems to be around 4% to 5% (up to 8% to 9% for women). Regarding the prevalence of CDH subtypes, NDPH is rare (0.1%), whereas the prevalence of TM (1.5% to 2%) and CTTH (2.5% to 3%) is clearly higher. In contrast to data from specialized clinics, only around a quarter of CDH subjects in the general population overuse analgesics; the prevalence of CDH subjects with analgesic overuse being 1.1% to 1.9% of the general population. Most of these patients with analgesic overuse are TM patients.     

Efficacy and safety of levetiracetam in pediatric migraine

BACKGROUND: Headache is a frequent occurrence among children and adolescents. Chronic headaches can be severe and disabling, and require prophylactic treatment; however, additional data on the use of prophylactic medications for migraine in children are needed. OBJECTIVE: To review the efficacy and safety of levetiracetam (Keppra) in pediatric patients with a history of recurrent headache. DESIGN/METHODS: Data from 19 pediatric patients were retrospectively reviewed. The initial dose of levetiracetam was usually 125 or 250 mg twice daily, but varied depending upon clinical judgment. RESULTS: Charts of 9 girls and 10 boys (mean age, 11.9 years) were reviewed. A variety of medications, including triptans, had been used before initiating treatment with levetiracetam. Mean headache frequency before treatment was 6.3 per month (standard deviation [SD], 3.8; confidence interval [CI], 4.4 to 8.1). Duration of headaches ranged from 0.25 to 8 years. Migraine (63.2%) and migraine with aura (15.8%) were the most common types of headache reported. Most patients (89.5%) had headaches that were severe. After treatment, the mean headache frequency decreased to 1.7 per month (SD, 2.7; CI, 0.4 to 3.0), representing a reduction compared with baseline (P <.0001). Levetiracetam eliminated headaches in 10 patients (52.6%), and 7 patients (36.8%) had less severe and less frequent headaches. Levetiracetam did not have an effect on headaches in 2 patients (10.5%). Mean duration of treatment with levetiracetam was 4.1 months. Doses ranged from 125 to 750 mg twice daily. Sixteen patients (84.2%) reported no side effects on levetiracetam. One patient experienced asthenia/somnolence and dizziness, and irritable, hyperactive, and hostile behavior led to discontinuation of levetiracetam in another patient. A third patient experienced irritability and moodiness that attenuated after 1 month of treatment and did not require discontinuation. CONCLUSIONS: In this small retrospective review, levetiracetam was found to be generally well tolerated and appears to be a promising candidate for additional evaluation in well-controlled clinical trials of pediatric patients with migraine.     

Management of Chronic Daily Headache: Challenges in Clinical Practice

Chronic daily headache (CHD) refers to a category of headache disorders that are characterized by headaches occurring on more than 15 days per month. This category is subdivided into long- and short-duration (>4 or <4 hours) CDH disorders based on the duration of individual headache attacks. Examples of long-duration CDH include transformed migraine (TM), chronic migraine (CM), new daily persistent headache (NDPH), acute medication overuse headache, and hemicrania continua (HC). The goal of this review is to enable clinicians to accurately diagnose and effectively manage patients with long-duration CDH. Patients with CDH often require an aggressive and comprehensive treatment approach that includes a combination of acute and preventive medications, as well as nondrug therapies.     

Proteomic analysis of urine in medication-overuse headache patients: possible relation with renal damages

Medication-overuse headache (MOH) is a chronic disorder associated with overuse of analgesic drugs, triptans, non-steroidal anti-inflammatory drugs (NSAIDs) or other acute headache compounds. Various epidemiologic investigations proved that different drug types could cause nephrotoxicity, particularly in chronic patients. The aim of the present work was to analyze, by a proteomic approach, the urinary protein profiles of MOH patients focusing on daily use of NSAIDs, mixtures and triptans that could reasonably be related to potential renal damage. We selected 43 MOH patients overusing triptans (n = 18), NSAIDs (n = 11), and mixtures (n = 14), for 2–30 years with a mean daily analgesic intake of 1.5 ± 0.9 doses, and a control group composed of 16 healthy volunteers. Urine proteins were analyzed by mono-dimensional gel electrophoresis and identified by mass spectrometry analysis. Comparing the proteomic profiles of patients and controls, we found a significantly different protein expression, especially in the NSAIDs group, in which seven proteins resulted over-secreted from kidney (OR = 49, 95% CI 2.53–948.67 vs. controls; OR = 11.6, 95% CI 0.92–147.57 vs. triptans and mixtures groups). Six of these proteins (uromodulin, α-1-microglobulin, zinc-α-2-glycoprotein, cystatin C, Ig-kappa-chain, and inter-α-trypsin heavy chain H4) were strongly correlated with various forms of kidney disorders. Otherwise, in mixtures and in triptans abusers, only three proteins were potentially associated to pathological conditions (OR = 4.2, 95% CI 0.33–53.12, vs. controls). In conclusion, this preliminary proteomic study allowed us to define the urinary protein pattern of MOH patients that is related to the abused drug. According with the obtained results, we believe that the risk of nephrotoxicity should be considered particularly in MOH patients who abuse of NSAIDs.