Migraine and epilepsy are fundamentally distinct disorders that can frequently coexist in the same patient. These two conditions significantly differ in diagnosis and therapy but share some widely- used preventive treatments. Antiseizure medications (ASMs) are the mainstay of therapy for epilepsy, and about thirty different ASMs are available to date. ASMs are widely prescribed for other neurological and non-neurological conditions, including migraine. However, only topiramate and valproic acid/valproate currently have an indication for migraine prophylaxis supported by high-quality evidence. Although without specifically approved indications and with a low level of evidence or recommendation, several other ASMs are used for migraine prophylaxis. Understanding ASM antimigraine mechanisms, including their ability to affect the pro-migraine calcitonin gene-related peptide (CGRP) signaling pathway and other pathways, may be instrumental in identifying the specific targets of their antimigraine efficacy and may increase awareness of the neurobiological differences between epilepsy and migraine. Several new ASMs are under clinical testing or have been approved for epilepsy in recent years, providing novel potential drugs for migraine prevention to enrich the treatment armamentarium and drugs that inhibit the CGRP pathway.

The aim of this review is to aid in decision-making when choosing safe and effective options for preventive migraine medications.

In Part 2, we have compiled clinically relevant safety considerations for commonly used migraine prophylactic treatments. Preventive treatment of episodic migraine includes nonspecific and migraine-specific drugs. While medications from several pharmacological classes-such as anticonvulsants, beta-blockers, and antidepressants-have an established efficacy in migraine prevention, they are associated with a number of side effects. The safety of migraine-specific treatments such as anti-CGRP monoclonal antibodies and gepants are also discussed. This review highlights safety concerns of commonly used migraine prophylactic agents and offers suggestions on how to mitigate those risks.

To compare the efficacy and tolerability of combination treatment of topiramate and greater occipital nerve block to topiramate monotherapy in adult chronic migraine patients.

Options for the preventive treatment of chronic migraine are limited and costly. Combination treatments do not have an evidence base yet.

This was a parallel group, 3 arms with 1:1:1 allocation ratio randomized controlled study in consecutive adult chronic migraine patients attending Headache Clinic in a tertiary care hospital. Patients received either topiramate monotherapy 100 mg/day (group A), or topiramate plus greater occipital nerve block with 40 mg lidocaine (2%) and 80mg (2 ml) methylprednisolone as the first injection followed by monthly injections of lidocaine for the next 2 months (group B) or topiramate plus greater occipital nerve block with 40 mg lidocaine (2%) injections monthly for 3 months (group C). The primary endpoint was the mean change in monthly migraine days at Month 3. Multiple secondary endpoints were assessed that included among others, achievement of ≥50% reduction in mean monthly headache days compared to baseline at Month 3 and assessment for any adverse events.

One hundred and twenty-five patients were randomized; 41 to group A, 44 to group B, and 40 to group C. Efficacy assessments were done for 121 patients. Patients receiving combination treatment of topiramate and greater occipital nerve block with steroids and lidocaine and greater occipital nerve block with only lidocaine compared to topiramate monotherapy showed greater reductions in monthly migraine days at Month 3 (-9.6 vs -7.3 days; p = 0.003) and (-10.1 vs -7.3 days; p < 0.001) respectively. Greater proportion of patients in both the combination treatment groups (added greater occipital nerve block with and without steroid) achieved ≥50% reduction in mean monthly headache days [71.4% vs 39%; OR (95% CI) 3.9(1.6-9.8); p = 0.004] and [62.4% vs 39%; OR (95% CI) 2.7(1.1-6.7); p = 0.034] respectively, compared to those receiving topiramate monotherapy. Adverse effects between the groups were comparable although patients receiving combination treatment with added greater occipital nerve block reported transient adverse effects like post-injection dizziness, local site swelling, and pain. No serious adverse event was reported.

Combination treatments of topiramate with monthly injections of greater occipital nerve block were more effective in reducing monthly migraine days in chronic migraine than topiramate monotherapy at Month 3. Combination treatments were well tolerated.

Since the recognition of angiotensin-converting enzyme inhibitors (ACEIs)-induced cough, drug has been considered as a potential cause of chronic cough. This review presents recent knowledge on drug-induced coughs in patients with chronic cough. The focus is placed on ACEIs, for which there are a multitude of studies documenting their associations with cough. Additional drugs are discussed for which there are reports of cough as a side effect of treatment, and the potential mechanisms of these effects are discussed.

Examine clinical profile of extended-release topiramate (Trokendi XR^®) and compare treatment-emergent adverse events (TEAEs) associated with Trokendi XR versus previous immediate-release topiramate (TPM-IR) treatment.

Pilot retrospective study analyzing data extracted from medical charts of patients ≥6 years of age prescribed Trokendi XR.

Trokendi XR was the most commonly used to prevent migraine. The most common TEAEs recorded during topiramate treatment were cognitive symptoms (word-finding difficulty, attention/concentration difficulty, slowed thinking), paresthesia, gastrointestinal problems and decreased appetite/weight loss. TEAE incidence was significantly (p < 0.001) lower during Trokendi XR versus previous TPM-IR treatment.

Trokendi XR use and outcomes in clinical practice were consistent with established profile of topiramate. Results supported the potential for better tolerability of Trokendi XR versus TPM-IR.

Drug-induced peripheral neuropathy had been rarely reported as an adverse effect of some antiepileptic drugs (AEDs) at high cumulative doses or even within the therapeutic drug doses or levels. We describe clinical and diagnostic features of a patient with peripheral neuropathy as an adverse effect of chronic topiramate (TPM) therapy. A 37-year-old woman was presented for the control of active epilepsy (2010). She was resistant to some AEDs as mono- or combined therapies (carbamazepine, sodium valproate, levetiracetam, oxcarbazepine and lamotrigine). She has the diagnosis of frontal lobe epilepsy with secondary generalization and has a brother, sister and son with active epilepsies. She became seizure free on TPM (2013-2017) but is complaining of persistent distal lower extremities paresthesia in a stocking distribution. Neurological examination revealed presence of diminished Achilles tendon reflexes, stocking hypesthesia and delayed distal latencies, reduced conduction velocities and amplitudes of action potentials of posterior tibial and sural nerves, indicating demyelinating and axonal peripheral neuropathy of the lower extremities. After exclusion of the possible causes of peripheral neuropathy, chronic TPM therapy is suggested as the most probable cause of patient's neuropathy. This is the first case report of topiramate induced peripheral neuropathy in the literature.

Migraine is the most frequent neurological disorder observed in clinical practice characterized by moderate to severe pain attacks associated with neurological, gastrointestinal, and dysautonomic symptoms. Each year, 2.5% of patients with episodic migraine develop chronic migraine (CM). CM is characterized by high frequency of the attacks that may result into chronic intake of abortive medications. Nearly, the 70% of CM patients referring to tertiary head centers show acute pain medications overuse that may lead to the development of medication overuse headache (MOH). The management of MOH requires three steps: (1) education, (2) withdrawal of the overuse drug and detoxification, and (3) re-prophylaxis. In the last years, several real-life prospective studies provided further evidence in clinical setting of the onabotulinumtoxinA 155-195 U efficacy for the headache prophylaxis in CM with MOH patients. There is a general agreement on two factors: (1) withdrawal of the overuse drug is condicio sine qua non to reverse the pattern to medium-low-frequency migraine, and (2) the focus of management needs to shift from acute treatment of pain to prevention of headache. CM patients close to developing MOH, patients with high-frequency episodic migraine, and those already abusing of drugs require special attention and should refer to tertiary headache centers. For all of them, a solution could be an "early treatment." Early should be their referral to a tertiary headache center, early should be the withdrawal of the overuse drug and a proper detoxification, and perhaps early should be the start of a preventative therapy.

Migraine is a complex, multifactorial, neurovascular disorder of the brain. Patients frequently have pericranial trigger points, but trigger point (TP) therapy for migraine has not yet been adequately studied. In contrast, lymphatic drainage (LD) has been studied in patients with migraine. The multifactorial origin of migraine suggests using a combination of approaches such as TP therapy and lymphatic drainage. The present study evaluated the effectiveness of TP therapy alone and in combination with LD in preventing migraine during treatment period and over an 8‑week period after completion of treatment. A wait list control group served as a control group. Patients completed a headache calendar. The results of this pilot study suggest a beneficial effect for TP alone and TP combined with LD for migraine prophylaxis for 8 weeks after completion of treatment.

In evidence-based guidelines published in 2000, topiramate was a third-tier migraine preventive with no scientific evidence of efficacy; recommendation for its use reflected consensus opinion and clinical experience. Its neurostabilizing activity, coupled with its favorable weight profile, made topiramate an attractive alternative to other migraine preventives that caused weight gain. When guidelines for migraine prevention in episodic migraine were published in 2012, topiramate was included as a first-line option based on double-blind, randomized controlled trials involving nearly 3000 patients. The scientific and clinical interest in topiramate has generated a large body of data from randomized controlled trials, meta-analyses, patient registries, cohort studies, and claims data analyses that have more fully characterized its role as a migraine preventive.

This article will review the profile of topiramate that has emerged out of the past decade of research and clinical use in migraine prophylaxis. It will also address the rationale for extended-release (XR) formulations in optimizing topiramate therapy in migraine.

Topiramate has activity at multiple molecular targets, which may account for why it is effective in migraine and most other, more specific, anticonvulsants are not. Based on randomized controlled trials, topiramate reduces migraine frequency and acute medication use, improves quality of life, and reduces disability in patients with episodic migraine and in those with chronic migraine with or without medication overuse headache. Its efficacy in chronic migraine is not improved by the addition of propranolol. Topiramate's ability to prevent progression from high-frequency episodic migraine to chronic migraine remains unclear. Consistent with clinicians' perceptions, migraineurs are more sensitive to topiramate-associated side effects than patients with epilepsy. Paresthesia is a common occurrence early in treatment but is rarely cause for terminating topiramate treatment. Cognitive problems occur much less frequently than paresthesia but are more troublesome in terms of treatment discontinuation. Cognitive complaints can often be managed by slowly increasing the topiramate dose in small increments to allow habituation. As with other carbonic anhydrase inhibitors, topiramate has metabolic effects that favor the development of metabolic acidosis and possibly renal stones. Because migraineurs have an increased risk of renal stones independent of topiramate exposure, clinicians should counsel all migraine patients to maintain hydration. Abrupt onset of blurring, other visual disturbances, and/or ocular pain following topiramate's initiation should be evaluated promptly since this may indicate rare but potentially sight-threatening idiosyncratic events. Postmarketing evidence has shown that first-trimester exposure to topiramate monotherapy is associated with increased occurrence of cleft lip with or without cleft palate (Pregnancy Category D). Even though topiramate's long half-life would seemingly support q.d. dosing, randomized controlled migraine trials used b.i.d. administration of immediate-release (IR) topiramate, which has more favorable plasma concentration-time profile (ie, lower peak concentrations and higher trough concentrations) than q.d. IR dosing. Given the sensitivity of migraineurs to topiramate-related adverse events, particularly cognitive effects, pharmacokinetic profiles should be considered when optimizing migraine outcomes. The extended-release (XR) formulations Qudexy^® XR (Upsher-Smith Laboratories) and Trokendi XR^® (Supernus Pharmaceuticals) were specifically designed to achieve the adherence benefits of q.d. dosing but with more favorable (ie, more constant) steady-state plasma concentrations over the 24-hour dosing interval vs IR topiramate b.i.d. Intriguing results from a study in healthy volunteers showed consistently less impairment in neuropsychometric tests of verbal fluency and mental processing speed with an XR topiramate formulation (Trokendi XR) vs IR topiramate b.i.d. These findings suggest a pharmacodynamic effect associated with significantly reducing plasma concentration fluctuation when topiramate absorption is slowed. Results of retrospective studies in migraineurs treated with XR topiramate appear to support a clinically meaningful benefit of XR topiramate vs IR topiramate in terms of significantly fewer cognitive effects, improved adherence, and overall better outcomes of migraine prophylaxis with topiramate.

Medication-overuse headache-i.e., a too-frequent consumption of acute headache medications leading to increased headache frequency and reduced effectiveness of acute and preventive treatments-is a serious medical condition whose pathophysiology still remains incompletely known, which is reflected into a lack of mechanism-based treatments. The first mandatory step in the therapeutic strategy remains withdrawal of the abused drug, preferably abrupt, in concomitance with a detoxification pharmacological regimen to lessen withdrawal symptoms. Intravenous hydration, antiemetics, corticosteroids (prednisone), tranquilizers (benzodiazepine), neuroleptics, and rescue medication (another analgesic than the overused) should be delivered in various combinations, on an inpatient (hospitalization and day hospital) basis or outpatient basis, depending on the characteristics of the specific patient and type of overuse. Inpatient withdrawal should be preferred in barbiturate and opioid overuse, in concomitant depression, or, in general, in patients who have difficulty in stopping the overused medication as outpatients. In contrast, in overuse limited to simple analgesics in highly motivated patients, without high levels of depression and/or anxiety, home detoxification should be chosen. Re-prophylaxis should immediately follow detoxification, ideally with local injections of onabotulinumtoxinA every 3 months or topiramate orally for at least 3 months. Adequate information to patients about the risks of a too-frequent consumption of symptomatic headache medications is essential and should constantly parallel treatment to help preventing relapse after detoxification and re-prophylaxis.

We report a 49-year-old female migraineur who experienced paradoxical hyperphagia and concurrent intrusive food thoughts leading to rapid weight gain and a substantial increase in waist circumference. A significant reduction in migraine frequency was also observed during topiramate treatment, a widely used migraine prophylactic agent which is generally associated with weight loss. Withdrawal of topiramate saw appetite return to baseline levels, however, migraine frequency was again increased. Topiramate was reinitiated in combination with phentermine, a drug indicated for weight management, without reoccurrence of adverse effects. Migraine control was maintained and progressive weight loss ensued. Combination treatment with phentermine may be a useful strategy should other patients experience this adverse reaction while gaining therapeutic anti-migraine benefit from topiramate.

Anticonvulsants represent one of the main substance classes used for the preventive treatment of migraine. Efficacy has been demonstrated in randomized placebo-controlled trials for topiramate and valproic acid including divalproex sodium. In the case of topiramate, efficacy has recently been proven for chronic migraine and even medication overuse headache, questioning the established concept of medication withdrawal. However, preventive treatment with anticonvulsants is frequently hampered by side effects that occasionally require treatment discontinuation. In addition, these data indicate that some anticonvulsant drugs are effective in migraine, while a number are clearly not useful. Effective anticonvulsants, such as topiramate and valproate, target nociceptive trigeminovascular and trigeminothalamic dural pathways or mechanisms involved in cortical spreading depression. Dissecting out how the anticonvulsants that do not work differ mechanistically from those that do will almost certainly provide avenues through which one can develop new treatments to bring to patients with migraine.

Systematic review of preventive pharmacologic treatments for community-dwelling adults with episodic migraine.

Electronic databases through May 20, 2012.

English-language randomized controlled trials (RCTs) of preventive drugs compared to placebo or active treatments examining rates of ≥50 % reduction in monthly migraine frequency or improvement in quality of life.

We assessed risk of bias and strength of evidence and conducted random effects meta-analyses of absolute risk differences and Bayesian network meta-analysis.

Of 5,244 retrieved references, 215 publications of RCTs provided mostly low-strength evidence because of the risk of bias and imprecision. RCTs examined 59 drugs from 14 drug classes. All approved drugs, including topiramate (9 RCTs), divalproex (3 RCTs), timolol (3 RCTs), and propranolol (4 RCTs); off-label beta blockers metoprolol (4 RCTs), atenolol (1 RCT), nadolol (1 RCT), and acebutolol (1 RCT); angiotensin-converting enzyme inhibitors captopril (1 RCT) and lisinopril (1 RCT); and angiotensin II receptor blocker candesartan (1 RCT), outperformed placebo in reducing monthly migraine frequency by ≥50 % in 200-400 patients per 1,000 treated. Adverse effects leading to treatment discontinuation (68 RCTs) were greater with topiramate, off-label antiepileptics, and antidepressants than with placebo. Limited direct evidence as well as frequentist and exploratory network Bayesian meta-analysis showed no statistically significant differences in benefits between approved drugs. Off-label angiotensin-inhibiting drugs and beta-blockers were most effective and tolerable for episodic migraine prevention.

We did not quantify reporting bias or contact principal investigators regarding unpublished trials.

Approved drugs prevented episodic migraine frequency by ≥50 % with no statistically significant difference between them. Exploratory network meta-analysis suggested that off-label angiotensin-inhibiting drugs and beta-blockers had favorable benefit-to-harm ratios. Evidence is lacking for long-term effects of drug treatments (i.e., trials of more than 3 months duration), especially for quality of life.

Migraine has been linked with an increased risk of stroke and an increased prevalence of clinically silent brain lesions and white-matter hyperintensities. As it is known that stroke and structural brain lesions are associated with an increased risk of cognitive decline, it has been hypothesized that migraine may be a progressive brain disorder and associated with an increased risk of cognitive impairment. Given the prevalence of migraine in the population, especially among women, and the aging of the population, an association between migraine and cognitive impairment would have substantial public health implications. In this review, we will summarize the existing evidence evaluating the association between migraine and cognitive function. Additionally, we will discuss methodological issues in migraine and cognitive function assessment and elaborate on study design strategies to address this important question.

Chronic Daily Headache is a descriptive term that includes disorders with headaches on more days than not and affects 4% of the general population. The condition has a debilitating effect on individuals and society through direct cost to healthcare and indirectly to the economy in general. To successfully manage chronic daily headache syndromes it is important to exclude secondary causes with comprehensive history and relevant investigations; identify risk factors that predict its development and recognise its sub-types to appropriately manage the condition. Chronic migraine, chronic tension-type headache, new daily persistent headache and medication overuse headache accounts for the vast majority of chronic daily headaches. The scope of this article is to review the primary headache disorders. Secondary headaches are not discussed except medication overuse headache that often accompanies primary headache disorders. The article critically reviews the literature on the current understanding of daily headache disorders focusing in particular on recent developments in the treatment of frequent headaches.

The most common causes of chronic cough in nonsmokers are postnasal drip syndrome, asthma, and gastroesophageal reflux disease. Drugs are also important in the etiology of resistant cough. Most common drugs inducing cough are the ACE inhibitors. Many drugs other than ACE inhibitors can also cause dry cough and one among them is topiramate. It is a new generation, efficacy-proved antiepileptic drug that is used widely for migraine prophylaxis in many countries. Most common adverse events of topiramate are paresthesia, cognitive symptoms, fatigue, insomnia, nausea, loss of apetite, anxiety, and dizziness. There is only one case report about topiramate associated cough in the literature. The present report refers to a patient, presenting with cough who is on topiramate treatment for migraine prophylaxis.

Migraine is a widespread disorder. Migraine patients experience worse health-related quality of life than the general population. The availability of effective and tolerable treatments for this disorder is an important medical need. This narrative review focuses on the clinical pharmacology of topiramate, an antiepileptic drug that was approved for the prophylaxis of migraine where it should act as a neuromodulator.

A PubMed database search (from 2000 to 24 January 2011) and a review of the human studies published on topiramate and migraine was conducted.

Topiramate is an important option for the prophylaxis of migraine and is of proven efficacy and tolerability. It has also been studied in chronic migraine with encouraging results, even in patients with medication overuse. However, in migraine prevention its efficacy is comparable to the other first-line drugs and there are no published trials with a superiority design which can establish topiramate's role in the available therapeutic armamentarium.

Migraine headaches are typically episodic in nature and may affect nearly 10% of the population. In addition to treatment, prevention of subsequent episodes or progression to a chronic migraine state is an important therapeutic area. Topiramate is a centrally acting medication approved for both the prevention of seizures and migraine headache. At this time, the exact mechanism of how topiramate assists in migraine prevention is unknown. Several large randomized, controlled trials have aided in establishing topiramate's role in migraine prevention. Despite a favorable pharmacokinetic and adverse effect profile established in clinical trials, several additional studies, case reports and toxicology reports have demonstrated topiramate as a cause of cognitive and behavioural changes. The use of topiramate in migraine prevention can improve a patient's quality of life and is a cost-effective option for migraine prevention.

Headache is among the most common neurological symptoms in clinical practice. In some cases of episodic migraine, the headache intensifies into a chronic form, defined as chronic migraine (CM) and such a condition encompasses a headache frequency of 15 days/month, with features similar to those of migraine attacks. The assessment of CM in the US general population ranges around 1.3-2%. Migraine progression from an episodic into a chronic form is realized through a period of time involving several months or years, during which an increase attack frequency occurs. Both Topiramate and Onabotulinum toxin A can be considered to be safe as well as effective medications, therefore, representing a treatment choice. Regarding drug abusers, the initial relief step always consists of drug interruption. Only after detoxification can a new prophylaxis therapy be commenced, which otherwise would be useless from the start. The feasible diagnostic setting for the tailored treatment of CM based on the application of pharmacogenomics will allow us in predetermining the efficacy of a single old and new drugs by avoiding abuse due to non-responsivity of the abused drug.

To critically review the literature on topiramate in the treatment of substance-related disorders.

A PubMed search of human studies published in English through January 2009 was conducted using the following search terms: topiramate and substance abuse, topiramate and substance dependence, topiramate and withdrawal, topiramate and alcohol, topiramate and nicotine, topiramate and cocaine, topiramate and opiates, and topiramate and benzodiazepines.

26 articles were identified and reviewed; these studies examined topiramate in disorders related to alcohol, nicotine, cocaine, methamphetamine, opioids, Ecstasy, and benzodiazepines.

Study design, sample size, topiramate dose and duration, and study outcomes were reviewed.

There is compelling evidence for the efficacy of topiramate in the treatment of alcohol dependence. Two trials show trends for topiramate's superiority over oral naltrexone in alcohol dependence, while 1 trial suggests topiramate is inferior to disulfiram. Despite suggestive animal models, evidence for topiramate in treating alcohol withdrawal in humans is slim. Studies of topiramate in nicotine dependence show mixed results. Human laboratory studies that used acute topiramate dosing show that topiramate actually enhances the pleasurable effects of both nicotine and methamphetamine. Evidence for topiramate in the treatment of cocaine dependence is promising, but limited by small sample size. The data on opioids, benzodiazepines, and Ecstasy are sparse.

Topiramate is efficacious for the treatment of alcohol dependence, but side effects may limit widespread use. While topiramate's unique pharmacodynamic profile offers a promising theoretical rationale for use across multiple substance-related disorders, heterogeneity both across and within these disorders limits topiramate's broad applicability in treating substance-related disorders. Recommendations for future research include exploration of genetic variants for more targeted pharmacotherapies.

To explore efficacy and safety outcomes of topiramate for episodic migraine prevention in community practice.

Open-label, multicenter, flexible-dose clinical trial consisting of a 4-week baseline phase, 24-week core phase and an optional 24-week follow-up phase in patients (18-80 years) with episodic migraine treated in community practices outside tertiary care centers.

The primary efficacy endpoint was the change in the number of migraine days/28 days (baseline vs. the last 4 weeks of core treatment) Secondary efficacy parameters included aspects of quality of life (QoL) and subjective patient ratings.

A total of 360 patients entered the core phase (ITT population); 37.6% (97 patients) discontinued prematurely, mainly due to adverse events (AEs; 23.6%). Mean topiramate dosage was 90 mg/day. Migraine days decreased from 8.30/28 days to 5.65/28 days and QoL (HIT-6 and MIDAS) was improved. Efficacy, tolerability and satisfaction were rated as 'good' or better by 56, 61 and 63% of patients, respectively. A total of 321 of 364 patients (88.2%) reported at least one treatment emergent AE, and the most common during the core phase were paraesthesia (46.4% of 364 patients), fatigue (17.0%), nausea (15.4%), dizziness (12.9%), viral infection (12.9%), weight decrease (12.6%) and impaired concentration (10.2%). Of 227 patients completing the core phase, 199 (88%) participated in the follow-up phase. A total of 187 patients received topiramate and 38 (20.3%) of these stopped treatment prematurely due to insufficient efficacy (6.4%), AEs (4.8%) or other reasons (10.2%). Reduction in migraine days and improvements in QoL (HIT-6) were maintained or improved (MIDAS) during follow-up, and 84% rated their satisfaction with topiramate therapy as 'good to very good'.

This community practice study showed that long-term treatment with topiramate in the prevention of episodic migraine was effective and well-tolerated, and it was associated with clinically relevant improvements in several aspects of QoL.

Migraine is a very common disorder characterized by the combination of typical headache with associated autonomic symptoms and/or the presence of aura. Considerable advances have been made in recent years to understand the pathophysiology of migraine, which has led to improved treatment options for the acute migraine attack as well as migraine prophylaxis. Unfortunately, preventive treatment is often insufficient to decrease migraine frequency substantially or is not well tolerated. Topiramate is an antipileptic drug with a complex mode of action which has proven its efficacy and safety in the prophylactic treatment of episodic migraine in a number of randomized controlled clinical trials. Topiramate is also effective in treating patients with chronic migraine. It has little pharmacological interaction with other drugs and is generally well tolerated by patients.

The introduction of triptans in migraine treatment was apparently a revolution. Comparative randomized clinical trials (RCTs) with triptan and other drugs do not give a clear-cut picture. Oral triptans are superior to oral ergotamine most likely because the bioavailability oral of ergotamine is extremely low (<1%). Compared with NSAIDs, in most cases aspirin, triptans were not superior and in several RCTs triptans caused more adverse events than aspirin plus metoclopramide. Guidelines for treatment of migraine should be evidence-based. It is suggested that based on current evidence, effervescent aspirin should be the first-line drug for the treatment of migraine. Aspirin is also much cheaper than the triptans.

Few data are available on cognitive and psychiatric effects of topiramate (TPM) monotherapy in migraine. Twenty patients affected by migraine were treated with TPM monotherapy. At the same time, twenty control subjects were selected. A comprehensive neuropsychological and behavioural battery of tests were performed at baseline (T0), at titration (T1) and in maintenance period (T2). Topiramate serum levels were also investigated at T1 and T2. On comparison with the control group, no cognitive and psychiatric differences were detected at baseline. A significant reduction of word fluency score (P < 0.05) was evident after TPM treatment, both at T1 and T2. No patient developed psychiatric adverse events. TPM induced an impairment of verbal fluency and no psychiatric adverse events, demonstrating selective negative cognitive profile in migraine therapy. Slow titration, low doses, lack of previous psychiatric disorders and/or familial history may explain our data.