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Topamax (Topiramate) For Migraines: An Effective Prophylactic?

Topamax (Topiramate) is an anticonvulsant agent discovered in 1979 by Bruce Maryanoff and Joseph Gardocki while working for McNeil Pharmaceutical (a subsidiary of Johnson & Johnson).  When compared to other anticonvulsant agents, Topamax is regarded as unique in that it is pharmacologically classified as a sulfamate-substituted monosaccharide derivative, indicating that its chemical structure is similar to that of fructose.  After its synthesis, preliminary evaluation lead researchers to speculate that Topamax may prevent seizures.

As a result of safety and efficacy in human clinical trials, Topamax received FDA approval in 1996 for the treatment of partial seizures in adults; thereafter it was also approved for usage among pediatrics.  Knowing that the mechanisms of anticonvulsants may be useful for the prevention of migraines resulted in some physicians prescribing Topamax (from 1996 to 2004) as an off-label migraine prophylactic.  In 2004, Topamax had met clinical trial endpoints and received official FDA approval for the prophylaxis of migraine.

Although Topamax is still frequently utilized as a seizure preventative, and is sometimes administered for psychiatric conditions (e.g. bipolar disorder) – it remains most commonly prescribed as a migraine prophylactic.  Unlike other migraine prophylactics, Topamax is regarded as well-tolerated with few unwanted adverse effects.  Moreover, Topamax has robust, “Level A” evidence to support its clinical usage as a first-line agent the prevention of migraine.

How Topamax (Topiramate) May Prevent Migraines (Mechanism of Action)

According to the website of the manufacturer, Topamax is hypothesized to function by keeping excitable nerve cells in the brain “calm.”  It does this via modulation of charged particle inflow and outflow.  In other words, when a person takes Topamax and the topiramate chemical crosses the blood-brain-barrier (BBB), it essentially relaxes or downregulates overexcitability of neurons, thereby preventing the series of neurologic events that triggers a migraine attack.

More specifically, Topamax functions as an inhibitor of voltage-gated sodium channels (VGSC), high-voltage calcium channels, and kainate receptors.  It also appears to enhance activity of GABA, the predominant inhibitory neurotransmitter in the brain.  It remains unclear as to whether one mechanism contributes more substantially to its efficacy as a migraine prophylactic compared to others, or if all hypothesized mechanisms act synergistically to prevent migraines.

Voltage-gated sodium channels (VGSC) inhibition: Many inhibitors of voltage-gated sodium channels are effective in prophylaxis of migraines.  Whether this particular mechanism plays a significant role in the migraine prophylactic effect associated with Topamax is unclear.  It is well-understood that dysfunction of voltage-gated sodium channels can facilitate neuronal excitability (as is often implicated in the pathogenesis of migraines).

Analyses of the human genome have revealed specific mutations in the SCN1A gene can directly cause migraines.  The SCN1A gene encodes for the alpha-subunit of voltage-gated sodium channel NaV1.1, and when dysfunctional from a genetic mutation, neurons are more prone to hyperexcitability.  Those prone to neuronal hyperexcitability are more likely to experience migraines due to the fact that the increase in homeostatic excitement results in a lower threshold for triggering cortical spreading depression; brief contraction of intracranial blood vessels followed by expansion.

For many individuals, especially those with migraines resulting from an SCN1A mutation, the voltage-gated sodium channel inhibition provided by Topamax may be a critical mechanism by which migraines are prevented.  Furthermore, blockage of voltage-gated sodium channels can decrease neuroinflammation, ultimately reducing proinflammatory biomarkers and neuropeptides responsible for pain-signaling (e.g. substance P).  In other words, voltage-gated sodium channel inhibition may reduce likelihood of migraines caused by inflammation and decrease the perceived pain associated with migraines.

While not all voltage-gated sodium channel inhibitors are effective migraine prophylactics (e.g. carbamazepine, phenytoin, etc.), others are (e.g. lidocaine).  Based on the literature, we could speculate that those deriving antimigraine benefit from Topamax are responding to its inhibition of voltage-gated sodium channels.  That said, other complementary mechanisms may be necessary for clinically effective prophylaxis of migraines.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/10768295
  • Source: http://www.ncbi.nlm.nih.gov/pubmed/10768299
  • Source: http://www.ncbi.nlm.nih.gov/pubmed/16054936
  • Source: http://www.ncbi.nlm.nih.gov/pubmed/26718459

Glutamate receptor inhibition: An important mechanism by which Topamax may prevent migraines is via inhibition of glutamate receptors.  Glutamate is the chief excitatory neurotransmitter in the CNS and binds to ionotropic receptors such as NMDA, AMPA, and kainate receptors.  Numerous studies have linked glutamatergic abnormalities in the pathogenesis of migraines.

Research has shown that Topamax selectively inhibits kainate receptors containing the GluR5 subunit.  Kainate receptors with the GluR5 subunit are responsible for mediating excitatory synaptic currents, and as is understood, excess excitement resulting from glutamate stimulation could trigger cortical spreading depression and inevitably, migraine attacks.

In 2011, researchers Andreou and Goadsby published a study assessing the effect of Topamax on trigeminovascular activity in the trigeminocervical complex (TCC) and ventroposteromedial thalamic nucleus (VPM).  They also used a technique called microiontophoresis to assess the effect of Topamax on ionotropic glutamate receptors. Results indicated that Topamax inhibited trigeminovascular activity in the TCC and VPM, as well as substantially blunted kainate receptor firing.

It is thought that kainate receptor antagonism induced by Topamax altered the trigeminovascular activity within the trigeminothalamic pathway, possibly decreasing the release of neurochemicals and neuropeptides such as: substance P, CGRP, and gastrin-releasing peptide.  In addition to preventing migraine attacks by antagonizing kainate receptors, this mechanism may also reduce migraine-related pain due to the fact that kainate receptors can be found in the central pain neuraxis.  Therefore, users of Topamax may not only experience fewer migraines from its modulation of kainate receptors, but also less migraine-related pain.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/17691981
  • Source: http://www.ncbi.nlm.nih.gov/pubmed/12904467
  • Source: http://www.ncbi.nlm.nih.gov/pubmed/21893557
  • Source: http://www.ncbi.nlm.nih.gov/pubmed/23095167

Voltage-gated calcium current reduction (L-type):  Another way by which Topamax may prevent migraines is via reducing activity of L-type voltage-gated calcium channels.  It is understood that L-type calcium channels play a role in modulating excitability of dendrites.  An overactive L-type calcium channel current may facilitate overexcitability, which could induce neurological events preceding cortical spreading depression and migraines.

Evidence suggests that Topamax attenuates activity of L-type (long-lasting) voltage-gated calcium channels.  This reduces dendritic excitability and possibly increases the stimulatory threshold required to provoke a migraine.  It is known that mutations in CACNA1A, a gene that encodes for the alpha-1 subunit of CaV2.1 (P/Q-type) channels causes familial hemiplegic migraine type 1 (FHM1).

This finding suggests that voltage-gated calcium currents may play a role in the pathogenesis of migraines (for certain individuals).  Although Topamax does not appear to modulate the P/Q-type voltage-gated calcium channels, its modulation of the L-type channels may be enough to reverse some calcium channel abnormalities exhibited among migraine patients.  Other drugs such as Verapamil, an L-type calcium channel blocker, are useful in migraine prophylaxis; possibly from the L-type channel blocking.

That said, other drugs that inhibit L-type calcium channels also tend to act on P/Q-type calcium channels.  P/Q-type channels are more implicated in the pathogenesis of migraines compared to L-type, and since Topamax doesn’t appear to block P/Q-type calcium channels, it may be wrong to assume that a reduction of L-type calcium channel activity facilitates an antimigraine effect.  Nonetheless, L-type calcium channel modulation provided by Topamax cannot be fully ruled out as a possible prophylactic mechanism.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/10768302
  • Source: http://www.ncbi.nlm.nih.gov/pubmed/23165010

GABA modulation: Studies evaluating the pharmacodynamics of Topamax reveal that it increases the frequency of GABA-mediated chloride channel opening.  GABA is the chief inhibitory neurotransmitter of the CNS and abnormalities in GABAergic turnover have been implicated in migraines and migraine-related pain.  Researchers believe that GABAergic modulation induced by Topamax may be most important for the treatment of “common migraine” (or migraine without aura).

Topamax’s ability to augment GABAergic activity may ensure proper stimulation of GABAA and GABAB receptor sites.  Stimulation of GABAA and GABAB sites decreases excitability of nociceptive neurons, thereby blunting the perception of migraine-related pain.  Essentially, this may raise a user’s threshold for enduring the throbbing or sharp pain that occurs during a migraine attack.

What’s more, those with migraines often exhibit abnormally low levels of GABA prior to an attack, however, during an attack, GABA concentrations tend to spike.  This suggests that those with migraines exhibit [possibly predictable] abnormal GABAergic metabolism with peaks (during attacks) and valleys (between attacks).  Agents such as Valproate (inhibitors of GABA transaminase) appear to effectively treat migraines by increasing baseline concentrations of GABA.

Although Topamax doesn’t inhibit GABA transaminase (the enzyme that metabolizes GABA), it appears to enhance GABAergic activity – possibly generating a similar neural effect to that of Valproate.  We also know that polymorphisms of GABA receptor genes (particularly those encoding GABAA receptors) tend to increase migraine susceptibility.  For these reason, we can hypothesize that GABAergic enhancement elicited by Topamax may be an important antimigraine mechanism, at least in a subset of patients.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/24040174
  • Source: http://www.ncbi.nlm.nih.gov/pubmed/19300616
  • Source: http://www.ncbi.nlm.nih.gov/pubmed/9332882

It should also be noted that Topamax enhances the conductance of potassium, as well as functions as an enzymatic inhibitor of carbonic anhydrase.  While it is unclear as to whether potassium conductance inhibition helps prevent migraines, it is unlikely that carbonic anhydrase inhibition contributes to antimigraine properties.  In fact, inhibition of carbonic anhydrase has been documented as causing vasodilation (the opposite of what migraine sufferers need during an attack).  Finally, a lesser discussed mechanism by which Topamax may prevent migraines is through action on mitochondrial permeability transition pores.

Benefits of Topamax for Migraines (Possibilities)

There are many potential benefits to be attained from taking Topamax for the prevention of migraines.  Not only will it likely reduce the number of migraine attacks you experience per month, but it may prevent seizures (among those with comorbid epilepsy), preserve brain function, and facilitate weight loss.  Topamax may also be perceived as advantageous compared to other interventions based on its ability to reduce non-migraine headaches.

  • Adjunctive option: Those who are only deriving partial benefit from an existing migraine prophylactic may be able to add Topamax to their regimen for additional symptomatic relief.  In some cases, Topamax may act synergistically with another prophylactic to prevent migraine attacks better than either as a standalone.  Furthermore, Topamax can often be taken along with triptans (abortive therapies) without any interactions.  For cases of refractory migraines, Topamax may serve as a much-needed adjuvant prophylactic.
  • All ages: It is extensively documented that Topamax can prevent the occurrence of migraine attacks in adults.  What’s more, it appears as though Topamax may be safe and well-tolerated among pediatrics (children and adolescents).  Some studies have discovered that Topamax prevents migraines among pediatrics (at a low dose – less than 2 mg/kg/day).  Although not formally FDA approved to treat pediatric migraines, it appears effective and may be a much-needed (safe / effective) intervention for younger migraine patients.
  • Clinical efficacy: Topamax is considered clinically effective with “Level A” evidence (among much of the medical community), as well as the FDA – for the prophylaxis of migraines among adult patients. It was FDA approved for adult migraine prevention in 2004 and was considered a safe anticonvulsant medication in 1996.  Many professionals prescribe Topamax to adult migraine patients as a first-line therapy.
  • Comorbidities: A subset of patients may be able to essentially treat multiple conditions simultaneously with Topamax. It is FDA approved for the treatment of partial seizures, potentially making it an optimal intervention for patients with both migraines and seizures; it seems to prevent them both.  Additionally, though not approved as a standalone agent for weight loss, it may help treat obesity among overweight migraine patients.
  • Headaches: Not only does Topamax prevent migraines, but it also is capable of preventing non-migraine headaches. Some studies measuring number of migraines per month, as well as number of non-migraine headaches per month – discovered that Topamax treatment significantly reduced counts of both.  Although it is unclear as to whether Topamax is capable of preventing every subtype of headache, it appears effective in the prevention of cluster headaches.
  • Inhibits migraine progression: Some migraine experts believe that individuals with migraines may experience a worsening of attacks over time (e.g. years). They speculate that migraines can become more severe and numerous over extended durations – especially if left untreated.  In other words, someone with episodic migraine (less frequent) may eventually develop chronic migraine (highly frequent) if they fail to seek treatment.  Researchers believe that Topamax could prevent the progression of episodic to chronic migraine if administered at an early stage of the disease.
  • Migraine subtypes: Evidence suggests that Topamax can effectively prevent both classic migraine (with aura) and common migraine (without aura). It can also treat cases of episodic migraine, chronic migraine, as well as transformed migraine.  It may be more effective among patients with episodic migraine that chronic migraine, but appears to benefit both subtypes.
  • Neuroprotective agent: An added benefit associated with using Topamax is that you may preserve brain cells. It is known that epileptic seizures are capable of damaging the brain and killing brain cells in multiple regions.  More troubling is the fact that anticonvulsants used to prevent seizures (and migraines) can also trigger apoptosis (programmed neuronal death).  Thankfully, at clinically recommended concentrations, Topamax can function as a neuroprotective agent, possibly protecting your precious neurons.  (Source: https://www.ncbi.nlm.nih.gov/pubmed/15727029).
  • Side effects: Compared to most drugs, Topamax is considered well-tolerated and unlikely to provoke unwanted side effects. Most side effects resulting from treatment are of mild-to-moderate severity.  Due to the fact that side effects resulting from Topamax aren’t as substantial as those associated with many other anticonvulsants and migraine prophylactics, users may prefer this drug as a treatment.
  • Weight loss: On average, users of Topamax lose around 5 lbs. body weight after several months of treatment. The exact mechanisms responsible for facilitating this weight loss remain unclear, however, weight loss is often welcomed by patients.  Many women deliberately seek out Topamax for weight loss because no upfront effort is required to lose the weight.  Furthermore, medical professionals may prefer to use a drug that promotes weight loss among obese patients (or those at risk of obesity) – as opposed to a drug associated with weight gain.

Drawbacks of Topamax for Migraines (Possibilities)

Although there are a significant number of potential benefits to be attained by Topamax users, not everyone responds well to this drug.  In some cases, a patient may take the clinically recommended dose of Topamax and find that it is completely useless as a migraine prophylactic.  Others may dislike its side effects (e.g. cognitive deficits) and the fact that it carries withdrawal symptoms (upon discontinuation).

  • Cognitive deficits: One of the biggest drawbacks associated with using Topamax is that it causes cognitive impairment and brain fog (impaired clarity of thinking) in many users. You may feel spaced out and perhaps a bit “dopey” while using this drug, hence the reason some patients have nicknamed the drug “Dopamax” (a portmanteau of dopey and Topamax).  The most commonly reported cognitive deficits among migraine patients include: memory loss and inability to concentrate.  Assuming these cognitive deficits impair your ability to perform in an occupational or educational setting, you may need to opt for a different treatment. (Source: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3707352/).
  • Daily administration required: To derive sufficient prophylactic benefit from Topamax, it needs to be administered on a daily basis for at least 1-3 months. Users cannot take “breaks” by skipping a day or two if they expect to continuously prevent migraine attacks – daily administration is required. This means that your body will be under the influence of a drug (topiramate) potentially for years or decades; probably not something most people want.
  • Ineffective: Most research suggests that while a majority of patients may derive therapeutic benefit from Topamax, not everyone will. This means that for some individuals the drug will be completely ineffective as a migraine prophylactic.  There are many underlying causes of migraine attacks, each of which are subject to interindividual variation.  Since Topamax doesn’t correct or target all possible migraine causes, it will be an ineffective intervention for some.
  • Pregnancy: Another drawback associated with Topamax is that it should be avoided during pregnancy. Some small-scale studies suggest that administration of Topamax during pregnancy may elevate risk of birth defects.  Examples of some birth defects resulting from Topamax included: cleft palates and genital abnormalities.
  • Side effects: Many people dislike taking Topamax due to its side effect profile. Perhaps most problematic are the cognitive deficits such as memory loss, inability to concentrate, and feeling spaced out.  Additionally, other side effects such as paresthesia (numbness and tingling), anorexia, fatigue, and change in taste.
  • Unwanted weight loss: Though weight loss resulting from Topamax is not a guarantee for all users, many notice decreases in body weight after several months of treatment. Weight loss may be a small amount (e.g. 5 lbs.) or more substantial (e.g. 15-20 lbs.).  Some individuals that are already at low body weight and small statured – may consider the weight loss to be a problematic reaction.
  • Withdrawal: Assuming you were using Topamax for awhile and wish to discontinue treatment, you’re likely going to experience some discontinuation effects. Users are often uninformed of potential Topamax withdrawal symptoms that they may experience when stopping treatment.  These withdrawal symptoms may be long-lasting (e.g. months) and impair quality of life.  Even more problematic is that users may experience rebound migraines of greater frequency and severity during withdrawal than pre-treatment.

Topamax (Topiramate) For Migraines (Review of Research)

Nearly all of the published research suggests that Topamax is a highly-effective medication for the prophylaxis of migraines.  The drug has undergone sufficient testing to satisfy the United States FDA, and was officially approved in 2004 for the prophylaxis of migraines in adults.  An issue of American Family Physician published January 2006 indicates that Topamax as a migraine prophylactic is backed by “Level A” evidence.

In other words, there appear to be ample, well-designed trials suggesting that the drug is capable of preventing adult migraines.  Though it isn’t FDA approved to treat pediatric migraines, it appears effective at low-doses.  Moreover, Topamax is considered well-tolerated and may be preferred over other agents due to the fact that it causes weight loss (rather than gain).

  • Source: http://www.aafp.org/afp/2006/0101/p72.html

2013: Efficacy and safety of topiramate in migraine prophylaxis: an open controlled randomized study comparing Sincronil and Topamax formulations.

A study conducted by Cosentino et al. (2013) aimed to analyze the efficacy, tolerability, and safety of topiramate for the prophylaxis of migraine without aura.  It should be noted that topiramate is the active ingredient in the brand name drug Topamax, as well as Sincronil (an Italian version of Topamax).  For the study, researchers implemented an open-label, parallel-group, randomized, controlled design.

A total of 60 patients (between 18 and 65 years of age) were recruited for participation, all of which experienced a migraine frequency between 3 and 15 attacks per month.  After trial enrollment and acceptance, dosages of Topamax and Sincronil were titrated upwards over a period of 20 days until patients were taking 25 mg (b.i.d.).  Thereafter, the twice-daily dosing of 25 mg was maintained for a 3-month duration.

Of the 30 patients receiving Sincronil, 15 patients experienced improvement in clinical symptoms of migraine without aura and exhibited reductions in frequency of migraine attacks greater than 50% compared to the baseline (run-in) phase.  A total of 6 patients experienced some benefit from the Sincronil, but discontinued treatment due to adverse reactions.  The remaining 9 patients (of the 30) experienced no change in clinical symptoms from the medication.

Results indicated that patients able to continue Sincronil for the entire 3 months experienced a decrease in attack frequency from 7 days per month to 3.7 days per month.  Additionally, by the third month, migraine severity had plummeted from a score of 2.5 to just 1.7 – and the MIDAS (migraine disability assessment) scores dropped from 14.3 to 8.6.  Among those receiving Sincronil (or topiramate marketed in Italy), migraines were successfully prevented.

Of the 30 patients that received Topamax, a total of 16 patients experienced a reduction in migraine attack frequency by at least 50% (compared to the baseline “run-in” phase) by the third month of treatment.  A total of 4 of the remaining patients ended up discontinuing Topamax within 1 week as a result of adverse effects, whereas the other 10 patients derived insufficient therapeutic benefit in regards to migraine reduction.  Evaluation of the 26 patients able to continue Topamax through the third month of the trial indicated that it significantly: decreased headache frequency (from 7.3 days to 3.5 days), diminished migraine severity (from scores of 2.4 to 1.6), and axed MIDAS (migraine disability assessment) scores (from 14.1 to 6.8).

Pooling results from each trial suggests that topiramate is clinically effective in over 51% of patients with common migraine, ineffective for approximately 32%, and intolerable in around 17% of patients.  Though these were two relatively small-scale trials with just 30 participants in each, we can conclude that topiramate (administered as Topamax and Sincronil) effectively prevents migraines.  It also reduces the severity of migraine attacks and attenuates migraine-related disability.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/24088805

2013: Prophylaxis of childhood migraine: topiramate versus propranolol.

Although select medications are safe and tolerable among children with migraines, their respective efficacies are often considered questionable.  In effort to determine the therapeutic values of prophylactics among children, Tonekaboni et al. (2013) conducted a study comparing the efficacy of topiramate (an anticonvulsant) to that of propranolol for migraine.  The study was classified as a randomized clinical trial and recruited 78 children that had been diagnosed with migraine (in accordance with International Headache Association criteria).

Participants were randomly assigned to receive either: Topamax or Propranolol – groups were matched by age and sex.  A total of 38 patients received Topamax and were labeled “Group A” whereas the remaining 40 patients received Propranolol and were labeled “Group B.”  Efficacy was determined based on changes in frequency, severity, and duration of migraine attacks after 1 and 4 months of treatment.

Results indicated that frequency, severity, and duration of migraine attacks significantly decreased in both the Topamax and Propranolol groups, but neither treatment was more efficacious than the other.  It was concluded that Topamax and Propranolol equally viable migraine prophylactics for children with migraine.  Authors suggested that the decision to use one intervention over the other should be made based on the specific patient.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/24665283

2012: Effective dose of topiramate in pediatric migraine prophylaxis.

A study by Abbaskhanian et al. (2012) was carried out to determine optimal dosing of Topamax among pediatrics for migraine prophylaxis.  Researchers discussed the fact that migraine is a common neurological disorder that can occur throughout childhood and adolescence.  They mentioned that Topamax (at the time) was a newer anticonvulsant agent that was effective for prophylaxis of migraine in adults.

It was emphasized that the FDA had not yet approved Topamax for the prophylaxis of migraines among pediatric populations.  Knowing that Topamax was considered safe with few adverse effects in adults, they decided to test it as a prophylactic in pediatrics at a low-dose.  A total of 60 pediatrics that had been diagnosed with migraines were recruited for participation.

The 60 pediatrics were divided into two treatment groups and randomly assigned to receive Topamax at a dose of either: less than 2 mg/kg/day OR more than 2 mg/kg/day – for a period of 2 months.  To determine efficacy of each dosage, patients underwent symptomatic evaluation at baseline (0 weeks), 4 weeks, and 8 weeks.

Results suggested that pediatrics receiving a dosage under 2 mg/kg/day experienced reductions in: migraine frequency (from 6.2 to 3 episodes per month), headache intensity (from 7.2 to 3.7 on a severity scale), and headache duration (from 5.4 to 2.2 hours).  Among those taking dosages over 2 mg/kg/day, reductions were noted in: headache frequency (from 6.9 to 3.24), headache intensity (from 7.11 to 3.14), and headache duration (from 5.2 to 1.8 hours).  Side effects noted in the pediatrics included: paresthesia, anorexia, and drowsiness.

Based on the results, it is apparent that dosages exceeding 2 mg/kg/day were no more effective than those under 2 mg/kg/day.  In conclusion, it appears as though low-dose Topamax (under 2 mg/kg/day) is safe, tolerable, and effective among pediatrics with migraines.  Since it is not formally approved by the FDA, it could be considered as an off-label alternative for pediatric patients that do not respond to other recommendations.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/23559999

2011: Zonisamide versus topiramate in migraine prophylaxis: a double-blind randomized clinical trial.

A study by Mohammadianinejad et al. (2011) compared the efficacy of the drug Zonegran (Zonisamide) to that of Topamax (Topiramate) for the prevention of migraines.  Researchers noted that Topamax is an antiepileptic agent that is FDA approved as a migraine prophylactic, but a subset of patients are unable to tolerate its side effects.  Therefore, they sought to determine whether Zonegran would be an effective, well-tolerated alternative for migraine patients unable to tolerate Topamax.

For the study, a total of 80 patients diagnosed with migraines were assigned to receive either Zonegran (titrated from 50 mg to 200 mg per day) or Topamax (titrated from 25 mg to 100 mg per day).  All patients were evaluated at pre-treatment baseline, after 4 weeks, and after 12 weeks.  Evaluations sought to determine whether there were significant changes in: frequency of migraine, headache severity, abortive medication usage, migraine disability scores, and adverse reactions.

Results indicated that both Zonegran and Topamax significantly reduced frequency of migraines, severity of migraines, usage of abortive medication, and migraine-related disability among sufferers.  Interestingly, on measures of general headache severity, Zonegran was more effective than Topamax.  That said, both drugs were considered well-tolerated with few adverse events.

This study provides evidence to support the usage of Topamax for the prophylaxis of migraines.  There remains more clinical evidence to support the prophylactic efficacy of Topamax than to support the prophylactic efficacy of Zonegran.  Nevertheless, it appears as though Zonegran may be equally as effective as Topamax as a prophylactic and serve as a feasible alternative among patients unable to tolerate Topamax.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/21738025

2011: Topiramate vs divalproex sodium in the preventive treatment of migraine: a prospective “real-world” study.

Researchers Krymchantowski and Jevoux compared the efficacy of Topamax and Depakote for the prevention of migraine.  Prior to the study, researchers were aware of the fact that both agents were capable of preventing migraine attacks.  However, it was unclear as to whether one agent (e.g. Topamax) was more effective than the other as a prophylactic.

For the study, researchers recruited a total of 120 patients that had been diagnosed with migraine.  Of the 120 patients, 69 received Topamax and the remaining 51 received Depakote – for a duration of 12 months.  Those receiving Topamax started at a dose of 25 mg/day and titrated the dosing upwards every 10 days by an additional 25 mg until they reached 150 mg/day (in 2 divided doses).

Participants receiving Depakote began at a dosage of 250 mg/day and titrated their dosing upwards to 500 mg (b.i.d.).  It should be mentioned that none of the participants had ever utilized Topamax nor Depakote prior to this study.  To determine efficacy of each treatment, researchers collected data from each participant, documenting: headache frequency, tolerability (after 3 months), and adherence to treatment.

At pre-treatment baseline, headache frequency of the Topamax and Depakote groups were similar at around 8 headache days per month.  After 3 months of treatment, 40/69 (58%) patients receiving Topamax experienced a reduction in headache frequency of at least 50%.  By comparison, 26/51 (51%) patients receiving Depakote for 3 months experienced a reduction in headache frequency of at least 50%.

Documentation of side effects revealed that Topamax users experienced: weight loss, paresthesia, and cognitive deficits – whereas those taking Depakote experienced: weight gain, hair loss, and gastrointestinal disturbances.  Despite the fact that this study was open-label and non-randomized, it appears as though Topamax and Depakote are equally effective and well-tolerated for the prophylaxis of migraine.  That said, some patients may prefer one over the other based on side effects; typically weight loss is preferred.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/21457240

2009: Topiramate treatment of chronic migraine: a randomized, placebo-controlled trial of quality of life and other efficacy measures.

A study by Silberstein et al. (2009) sought to assess the therapeutic value of Topamax for the treatment of chronic migraine.  Previously conducted research by Silberstein (in 2007) demonstrated that Topamax (at 100 mg/day) is effective in reducing the number of migraine days per month among chronic migraine sufferers, thereby making it a therapeutic prophylactic.  However, researchers sought to strengthen the findings from 2007 establishing its efficacy as a migraine prophylactic, as well as investigate its therapeutic potential for the improvement of secondary symptoms.

Researchers organized a placebo-controlled, double-blinded, randomized trial incorporating a solid sample size of 306 participants – all of which had been diagnosed with chronic migraines.  The participants were divided into 2 equal-sized groups of 153 and were assigned at random to receive either: Topamax or a placebo.  To gauge the efficacy of Topamax among patients with chronic migraine, researchers compared an array of pre-treatment and post-treatment variables such as: percentage of responders (in each treatment group), rate of headaches, number of headache-free days per month, headache severity, use of acute (abortive) antimigraine pharmaceuticals, and headache index scores.

Secondary measures of photophobia (light sensitivity), phonophobia (sound sensitivity), and nausea – all common features of migraine attacks – were carefully analyzed.  Other assessments utilized by researchers included:  Migraine-Specific Quality of Life Questionnaire scores, Migraine Disability Assessment Scale scores, and Global Impression of Change (as perceived by subjects and physicians).  Results indicated that administration of Topamax significantly reduced the average number of migraine days per month (by at least 25%) compared to the placebo.

Secondary analyses suggested that Topamax significantly improved scores on in subsections of the Migraine-Specific Quality of Life Questionnaire, specifically the Role Restrictive and Emotional Function measures.  It also ameliorated migraine-associated symptoms such as: photophobia, phonophobia, pain (unilateral and pulsatile), and decreased likelihood of vomiting.  That said, it is important to note that Topamax was not more effective than a placebo for reducing average number of migraine days per month by over 50% or 75%.

The total number of headache days and headache-free days per month did not significantly differ between the Topamax and placebo groups.  Moreover, although trends favored Topamax for reducing: daily severity of migraine attacks, acute medication usage, nausea, and quality of life – it was not significantly more effective than the placebo.  While the therapeutic value of Topamax shouldn’t be undermined or dismissed, many measures indicated that it wasn’t highly effective (compared to a placebo) among chronic migraine patients.

Based on these results, from a relatively large-scale trial, we can conclude that Topamax can reduce migraine days per month by at least 25% – but not greater than 50% or 75% (in most patients).  Additionally, Topamax is likely to improve a subset of secondary symptoms associated with chronic migraine (e.g. sensory hypersensitivity, pain, etc.).  Although not all patients with chronic migraine may derive full symptomatic remission from Topamax, it is likely to provide some benefit.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/19719543

2009: Topiramate in migraine progression.

Ruiz and Ferrandi (2009) confer the fact that, in a subset of individuals, migraine is a chronic and progressive disorder.  In other words, the severity and frequency of migraine attacks may worsen if left untreated or insufficiently treated.  These researchers speculate that since topiramate is considered highly effective as a migraine prophylactic, it may also be useful for inhibiting the progression of migraine disorders from episodic to chronic.

It is thought that many migraine patients experience structural changes within the brain and altered pain perception following each attack (or a series of attacks).  Additionally, some findings suggest that duration and frequency of attacks may transform episodic migraine to chronic migraine – resulting in greater disease burden among patients.  Topiramate exhibits a multi-modal pharmacodynamic profile that facilitates stabilization of neuronal activity by decreasing hyperexcitability.

Hyperexcitability is understood to play a substantial role in the pathogenesis of migraine, and more specifically, cortical spreading depression.  Ruiz and Ferrandi believe that regular administration of topiramate (to reduce migraine frequency) may inhibit or slow progression from episodic (less frequent) to chronic (frequent) migraine.  At doses of 100 mg/day, topiramate is capable of treating patients at any stage of migraine progression (infrequent, episodic, or chronic migraine).

In conclusion, researchers recommend administration of a prophylactic agent such as topiramate as soon as possible among patients at risk for migraine progression (from episodic to chronic).  Although it is only hypothesized that topiramate may slow progression of migraine disease, it should be considered.  Further research is warranted to determine whether topiramate is likely effective for preventing progression of migraine.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/19838625

2009: Topiramate versus amitriptyline in migraine prevention: a 26-week, multicenter, randomized, double-blind, double-dummy, parallel-group noninferiority trial in adult migraineurs.

A study carried out by Dodick et al. (2009) compared the tolerability and prophylactic efficacy of Topiramate to that of Amitriptyline for migraines.  A total of 331 adults diagnosed with migraines were recruited for this 26-week, randomized, double-blind, parallel-group study.  All adults had experienced between 3 and 12 migraines per month and were assigned at random to receive either Topamax or Amitriptyline at 25 mg/day.

Dosages were then titrated upwards from 25 mg to 100 mg/day or a maximum tolerated dose.  Efficacy of these interventions was determined based on changes in average number of migraine attacks from pre-treatment baseline.  Secondary endpoints included: changes in rate of days with migraine, average number of days with headache per month, frequency of abortive medication usage, average migraine duration, and severity of migraine.

Researchers also documented: migraine-related symptoms (e.g. sensory hypersensitivity and nausea), quality of life, weight satisfaction, and adverse effects from medication.  A total of 172 patients ended up receiving the Topamax, whereas the other 159 patients received Amitriptyline.  Results indicated that neither treatment was significantly more effective than the other in reduction of number of migraine attacks per month.

Furthermore, no significant differences were noted between treatment groups in any of the secondary endpoints.  It was noted that individuals taking Topamax exhibited greater improvement in disability scores during migraine attacks and in several domains of the MSQ (migraine-specific quality of life questionnaire).  Also, those taking Topamax lost over 5 pounds (on average), whereas individuals taking Amitriptyline gained over 5 lbs.

Adverse effects associated with each medication occurred in an equal number of participants within each group, indicating that neither agent is better tolerated than the other.  While one drug cannot be recommended over the other based on efficacy, patients may prefer Topamax over Amitriptyline for prophylaxis of migraines due to the fact that it promotes slight weight loss (rather than weight gain).  Moreover, it may also be advantageous for improving quality of life among migraine patients compared to Amitriptyline.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/19393844

2007: Efficacy and safety of topiramate for the treatment of chronic migraine: a randomized, double-blind, placebo-controlled trial.

A study conducted by Silberstein et al. (2007) assessed the efficacy of Topamax for the treatment of chronic migraine among 306 patients diagnosed with chronic migraines.  All participants were between the ages of 18 and 65 and had reported at least 15 headache days per month with at least 50% being migraine-related.  Researchers set-up a placebo-controlled, double-blinded, randomized study and divided the 306 recruited participants into 2 groups of 153.

One group of 153 participants received Topamax, and the remaining 153 participants received a placebo – for a 16-week duration.  Those receiving the Topamax started at a low-dose of just 25/mg per day (for neurophysiologic adjustment) and the dose was titrated upwards over several weeks until participants reached a fitting dose (the maximum dose was 100 mg/day).  It is important to mention that none of the participants in this study used an adjunct migraine prophylactic during the trial.

To determine whether Topamax was more effective than a placebo, researchers compared pre-treatment (baseline) data to that collected during the 16-week treatment term.  They specifically examined the change in the number of migraine days from pre-treatment to post-treatment.  Results indicated that Topamax (up to 100 mg/day) significantly reduced the number of days with migraine headaches compared to the placebo.

There were a few side effects reported in the Topamax group such as paresthesia (pins and needles), respiratory tract infection, and fatigue.  That said, compared to those receiving the placebo, side effects weren’t significantly different.  Authors of the study concluded that administration of Topamax (up to 100 mg) is a safe, effective way to improve symptoms of chronic migraine compared to a placebo.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/17300356

2006: Topiramate for migraine prevention in adolescents: a pooled analysis of efficacy and safety.

A previous study had tested the efficacy of Topamax among pediatric populations and discovered that its therapeutic benefit was not significant compared to a placebo.  Some of the same researchers as the previous study, Winner et al. (2006), conducted an analysis to determine the efficacy and safety of Topamax solely among adolescents.  In this study, researchers gathered data from 3 randomized, double-blind, placebo-controlled trials – that had taken place over a term of 26-weeks.

In adults, it was understood that dosages of 100 mg/day and 200 mg/day were efficacious and well-tolerated for migraine prophylaxis.  In pediatric populations (children and adolescents), the efficacy of Topamax was questionable, but the drug appeared to be well-tolerated.  This study gathered data from 51 patients between the ages of 12 and 17.  All of these individuals were formally diagnosed with migraines.

Results from this analysis revealed that daily treatment with Topamax at dosages of 50 mg, 100 mg, and 200 mg decreased frequency of migraines from baseline by 46% (insignificant), 63% (significant), and 65% (significant), respectively – compared to the placebo.  This suggests that the 50 mg/day dose provided insufficient symptomatic prophylactic benefit, whereas the 100 mg/day and 200 mg/day doses were effective.  Average number of migraine days per month decreased by 1 day (50 mg), 4 days (100 mg), and 5 days (200 mg).

Tracking of abortive medication administration revealed that Topamax treatment reduced usage by 59% (50 mg), 54% (100 mg), and 67% (200 mg) – but these percentages were not significant compared to reduction resulting from the placebo (42%).  Researchers concluded that Topamax at dosages of 100 mg/day and 200 mg/day were both effective as migraine prophylactics.  The 200 mg/day dose was not significantly more effective than the 100 mg/day dose.

Although trends suggested that the 50 mg dose may provide some benefit, it was not significantly more effective than the placebo.  Since 200 mg/day was no more effective than 100 mg/day, and higher doses are associated with more pronounced side effects, we can conclude that 100 mg/day doses should be recommended to adolescents with migraine.  Moreover, this publication provides additional evidence to support the usage of Topamax for migraines.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/17115983

2006: Topiramate prophylaxis and response to triptan treatment for acute migraine.

Published in 2006 was a study by Becker et al. evaluating whether the prophylactic effect provided by Topamax may enhance the efficacy of abortive migraine medications such as triptans.  Triptans are tryptamine-based agents that function as serotonin receptor agonists to rapidly alleviate symptoms of a migraine attack.  Researchers speculated that ongoing Topamax administration may enhance efficacy of these agents among those experiencing a migraine attack.

They set-up an open-label study with an initial 6-week baseline phase, succeeded by a 16-week term of Topamax administration.  A total of 40 individuals that met International Headache Society criteria for migraine participated in the study long enough to receive Topamax, but only 21 participants completed 12 weeks of treatment.  Results indicated that Topamax significantly reduced migraine frequency, but did not enhance the efficacy of abortive triptan medication.

A substantial number of participants (13) discontinued treatment as a result of adverse reactions such as anxiety, dizziness, fatigue, and paresthesia.  Although Topamax is effective for the prevention of migraines, it is not well-tolerated.  Furthermore, it does not strengthen therapeutic effects provided by p.r.n. (pro re nata) triptans.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/17040339

2006: Topiramate in the prevention of migraine: a review of its efficacy, tolerability, and acceptability.

A report by D’Amico, Grazzi, and Bussone (2006) outlines results from placebo-controlled trials involving topiramate for the prevention of migraines at a dosage of 100 mg/day.  In this report, researchers pooled the data from the trials and determined whether topiramate was effective and tolerated as a migraine prophylactic.  The pooled data from these trials revealed that topiramate was effective in the prevention of migraine.

This supported anecdotal experiences of medical professionals that had been prescribing topiramate as a migraine prophylactic for years – especially outside the United States.  Authors note that topiramate is satisfactorily tolerated and a high percentage those with migraine respond favorably to its administration.  It was concluded that topiramate is a viable first-line intervention for migraine prophylaxis and that even patients may prefer topiramate to other interventions as a result of its side effect profile (e.g. weight loss).

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/19412473

2005: Topiramate for migraine prevention in children: a randomized, double-blind, placebo-controlled trial.

Most of the literature discussing Topamax as a migraine prophylactic evaluates its efficacy in adult populations.  A study by Winner et al. (2005) sought to determine whether Topamax could be effective and safe as an antimigraine agent among pediatrics.  Researchers prepared a double-blind, placebo-controlled trial and recruited 162 children (between 6 and 15 years of age) that had been diagnosed with migraine (with or without aura).

The 162 pediatrics with migraine were randomized at a 2:1 ratio to receive either: Topamax (112 patients) or a placebo (50 patients).  The trial was set-up to incorporate a titration phase (in which Topamax dosing was calibrated) and a maintenance phase (in which dosing was maintained).  During the 8-week titration phase, Topamax dosing started with 15 mg/day and was titrated upwards until the pediatrics received between 2 mg/kg and 3 mg/kg per day.

The maximum dose in the study allowed for the pediatrics was 200 mg/day.  After each pediatric had been titrated to a stable dose, the dosage was maintained for a duration of 12 weeks.  Efficacy of Topamax was determined based on change in average number of migraine days per month compared to a 4-week pre-treatment baseline phase.

Results indicated that Topamax administration decreased migraine days per month by 2.6 days, whereas the placebo decreased migraine days per month by 2 days.  Based on this finding, it appeared as though Topamax was not statistically therapeutic among pediatrics for the reduction of migraines.  It was noted that 32% of patients receiving Topamax experienced at least a 75% reduction in average number of migraine days per month compared to the placebo (just 14%).

Researchers concluded that Topamax could be an effective migraine prophylactic among pediatrics and was well-tolerated.  The evidence gathered from this study does not support the clinical usage of Topamax as a presentative agent for pediatric migraines.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/16324162

2005: Topiramate in migraine prevention.

A publication by Silberstein (2005) confers Topamax for the prophylaxis of migraines.  Silberstein noted that Topamax was significantly effective in multiple randomized, placebo-controlled, double-blind trials.  It was also approved in 2004 by the FDA for usage as a prophylactic for adults with migraine in the United States.

Other countries such as: Australia, Brazil, France, Ireland, Spain, and Switzerland – have also approved Topamax as migraine preventative.  Dosages of either 100 mg/day or 200 mg/day appear to significantly minimize the frequency of migraine headache frequency, total number of days with migraine, and administration of abortive pharmacology.  From the available research, Silberstein recommends that most patients undergoing treatment take 100 mg/day.

Some common adverse effects associated with treatment included: appetite reduction, diarrhea, fatigue, paresthesia, taste abnormalities, and weight loss.  Although the drug is not devoid of side effects, it is generally well-tolerated.  In conclusion, Silberstein notes that Topamax is a first-line migraine prophylactic and may be a preferred treatment among those with comorbid epilepsy and/or obesity.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/15833091

2005: Topiramate monotherapy in epilepsy and migraine prevention.

Pillaging through the literature of Topamax as a migraine prophylactic, it becomes apparent that Silberstein is a highly-dedicated migraine researcher.  In 2005, a publication by Silberstein et al. assessed the efficacy of Topamax as a monotherapy for migraine prophylaxis, as well as epilepsy.  For this report, Silberstein and his team collected data from controlled trials published in databases of PubMed and BIOSIS dating back to 1987.

An analysis of the literature evaluating the monotherapeutic value of Topamax for migraine prophylaxis suggested that 100 mg/day reduced monthly migraine frequency by at least 50% in around half of all patients tested (49-54%).  It was noted that trials of Topamax for the prevention of migraine attacks implemented a starting dose of just 25 mg/day and titrated up by 25 mg weekly until a threshold dose of 100 mg/day was reached.  While some adverse reactions were reported, most were managed with patient-provider communication.

This provides additional evidence to support the usage of Topamax as a monotherapy among migraine sufferers.  Around half of all patients appear to derive clinically significant benefit, characterized by at least a 50% reduction in the occurrence of migraines.  Moreover, any adverse or unwanted reactions are often mitigated with slight dosing adjustments.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/15811478

2005: Practical use of topiramate for migraine prevention.

A report by Brandes (2005) provided some guidelines to clinicians prescribing Topamax as a migraine prophylactic.  Brandes noted that when treating migraine, it is necessary to prescribe combinations of abortive and prophylactic interventions.  It was mentioned that effective migraine prophylactics should be reserved for patients experiencing at least 2 migraines per month or those with very severe, painful attacks.

In this report, Brandes highlights the fact that Topamax has been proven effective as a migraine prophylactic and is well-tolerated among adult patients.  Some adverse effects such as:  anorexia, diarrhea, fatigue, nausea, paresthesia, etc. – can occur among patients, but are usually considered tolerable.  On average, it can take between 2 and 3 months to reap the full therapeutic (prophylactic) effect of most medications.

That said, it appears as though Topamax can attenuate symptoms for many patients within the first month of administration.  The author underscores some practical ways in which Topamax can be utilized as a preventative agent among those with migraines, as well as outlines some strategies for maximizing its efficacy while reducing likelihood of side effects.  Based on this report, it is clear that the author is a supporter of using Topamax as a migraine prophylactic.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/15833092

2004: Topiramate in migraine prevention: results of a large controlled trial.

Researchers Silberstein et al. (2004) reflected upon the fact that Topamax appeared effective as a migraine prophylactic in small-scale, open-label trials.  Based on these findings, they aimed to evaluate Topamax’s efficacy (as a migraine prophylactic) and safety in a trial of their own.  They planned a randomized, placebo-controlled, double-blind study to take place over a duration of 26-weeks.

For the study, they recruited a total of 478 patients (between ages of 12 and 65) that had a 6-month history of migraine headaches, and experienced between 3 and 12 migraines per month (on average).  During a 28-day baseline phase of the trail, none of the participants experienced more than 15 headache days – suggesting that none were diagnosed with chronic migraine.  The 478 participants were randomly assigned to receive either: Topamax (50 mg, 100 mg, 200 mg – per day) or a placebo.

Those receiving the Topamax were titrated upwards with dosing by 25 mg per week for an initial 8-week term.  Thereafter, a maintenance phase took place for an additional 18-week period.  The efficacy of the intervention was determined based on a reduction in the average frequency of monthly migraine attacks over 6-months of the trial.

Secondary measures included: rates of response, duration to onset of symptomatic reduction, and average change in number of days in which patients utilized abortive medications.  Of the 460+ participants that completed the trial, those taking Topamax between 100-200 mg/day exhibited significant reductions in migraine frequency compared to the placebo groups.  Therapeutic benefit associated with Topamax was attained in less than 1 month.

Few adverse reactions were reported and the drug was considered well-tolerated.  Researchers concluded that Topamax is an effective agent for prophylaxis of migraines.  Since this study was large-scale (over 400 participants), occurred over a long-term (6+ months), and robustly designed (placebo-controlled, double-blinded, randomized) – it provides strong evidence to support the clinical use of Topamax for migraine prevention.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/15096395

2002: Prophylaxis of migraine, transformed migraine, and cluster headache with topiramate.

A report by Mathew et al. (2002) published in the journal “Headache” documented the efficacy of topiramate for the prevention of migraine and cluster headache.  Understand that at the time of this report, topiramate had not yet received FDA approval as a migraine prophylactic.  Researchers speculated that topiramate exhibited a multi-modal mechanism of action that was possibly useful as a migraine/headache prophylactic.

The team of researchers conducted a retrospective chart review by analyzing a total of 178 patients with either: transformed migraine (96 patients), episodic migraine (70 patients), or cluster headache (12 patients).  All patients had received Topamax as either a monotherapy or adjuvant intervention (along with conventional pharmacology).  Upon commencement of Topamax, dosages were administered at 25 mg/day for the first week and increased by 25 mg per week until patients reached a tolerable dose; maximum upper threshold for dosing was 200 mg/day.

It should be noted that all patients with transformed migraine and cluster headache received Topamax as an adjunct, whereas all individuals with episodic migraine received it as a standalone monotherapy.  To determine efficacy of Topamax, researchers evaluated: migraine frequency, severity of migraine, total number of headache days per month, abortive medication usage per month, the MIDAS (migraine disability assessment) scale, and patient global evaluation.  Results indicated that among those with transformed migraine: frequency of attacks dropped from 6.3 to 3.7 days (out of 28), migraine severity dropped from 7.1 to 3.8 (with 10 being the highest score), and average number of headache days per month dropped from 22.1 to 9.6 days – all as a result of adjuvant Topamax.

What’s more, it appeared as though adjuvant Topamax for those with transformed migraine reduced the number of abortive migraine pills administered per month from 28.7 to 10.6, and decreased migraine disability scores as evidenced by a change in MIDAS scale scores from 90.2 to 24.9.  Among the 70 patients with episodic migraine that received Topamax as a standalone monotherapy, migraine frequency decreased from 5.8 to 1.9 days (out of 28), and migraine severity was reduced from 8.1 to 2 (with 10 being the highest).  Around 61% of patients with episodic migraine claimed to experience substantial prophylaxis as a result of Topamax.

Of the 12 patients with cluster headaches receiving Topamax as an adjunct, 9 reported noticeable symptomatic improvement; the remaining 3 reported unchanged symptoms.  Though some patients discontinued treatment as a result of adverse reactions (e.g. paresthesia), none discontinued from lack of efficacy.  Researchers concluded that Topamax is an effective first-line monotherapy for those with episodic migraine, as well as an effective adjunct for those with transformed migraine and/or cluster headache.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/12390644

2002: Topiramate: a case series study in migraine prophylaxis.

In 2002, Young et al. gathered data from the electronic medical records of 74 individuals diagnosed with migraine; 50 with chronic (transformed) migraine and 24 with episodic migraine.  All patients included in this study had received Topamax as a treatment for a minimum of 6-weeks.  Approximately 81% of patients began treatment with 25 mg/day and titrated upwards until they were taking 100 mg twice daily (200 mg total).

Assessment of their records indicated that Topamax treatment reduced headache frequency from 20.6 to 13.6 days per month.  Data suggested that 44.6% of all migraine patients experienced at least 50% reduction in headache frequency; a greater percentage of episodic migraine patients (58.3%) responded than did chronic migraine patients (38%).  It was also evident that headache severity (on average) decreased from 6.2 to 4.8 (on a 10-point severity scale).

Regardless of whether patients took Topamax as a monotherapy or adjunct, headache frequency reductions were significant.  Over half of all participants experienced some mild/moderate adverse effects such as paresthesia and cognitive deficits.  Nonetheless, results from this study indicate that Topamax is effective for the prevention of migraine – perhaps more so among those with episodic subtypes compared to chronic (transformed) subtypes.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/12383061

2001: Topiramate in migraine prevention: a double-blind, placebo-controlled study.

A study by Storey et al. (2001) sought to determine the efficacy of Topamax as a prophylactic solely among those diagnosed with episodic migraine.  The International Headache Society considers episodic migraine as a subtype of migraine headache characterized by fewer than 15 headaches per month.  Comparatively, those with chronic migraine are said to exhibit 15 or more headaches per month over a 3-month term.

This study was published prior to the FDA approval of Topamax for migraines, but after its approval for partial seizures.  At the time, researchers noted that, based on preliminary findings, antiepileptic agents were effective for migraine prevention.  For this reason, researchers organized a double-blind, placebo-controlled trial of Topamax among 40 patients (between ages 19 and 62) diagnosed with episodic migraine.

The 40 patients were divided into two groups and assigned at random to receive either Topamax or a placebo.  Prior to administration of Topamax and the placebo, researchers assessed migraine frequency for a 1-month baseline period.  After the initial baseline phase, Topamax and placebo agents were administered; the Topamax was started at 25 mg/day and titrated upwards by 25 mg per week over an 8-week period for a maximum dose of 200 mg/day.

After the 8-week titration phase, an 8-week maintenance phase followed and all patients were monitored.  Throughout the entire study, patients receiving Topamax experienced significantly fewer migraines compared to the placebo.  Topamax appeared to reduce frequency of migraine attacks by approximately 36% compared to the 14% reduction as was noted among the placebo group.

It was also mentioned that more than 1-in-4 patients taking Topamax experienced at least a 50% reduction in the frequency of migraine attacks.  Furthermore, Topamax was well-tolerated with few unwanted or adverse effects.  Researchers concluded that while Topamax appeared therapeutically effective in this small-scale trial, larger-scale studies were necessary to confirm its hypothesized prophylactic.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/11903524

Limitations associated with research of Topamax for migraines

Most studies assessing the efficacy, safety, and tolerability of Topamax for migraines are well-designed (placebo-controlled and randomized).  In nearly all studies, the drug was more effective than a placebo in preventing migraines and headaches.  That said, some current limitations associated with the research include: unclear effects in pediatrics, unknown long-term effects, as well as uncertain sustainability of efficacy.

  • Long-term effects: Although the literature suggests that initial side effects tend to subside as an individual continues using Topamax, much of the research is of limited length. No studies have been conducted over a period of years (or longer) to determine whether users experience any adverse effects that emerge after a long-term.  Consider that the drug may provoke serious or unwanted long-term effects that haven’t been reported in literature (due to shortness of studies).
  • Pediatric populations: Research of Topamax has been able to demonstrate that the drug is well-tolerated and safe in pediatrics with migraine. However, one study found that despite its safety and tolerability, it was no more effective than a placebo.  Other research suggests that it is effective as a migraine prophylactic in pediatrics.  Due to this conflicting evidence and lack of FDA approval for the treatment of pediatric migraines, whether Topamax should be used among pediatrics is up for debate.  Furthermore, one must consider the potentially deleterious long-term implications of Topamax administration to individuals with developing brains.
  • Sustained efficacy: The prophylactic benefit of Topamax is first attained after 1-3 months of administration. At this point, it is unclear as to whether Topamax continues to effectively prevent migraines at the exact same dosage over a long-term.  One may suspect that the body develops a tolerance to the drug and its efficacy dwindles, thus requiring an increase in dose (which may increase side effects).  Furthermore, it is possible that the drug stops working – regardless of a dosage increase, thereby requiring users to switch to a different prophylactic.

Verdict: Topamax effective as a migraine prophylactic

Upon analysis of the full body of literature investigating the efficacy of Topamax as a migraine prophylactic, results (from nearly all studies) indicate that it is a highly-effective intervention.  Clinical guidelines list Topamax as a “first-line” therapy for the prophylaxis of migraines, and consider it to be safe and well-tolerated with few adverse effects.  The FDA supports usage of Topamax at dosages up to 100 mg/day, taken in 2 separate doses of 50 mg.

Certain studies suggest that adults may be able to tolerate Topamax at even higher dosages (of 200 mg/day, taken in 2 separate doses of 100 mg).  Among adolescents and children, smaller doses of Topamax appear to be more effective.  For pediatrics, the optimal dosage of Topamax is anything under 2 mg per kilogram (of body weight) per day.

Hypothetically speaking, a child weighing 60 pounds would be unwise to exceed a dosage of 55 mg per day; no additional benefit is attained from the higher dosing.  Additionally, regardless of whether a patient is adult or pediatric, the lower the dosage administered, the less severe the side effects.  For this reason, medical professionals should work with patients to find and utilize the minimal effective dose (or smallest amount of Topamax necessary to prevent migraines).

In summary, the research indicates that Topamax is effective, safe, and generally tolerable as a migraine prophylactic – regardless of migraine subtype.  It may be slightly more effective among those with episodic migraine compared to chronic migraine, but can work well for both.  Over half of all patients receiving Topamax for migraine prophylaxis experience at least a 50% reduction in average number of migraine attacks (per month).

  • Source: http://www.americanheadachesociety.org/assets/1/7/Topiramate_for_Migraine_Prevention_May_2012.pdf

Have you tried Topamax (Topiramate) for migraine prevention?

If you’ve used Topamax for the treatment of migraines, be sure to share your experience in the comments section below.  Discuss whether you found the drug to be an effective migraine prophylactic (or ineffective).  If you responded well to to treatment with topiramate, provide some additional details such as: degree of migraine reduction as a result of treatment (e.g. 60%) and how long it took for you to experience full prophylactic benefit (e.g. 2 months).

To help others get a better understanding of your situation, share: whether you take Topamax as a standalone intervention (or along with other medications and/or supplements), how long you’ve been using it, and your dosage (e.g. 100 mg/day).  Have you noticed any side effects resulting from your treatment that you particularly liked or disliked?  Do you believe that Topamax will remain effective for years or eventually stop working in the future as a result of tolerance?

Understand that while migraine patients may want to first consider non-pharmacological prophylactics (e.g. sleep optimization, dietary alterations, exercise, magnesium, etc.) before pharmaceuticals, Topamax is a viable intervention for those who wish to reduce the frequency of migraine attacks.  If a reduction from 12 to 6 migraine attacks per month would be life-changing and improve your ability to function, you could talk to your doctor about Topamax.  While there are other prophylactic options to consider, Topamax is among the most effective.

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