How Topiramate Is Used for the Treatment of Alcoholism

The problem with mixing Topamax and alcohol

How Topiramate Is Used for the Treatment of Alcoholism

If you’re wanting to imbibe after taking your migraine medicine, here’s what you should know

If you experience migraine, you’re not alone. Migraine is the third most prevalent illness worldwide—almost one in four households include someone with migraine. Migraine can be incapacitating, causing missed work and school days. In addition to throbbing pain, migraine is often accompanied by many other uncomfortable symptoms, such as visual disturbances, nausea, vomiting, and dizziness. 

With June being Migraine and Headache Awareness Month, we want to shine a light on things that can affect people with migraines. One such complication is drinking with your migraine medication, such as Topamax.

What is Topamax?

Topamax (topiramate) is a popularly prescribed drug used to treat certain types of seizures in people ages two years and older. The medication is also used to prevent migraine in people ages 12 years and older. Topamax is not used to treat a migraine attack. It is only used for prevention.

Topamax, any other medication, has many potential side effects. Some common side effects of Topamax include weakness, dizziness, drowsiness, appetite/weight loss, mood changes (anxiety, depression, suicidal thoughts and behavior), memory and sleep problems, and a feeling of pins and needles. 

One common question among people who take Topamax is: Can I mix Topamax and alcohol?

Can you take Topamax with alcohol?

Unfortunately, Topamax and alcohol do not mix. The manufacturing information for Topamax warns, “Do not drink alcohol while taking Topamax. Topamax and alcohol can affect each other, causing side effects such as sleepiness and dizziness.”

As for other forms of Topamax, it’s also a no.

Trokendi XR is an extended-release form of topiramate, the same ingredient in Topamax. Trokendi XR is indicated to treat certain types of seizures in people ages 6 years and older. It is also used to prevent migraine in patients ages 12 years and older.

Alcohol is contraindicated (must not be used) within six hours of taking Trokendi XR. The manufacturer of Trokendi XR states that the way the drug works is “significantly altered” when in the presence of alcohol.

This could result in significantly higher levels soon after taking Trokendi XR and too-low levels later on. 

Qudexy XR is another extended-release form of topiramate. The manufacturer warns, “Do not drink alcohol while taking Qudexy XR. Qudexy XR and alcohol can cause serious side effects such as severe sleepiness and dizziness and an increase in seizures.”

Topamax and alcohol use disorder

Although Topamax is often used to treat seizures or prevent migraines, it has some off-label uses, too.

Although there is not much data, some studies show that Topamax can help decrease alcohol consumption.

A review by the Agency for Healthcare Research and Quality (AHRQ) concluded that topiramate could reduce the number of drinking days, heavy drinking days, and drinks per day two trials.

Can you drink alcohol while taking anticonvulsants?

According to the National Institute on Alcohol Abuse and Alcoholism, alcohol should not be mixed with any anticonvulsant due to increased drowsiness and dizziness. In addition to Topamax, these medications include:

  • Dilantin (phenytoin)
  • Keppra (levetiracetam)
  • Klonopin (clonazepam)
  • Lamictal (lamotrigine)
  • Lyrica (pregabalin)
  • Neurontin (gabapentin)
  • Phenobarbital 
  • Tegretol (carbamazepine)
  • Trileptal (oxcarbazepine)

Does alcohol make seizures worse?

Keep in mind that everyone is different. Talk with your doctor to determine if you can drink alcohol at all, and if so, how much you can safely drink depending on your symptoms, medical history, and any medications you take. 

Small amounts of alcohol, such as an occasional one or two drinks, generally do not increase seizure activity or affect seizure medications in your body.

Seizures related to alcohol are often associated with alcohol withdrawal rather than the act of drinking; however, consuming three or more alcoholic beverages may significantly increase the risk of seizure.

Binge drinking and resulting alcohol withdrawal may lead to status epilepticus, which could potentially be fatal. 

Chronic alcohol abuse (alcoholism) may be linked to the development of epilepsy in some instances. People who have had seizures after binge drinking may begin to have seizures even when not consuming alcohol.

If your doctor says you may consume alcohol in small amounts or moderation, you should:

  • Avoid binge drinking because binge drinking can cause withdrawal seizures.
  • Not abuse alcohol—get help if you need it.
  • Drink small amounts—less than three drinks—and drink slowly.
  • Talk to your doctor about alcohol consumption as related to seizures and medication.
  • Not drive (this goes for alcohol consumption in general, of course) due to impaired coordination and increased sedation and dizziness.

Does alcohol make migraines worse?

According to the American Migraine Foundation, alcohol may trigger a migraine attack. Alcohol can trigger an attack within several hours. It can also cause a hangover headache.

If you find that a small amount of alcohol does not trigger a migraine attack or a hangover headache, consult your doctor about appropriate amounts to consume. However, keep in mind that the medication(s) you take to prevent and treat migraines may interact with alcohol.

Your doctor can examine your medical history and conditions as well as any medications you take, to determine how much alcohol, if any, is safe for you to consume.

People with liver problems may not eliminate topiramate properly, leading to increased topiramate levels, potentially increasing side effects. The manufacturer suggests using topiramate with caution in people with impaired liver function. 

In rare cases, people with liver problems who take Topamax, especially when also taking valproic acid, may be at higher risk for hyperammonemia (a dangerous condition caused by high levels of ammonia) with or without encephalopathy (brain disease or damage). Symptoms may include unexplained tiredness, vomiting, or mental status changes and should receive immediate medical attention. 

Suicidal thoughts and behavior

It is important to recognize that anticonvulsant drugs, including Topamax, increase the risk of suicidal thoughts and behavior, regardless of the indication for which the person is taking the medication. When taking an anticonvulsant, the patient must be monitored closely for mood or behavior changes, depression, and suicidal thoughts and behavior. 

A study looked at data about alcohol use and suicide. It found that “alcohol abuse is a means of easing one’s psychological stress but, at the same time, impacts on all other factors, rendering suicide more ly.” 

Since both alcohol and Topamax can potentially cause suicidal thoughts or behavior individually, the impact together could be greater. 

Consult your doctor

Medications and alcohol affect everyone differently. Talk to your healthcare provider if you have questions about Topamax and alcohol interactions or about alcohol in combination with your medical conditions. 

Источник: https://www.singlecare.com/blog/topamax-and-alcohol/

Topiramate for alcoholism treatment: novel pharmacogenetic evidence for the journey to personalized medicine?

How Topiramate Is Used for the Treatment of Alcoholism

Alcoholism, pharmacogenetics, topiramate

The small number of medications approved for the treatment of alcoholism is, by itself, an important justification for the significant efforts directed towards medication development.

Perhaps an even more important issue is why a medication (approved or used off-label) does not always reproduce the same results across randomized clinical trials (RCTs).

Indeed, even clinical trials that find effects report that there are both treatment responders and non-responders, and the ability to identify responders and non-responders could help explain variation across clinical trials.

This variation forms the foundation of ‘personalized medicine’ approaches, and highlights the need to identify patient sub-types that respond better to a certain medication.

Although typologies ( Leggio et al., 2009 ) provide phenotypic traits that may be applied in RCTs, pharmacogenetics ( Heilig et al., 2011 ) represents an even more compelling approach, as it is more reproducible, biologically-based and mechanistic.

Although in its infancy, the alcoholism pharmacotherapy literature has already shown the potential value of pharmacogenetics as a way to develop personalized medicine.

The functional OPRM1 polymorphism A118G plays an important role in the effects of naltrexone on alcohol consumption, with G-allele carriers responding more positively to treatment than A-allele homozygotes ( Oslin et al., 2003 ; Anton et al., 2008 ; Barr et al., 2010 ; Kranzler et al., 2013 ).

A functional polymorphism in the promoter region of the serotonin transporter gene, SLC6A4 , known as 5-HTTLPR, results in a long (L) and a short (S) allele. Alcoholic patients who were L homozygotes had significant reductions in alcohol use when treated with ondansetron, as compared to S carriers ( Kenna et al., 2009b , 2014; Johnson et al.

, 2011 , 2013 ). It has also been shown that the tri-allelic 5-HTTLPR polymorphism moderated the effects of sertraline and age at onset of alcohol dependence on the frequency of drinking and heavy drinking ( Kranzler et al., 2011 ).

Finally, clinical trials testing the role of acamprosate in alcoholism have generated conflicting results ( Kiefer and Mann, 2010 ), but preliminary findings suggested that an intronic SNP (rs13273672) in the gene for GATA-binding protein 4 ( GATA4 ) was associated with relapse, an effect that was mainly patients’ positive response to acamprosate ( Kiefer et al., 2011 ).

Topiramate is an anti-epileptic medication that is currently approved to treat epilepsy, prevent migraine, and (in combination with phentermine) promote weight loss.

Topiramate increases GABA A -facilitated neuronal activity and simultaneously antagonizes AMPA and kainate glutamate receptors ( Kenna et al., 2009a ). In the first RCT of topiramate, Johnson et al.

(2003) demonstrated the efficacy of this drug in reducing alcohol consumption and promoting abstinence in 150 alcoholic patients randomized to placebo or topiramate 300 mg/d.

A second, larger RCT ( n = 371) confirmed a robust effect of topiramate 300 mg/d as a treatment for alcoholism ( Johnson et al., 2007 ), while an additional small clinical trial ( n = 106) with alcoholic patients receiving a residential treatment program failed to show any differences between topiramate and placebo ( Likhitsathian et al., 2013 ).

The overall conclusion is that topiramate represents a promising medication for alcoholism ( Johnson and Ait-Daoud, 2010 ). However, no research has been conducted to identify possible endophenotypic characteristics of alcoholic patients who may or may not respond to topiramate.

Additionally, a clinical concern with topiramate has been the potential for significant adverse effects, especially cognitive and neurological ones. For example, in one study, paresthesia and difficulties with concentration were significantly more frequent in the topiramate than in the placebo group ( Johnson et al., 2007 ).

Of note, however, most adverse effects appear to be dose-related ( Kenna et al., 2009a ), suggesting that lower doses of topiramate may be safer. Interestingly, a human laboratory placebo-controlled pilot study comparing two doses of topiramate (200 and 300 mg/d) found that the effects of topiramate on alcohol use were evident by the third week of treatment (i.e.

while the drug was still being titrated), suggesting that lower doses than 300 mg/d may be effective ( Miranda et al., 2008 ).

This same study also found that topiramate, compared to placebo, reduced alcohol-related stimulation effects, which was suggested as a possible biobehavioral mechanism of action, but this was only observed for those receiving 200 mg/d of the medication ( Miranda et al., 2008 ). In summary, preliminary evidence suggested that investigating lower doses of topiramate, such as 200 mg/d, may be of scientific and clinical value.

A recently completed RCT by Kranzler et al., offers new and compelling evidence to support this view. This study, conducted in 138 heavy drinkers who were interested in reducing their alcohol consumption to safe levels, used the lower 200 mg/d dose of topiramate. The main results, published elsewhere ( Kranzler et al.

, 2014b ), indicate that even at this dosage, the medication was significantly better than placebo in reducing heavy drinking days and increasing abstinent days.

Perhaps more interesting, however, was the secondary finding that the efficacy of topiramate, which exerts effects on glutamate activity through kainate receptors containing GluK1 or GluK2 subunits, was moderated by a single nucleotide polymorphism (rs2832407) in GRIK1 , the gene encoding the GluK1 receptor subunit.

In the subsample of European Americans ( n = 122), topiramate was effective in reducing heavy drinking days only in rs2832407 C-allele homozygotes. In addition, a previous pharmacogenetic analysis of the human laboratory pilot study mentioned previously ( Miranda et al.

, 2008 ) showed that rs2832407 was associated with the severity of topiramate-induced side effects ( Ray et al., 2009 ). The RCT by Kranzler et al. (2014) did not find an effect of the SNP on adverse events, suggesting that the kainate receptor does not play a unique role in mediating topiramate-related adverse effects.

In the present issue of the International Journal of Neuropsychopharmacology , Kranzler et al. ( 2014a ) expand on their initial findings from the same RCT with respect to genetic moderation by GRIK1 .

They report that rs2832407*C allele homozygotes treated with topiramate consumed significantly less alcohol, as measured by patients’ daily reports obtained using interactive voice response (IVR) technology, an innovative approach that takes advantages of technology-based assessment techniques (for a review, see ( Gurvich et al., 2013 )). In addition, rs2832407*C allele homozygotes reported larger decreases in both positive alcohol expectancies and the desire to drink. Thus, the results of the present study corroborate findings from the parent report concerning drinking behavior ( Kranzler et al., 2014b ), and add novel information in the form of medication × genotype effects on the motivation to drink.

The present findings are of clinical relevance as they suggest a path to consider topiramate within a personalized medicine framework.

The authors provide a comprehensive discussion of possible directions that this research may lead in, including enrichment strategies for future RCTs (e.g.

prospective genotyping), development of animal models via the manipulation of GluK1, and medications development focused on the GluK1-containing kainate receptor.

While it may be premature to envisage genotyping rs2832407 to inform the decision on whether to treat individuals with topiramate, an RCT with prospective genotyping for this SNP could not only validate these findings but also provide an approach that, in the future, might be applied to real-world clinical settings. Although speculative at this stage, the present findings may represent the avant-première of a much anticipated future where primary care physicians can take a buccal swab, analyze patients’ genetic make-up, and then decide which medication to prescribe to their alcoholic patients.

A few years ago, Kranzler et al. (2009) reported a significant association between rs2832407 and alcohol dependence.

The more recent RCT provides additional evidence in support of the role of this SNP in alcohol use disorder by suggesting that the kainate receptor plays a key role in the mechanism by which topiramate affects not only drinking behavior but, perhaps at a more fundamental level, the motivation to drink. Despite these compelling pharmacogenetic data for topiramate, the need for functional validation remains. In this regard, genetic manipulations such as with GluK1 knockout (KO) mice may provide important information. Although one may dispute the clinical validity of KO models, a reverse translational approach could provide functional validation of the present clinical findings and generate useful information, even beyond the role of topiramate sensu stricto.

Last but not least, the present findings could also serve as the basis for the development of novel medications for alcoholism that specifically target the GluK1 receptor. Although selective GluK1 ligands have been synthesized (e.g. Venskutonyte et al.

(2011) ) and tested in humans, including healthy controls ( Petersen et al., 2014 ) and patients with chronic pain conditions ( Chappell et al., 2014 ), it may be some time before these compounds can be tested in alcoholic patients.

In actuality, the efficacy of topiramate may be due to its multiple pharmacological mechanisms of action, rather than those specific to the GluK1 receptor.

Nonetheless, the development of a selective GluK1 ligand with potential effects on alcohol consumption remains an important avenue for clinical research.

In summary, although additional studies are needed, including replications and extensions to non-European-American populations, the Kranzler et al. findings are of scientific, pharmacological, pharmacogenetic, and clinical interest and represent an exciting platform for future research aimed at novel personalized medicine approaches.

Acknowledgments

This work was supported by the Division of Intramural Clinical and Biological Research of the National Institute on Alcohol Abuse and Alcoholism (NIAAA) and the Intramural Research Program of the National Institute on Drug Abuse (NIDA). The content of this review is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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Источник: https://academic.oup.com/ijnp/article/17/10/1541/2356752

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