Does topiramate cause weight loss. How effective is topiramate for weight management. What are the side effects of using topiramate for weight loss. Is topiramate FDA-approved for weight loss. How does topiramate compare to other weight loss medications.

Understanding Topiramate: Uses and Mechanisms

Topiramate, commercially known as Topamax, is primarily classified as an anticonvulsant medication. Its primary uses include:

• Control of certain types of seizures in epilepsy
• Prevention of migraine headaches
• Treatment of partial-onset seizures
• Management of primary generalized tonic-clonic seizures
• Treatment of seizures associated with Lennox-Gastaut Syndrome

While not originally designed for weight loss, topiramate has shown a notable side effect of reducing body weight in many patients. This unexpected benefit has led to increased interest in its potential as a weight management tool.

How does topiramate work?

Topiramate’s mechanism of action is complex and not fully understood. However, it is believed to work through several pathways:

1. Blocking voltage-dependent sodium channels
2. Enhancing GABA activity
3. Antagonizing glutamate receptors
4. Inhibiting carbonic anhydrase enzymes

These actions collectively contribute to its anticonvulsant and migraine prevention properties. The weight loss effect is thought to be related to its impact on appetite regulation and metabolism, although the exact mechanisms remain under investigation.

Evidence of Weight Loss in Topiramate Studies

Clinical studies have consistently shown weight loss as a side effect of topiramate use, both in adults and children. The extent of weight loss appears to be dose-dependent, with higher doses generally resulting in more significant weight reductions.

Adult Studies

In studies focusing on seizure control in adults aged 16 and older:

• 6% of patients taking 50 mg/day experienced weight loss
• 17% of patients taking 400 mg/day reported weight loss

For migraine prevention in adults:

• 6% of patients on 50 mg/day experienced weight loss
• 9% of patients on 100 mg/day reported weight loss
• Only 1% in the placebo group lost weight

Pediatric Studies

In children aged 6 to 15 years taking topiramate for seizures:

• 7% experienced weight loss at 50 mg/day
• 17% reported weight loss at 400 mg/day

For migraine prevention in adolescents aged 12 to 17:

• 7% lost weight on 50 mg/day
• 4% lost weight on 100 mg/day
• 2% in the placebo group experienced weight loss

Topiramate and Appetite Suppression

One of the key factors contributing to weight loss in topiramate users is its effect on appetite. Anorexia, or loss of appetite, has been reported as a common side effect in clinical studies.

Anorexia rates in adults

For seizure control:

• 4% of patients on 50 mg/day reported anorexia
• 14% of patients on 400 mg/day experienced anorexia

For migraine prevention:

• 9-15% of patients on topiramate reported anorexia
• 6% in the placebo group also experienced anorexia

Anorexia in children

Interestingly, anorexia was not reported in children aged 6 to 15 taking topiramate for seizures. However, in adolescents aged 12 to 17 using it for migraine prevention:

• 9-10% experienced anorexia
• 4% in the placebo group reported anorexia

Topiramate for Weight Loss: FDA Approval Status

Despite its observed effects on weight, topiramate itself is not FDA-approved specifically for weight loss when used alone. However, it’s important to note that doctors may prescribe it off-label for weight management, especially in patients who also require its primary benefits for seizure control or migraine prevention.

Qsymia: FDA-approved combination therapy

While topiramate alone isn’t approved for weight loss, it is a component of an FDA-approved weight loss medication called Qsymia. This extended-release formulation combines topiramate with phentermine, an appetite suppressant.

Qsymia is indicated for:

• Treatment of obesity (BMI ≥ 30 kg/m²)
• Overweight individuals (BMI ≥ 27 kg/m²) with at least one weight-related comorbidity such as hypertension, dyslipidemia, or type 2 diabetes

It’s crucial to note that Qsymia is prescribed as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management.

Side Effects and Discontinuation of Topiramate

While weight loss can be a desirable effect for some patients, topiramate is associated with numerous other side effects that may impact its tolerability and long-term use.

Common side effects

Aside from weight loss and anorexia, other frequently reported side effects include:

• Paresthesia (tingling sensation)
• Fatigue
• Dizziness
• Nausea
• Difficulty with memory or concentration
• Insomnia
• Somnolence (drowsiness)
• Taste perversion

Reasons for discontinuation

Interestingly, weight loss itself is not listed as a common reason for discontinuing topiramate treatment. However, other side effects may lead to discontinuation:

• In adults (400 mg/day): 21% stopped due to memory issues, fatigue, weakness, insomnia, drowsiness, and paresthesia
• In children (400 mg/day): 14% discontinued due to concentration/attention problems, fever, flushing, and confusion

Comparing Topiramate to Other Weight Loss Medications

While topiramate has shown effectiveness in weight reduction, it’s essential to consider how it compares to other FDA-approved weight loss medications.

Topiramate vs. Orlistat

Orlistat (Xenical, Alli) works by inhibiting fat absorption in the intestines. Unlike topiramate, it doesn’t affect appetite or metabolism directly. Orlistat typically results in modest weight loss (about 5-10% of body weight) and has fewer systemic side effects but can cause gastrointestinal issues.

Topiramate vs. Liraglutide

Liraglutide (Saxenda) is a GLP-1 receptor agonist that reduces appetite and slows gastric emptying. It’s administered via injection and can lead to significant weight loss (5-10% of body weight or more). However, it may cause nausea and other gastrointestinal side effects.

Topiramate vs. Phentermine-topiramate (Qsymia)

The combination of phentermine and topiramate in Qsymia has shown greater efficacy in weight loss compared to topiramate alone. Clinical trials have demonstrated average weight loss of 6.7% to 8.9% of body weight, depending on the dosage.

Considerations for Using Topiramate for Weight Loss

While the weight loss effects of topiramate are well-documented, several factors should be considered before using it primarily for this purpose:

Medical supervision

Given its potent effects and potential side effects, topiramate should only be used under close medical supervision. Regular monitoring is essential to manage side effects and adjust dosage as needed.

Potential for cognitive side effects

Topiramate has been associated with cognitive impairment, including difficulties with concentration, memory, and word-finding. These effects can be particularly problematic for some individuals and may outweigh the benefits of weight loss.

Long-term effects

The long-term effects of using topiramate for weight loss have not been extensively studied. It’s unclear whether the weight loss effects are sustained over extended periods or if there are any long-term health implications.

Combination with lifestyle changes

As with any weight loss intervention, topiramate is most effective when combined with a healthy diet and regular physical activity. It should not be viewed as a standalone solution for weight management.

Future Research and Potential Applications

The observed weight loss effects of topiramate have sparked interest in its potential applications beyond epilepsy and migraine prevention. Ongoing research is exploring several areas:

Metabolic syndrome

Some studies are investigating topiramate’s potential benefits in treating various components of metabolic syndrome, including insulin resistance and dyslipidemia.

Binge eating disorder

Topiramate has shown promise in reducing binge eating episodes and associated weight gain in some studies, although more research is needed to establish its efficacy and safety for this indication.

Optimal dosing for weight management

Research is ongoing to determine the most effective and safe dosage of topiramate for weight loss, balancing efficacy with side effect profile.

Combination therapies

Building on the success of Qsymia, researchers are exploring other potential combination therapies that might enhance topiramate’s weight loss effects while minimizing side effects.

In conclusion, while topiramate has demonstrated significant weight loss effects, its use primarily for this purpose remains controversial and off-label. The decision to use topiramate for weight management should be made carefully, weighing potential benefits against risks, and always under the guidance of a healthcare professional. As research continues, we may gain a better understanding of topiramate’s role in weight management and its potential applications in treating obesity-related conditions.

Does topiramate cause weight loss?

Medically reviewed by Leigh Ann Anderson, PharmD. Last updated on Jan 19, 2023.

Key Points

• Yes, topiramate (Topamax) has been shown to cause weight loss when used for both seizure control and migraine prevention.
• Anorexia (loss of appetite), which may contribute to weight loss, has also been reported in studies in both children and adults, although no correlation was made in studies
• Topiramate (used by itself) is not specifically approved by the FDA for weight loss, but some doctors may prescribe it if you have seizures or migraine and need to lose weight, too. Side effects may hinder its use for weight loss when used alone.
• Topiramate is available in an extended-release medicine approved for weight loss known as Qsymia (phentermine and topiramate). Phentermine is an appetite suppressant (anorexiant) with characteristics similar to amphetamine. Qsymia is used along with diet and exercise to treat people who are either obese, or overweight with other risk factors like high blood pressure, high cholesterol or type 2 diabetes.

What is topiramate used for?

Topiramate is classified as an anticonvulsant (seizure) medication.

• Topiramate is a prescription medication, taken alone or with other drugs to control certain types of seizures due to epilepsy. Topiramate is used for the treatment of partial-onset seizures, primary generalized tonic-clonic seizures, and seizures associated with Lennox-Gastaut Syndrome.
• It is also used for the prevention of migraine headaches. Topiramate will not stop a migraine once it has started.

Brand names for topiramate available in the U.S. include Topamax, Trokendi XR, Topamax Sprinkle (discontinued), and Qudexy XR. Uses and dosage forms differ among products, and may not be interchangeable.

Related: Weight Loss and Diet Pills: Options to Know

Did weight loss occur in studies with topiramate?

Yes, weight loss was reported in studies of both children and adults. In general, weight loss was seen in 6% to 17% of patients, and tended to increase with higher doses.

Adults

Seizure control – Side effects were assessed in patients 16 years and older taking topiramate (Topamax) alone (without other seizure medicines) at two doses: 50 mg/day or 400 mg/day. Weight loss and loss of appetite (anorexia) were two of the most commonly reported side effects.

In the patients taking the lower 50 mg/day dose of topiramate, weight loss occurred in 6% of patients, and in the higher 200 mg/day dose, weight loss was reported in 17% of patients. Anorexia (loss of appetite), which may lead to weight loss, was also seen in 4% and 14% of patients, respectively.

When topiramate (Topamax) was studied in adults who used it in addition to other medicines (adjunctive treatment) for seizure control, weight loss occurred in 9% of patients receiving 200 mg/day to 400 mg/day, and 3% of those taking a placebo (an inactive pill). In children, these numbers were 9% and 1%, respectively.

Migraine prevention – In adults using doses of 50 mg/day for migraine prevention, 6% of patients experienced weight loss, while in the 100 mg/day group, 9% of patients reported weight loss. In contrast, 1% of patients in the placebo group lost weight. Anorexia occurred in 9% to 15% of those taking topiramate, but also occurred in 6% of those taking a placebo.

Children

Seizures – In children 6 to 15 years of age taking the 50 mg/day dose of topiramate (Topamax) for seizures, weight loss was seen in 7% of patients. In the higher dosage group (400 mg/day) weight loss occurred in 17% of children. Anorexia (loss of appetite) was not reported in either dose group for children 6 to 15 years old.

Migraine prevention – In adolescents 12 to 17 years of age, weight loss occurred in 7% (50 mg/day dose) and 4% (100 mg/day) compared to 2% in the placebo group. Anorexia occurred in 9% to 10% of patients taking topiramate and 4% of those taking a placebo.

Treatment discontinuation with topiramate

Weight loss is not listed in the product label as a common reason why patients discontinued treatment with topiramate (Topamax).

In studies, some patients stopped treatment due to other side effects.

• In adults 16 years and older in the high dose group (400 mg/day), 21% of patients stopped treatment due to difficulty with memory, fatigue, asthenia (weakness), insomnia (difficulty sleeping), somnolence (extreme drowsiness), and paresthesia (pins and needles or tingling feeling in extremities).
• In children 6 to 15 years of age in the high dose group (400 mg/day), 14% of patients stopped treatment due to difficulty with concentration/attention, fever, flushing, and confusion.

Topiramate is linked with many other side effects, including nausea, stomach pain, and taste perversion, which may impact weight loss or anorexia.

This is not all the information you need to know about topiramate for safe and effective use. Review the full topiramate (Topamax) information here, and discuss this and any questions you have with your doctor or other health care provider.

References

• Kramer CK, Leitão CB, Pinto LC, et al. Efficacy and safety of topiramate on weight loss: a meta-analysis of randomized controlled trials. Obes Rev. 2011 May;12(5):e338-47. PMID: 21438989
• Topiramate. Drugs@FDA: FDA-Approved Drugs. Accessed Jan. 29, 2021 at https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm
• Topamax [product monograph]. Drugs.com. Accessed Jan. 28, 2021 at https://www.drugs.com/pro/topamax.html
• Qysmia [product monograph]. Drugs.com. Accessed Jan 29, 2021 at https://www.drugs.com/pro/qsymia.html

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Medical Disclaimer

Does topiramate cause hair loss?

Medically reviewed by Leigh Ann Anderson, PharmD. Last updated on March 13, 2023.

• Yes, topiramate (Topamax) has been shown to cause hair loss (alopecia) in studies, but it is not a common side effect.
• Hair loss has been reported in 1% to 4% of children ages 6 to 16 years of age, and in 3% to 4% of patients older than 16 years of age.
• Higher daily doses (400 mg/day) of topiramate were associated with greater rates of hair loss than lower doses (50 mg/day) in both age groups.

Hair loss with topiramate has also been reported in case reports in the scientific literature.

• In one report, a 16-year old girl experienced hair loss after two months of using topiramate as an adjunctive treatment for epilepsy. The hair loss was reversed after treatment was stopped, but occurred again when topiramate treatment was restarted.
• In another case, an 18-year old patient being treated with topiramate 50 mg/day for migraines developed hair loss after 3 months. The medicine was tapered and discontinued and hair loss stopped. Two weeks after reintroduction of the topiramate hair loss developed again. Once again after treatment discontinuation, the hair loss ceased.

Hair loss is a common side effect reported with other antiepileptic agents such as valproic acid and carbamazepine, and may cause cosmetic, social and compliance consequences for patients.

What has the FDA approved topiramate to treat?

Topiramate is used to help prevent seizures, either used alone or with other seizure medicines, in certain forms of epilepsy in patients 2 years of age and older. It is approved for migraine prevention in patients 12 years and older.

Common brand names for topiramate or extended-release topiramate include:

• Topamax
• Qudexy XR
• Trokendi XR

Generic topiramate is available as an oral tablet, capsule or extended-release capsule in various strengths and may be less expensive than brand names. If preferred, ask your doctor if a generic formulation is possible for your condition.

Which side effects can I expect with topiramate?

The most common side effects (≥10% and more frequent than placebo) reported in epilepsy studies in both adults and children include:

• paresthesia (unusual feeling of the skin, such as burning, numbness, tingling, or “pin-and-needles”)
• anorexia (loss of appetite)
• weight loss
• speech disorders
• fatigue and somnolence (drowsiness)
• dizziness
• nervousness
• mental slowing, slowed reflexes
• vision changes
• fever

In migraine studies in adults and children, side effects (incidence ≥5% and more frequent than placebo) were:

• paresthesia
• anorexia, weight loss, nausea
• trouble with memory
• altered taste
• diarrhea
• hypoesthesia (a decrease in sensations such as the feeling of touch or temperature)
• stomach pain
• respiratory tract infection

Related: View topiramate side effects, warnings and drug interactions (in more detail)

This is not all the information you need to know about topiramate for safe and effective use and does not take the place of talking to your doctor about your treatment. Review the full patient information for topiramate and discuss this information and any questions you have with your doctor or other health care provider.

References

• Topamax (topiramate) Product Information. Revised 6/2020. Janssen Pharmaceuticals, Inc. Titusville, NJ. Accessed March 22, 2021 at https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020505s061,020844s052lbl.pdf
• Chuang Y, Chang W, Chen I, et al: Topiramate-Induced Hair Loss: Case Report. Dermatol Psychosom 2002;3:183-184.
• Ghafoor I, Hosseini H. Hair Loss Following The Topiramate Treatment. JBUMS. 2017; 19(2):71-74
• Trokendi XR (topiramate extended-release). Product information. Supernus Pharmaceuticals, Inc., Rockville, Maryland. Revised Nov. 2020. Accessed March 22, 2021 at https://www.trokendixr.com/assets/TrokendiXRPrescribingInformation.pdf

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Medical Disclaimer

Topiramate – Family clinic at home

Topiramate is an antiepileptic drug from the group of sulfate-substituted monosaccharides, used as mono- or combination therapy in almost all types of paroxysmal conditions. In the UK and USA, it is the drug of choice for patients with newly or recently diagnosed partial or generalized epileptic seizures. In pediatrics, indications for its use are Lenox-Gastaut syndrome, other paroxysmal conditions and developmental delay. In addition to the registered indications, topiramate can be used to treat obesity, bipolar affective disorder, nicotine addiction, post-traumatic stress disorder, neuropathic pain, bulimia, periventricular leukomalacia in premature infants, and to prevent migraine attacks. In bipolar disorders, it is used to normalize mood in all phases of the disease. Its possible therapeutic effect is being studied in patients with alcohol withdrawal syndrome, drug addiction. Against the background of taking topiramate, a dose-dependent decrease in body weight is observed; this process is reversible with a decrease in the dose of the drug.

The mechanism of action of topiramate is associated with the blockade of sodium and calcium channels, increased activity of GABAergic neurotransmission and blockade of the glutamatergic system, which leads to a weakening of epileptoform discharges in nerve cells.

The bioavailability of topiramate is about 80%, food intake does not affect its absorption. When taken orally, the drug is rapidly and efficiently absorbed and weakly binds to plasma proteins (13-17%). The pharmacokinetics of topiramate is linear: the plasma concentration of the drug is proportional to the dose taken. A stable blood level is achieved within 4-8 days of regular administration of the drug. Topiramate is metabolized by the liver by hydroxylation, hydrolysis and glucuronidation to form 6 inactive metabolites. Excreted by the kidneys mainly unchanged (70% of the drug). The half-life is 19-23 hours. In case of impaired renal or hepatic function, the clearance of the drug is reduced.

While taking topiramate, headache, dizziness, drowsiness, lethargy, impaired concentration, paresthesia, fatigue, taste perversion, in rare cases visual impairment, amnesia, ataxia, depression, emotional lability may occur. Side effects are believed to be dose dependent.

It is recommended to determine the level of the drug in the blood in cases of suspected overdose, as well as in patients with impaired liver and kidney function.

Do not eat for 4 hours before the test, you can drink pure non-carbonated water.
Do not smoke for 30 minutes prior to analysis.

Reference values: 5 – 20 mcg/ml.

The optimal therapeutic blood concentration of topiramate is 2-20 µg/ml, however, for some patients, the individual tolerated dose may vary significantly, and side effects may occur at low concentrations.

The toxic concentration of the drug in the blood has not been established.

What can influence the result?

Drugs that can reduce the concentration of topiramate in the blood: phenytoin, carbamazepine.
It is possible to increase the concentration of the drug in the blood in case of impaired liver and kidney function.

On the question of the balance of efficacy and safety when choosing topiramate as the main or additional treatment for epilepsy

Author:
I.A. Martsenkovsky

01/15/2018

Article PDF

Topiramate (original name – Topamax) is an antiepileptic drug (AED) with a non-standard chemical structure and a wide spectrum of action, introduced into clinical practice in the mid-1990s [1]. To date, there is a strong evidence base for its effectiveness as monotherapy or adjunctive therapy in adults and children over 2 years of age with generalized tonic-clonic seizures, partial seizures with or without secondary generalization, and seizures in Lennox-Gastaut syndrome.
All relevant indications are registered in Ukraine. In addition, topiramate is recommended as a drug for the prevention of migraine attacks in adults, which is also reflected in the official instructions for use.

According to the mechanisms of anticonvulsant action, topiramate differs from such classical AEDs as phenytoin and carbamazepine. Possessing the properties of a neuronal sodium channel blocker and, like many other AEDs, exhibiting membrane stabilizing activity, topiramate also interacts with GABA-A (gamma-aminobutyric acid) receptors and kainate/AMPA glutamate receptors (α-amino-3-hydroxy- 5-methyl-4-isoxazolepropionic acid) [2]. The complex receptor profile is thought to account for the wide range of efficacy of topiramate for various types of seizures, although the clinical significance of some of the mechanisms of action has not yet been fully elucidated.

Topiramate is characterized by attractive pharmacokinetics in terms of safety: it is excreted mostly unchanged, without the formation of pharmacologically active metabolites; practically does not affect the activity of liver enzymes in the therapeutic dose range. Hence, there are minimal interactions with other AEDs. The high oral bioavailability of the drug determines the possibility of its use regardless of meals [2].

In pediatric practice, the use of topiramate is accompanied by a discussion about the interchangeability of the original drug Topamax with generics.

Small differences between therapeutic and toxic doses necessitate very careful titration and careful monitoring of the side effects of AEDs. As shown by world practice, reflected in post-marketing prospective registries and the results of observational studies, bioequivalence data are not enough to identify generics with the original AED, with which all registration controlled studies were conducted [3, 4]. It is also unjustified to transfer the data obtained in the course of studies involving adult patients to children. For the safe and effective use of AEDs in children of different ages, it is necessary to take into account the high variability of individual pharmacokinetics and pharmacodynamics, to slowly titrate the dose of the drug to achieve the minimum effective one with an acceptable level of side effects. Doses recommended for one drug should not be automatically transferred to its generic drug in the event of a change.

Another concern is the availability of multiple generics on the market at once, which creates a “temptation” to use the drug that is currently more affordable. So the patient can change the drug many times during the year. Switching from one drug analogue to another occurs at best by consultation with the attending physician, without repeated dose titration, without taking into account the period of time required to restore a stable therapeutic concentration of the drug in the blood serum. During these periods of instability, the patient is at risk of recurrence or increased frequency of seizures. To date, there is no scientific basis that would justify the safety of switching from one AED generic to another without sacrificing efficacy [5].

Topiramate generics have been distributed in European countries since 2009, and in the North American continent since 2006. Over the past time, enough data has accumulated to state that the original and generic topiramate molecules differ in clinical efficacy and safety. Moreover, switching from original to generic topiramates increases the incidence of side effects and hospitalizations, and the pursued economic benefit may unexpectedly turn into a loss.

A cohort study in Quebec (Canada) using a health insurance database for the period 2006-2007 [5] studied the clinical and economic consequences of replacing the original topiramate with generic. A total of 948 patients, 1105 patient-years of branded topiramate therapy, 233 patient-years after switching to the first generic, and 92 patient-years of therapy with multiple consecutive generics were analyzed. 23% of patients who were switched to generic topiramate took at least two generics as a result. Compared to experience with brand-name topiramate, generic use was associated with more frequent use of other prescription drugs (case rate ratio, OR 1. 27; 95% confidence interval, CI 1.24-1.31), increased hospitalizations (0.48 vs. 0.83 visits per patient-year; RR 1.65; 95% CI 1.28-2.13), and also an increase in the time spent by patients in the hospital (2.6 versus 3.9 days per patient-year; RR 1.43; 95% CI 1.27-1.60). The risk of head injury or fracture after switching to the second generic compared with the period of treatment with the original drug increased by almost 3 times (relative risk 2.84; 95% CI 1.24-6.48). Total annual cost per patient increased by an average of CAD 1,716 (expenditure ratio 1.21; p=0.042).

In another study [6], Canadian experience with generic topiramate was extrapolated by mathematical modeling to European countries (where generics were expected at the time), taking into account differences in healthcare systems. The use of generic drugs in Canada in 1164 patients over 2.6 years of follow-up was associated with a significant increase in the frequency of prescribing other drugs (other AEDs +0.65 per 1 patient-year; non-AEDs +12. 28 per 1 patient-year; p<0.001) , an increase in hospitalizations and an increase in their duration. Excluding the cost of topiramate, the cost per patient increased by an average of $1,060 (p=0.005).

Based on the results of modeling the use of generic topiramate in four European countries (France, Germany, Italy and the UK), researchers predicted a similar increase in the cost of treating patients with epilepsy. With the exception of the cost of topiramate itself, the differences in costs per patient were 706-815 euros per year, adjusted for the specifics of health care systems (all comparisons are significant; p<0.001). The overall projected increase in costs is from 3.5 to 24.4% one year after the introduction of generics.

Broad-spectrum AEDs, to which topiramate belongs, have multiple mechanisms of action that explain their high effectiveness in various types of seizures, but at the same time, they can cause undesirable changes in emotions and behavior. If titrated incorrectly, the expected antiepileptic effect of topiramate may not be achieved due to the appearance of unacceptable side effects. The most common among these side effects are slow psychomotor reactions, fatigue, impaired verbal memory, speech, attention, behavioral and mood disorders. These cognitive and emotional disturbances are usually dose-dependent and completely reversible [7]. Reception of topiramate may be accompanied by a violation of appetite and weight loss. Weight loss usually appears in the first 3 months of admission and reaches its peak after 1-1.5 years [8]. The latter effect is considered by many patients as positive. It is worth recalling that in some countries the combination of phentermine with topiramate has already received registration as a treatment for obesity.

One possible but often underestimated side effect of topiramate is depressive disorder. The frequency of depressive symptoms shows a clear dose dependence; they are experienced by every fifth patient as a result of too rapid titration. Marco Mula et al. [9] studied how the rate of topiramate titration affects the incidence of depression, taking into account other known risk factors – past episodes of depressive disorder, febrile seizures, and hippocampal sclerosis. The study included 423 patients (51.8% women; mean age 35.5±11.8 years) with an average duration of epilepsy of 22.2±11.5 years. In 44 patients (10.4%) during topiramate therapy, periods of time were recorded when the diagnostic criteria for a depressive episode (major depressive disorder) were met. At the time of starting topiramate, 27% of patients were receiving monotherapy, 48.7% were taking two AEDs, and 24.3% were taking three or more AEDs. In most cases (70%), topiramate was added to previous therapy, and in 30% of patients, it replaced the previous treatment regimen, mainly with insufficient effectiveness of polytherapy. The standard dose titration regimen for topiramate suggested a starting dose of 25 mg/day with an increase of 25 mg every 1–2 weeks. This slow dose escalation was used in 73.8% of patients. In the rest of the patients, the starting dose was 50 mg with a titration step of 50 mg as well. Rapid titration resulted in a five-fold increase in the risk of depression in patients without considering additional risk factors. With a history of febrile seizures, the risk of developing depression increased by 12.7 times; in the presence of past episodes of depression in the past – 23.3 times, in patients with hippocampal sclerosis – 7.6 times.

Thus, accelerated dose titration of topiramate in the treatment of epilepsy leads to a significant increase in the likelihood of developing a depressive disorder. If there is a history of depressive episodes or febrile seizures, it is contraindicated to start treatment with topiramate from 50 mg / day and increase the dose by 50 mg.

At the same time, according to multicenter studies, at the recommended titration rate, the side effects of topiramate are largely smoothed out and do not lead to premature refusal of treatment [10, 11]. Starting therapy at 25 mg/day and increasing the dose by 25 mg per week, an average therapeutic dose of 300 mg can be reached while maintaining an acceptable level of side effects. The most common side effects during topiramate therapy were dizziness (10%), drowsiness (3. 3%), anorexia (2.3%) and loss of 1-2 kg of body weight (2.3%), but they did not lead to withdrawal drug [11].

Pediatric use of topiramate should follow the recommended dosing regimen based on body weight. It is also recommended to use formulations of the drug that allow you to select the required minimum clinically effective dose as accurately as possible.

Literature

1. Lyseng-Williamson K.A., Yang L.P. Topiramate: a review of its use in the treatment of epilepsy. drugs, 2007; 67(15): 2231-56.
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PHUA/TOP/1217/0002a

Thematic issue “Neurology, Psychiatry, Psychotherapy” No. 4 (43), chest 2017

• Number:
• Thematic issue “Neurology, Psychiatry, Psychotherapy” No. 4 (43), chest 2017

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…

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