Is topiramate effective for weight loss. What are the potential side effects of using topiramate for weight management. How does topiramate compare to other weight loss options. What precautions should be taken when using topiramate for weight loss.

Understanding Topiramate and Its Primary Uses

Topiramate, commonly known by its brand name Topamax, is an anticonvulsant medication primarily approved by the Food and Drug Administration (FDA) for treating epilepsy and migraines. However, its notable side effect of weight loss has garnered significant attention in recent years.

Primary Indications for Topiramate

• Epilepsy management
• Migraine prevention
• Treatment of alcohol use disorder

While these are the primary approved uses, the weight loss effects of topiramate have led to its off-label use for weight management in some cases.

The Mechanism Behind Topiramate-Induced Weight Loss

Topiramate’s weight loss effects are primarily attributed to two main factors:

1. Appetite suppression
2. Potential increase in metabolism

Studies have shown that individuals taking topiramate often experience reduced appetite, leading to decreased food intake. Additionally, some research suggests that topiramate may accelerate metabolism, causing the body to digest food more quickly than usual.

How Effective is Topiramate for Weight Loss?

Clinical trials have demonstrated that approximately 6-17% of individuals taking topiramate experience weight loss. Dr. Kuldeep Singh, a renowned weight loss surgeon and Director of The Maryland Bariatric Center at Mercy Medical Center, notes that most people will experience moderate weight loss from topiramate use.

Studies have shown that individuals taking topiramate for weight loss can lose an average of 11 pounds compared to placebo groups when the drug is taken for at least four months. Furthermore, the weight loss effects of topiramate tend to increase with both the duration of treatment and dosage.

Topiramate Dosage Considerations for Weight Loss

As topiramate is not FDA-approved specifically for weight loss, there is no standardized dosage for this purpose. However, when used off-label for weight management, dosages typically follow a pattern:

• Starting dose: 25mg to 50mg once daily
• Gradual increase over weeks
• Maximum dose: Typically not exceeding 200mg per day for weight loss purposes

It’s important to note that dosages are individualized and should be determined by a healthcare professional based on the patient’s specific needs and response to the medication.

Qsymia: A Topiramate-Containing Weight Loss Medication

An extended-release formulation of topiramate co-formulated with phentermine is available as a product called Qsymia, which is specifically indicated for chronic weight management. The topiramate dose in Qsymia ranges from 23mg to 96mg once daily.

Safety Considerations and Risks of Using Topiramate for Weight Loss

While topiramate can be effective for weight loss, it’s not suitable for everyone. Certain groups of people should exercise caution and consult with their healthcare provider before considering topiramate for weight management:

• Individuals with kidney disease
• People with lung disease or breathing problems
• Those with a history of kidney stones
• Individuals with liver problems
• Pregnant women or those planning to become pregnant

It’s crucial to understand that rapid weight loss can be unhealthy. If you’re taking topiramate and experiencing rapid weight loss, it’s important to consult with your healthcare provider.

Potential Side Effects of Topiramate

Like all medications, topiramate can cause side effects. Some common side effects include:

• Tingling sensations in extremities
• Fatigue
• Dizziness
• Nausea
• Cognitive difficulties (sometimes referred to as “Topamax brain”)

More serious side effects, while rare, can include metabolic acidosis, kidney stones, and eye problems. It’s essential to discuss all potential risks with your healthcare provider before starting topiramate for any purpose, including weight loss.

Off-Label Use of Topiramate for Weight Loss: Legal and Ethical Considerations

Off-label prescribing, which occurs when a doctor prescribes a medication for a purpose other than its FDA-approved indications, is legal and common in medical practice. An estimated 1 in 5 prescriptions are written off-label.

In the case of topiramate, some healthcare providers may prescribe it off-label for weight loss or to treat eating disorders that lead to weight gain. However, it’s important to note that this use is not FDA-approved, and patients should be fully informed about the potential risks and benefits.

Criteria for Prescribing Weight Loss Medications

According to Dr. Singh, to be prescribed any weight loss medication, including topiramate, an individual typically must have a body mass index (BMI) of 30 or higher. This criterion helps ensure that weight loss medications are prescribed to those who may benefit most from them while minimizing unnecessary use.

Comparing Topiramate to Other Weight Loss Options

While topiramate has shown promise in promoting weight loss, it’s important to consider how it compares to other weight management options:

Lifestyle Modifications

Dietary changes and increased physical activity remain the cornerstone of weight management. These lifestyle modifications are generally considered the safest and most sustainable approach to weight loss.

FDA-Approved Weight Loss Medications

Several medications are FDA-approved specifically for weight loss, including:

• Orlistat (Xenical, Alli)
• Liraglutide (Saxenda)
• Phentermine-topiramate (Qsymia)
• Naltrexone-bupropion (Contrave)

These medications have undergone rigorous testing for their efficacy and safety in weight management.

Bariatric Surgery

For individuals with severe obesity or obesity-related health conditions, bariatric surgery may be a consideration. This approach can lead to significant weight loss but comes with its own set of risks and considerations.

When comparing topiramate to these options, it’s important to consider factors such as efficacy, safety profile, cost, and individual health circumstances. A healthcare provider can help determine the most appropriate weight management approach for each individual.

Long-Term Considerations of Topiramate Use for Weight Loss

While topiramate can be effective for short-term weight loss, there are several long-term considerations to keep in mind:

Weight Regain After Discontinuation

Some individuals may experience weight regain after stopping topiramate. This underscores the importance of developing sustainable lifestyle habits alongside any medication use.

Potential for Dependence

While topiramate is not considered addictive, the body may become accustomed to its effects. Abrupt discontinuation can lead to withdrawal symptoms in some cases.

Long-Term Safety

The long-term safety of using topiramate specifically for weight loss has not been extensively studied. This is an important consideration for individuals contemplating long-term use.

The Role of Healthcare Providers in Topiramate Use for Weight Loss

Healthcare providers play a crucial role in the responsible use of topiramate for weight loss:

• Assessing suitability: Providers should carefully evaluate each patient’s medical history and current health status to determine if topiramate is an appropriate option.
• Monitoring: Regular check-ups are essential to monitor weight loss progress and potential side effects.
• Dosage adjustment: Healthcare providers may need to adjust dosages based on individual response and tolerability.
• Comprehensive approach: Providers should emphasize the importance of combining medication use with lifestyle modifications for optimal results.

It’s crucial for patients to maintain open communication with their healthcare providers throughout their weight loss journey, reporting any concerns or side effects promptly.

Future Perspectives on Topiramate and Weight Management

As research continues, our understanding of topiramate’s role in weight management may evolve. Some areas of ongoing investigation include:

• Long-term efficacy and safety studies
• Combination therapies involving topiramate
• Genetic factors influencing response to topiramate
• Potential new formulations or delivery methods

These areas of research may provide valuable insights into optimizing the use of topiramate for weight management while minimizing risks.

In conclusion, while topiramate has shown promise as a weight loss aid, its use for this purpose remains off-label and should be approached with caution. Individuals considering topiramate for weight loss should have thorough discussions with their healthcare providers, weighing the potential benefits against the risks and considering all available weight management options. As with any weight loss approach, the most effective strategies typically involve a combination of medication (when appropriate), dietary changes, increased physical activity, and ongoing medical supervision.

Topamax for weight loss: Off-label safety and efficacy

Topamax is prescribed to treat epilepsy and migraines, but the drug is also well known for causing weight loss

Is Topamax approved for weight loss? | Dosage | Safety | Risks | Weight gain after Topamax | Other ways to lose weight | FAQs

Topamax is the brand name of a generic medication called topiramate. It’s an anticonvulsant medication that’s used to treat conditions like epilepsy, migraine headaches, and alcohol use disorder. Topamax is great for treating conditions like this, but many people who take it will experience weight loss as a main side effect. Let’s take a more in-depth look at how safe and effective Topamax is, and see how it’s related to weight loss. 

Is Topamax approved for weight loss?

Topamax is approved by the Food and Drug Administration (FDA) to treat epilepsy and migraines, but the drug is also well known for causing weight loss. Even though weight loss may be a positive benefit of taking Topamax, the FDA hasn’t approved it for weight loss alone.  

Topamax causes weight loss because it affects the appetite. People who take it and have a reduced appetite may feel hungry less often and eat less because of this. Studies have shown that Topamax may also speed up metabolism, which means that the body would be digesting food quicker than normal. 

 Clinical trials have shown that about 6%-17% of people who take Topamax will experience weight loss, and while many people may see this as an added benefit, losing too much weight isn’t a good thing. Dr. Kuldeep Singh, a top weight loss surgeon in the Baltimore Metropolitan area and Director of The Maryland Bariatric Center at Mercy Medical Center, says that most people will experience moderate weight loss from Topamax. Losing weight rapidly can be unhealthy, and it may be time to see a doctor if you’re taking Topamax and this happens to you. Maintaining a healthy weight is important, and the best way to find out what target weight is best for you is to ask your doctor. Falling below your target body weight because of Topamax would be another sign that it’s time to talk with your doctor.  

Topamax dosage for weight loss

Because the use of Topamax for weight is off-label and truly a side effect of its use in clinical practice, no specific dose can be specified for this indication. Topamax’s weight loss side effect has resulted in its off-label use to treat binge eating disorders in adults, and the dosing for this indication does not differ greatly in comparison to other approved indications, ranging from 25mg per day to a maximum of 400mg per day. If used off-label for weight loss, the dose will likely begin low at 25mg to 50mg once daily and increase slowly over weeks until a benefit of weight loss is noted – balancing this desirable side effect with those which are less desirable. It is unlikely the dose of topiramate for the indication of weight loss needs to exceed 200 mg per day, as clinical trials have not demonstrated additional benefit in percent body weight lost beyond this dose. An extended-release formulation of topiramate co-formulated with phentermine is available as a product called Qsymia, which is indicated for chronic weight management. The dose of topiramate in this co-formulated product ranges from 23 mg once daily to a maximum of 96 mg once daily. 

Is it safe to take Topamax for weight loss?

Sometimes Topamax can be prescribed off-label to help someone lose weight. Off-label prescribing happens when a doctor writes someone a prescription for a medication that’s approved by the FDA to treat a condition that’s different from what their patient has. This is legal and frequently happens in the medical industry, with an estimated 1 in 5 prescriptions being written off-label. 

A doctor may choose to write someone a prescription for Topamax to help with their weight loss or to treat eating disorders like binging and purging that lead to weight gain. According to Dr. Singh, someone must have a body mass index (BMI) that’s 30 or higher in order to be prescribed any weight loss medication, including Topamax. 

Studies have shown that people who take Topamax for weight loss lose about 11 pounds in comparison to placebo groups if they take the drug for at least four months, and that the weight loss effects of Topamax increase with both duration of treatment and dosage. Studies have also shown that topiramate treatment can increase the chance of statistically significant weight loss by more than sixfold. 

Risks of using Topamax for weight loss

Even though Topamax can be very effective for weight loss, it isn’t safe for everyone. The following groups of people should talk with their doctor before taking Topamax because they may have an increased risk of experiencing serious adverse events if they take it: 

• People with kidney disease
• People with lung disease or breathing problems
• People with liver disease
• People with eye problems such as glaucoma 
• People with depression
• People with suicidal thoughts or behaviors
• People with osteoporosis 
• People with metabolic ketoacidosis 

It may be safe for pregnant women to take Topamax if the benefits of taking the medication outweigh its potential risks. Topamax can cause fetal harm and oral birth defects if it’s taken by pregnant women, which is why it’s prescribed with caution. It’s also excreted in human milk, but it’s unknown whether or not it will negatively impact breastfeeding infants. Topamax can make birth control pills less effective, so it’s important to talk with your doctor about using non-hormonal birth control methods if you don’t want to become pregnant while taking Topamax. 

Side effects of using Topamax for weight loss

People who aren’t pregnant and who don’t have any of the health conditions mentioned above can safely take Topamax, but they may still experience side effects from taking it. Here are some of the most common side effects of Topamax aside from weight loss: 

• Dizziness
• Tiredness
• Numbness
• Diarrhea
• Loss of appetite 
• Loss of coordination
• Paresthesia (burning sensations) 

Although it’s rare, Topamax can cause more serious side effects that may require medical attention like confusion, memory problems, trouble concentrating, and trouble speaking. Some people will also experience mental health side effects like depression, panic attacks, mood changes, and suicidal thoughts or behaviors. If you have any of these symptoms, you should seek medical advice as soon as possible. 

The other rare side effect of Topamax that’s worth mentioning is eye problems that can lead to vision changes and blindness, which is why it’s so important to call your doctor if your vision starts to change. This list of side effects is not comprehensive; if you’d like a complete list of Topamax side effects, you can always ask your doctor or pharmacist for a medication guide. 

If Topamax is causing too many side effects for you, know that you have other options. The active ingredient in Topamax, topiramate, is the main ingredient in the weight loss drug Qsymia, which also contains phentermine. According to Dr. Singh, Qsymia is one of the best medications to use long-term in combination with diet and lifestyle changes for weight loss, especially for obese patients with class 1 or class 2 obesity. So if you’re not able to take Topamax because of an underlying health problem or because you’re experiencing too many adverse effects, you might try asking your doctor about Qsymia or other ways to lose weight. 

How to take Topamax to lose weight

Topamax can be taken to promote weight loss and help control binging and purging, but it’s important to remember that it isn’t a substitute for going to a doctor and creating a well-rounded weight loss plan. If you’re interested in taking Topamax, it’s best to schedule an appointment with your doctor to see if it’s right for you. Your doctor will do a complete physical exam and ask about your medical history. If you and your doctor decide that Topamax can safely help you lose weight, then you may receive a prescription for it.

If you do receive a prescription from your doctor, it’s important to know how to take Topamax to get the best results. The starting dose of Topamax for weight loss is a low dose of 25 mg per day, but this dosage strength can be increased on a case-by-case basis based on each individual’s medical history and how much weight they have to lose.  

In a study done by the Journal of Clinical Psychiatry, bipolar and schizophrenic patients who were given an average dose of 195 mg of topiramate per day lost about 22 pounds over time. This just goes to show that the range of Topamax dosages can vary from low to high and that doctors may increase or decrease the amount of Topamax that someone takes over time-based on the results they are or aren’t getting. 

It can take some time to see weight loss results from taking Topamax. Some people may not notice a difference until they’ve taken the drug for at least four months, while other people may start to lose weight in their first month of taking it. Weight loss results from topiramate are proven to increase over time. 

Topamax can be taken with or without food and is generally taken at the same time each day. It shouldn’t be taken at the same time as certain other medications because of the potential for drug interactions. Here’s a list of medications Topamax shouldn’t be taken with:

• Antiepileptic drugs
• Carbonic anhydrase inhibitors
• CNS depressants
• Oral contraceptives
• Hydrochlorothiazide (HCTZ) 
• Pioglitazone
• Lithium
• Amitriptyline 

In addition to these medications, Topamax shouldn’t be taken with alcohol because this can cause sleepiness, increase the risk of getting kidney stones, and cause metabolic acidosis. Metabolic acidosis is a condition where too much acid builds up in body fluids, and it can become life-threatening if it goes untreated. If you start to experience rapid breathing, confusion, extreme tiredness, and an increased heart rate while taking Topamax, you should seek medical attention as soon as possible because these are signs that you may have metabolic acidosis.

Related: Saxenda for weight loss

Weight gain after Topamax

When someone stops taking Topamax, it’s possible that they might experience some weight gain over time, especially if they haven’t been combining Topamax with healthy lifestyle changes. In an observational study done by the National Library of Medicine, discontinuation of Topamax for at least six months showed a trend for returning to a baseline weight. So people may be more likely to return to what they weighed before they started taking Topamax, but this may take some time. 

This return to a baseline weight may happen because the body is no longer experiencing a reduced appetite and faster metabolism. The best way to make sure you’re able to keep weight off after stopping Topamax is to adopt healthy lifestyle changes that will support you on your weight loss journey. 

5 safe ways to lose weight

Topamax can be helpful on your weight loss journey if your doctor approves it, but it’s not the only way to lose weight. Lifestyle changes can help you lose weight and keep it off so that you can enjoy the benefits of weight loss without taking Topamax, while taking it, or after taking it. Here are some of the safest ways to lose weight. 

1. Improving your eating habits

Eating healthy is one of the safest and best ways to lose weight. Being mindful of what and how much you’re eating can help you lose weight if you do it right. For the best advice on what to eat to lose weight, you should talk with your doctor, but making some small changes like eating more fruits and vegetables can be a great way to start. 

Processed foods, refined carbohydrates, sugar, and alcohol are all examples of foods that can cause weight gain. Fresh fruits, vegetables, and high-quality proteins like salmon, beans, and eggs are all great examples of foods that the body can easily process and get vital nutrients from. 

2. Exercising regularly 

According to the Centers for Disease Control and Prevention (CDC), exercise not only helps control weight, but it reduces high blood pressure, reduces the risk of getting Type 2 diabetes, and can even reduce the symptoms of depression and anxiety. People vary in how much physical exercise they need to lose weight, so it’s a good idea to talk with your doctor about how often you should be exercising. Some great exercises for weight loss include walking, biking, swimming, and weight training. 

3. Reducing stress

Stress is linked to many health problems, such as anxiety and depression, but it’s also been linked to unexpected weight gain. Feeling stressed out can lead to emotional eating, which can lead to weight gain over time. Finding ways to reduce stress may help you lose weight. You might try meditating, yoga, going for walks in a park, or calling a friend or family member. You can also ask your doctor or a counselor for proven ways to reduce stress that might fit into your lifestyle. 

4. Getting enough sleep 

According to the Sleep Foundation, a lack of sleep may increase the appetite and lead to metabolic problems. Getting enough sleep can help your body function properly and give you more energy to do things like exercise, which will help you lose weight. Getting enough sleep can also reduce your stress levels, which will help you control any urges you might get to overeat. 

5. Trying safe diet pills & supplements 

There are countless diet pills and supplements on the market that claim to cause weight loss, such as Hydroxycut and glucomannan, but they shouldn’t serve as a substitute for healthy lifestyle changes. “When people go for weight loss medications, most of them do it because it’s easy to do,” says Dr. Singh. “If somebody seriously changes their lifestyle and eating habits first, they will really see a solid improvement with Topamax or other weight loss medications. The mindset is the most important thing. Medications cannot serve as a substitute for proper eating and exercising habits,” says Dr. Singh. 

Frequently asked questions about Topamax and weight loss

Can Topamax cause rapid weight loss?

Because the weight loss seen with Topamax is related to a decrease in appetite, you won’t begin to see weight loss for a few weeks, if not a couple of months. In addition, the weight loss with Topamax is unlikely to be drastic—most studies have shown a decrease in Body Mass Index (BMI) around the 5-10% mark. 

How much Topamax should I take to lose weight?

For all indications, the Topamax dose is usually started low and increased slowly over time so as to be able to monitor for the onset of unwanted side effects. Clinical studies have shown a plateau of this side effect approaching a dose of 200mg per day, meaning patients exceeding this dose did not demonstrate greater weight loss. 

How long does it take to lose weight on topiramate?

Weight loss by Topamax can be noticed within weeks of starting the medication as it decreases appetite and potentially stimulates metabolism. The additional benefit of Topamax in comparison to other weight loss medications on the market is that there does not seem to be a plateau of weight loss at six months, so the weight loss may be an ongoing effect. 

What is the difference between phentermine and topiramate?

Phentermine is a sympathomimetic medication that is specifically indicated for weight loss. Aside from its FDA-approved indication, due to its mechanism of stimulating the central nervous system, the main difference between the two medications is that phentermine should only be used short-term. 

What is the best weight loss pill?

The best weight loss pill should be individualized to a person since so many weight loss medications are approved to be used to manage additional conditions. Some medications that help manage Type 2 diabetes with a side effect of weight loss make more sense to use in a diabetic patient, whereas topiramate might be best suited for someone that suffers from migraines and needs to lose a little weight. While weight loss might be considered a beneficial side effect, it might not be in all patients; in addition, the other side effects of these medications should be considered in case they won’t jive with a person. Any decision on weight loss medications should be made in conjunction with a healthcare professional with a good understanding of all of a patient’s needs and conditions.

Can Topiramate Help Me Lose Weight?: Southwest Family Physicians: Family Practice

Can Topiramate Help Me Lose Weight?: Southwest Family Physicians: Family Practice

Topiramate for Weight-loss

Anticonvulsant drug, topiramate, is used to treat epilepsy, generalized or focal seizures, migraine prevention, and alcohol addiction. When used to manage seizures and prevent migraine, it has also been demonstrated to produce weight loss. Although the Food and Drug Administration (FDA) has not yet approved this as a weight-loss drug, some doctors give it to patients who are suffering from seizures or migraines and need to lose weight. However, Qysmia, a combination of Phentermine and Topiramate, is an FDA-approved weight-loss medication for obese or overweight adults with type 2 diabetes, high cholesterol, or high blood pressure who also need to exercise.

What Does the Research Reveal?

Weight-loss happens in 6% to 17% of individuals in clinical studies using topiramate in both adolescents and adults. Weight-loss and loss of appetite are common adverse effects in persons 16 years and older who are taking 50 mg or 400 mg of topiramate per day. Patients using a 50mg/day dose lost 6% of their body weight, and weight loss was found in 17% of patients using 400mg/day. Patients who get topiramate as an additional medication lose significantly more weight than those who receive a placebo.

About 7% of children aged 6 to 15 years old who were receiving 50mg/day for seizure management lost weight, and when increased to 400mg/day, weight loss was observed in 17% of children of the same age group. There was no loss of appetite in any dose group for children. Patients aged 12 to 17 years old who took 50mg/day for migraine prevention lost 7% of their weight, whereas those who took 100mg/day lost 4%. Patients on topiramate experienced a loss of appetite in 9% to 10% of cases, compared to 4% of those taking placebo.

Is it Suitable for All?

While topiramate is beneficial for weight loss, it is not for everyone. Disorders such as glaucoma, osteoporosis, metabolic ketoacidosis, depression, and suicidal thoughts and behaviors may be made worse by taking topiramate.  Let your provider know of any existing conditions like those above as well as kidney disease, liver disease, lung disease, or breathing problems.

Topiramate should not be recommended for the purpose of weight loss in pregnant women. Both the mother and the baby in her womb may suffer fatal damage as a result of this. Although topiramate may be safe for pregnant women if it helps with a medical issue, it is always best to talk with a doctor.

Topiramate Side Effects

Patients stopped usually stop using topiramate because of other adverse effects, not because of weight reduction. Adults 16 and older who were using 400mg/day quit taking the medication because of memory problems, weariness, weakness, insomnia, excessive sleepiness, and tingling in the extremities. Fever, flushing, disorientation, and difficulties concentrating were reported in children aged 6 to 15 who were taking 400mg per day. Although common side effects of topiramate are diarrhea, loss of appetite, loss of coordination, dizziness, sleepiness, and numbness, topiramate can be taken safely by people who do not have any of the disorders listed in the above section and are not pregnant.

Sources: Clinical utility of phentermine/topiramate (Qsymia™) combination for the treatment of obesity

Does topiramate cause weight loss?

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Topiramate in Bipolar and Schizoaffective Disorders: Weight Loss and Efficacy – Empathy

Weight gain puts the patient at risk for hypertension, coronary heart disease, type 2 diabetes, dyslipidemia and cancer. Weight gain can lead to non-compliance with an increased risk of relapse and subsequent readmission. Mood stabilizers, including lithium and valproic acid, can lead to weight gain.

Introduction

Reference: While mood stabilizers such as lithium, divalproex sodium, and carbamazepine are helpful in bipolar disorder, they can cause significant weight gain.

Method: We conducted a retrospective chart review of 5 patients with DSM-IV bipolar disorder or schizoaffective disorder who received topiramate as add-on therapy or monotherapy.

Results: All 5 patients had a good response to treatment at a mean dose of topiramate 195 mg/day (range 100-375 mg/day). All patients significantly lost weight during treatment with topiramate. Average weight loss was 22 lbs (10 kg; range 8-56 lbs [4-25 kg]). None of the patients stopped taking topiramate due to side effects.

Conclusion: Topiramate may represent a valuable alternative to current mood stabilizers either as adjunct or monotherapy in patients with bipolar disorder or schizoaffective disorder.

Weight gain is a common and important side effect of many psychotropic drugs.

Contents

In a double-blind, controlled trial of valproic acid for the maintenance treatment of bipolar disorder, weight gain greater than 7% was reported in 4% of patients on placebo, 16% of patients on lithium, and 23% on valproic acid. Atypical antipsychotics, especially clozapine and olanzapine, are associated with significant weight gain. In a recent meta-analysis by Allison et al., after 10 weeks of treatment, the mean weight gain with clozapine was 4.45 kg and with olanzapine was 4.1 kg. Nemeroff reported that the mean weight gain after 1 year of olanzapine treatment was 11. 8 kg.

Topiramate is a new antiepileptic drug that blocks sodium channels, similar to carbamazepine and valproate, and also enhances γ-aminobutyric acid (GABA) neuroinhibition, similar to valproate. Topiramate also antagonizes the effects of glutamate on non-N-methyl-d-aspartate (non-NMDA) receptors and inhibits certain carbonic anhydrase isoenzymes. Peak levels of topiramate are reached within 1.75-4.3 hours after oral administration. The relative bioavailability of the drug from the tablet form is 80% compared to the solution. Food reduces the rate, but not the extent, of topiramate absorption. The drug has a linear pharmacokinetics and binds to plasma proteins by only 9-17%. Topiramate binds extensively to erythrocytes. The average half-life is from 18.7 to 23 hours. Seventy percent of the administered dose is excreted in the urine unchanged. Topiramate is metabolized by hydroxylation, hydrolysis and glucuronidation. No correlation with plasma levels is known, and therefore there is no clinical indication for their measurement.

Common side effects of topiramate include sedation, fatigue, diplopia, dizziness, ataxia, psychomotor retardation, difficulty concentrating, anorexia, headache, speech problems, memory problems, nystagmus, and paresthesias. Topiramate is classified as a pregnancy category C drug. This may reduce the effectiveness of some oral contraceptives. The total daily dose recommended for epilepsy is 400 mg/day in divided doses; however, clear recommendations for the treatment of bipolar disorder have not yet been given. For patients with impaired renal function, half the adult dosage is recommended.

Several studies have demonstrated the efficacy of topiramate in the treatment of bipolar disorder, including resistant populations, and in the treatment of post-traumatic stress disorder. In these studies, topiramate resulted in significant weight loss in patients with bipolar disorder. Topiramate has been shown to be effective as an add-on treatment in patients with mood disorders. Marcott found that 11 out of 18 patients with refractory bipolar disorder (types I and II) responded to an average topiramate dose of 200 mg/day after 8.5 weeks of treatment. Chengappa et al. treated 20 patients with bipolar I disorder or schizoaffective disorder with adjunctive topiramate (median dose = 210.5 mg/day) over a 5-week period. Twelve patients (60%) responded to topiramate and time to response ranged from 2 to 4 weeks. Side effects included paresthesias, anorexia, slow thinking, fatigue, sedatives, and difficulty finding words. Fifty-five percent of patients reported no side effects. Only 1 patient terminated the study prematurely due to “acute confusional conditions”. Wooten and Kramer used high doses of topiramate to treat 8 patients with bipolar disorder, schizoaffective disorder, or schizophrenia. The median dosage was 868 mg/day in divided doses (range 50-2000 mg/day). Sixty percent of patients responded to topiramate. One patient experienced mild paresthesia and 2 patients experienced transient delirium at high doses (1600 and 2000 mg/day).

Kusumakar et al treated 27 female patients diagnosed with DSM-IV bipolar I and bipolar II who were refractory to at least two mood stabilizers and who had gained more than 20% in weight in the previous 24 months while taking topiramate (100-150 mg/day). Fifteen of the 27 patients showed a significant improvement, and only 4 patients discontinued the drug due to adverse events. Fourteen patients lost weight during the 16 week study. Nine patients had more than 5% weight loss.

We describe a case series of 5 patients treated with topiramate, either as adjunctive therapy or as monotherapy, who experienced improvement in mood symptoms as well as significant weight loss.

Results

With each of these patients, a detailed discussion of the use of topiramate was held to obtain consent for use. They were told that it had been approved by the US Food and Drug Administration (FDA) for the treatment of epilepsy, not bipolar disorder. All 5 patients responded to topiramate supplementation for bipolar or schizoaffective disorder. The mean dose of topiramate was 195 mg/day (range 100-375 mg/day). All patients lost a significant amount of weight on topiramate. Average weight loss was 22 lbs (10 kg; range 8-56 lbs [4-25 kg]). No patient discontinued topiramate due to side effects. We started topiramate at 25-50mg daily and titrated gradually in 25mg increments. Slow titration may have been the reason for the lack of significant side effects.

Case reports

Case 1. Ms. A, a 58-year-old Caucasian woman, suffered from bipolar affective disorder, manic-type, with psychotic features, for 37 years. She was admitted to the inpatient department of a local community hospital due to severe symptoms of mania, such as compulsive speech and sexual inadequacy. Ms. A had previously undergone multiple psychiatric hospitalizations. She had a history of Parkinson’s disease, 2 seizures, obesity, and urinary incontinence. She had no history of significant alcohol or drug use. Her mother had a family history of schizophrenia.

Ms. A has been treated with divalproex sodium for several years and has recently experienced compliance problems. She experienced significant weight gain over several years, which led to her discontinuation of divalproex. Previous trials of lithium carbonate and divalproex resulted in no response to either monotherapy or combination; therefore, a study of topiramate was considered. Laboratory findings, including blood work, electrolytes, thyroid tests, serum cholesterol levels, lithium levels, and urinalysis for drugs, were within normal limits. Weight at admission was 284 pounds (128 kg).

On examination of the mental status of Ms. A was her declared age. She was vigilant and oriented in all areas (person, place, time). She had difficulty speaking and increased psychomotor activity. Mrs A’s mood was upbeat and her affect was manic. She had a flight of ideas, absent-mindedness and a decrease in concentration. Her judgment and insight were fair. Her YMRS score was 20.

Topiramate was started at 25 mg/day and gradually increased in 25 mg increments to 125 mg in the morning and 150 mg at bedtime. In connection with the persistence of symptoms in combination with topiramate, lithium carbonate was added at a dose of 300 mg at bedtime and the dose was gradually increased to 1200 mg at bedtime. This lithium supplementation resulted in improved sleep and reduced manic symptoms. Miss A’s plasma lithium level was 1.0 meq/L. She continued to take olanzapine 20 mg at bedtime. Her other medications included celecoxib at 200 mg/day; furosemide at a dose of 40 mg/day; potassium chloride at a dose of 20 meq/day; conjugated estrogen and medroxyprogesterone acetate at a dose of 0.625/2.5 mg/day; carbidopa-levodopa at a dose of 25/250 mg / day, half a tablet twice a day; and oxybutynin 5 mg twice daily. She got better and was discharged to a boarding school. Her YMRS score was 1 and her BPRS score was 18.

Ms. A was followed up as an outpatient for 2 months and her symptoms and weight were monitored during visits. She was still doing well, with no reported side effects. Her YMRS score was 0 and her BPRS score was 18. Her weight has continued to decline since she was discharged from the hospital. Her pre-topiramate weight was 284 pounds (128 kg), which dropped to 242 pounds (109 kg) at 1 month, 240 pounds (108 kg) at 2 months, and to 228 pounds (103 kg) at 3 months of follow-up. She had a weight loss of 56 pounds (25 kg) while on topiramate treatment.

Case 2 . Ms. B., a 42-year-old white woman with a 27-year history of bipolar disorder, was followed up in a continuous day care program. She had a history of obesity, fibromyalgia, and diabetes. Her family history included obesity, cardiovascular disease, diabetes mellitus, multiple sclerosis, and alcoholism, as well as depression with her mother’s suicide attempts. Ms B reported irritability and at times depressed mood. She also reported concerns about taking divalproex due to weight gain. Before starting topiramate, she weighed 176 pounds (79kg), and she was diagnosed with DSM-IV – bipolar disorder.

On examination of mental status, Miss B was well dressed and well groomed, and spoke clearly and coherently. She had an anxious mood and affect. Her judgment and insight were fair. Her YMRS score was 4 and her HAM-D score was 8. Her medications included divalproex 500 mg in the morning and 1000 mg at bedtime; zolpidem 10 mg at bedtime; citalopram at a dose of 40 mg/day; and lithium carbonate at a dose of 900 mg at bedtime.

Various options were discussed, including returning to carbamazepine (which she had previously received), reducing the dose of divalproex, or trying topiramate. Consent was given and Ms. B was started on topiramate 25 mg at bedtime. The dosage of divalproex was reduced to 500 mg twice daily. The rest of her medications remained the same.

At a 3-week follow-up, Miss B reported problems at home that caused significant irritability and moodiness. Her weight dropped to 165 pounds (74 kg). The dose of topiramate was increased to 25 mg twice daily for 2 weeks and then gradually increased in 25 mg increments to 75 mg twice daily. Divalproex was reduced and then discontinued. A few weeks later, Miss B. ordered an intermittent appointment due to increased irritability, poor sleep, and increased sex drive. A mental status examination showed that her mood was extremely irritable. Her affect was also irritable. Her judgment and insight were fair. Her YMRS score was 8 and her HAM-D score was 7. Lithium carbonate was increased to 1200 mg at bedtime and other medications remained at the same dosages. Laboratory findings, including serum lithium, serum cholesterol, fasting lipid profile, and complete blood count, were within normal limits.

Six weeks later, at follow-up, Miss B reported a reduction in irritability and improved sleep. No manic symptoms were noted. Her YMRS score was 0 and her HAM-D score was 6. She denied any side effects from topiramate. Her weight continued to drop. Her weight before topiramate treatment was 176 pounds (79 kg), which decreased to 165 pounds (74 kg) after 1 month, to 162 pounds (73 kg) after 2 months, and to 156 pounds (70 kg) after 3 months of follow-up. She lost 20 pounds (9kg) on ​​topiramate treatment.

Case 3. Ms. C, a 35-year-old Caucasian female with a 22-year history of rapid cycling bipolar affective disorder, was seen as an outpatient. She had several previous psychiatric hospitalizations. Ms. C had a history of hypothyroidism and weight gain. Prior to being prescribed topiramate, she weighed 180 pounds (81 kg) and had a DSM-IV diagnosis of schizoaffective disorder. Her maximum weight was 199 pounds (90 kg). She also had a history of dependence on alcohol and cannabis. Family history included a sister who committed suicide and a brother with manic-depressive symptoms. Miss C had cycles of manic as well as depressive symptoms. Previous drug trials have included lithium, risperidone and olanzapine with poor results. Lithium in combination with divalproex resulted in minimal improvement, while divalproex in combination with lamotrigine resulted in a 30% improvement according to the patient report.

Miss C was observed for follow-up. She reported that she stopped taking mood stabilizers 3 and a half months ago. She reported that she felt depressed and was concerned about her weight. On mental status examination, she had a low mood and an affect that corresponded to the mood in the full range. Her thought process was organized and her judgment and insight were fair. Her YMRS score was 5.

Because of her many previous failed drug trials, the use of topiramate has been discussed. Consent was obtained, and Ms. C started taking topiramate at a dose of 25 mg/day. This dosage was gradually adjusted to 100 mg twice daily. Concomitant medications included levothyroxine sodium at a dose of 75 mcg/day; zolpidem 10 mg at bedtime; and sustained release bupropion at 100 mg/day. Laboratory findings, including thyroid tests, complete blood count, and liver function tests, were within normal limits. After 2 months of follow-up, Miss C reported improved sleep. She had no manic symptoms. Her YMRS score was 2. She did not experience any side effects from topiramate. Her weight was dropping; her pre-treatment weight with topiramate was 180 pounds (81 kg), which dropped to 162 pounds (73 kg) by the third month. She lost 18 pounds (8 kg) on ​​topiramate treatment.

Case 4. Ms. D., a 43-year-old white female with an 18-year history of bipolar affective depressive disorder, was seen as an outpatient. Previously, she was repeatedly subjected to psychiatric hospitalization and was discharged from the hospital for 10 years. Her medical history included weight gain. Family history included depression and alcoholism in her father.

During an outpatient follow-up visit, Ms. D reported irritability due to workplace tensions. She felt a lack of energy and was also concerned about the 14 pounds (6 kg) weight gain. Her affect was anxious and her mood irritable. Her YMRS score was 3. Her medications included divalproex 500 mg in the morning and 1000 mg at bedtime; lithium carbonate at a dose of 600 mg at bedtime; and fluoxetine at a dose of 20 mg/day. The patient’s serum valproate level was 76 µg/ml, and the plasma lithium level was 0.8 meq/l. The dose of Divalproex was reduced to 1000 mg at bedtime. Lithium carbonate has been increased to 900 mg at bedtime and fluoxetine continued at 20 mg/day. The possibility of monotherapy, such as lithium carbonate alone or a combination of lithium with topiramate, has been discussed. Diet and exercise were also recommended.

Miss D was seen for follow-up 2 months later. She reported increased irritability and depression. Weight gain continued to be a concern. Her weight was 196 pounds (88 kg). Due to the lack of efficacy of previous studies of lithium carbonate and divalproex, both alone and in combination, the use of topiramate was discussed and agreement was obtained. Ms. D started topiramate 25 mg in the morning, gradually increasing the dose to 50 mg twice daily. Lithium continued at the same dose, and divalproex was reduced and discontinued. Laboratory findings, including a complete blood count and liver function test results, were within normal limits.

On follow-up, Ms. D was vigilant and oriented in all areas. Her speech was clear and her affect was vivid, with an improved mood. Irritability was not noted. She reported that she felt better and that her weight was decreasing. Her YMRS score was 2, her BPRS score was 19, and her HAM-D score was 1. Her pre-topiramate weight was 196 pounds (88 kg). Her weight dropped to 192 pounds (86 kg) after 1 month and to 185 pounds (83 kg) after 2 months of follow-up. She lost 11 pounds (5 kg).

Case 5. Ms. E, a 38-year-old Native American woman with a 12-year history of schizoaffective disorder, was seen in a continuous day treatment program. She had several previous psychiatric hospitalizations. At a routine visit, she reported problems with weight gain, trouble sleeping, and low sex drive. Her YMRS score was 3, BPRS 19, and HAM-D 6. Her weight was 282 pounds (127 kg). Ms. E.’s medications included divalproex 1000 mg twice daily; risperidone 6 mg at bedtime; and venlafaxine 75 mg three times a day. There was a detailed discussion of her medications. The risperidone dosage was reduced to 3 mg at bedtime and the divalproex dosage was changed to 500 mg in the morning and 1500 mg at bedtime.

A month later, Ms. E reported improved sleep and sex drive, but her weight continued to be a concern. She was started on topiramate 25 mg twice daily, which was gradually increased to 75 mg twice daily. Divalproex was reduced and discontinued. Laboratory findings, including complete blood count, liver function test results, and fasting lipid profile, were within normal limits.

At follow-up a month later, Miss E was vigilant and oriented in all areas. Her affect was intense and her mood neutral. Her thought process was organized. Her YMRS score was 1 and her HAM-D score was 2. She reported no side effects from topiramate and denied depressive or psychotic symptoms. Her weight was dropping; her pre-topiramate weight was 282 lb (127 kg), which dropped to 274 lb (123 kg) at 3-month follow-up. She had an 8 lb (4 kg) weight loss.

Terminals

Topiramate may be a useful alternative to existing mood stabilizers in primary care settings for several reasons. First, many primary care physicians now see psychiatric patients; weight gain with psychiatric medication is an ongoing problem, and there is no known drug with efficacy in mental illness that would also cause weight loss. Second, primary care physicians also have patients with epilepsy on phenobarbital and valproate who may have gained weight, and topiramate may be an alternative. Finally, the primary care physician coordinates patient care, and in the treatment of conditions such as diabetes, heart disease, hypertension, and arthritis, obesity is an important risk factor. We do not recommend the use of topiramate specifically as a weight loss drug, but it should be considered as an option if there is an indication for the use of a drug of this class. In future controlled studies, it is recommended to repeat these results in different patient groups.

Weight gain

Numerous studies suggest that psychotropic drugs, including modern atypical antipsychotics, can lead to weight gain while indirectly impairing glucose metabolism and promoting diabetes. Weight gain is also associated with hypertension, coronary heart disease, stroke, varicose veins, and some other somatic diseases.

Only a few authors believe that overweight is less common in patients with schizophrenia than in other people.

Drugs with a sedative effect that limits the patient’s physical activity can slow down the metabolism of substances, which also contributes to the patient’s weight gain.

Mechanisms of weight gain with antipsychotics:

1. Restriction of physical activity as a result of the sedative effect of the drug.
2. The pleasure of eating as a means of combating depression.
3. Changing the mechanism of saturation.
4. Metabolism slowdown due to the effect of antipsychotics on various networks of neurons: serotonin (5HT1A receptor agonists cause hyperphagia, 5HT2 antagonists cause hypophagia), histamine (blockade), dopamine, norepinephrine, muscarinic, etc.
5. Fluid retention in the body.
6. Endocrine disorders: increase in prolactin, changes in insulin and cortisol secretion.
7. Changes in the level of the hormone – leptin peptide in the blood plasma and changes in the sensitivity of the hypothalamus receptors to it.

Patients with schizophrenia have been observed to prefer sweet foods, drink large amounts of high-calorie drinks (cola and sprite), eat more, while getting a certain pleasure from eating.

Many psychotropic drugs also have an anticholinergic effect that reduces metabolic processes. They delay the release of fluid from the body, contributing to endocrine system disorders (increase in prolactin, changes in the secretion of cortisol, insulin, etc.), which also increases the weight of patients.

In the development of obesity that occurs while taking some atypical antipsychotics, the hormone peptide leptin is of great importance, which is produced by adipocytes in an amount that is directly proportional to the amount of fat in the cells of the body.

Leptin plays an important role in the regulation of body weight, affects appetite by blocking leptin receptors in the hypothalamic satiety center proportional to the mass of adipose tissue. It stimulates a sequence of responses that regulate appetite, metabolism, energy expenditure, and food satisfaction.

The peripheral effect of leptin is expressed in the suppression of intracellular lipid metabolism. Taking leptin reduces appetite and thus leads to weight loss. However, obesity is often accompanied by an increase in the level of leptin in the blood and, probably, a decrease in the sensitivity of the hypothalamic receptors to this hormone, which in turn leads to an increase in appetite and an increase in body weight.

Elevated blood leptin also has an effect on tissue insulin resistance. The connection of the latter with the development of obesity is well known. Insulin stimulates the secretion of leptin by adipocytes. The effect of leptin, both stimulating and inhibitory in relation to insulin, on the function of pancreatic beta cells was noted. In other words, not all patients with schizophrenia, even receiving antipsychotics such as olanzapine and clozapine, show weight gain. Currently, many experts explain this phenomenon as a genetic variation of pharmacodynamic factors. There is ample evidence to support this view, as well as the influence of genetic factors on eating behavior. Some researchers have found a relationship between single nucleotide polymorphisms – 759C/T and weight gain at 6 and 10 weeks of hospitalization in patients with a first psychotic episode treated with antipsychotics such as clozapine and risperidone. Other authors have determined that patients without the 759T allele have a higher risk of weight gain during a 6-week course of olanzapine therapy than patients with the 759T allele. At the same time, individuals without the allele – 759T of the 5HT2C receptor gained weight to a much greater extent than individuals with the T allele. Thus, it turned out that carriers of the T allele have a lower risk of weight gain than individuals without this allele. The study of polymorphisms of promoter regions in the 5HT2C serotonin receptor and leptin genes for the presence of an association with weight gain as a result of taking antipsychotics showed that patients prone to weight gain had a 5HT2C receptor polymorphism – 759C/T and leptin polymorphism – 2548A/G. Leptin polymorphism – 2548 did not correlate with short-term weight gain, but significantly correlated with this indicator after 9 months of antipsychotic therapy. At the same time, variations in the H1 and H2 receptor genes were not associated with weight gain in patients treated with clozapine for 5 weeks.

Tricyclic and tetracyclic antidepressants (amitriptyline, nortriptyline) significantly increase weight. Selective serotonin reuptake inhibitors (SSRIs), with the exception of paroxetine, are neutral in relation to weight gain, mirtazapine, on the contrary, increases body weight. Valproate and lithium have a fairly high potential in terms of weight gain. Among the classic antipsychotics, thioridazine increases weight the most, and pimozide has been reported to reduce body weight.

Usually, weight gain is observed in the first months of therapy and subsequently its rate decreases markedly in its severity. At the same time, the stigma of schizophrenia is aggravated by the stigma of obesity, which significantly affects the social status and the level of compliance of the patient with the medical staff.

Weight gain at 3-6 weeks of therapy is a predictor of overall weight gain.

The total level of high and low density lipoproteins practically differs little when taking various antipsychotics. When taking classical neuroleptics, the average level of triglycerides corresponds to 1.8 mmol / l.

The central norepinephrine and dopamine neural networks play an important role in the regulation of food intake.

It is likely that weight gain during treatment with some atypical antipsychotics (olanzapine) depends on many factors and includes effects on histamine (H1), serotonin receptors (5HT2A, 5HT2C), and alpha-adrenergic receptors (alpha 1 and alpha 2) , muscarinic M3 receptors and changes in plasma leptin levels.

Note that sulpiride (selective blocker of D2/D3 receptors), which noticeably increases the body weight of patients with schizophrenia, does not affect histamine receptors (H1).

Among atypical antipsychotics, clozapine therapy is most often associated with an increase in triglyceride levels and does not affect cholesterol levels.

Comparative studies of the effect of atypical antipsychotics on lipid metabolism in patients with schizophrenia indicate that patients treated with olanzapine exhibit higher triglyceride levels (mean level – 2.3 mmol / l) than those patients who received risperidone (mean level – 1.7 mmol / l) and ziprasidone.

Despite the small number of publications on the effect of quetiapine and zotepine on lipid metabolism, it can be assumed that due to the structural similarity of the latter with clozapine and olanzapine, these drugs may affect lipid levels.

In patients receiving clozapine and olanzapine, there is an increase in serum leptin levels, while, as noted above, white adipocyte leptin regulates insulin secretion and energy metabolism by acting on specific receptors (OB-R) of the hypothalamus, fat cells and skeletal muscles .

With respect to amisulpiride and aripiprazole, there are no data in the literature regarding their effect on lipid metabolism.

The risk group for weight gain includes women, individuals prone to narcissism, and patients with a hereditary burden of obesity.

Weight gain during therapy with psychotropic drugs makes it difficult to cooperate with the doctor and is, especially in women, one of the main reasons for discontinuation of the drug.

Unfortunately, at present, almost 60% of patients with schizophrenia with signs of dyslipedemia do not receive the therapy they need, aimed at correcting metabolic disorders.

If weight gain due to the use of antipsychotics is detected, a psychoeducational program specially designed for a particular case should be carried out with the patient and his relatives. Typically, the duration of such a program, which includes information about the features of the action of antipsychotics and a healthy lifestyle, is several weeks.

A strict diet, including the restriction of high-calorie foods, and physical exercise reduce the severity of the development of obesity that occurs against the background of taking psychotropic drugs.

A significant increase in body weight when taking atypical antipsychotics (olanzapine, quetiapine, risperidone) is usually observed in 14-27% of cases by 6-8 weeks of therapy, in 40% of patients after 3.5 years.

Patients taking clozapine gain an average of 4.5 kg of weight within 10 weeks (Allison D. et al., 1999), with an annual weight gain ranging from 5.7 to 8.0 kg (Lamberti Y. et al., 1992). Up to 94% of patients taking olanzapine also gain weight (Gupta S. et al., 1999). Patients using olanzapine for 10 weeks increase their weight by
4.15 kg (Allison D. et al., 1999), an average of 12 kg per year (Beasley C., 1997).

Risperidone causes moderate to minimal weight gain (2.1 kg in 10 weeks (Allison D. et al., 1999), patients gain an average of 1. 7 kg in one year) (Sachs G. 1999) .

For quetiapine, average weight gain over several months of therapy is between 1.0 and 4.0 kg (Borison R. et al., 1996). If against the background of taking respiridone, weight gain is especially noticeable in the first year and a half of using the drug, then the effect of quetiapine on this indicator lasts up to two years.

Ziprasidone causes the least weight gain (Allison D. et al., 1999). According to some researchers, almost the same weight gain is observed against the background of taking amisulpiride.

Weight changes with antipsychotics are shown in Table 42.

Table 42. Weight changes with antipsychotics

Weight gain while taking atypical antipsychotics does not depend much on the dosage of the atypical antipsychotic, but is associated with the effectiveness of the drug (positive therapeutic response), body mass index before the start of the medication, the age of the patient and, apparently, from belonging to one or another different ethnic group of people.

Due to the high risk of developing this complication of antipsychotic therapy, preliminary screening of patients at risk of weight gain with subsequent special control of body weight of this group of individuals is recommended.