Discover How Topiramate Can Boost Weight Loss in Bipolar Disorder

The weight loss medication boom has introduced several potential treatments for the obesity crisis. Among these is topiramate, an anti-epileptic drug sold under the brand name Topamax. While not FDA-approved for weight loss, healthcare providers are increasingly prescribing topiramate to help patients achieve and maintain a healthy weight. This article examines topiramate’s efficacy as a weight loss drug, how it works, and what to consider before taking it, especially in the context of bipolar disorder.

What is Topiramate (Topamax)?

Topiramate is an anticonvulsant medication prescribed to treat tonic-clonic and partial-onset seizures and epilepsy. It is also used for migraine prevention in adults and children over 12. Topiramate is being studied for its efficacy in treating alcohol use disorder (alcoholism), post-traumatic stress disorder (PTSD), bipolar disorder, and certain eating disorders, such as binge eating.

Topiramate primarily affects the central nervous system (CNS). While its exact mechanism of action is not entirely understood, it is thought to help treat seizures and migraines by calming down nerve signals and channels in the brain. Topiramate's effect on migraines is preventative rather than therapeutic, helping to dampen specific triggers that can cause migraines.

Topiramate is supplied as an oral capsule (regular or extended-release) or a fine powder to be sprinkled on food.

How Topiramate Works for Weight Loss

Topiramate has been shown to cause weight loss in some patients, alongside its anti-epileptic properties. The exact way that it does so is not fully understood, but research suggests several possible mechanisms. In multiple clinical trials, topiramate produced more significant weight loss in individuals who took the medication than those in the placebo group.

Possible mechanisms include:

Appetite suppression: Reducing calorie intake.
Preventing fat storage: Preventing the body from storing excess fat.
Lowering fat and cholesterol levels: Affecting the body's metabolism of fats.
Brain's reward system: Potentially preventing binge eating.

Topiramate may influence leptin, a hormone that plays a role in fat storage. Some studies have found that topiramate can lower leptin levels, which may contribute to weight loss. Additionally, topiramate may affect genes related to neuropeptide Y, which can influence the body's weight regulation system. Moreover, topiramate may work by blocking carbonic anhydrase, a substance that affects how the body metabolizes sugar and lipids (fat cells).

Overall, topiramate has various effects on the body's metabolism and weight management.

Safety, Side Effects, and Precautions

The Food and Drug Administration (FDA) approved Topiramate in 1996 for treating epilepsy and certain types of seizures. Topiramate is considered safe and effective for most adults and children over 12 but may cause adverse side effects in some patients.

Common side effects of topiramate include numbness, tingling (paresthesia), slowed reactions, nervousness, headache, drowsiness, weakness, shaking, eye movements, weight loss, digestive problems (constipation, nausea, stomach pain), altered taste, dry mouth, nosebleeds, and menstrual irregularities.

Topiramate can cause dizziness and impair coordination. Avoid alcohol and other central nervous system (CNS) depressants, such as sedatives and certain pain medications, as they can increase these side effects.

Serious side effects are rare but may include:

Skin issues (rash, blisters, peeling)
Vision problems (blurred vision, loss of vision, double vision, eye pain, redness)
Seizures
Feeling cold, chills, or a low body temperature
Cognitive issues (difficulty concentrating, speech problems, confusion, memory problems)
Coma (loss of consciousness)
Coordination problems
Heart-related symptoms (pounding or irregular heartbeat, chest pain, shortness of breath)
Altered mental state (inability to respond to surroundings or mood changes)
Tiredness
Gastrointestinal problems (diarrhea, vomiting, loss of appetite)
Kidney issues (intense back or side pain, abnormal urine)
Frequent urination, pain while urinating
Signs of infection (fever)
Bleeding or bruising problems
Osteoporosis

Higher doses of topiramate are associated with an increased risk of adverse reactions. Seek medical advice from a licensed healthcare provider if you begin to notice the side effects of topiramate.

Before starting treatment with topiramate, tell your provider about any medical conditions you have, any medications or supplements you are taking, and any adverse reactions to medicines in the past. Topiramate may reduce the efficacy of certain medications, such as birth control pills.

Topiramate may be unsafe for certain individuals with previously diagnosed health conditions. Healthcare providers may avoid prescribing topiramate for individuals with:

A history of suicidal thoughts or behaviors
A history of kidney stones
Metabolic acidosis
Bone conditions like osteopenia, osteomalacia, or osteoporosis
Glaucoma
Respiratory issues like asthma or COPD
Depression or mood disorders
Growth problems
Thyroid disease
Liver disease
Kidney diseases

Topiramate can increase the risk of kidney stones, so it's essential to stay well-hydrated while taking the medication. Drink plenty of water, and consider discussing with your health care provider whether you should take supplements like potassium citrate to reduce the risk of kidney stones.

Tell your provider if you are following a ketogenic diet (a high-fat, low-carbohydrate diet that is used to control seizures), as taking topiramate while on a keto diet can increase your risk of metabolic acidosis.

Topiramate may not be prescribed to pregnant women, women who are trying to conceive, or women who are breastfeeding.

Topiramate Dosage for Weight Loss

Topamax is supplied as an oral tablet in 25, 50, 100, and 200 milligrams (mg) doses. Because Topamax is not approved as a weight loss aid, there is no standard recommended dosage. Standard starting doses can range from 25 to 50 milligrams per day and may be increased to 100 milligrams or more. Individual responses to the medication can vary, and your healthcare provider will determine the appropriate dosage for you based on your medical history and other factors.

If you have been prescribed Topamax, inform your healthcare provider if you begin to experience side effects. Your provider may reduce your dosage or prescribe an alternative treatment option in this event.

Who Should Consider Topiramate for Weight Loss?

Topiramate is FDA-approved as a treatment for epilepsy and certain types of seizures. It is also approved as a preventative measure against migraines in adults and children over 12. The use of topiramate as a weight reduction agent is off-label, meaning that this effect is not FDA-approved.

Higher doses of Topamax produce more significant effects on body weight but are also linked to an increased risk of side effects. Talk to your healthcare provider about whether topiramate is right for you and your condition.

Alternatives to Topiramate

Topiramate is one of many prescription drugs currently being used for weight management. However, it is most effective for weight loss at higher doses, which can increase the risk of adverse side effects. If you are looking for an alternative to topiramate, talk to your doctor about:

Semaglutide (Ozempic, Wegovy, or Rybelsus): A diabetes drug that assists with weight loss when prescribed with a healthy diet and regular exercise. Semaglutide manages blood sugar levels, curbs appetite, and slows stomach emptying. Wegovy is specifically approved for the treatment of obesity in patients without type 2 diabetes.
Tirzepatide (Mounjaro or Zepbound): Like semaglutide, tirzepatide is a GLP-1 receptor agonist used to treat type 2 diabetes and obesity. It regulates blood sugar levels, reduces appetite, and slows stomach emptying. Zepbound is specifically approved to treat obesity in patients without type 2 diabetes.
Liraglutide (Saxenda): A GLP-1 receptor agonist approved by the FDA to treat obesity in adults and children over 12. It works by reducing blood sugar levels and appetite while slowing stomach emptying.
Naltrexone/Bupropion (Contrave): Bupropion helps reduce appetite and increase the feeling of fullness, making it easier to control calorie intake. Naltrexone reduces the rewarding effects of food and cravings, particularly for high-calorie, high-sugar foods. Contrave is FDA-approved as a weight management aid for patients with obesity or individuals who are overweight and have a weight-related health condition.
Metformin: A prescription diabetes drug that has been shown to cause weight loss in some patients. It works by regulating blood sugar levels and improving insulin sensitivity. Increased insulin usage lowers the amount of sugar circulating in the blood.
Qsymia (topiramate/phentermine): A weight management medication that combines topiramate with phentermine, an appetite suppressant.

Topamax vs. Qsymia

Topamax is approved to treat epilepsy and certain types of seizures and prevent migraines. Qsymia contains topiramate combined with phentermine. Unlike Topamax, Qsymia is an FDA-approved weight management medication.

Qsymia is indicated for use in adults with obesity (with a body mass index-BMI-of 30 kg/m2 or greater) or overweight adults (with a BMI of 27 kg/m2 or greater) who also have weight-related medical problems such as type 2 diabetes, high blood pressure, high cholesterol, or cardiovascular disease.

Qsymia is prescribed as an extended-release oral capsule, generally taken once a day, usually in the morning. Healthcare providers will prescribe a low dose of Qsymia before gradually increasing its dosage, depending on how the patient tolerates the medication. It is prescribed with lifestyle changes such as a reduced-calorie diet and increased exercise.

Qsymia may increase the risk of congenital disabilities if taken while pregnant and is not appropriate for every patient seeking to manage their weight.

Obtaining a Prescription for Weight Loss Drugs

Topiramate is a prescription drug, meaning that you must have a written order from a licensed healthcare provider to get it. You cannot buy generic topiramate or Topamax over the counter.

Weight loss drugs are prescribed to individuals with obesity or individuals who are overweight and managing a weight-related health condition. Talk to your healthcare provider about whether these treatment options are right for you. This is also an excellent time to discuss costs, potential side effects, and concerns.

Topiramate in Bipolar Disorder: Weight Management and Off-Label Uses

Psychiatric patients who receive long-term mood-stabilizing agents can gain excess body weight, which can lead to poor compliance and increased cardiovascular morbidity. Weight gain is induced by the majority of antipsychotics, lithium, antidepressants, and valproate.

Topiramate has been shown to cause weight loss in various patient groups. It has also shown effectiveness in open trials as a mood stabilizer in patients with affective disorders, but not in controlled trials in the acute treatment of mania.

One study prescribed topiramate to 12 patients with affective disorders who had a body-mass index >30 kg/m2. Topiramate was prescribed as part of routine clinical practice, as an add-on medication, or as a replacement of a mood stabilizer. Patients' weight was recorded in 1 to 2 monthly intervals. Patients were followed up for between 6 and 12 months. The final dose of topiramate varied from 200 to 600 mg/day. Topiramate was effective in reducing the weight in 10 out of the 12 patients.

Topiramate could be considered in the treatment of bipolar patients who are overweight or whose concerns about weight gain compromise their compliance with long-term prophylactic medication.

Topiramate: Proposed Uses for Comorbidities Common in Bipolar Disorder

There appears to be some confusion regarding the efficacy of topiramate in bipolar disorder. The evidence does not support its use for mania or depression. Topiramate has a significant adverse effect burden, including kidney stones, glaucoma, suicidal ideation, cognitive and memory impairment, numbness and tingling in the extremities, and hyperchloremic acidosis. Topiramate is FDA approved for seizures and for migraine prophylaxis.

There are some off-label proposed uses for topiramate in comorbidities that are common in patients with bipolar disorder. It has been used as an adjunct to olanzapine to mitigate or even prevent weight gain. This is not recommended as something to do routinely (because of all those adverse effects), but at times this can be helpful and worth the risks. Topiramate in low doses (up to 92 mg) is a component of a weight loss combination product (with phentermine) that is on the market.

Some patients with bipolar disorder who experience weight gain also have binge eating disorder (BED). Topiramate has two positive studies in BED with good results.

Some substance abuse disorders (SUDs) may benefit from topiramate for prevention of relapse. There may be mild benefit in alcohol use disorder, and there are two positive studies of patients with cocaine use disorder, only one of which showed benefit at end point-at doses up to 300 mg daily. Note that all of these studies used substantial doses of topiramate. One encounters patients on low doses like 25 mg twice a day. These may be placebo-level doses for any of the possible SUD indications.

Several trials have examined the effect of topiramate on posttraumatic stress disorder (PTSD).

Three small placebo-controlled trials of topiramate at up to 200 mg daily in patients with borderline personality disorder (BPD) are all from the same research group in Germany/Austria. Large improvements in hostility, interpersonal sensitivity, and anxiety symptoms were reported, larger than have been seen in other psychopharmacology studies of BPD.

Studies on Topiramate and Weight Loss in Bipolar Disorder

A retrospective chart review was conducted of 5 patients with a DSM-IV diagnosis of bipolar disorder or schizoaffective disorder placed on topiramate treatment. The patients had been placed on topiramate treatment owing to partial response to their therapeutic regimen. All 5 patients responded to adjunctive topiramate for the treatment of the bipolar or schizoaffective disorder. The mean dose of topiramate was 195 mg/day (range, 100-375 mg/day). All patients lost a substantial amount of weight on topiramate. The average weight loss was 22 lb (10 kg; range, 8-56 lb [4-25 kg]). No patient discontinued topiramate because of side effects.

Eighteen patients with DSM-IV bipolar I disorder [mania (n = 12), hypomania (n = 1), mixed episode (n = 5), and rapid cycling (n = 6)], and two subjects with schizoaffective disorder bipolar type, resistant to current mood-stabilizer treatment were initiated on topiramate, 25 mg/day, increasing by 25-50 mg every 3 7 days to a target dose between 100 and 300 mg/day, as other medications were held constant for 5 weeks. By 5 weeks, 12 (60%) subjects were responders, i.e., 50% reduction in the Y-MRS scores and a CGI of 'much' or 'very much improved'. Six subjects had parasthesia, three experienced fatigue, and two had 'word-finding' difficulties; in all cases, side effects were transient. Topiramate appears to have efficacy for the manic and mixed phases of bipolar illness. Other preliminary data suggest antidepressant efficacy too. Among obese bipolar subjects, the weight loss potential of topiramate may be beneficial.

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