Topiramate, commonly known by brand names including Topamax, Trokendi XR, Eprontia, and Qudexy XR, is a prescription medication primarily used as an anticonvulsant to manage seizures and prevent migraines. While not specifically approved by the FDA as a standalone weight loss drug, topiramate has been observed to cause weight loss in both adults and children when used for its approved purposes. This article aims to provide a comprehensive overview of topiramate's effects on weight loss, its mechanisms of action, clinical evidence, potential side effects, and important considerations for its use.
Introduction
Obesity has emerged as a widespread disease with epidemic proportions, necessitating effective management to enhance the overall health outcomes of patients. Medical intervention for weight loss becomes necessary when diet and exercise prove ineffective, and topiramate emerges as a potential treatment option for this global problem. Topiramate is classified as an anticonvulsant (seizure) medication.
Observed Weight Loss with Topiramate
Weight loss was reported in studies of both children and adults taking topiramate. Clinical studies have indicated that weight loss occurs in a notable percentage of patients taking topiramate. In general, weight loss was seen in 6% to 17% of patients and tended to increase with higher doses. The extent of weight loss can vary depending on the dosage and the population studied.
Seizure Control
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 patients aged 16 years and older taking topiramate (Topamax) alone (without other seizure medicines), weight loss occurred in 6% of patients taking the lower 50 mg / day dose, and in 17% of patients taking the higher 400 mg / day dose. 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.
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. 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.
Read also: Comprehensive Study: Metformin and Phentermine/Topiramate
Topiramate and Qsymia
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.
How Topiramate Works
Multiple physiological mechanisms are described for topiramate, which enhances its ability to treat a wide array of seizure types. The main effects associated with topiramate are to reduce neuronal excitation and to enhance neuronal inhibition. The drug possesses sodium-channel blocking activity, enhancement of cerebral GABA concentrations, and antagonism of the AMPA/kainite receptors, leading to decreased glutamate-mediated excitation and subsequent reduction in neuronal excitation. TPM also increases the frequency of GABA-mediated chloride channel opening and increases potassium induction, further alleviating seizures by enhancing neuronal inhibition.
Although the specific mechanism of action concerning weight loss remains uncertain, various hypotheses have been reported. Notably, topiramate may contribute to weight loss by reducing calorie intake, decreasing fat gain, and lowering triglyceride and cholesterol levels. Additionally, its impact on reward pathways associated with food could play a role.
Impact on Energy Utilization and Metabolism
Although the biological mechanism behind TPM-induced weight loss is not well-described, possible mechanisms include lowering calorie intake, decreased fat gain, and decreased triglycerides and cholesterol levels. Studies show that TPM reduces energy deposition without changing food consumption by disrupting efficient energy utilization. This suggests TPM can stimulate lipoprotein lipase in brown adipose tissue and skeletal muscle, increasing thermogenesis and substrate oxidation.
Role in Leptin Pathways
Other sources have described that TPM may play a role in the gene encoding for neuropeptide Y, which influences the leptin pathway. Leptin, a hormone involved in fat storage, is released by adipose tissue and binds receptors in the hypothalamus, which modulates the secretion of neuropeptide Y. Studies have described reduced leptin levels while patients were on topiramate, which directly correlated with weight reduction, A study in 2003 described reduced leptin levels in patients who were losing weight, and in patients who lost 10% or more body weight, leptin levels were reduced by 36% at three months. Overall, body weight and metabolism are also constantly regulated by signals from leptin and insulin in the hypothalamus. Pro-opiomelanocortin (POMC) neurons within the arcuate nucleus release melanocortin, which acts on the paraventricular hypothalamus to release thyrotropin-releasing hormone (TRH) and corticotropin-releasing hormone (CRH). Insulin and leptin act on this pathway to regulate metabolism.
Read also: Antipsychotic-Induced Obesity Treatment
Effects on Blood Glucose and Insulin Sensitivity
TPM has also been determined to lower fasting blood glucose, cholesterol, triglycerides, and HDL levels. One study observed significant blood glucose reductions in overweight patients undergoing TPM therapy and more profound blood glucose reductions in obese patients. TPM is a carbonic anhydrase inhibitor, which can influence the carbonic anhydrate enzymes involved in cellular lipogenesis. Eliasson et al. noted that in obese patients diagnosed with Type 2 diabetes, treatment of topiramate for 11 months as an adjunctive showed significantly reduced body weight and improved glycemia control. In 2005, Wilkes et al. studied female Zucker diabetic fatty rats treated with topiramate. Treatment decreased the glucose levels compared to untreated rats of the same weight. The study determined that TPM treatment improved insulin sensitivity in diabetic mice and skeletal muscle. These data were confirmed in a separate 2011 study showing that TPM induces weight loss and improves insulin sensitivity in dietary obese rats compared to sibutramine.
Clinical Studies on Topiramate for Weight Loss
Multiple clinical studies have supported the use of topiramate as a weight-loss medication. Notably, the medication demonstrates effectiveness in reducing body weight across different dosages and sustaining weight loss over time, outperforming alternative weight loss methods. Moreover, it was generally well-tolerated in clinical studies, with few side effects observed.
Khera et al.’s meta-analysis showed that patients treated with phentermine-topiramate, 15 mg/92 mg once daily, are associated with the highest probability of achieving at least a 5% weight loss. Domecq et al.’s meta-analysis also showed that patients on topiramate for over 3 months experienced 3.7 kg of weight loss.
Bray et al. Study
Bray et al. evaluated the efficacy and safety of TPM for weight reduction in obese and healthy participants. It was a double-blind, randomized, placebo-controlled trial conducted with three hundred and eighty-five subjects aged 18-75 with a BMI of ≥30 to <50 kg/m2 or ≥27 to <50 kg/m2 if the subjects also had controlled hypertension and/or dyslipidemia. They were randomized into either a placebo group or treatment group of TPM at 60 mg, 96 mg, 192 mg, or 384 mg daily. The participant dosages were slowly increased by 16 mg weekly until they hit their target doses. After twenty-four weeks of treatment, all participants were tapered off by a 50% dose reduction. Importantly, all participants partook in similar lifestyle plans. The mean percent weight loss from baseline to week 24 was −2.6% in the placebo group and −5.0%, −4.8%, −6.3%, and −6.3% in the TPM groups. Common adverse events mainly consisted of paresthesia, somnolence, and concentration, which improved after dosage adjustments. In the placebo group, 11% of the participants withdrew due to adverse events vs. 21% in the TPM group.
Moradi et al. Study
Moradi et al. evaluated the effect of TPM on weight loss in patients with type 2 diabetes. During 2008-2010, this 32-week randomized clinical trial of 69 participants was split into a placebo (30 patients) group and a TPM (39 patients) group. Both groups were randomly assigned to participate in a nonpharmacological lifestyle intervention group. BMI, blood pressure, lipid profile, and glycosylated hemoglobin (HgA1c) were evaluated. Based on the 69 intended treated patients, the mean BMI changes were significantly higher (p = 0.006), the mean weight loss was significantly higher (p = 0.005), and the systolic blood pressure and glycosylated HgA1c were significantly decreased in the TPM group (p = 0.021 and p = 0.047).
Read also: Weight Loss with Contrave and Topiramate
Toplak et al. Study
Toplak et al. evaluated the safety and efficacy of TPM in obese patients with type 2 diabetes concurrently treated with metformin. It was a multicenter, double-blind, placebo-controlled trial consisting of 646 obese men and women (aged 18-75 with a BMI of 27-50 kg/m2). Diet, exercise, and behavioral modification were adjusted, as well as maintaining the patients on a 600 kcal diet reduction based on their metabolic requirements. First, a 6-week single-blind run-in was used, followed by randomization to the placebo, 96 mg/day of TPM or 192 mg/day of TPM. After 8 weeks of titration, the participants used the treatment or placebo for 52 weeks. The mean percentage change in weight and HgA1c from baseline to week 24 was assessed. The placebo, TPM 96 mg group, and TPM 192 mg group lost 1.7%, 4.5%, and 6.5% of their baseline body weight. Both TPM groups had significant mean percentage weight changes with a p < 0.001. Additionally, the TPM groups appreciated significant decreases in systolic blood pressure.
Other Uses of Topiramate
One of the labeled indications for TPM is the treatment of epilepsy. A 2007 randomized but unblinded study investigated the effectiveness of lamotrigine, gabapentin, carbamazepine, oxcarbazepine, and TPM in treating partial epilepsy. The study found no significant difference in efficacy between these drugs for seizure control, though lamotrigine was better tolerated than the others. This study supports that TPM is an effective treatment for partial epilepsy. A 2007 randomized but unblinded study by the same team investigated the effectiveness of valproate, lamotrigine, and the effectiveness of TPM in treating generalized and unclassifiable epilepsy. The study found that, while valproate was superior to topiramate, this was based not on efficacy but on tolerability. Valproate and TPM were equivalent, while lamotrigine was less effective. A 2005 double-blind, randomized, placebo-controlled, parallel-group trial investigated the efficacy of topiramate as an adjunct therapy for patients with juvenile myoclonic epilepsy. The study found a 50% or more reduction of primarily generalized tonic-clonic seizures in 73% of patients compared to 18% in the placebo group. This study supports topiramate in treating juvenile myoclonic epilepsy. A 1999 double-blind, randomized study investigated the efficacy of TPM in treating Lennox-Gastaut syndrome. The study found an improvement in seizure frequency of 52% in patients taking TPM compared to 38% in the placebo group. Additionally, there was a 15% reduction in drop attacks in the topiramate group compared to a 5% increase in the placebo group.
The other labeled indication for TPM is migraine prophylaxis. A 2004 randomized, double-blinded, parallel-group trial investigated the difference in efficacy of TPM at 100 mg/day, 200 mg/day, and immediate-release propranolol 160 mg/day as an active control. The study found that TPM, when given at a dose of 100 mg/day, is effective in the metrics of a mean reduction in the average monthly migraine frequency, average monthly migraine days, rate of rescue medication, and responder rate compared to the placebo. This data shows that topiramate is an option for migraine prophylaxis. A 2004 randomized, double-blind, placebo-controlled study investigated the efficacy of topiramate at 50 mg/day, 100 mg/day, or 200 mg/day doses. The study found that the monthly migraine frequency was decreased in the 100 mg/day and 200 mg/day groups compared to the placebo, with improvements occurring in the first treatment month.
A 2015 meta-analysis evaluated information from studies about off-label TPM use for essential tremors. The study found that, compared to the placebo, TPM use led to significant improvements for patients measured by a change in the Fahn-Tolosa-Marin tremor rating scale and improvements in motor tasks/functions and function disability scores.
A 2015 literature review compiled information from studies of off-label TPM use for alcohol use disorders. This review found that TPM significantly impacted reducing drinks per day, drinks per drinking day, and the number of heavy drinking days, as well as increasing the percentage of days abstinent. Overall, the review found that the current studies on the subject support that the off-label use of TPM is beneficial for treating alcohol use disorders.
Potential Side Effects
The side effect profile of TPM is extensive and can be a barrier to patient use. One of the most distressing and unique side effects of TPM use is word-finding problems with slowed mental processing and attention and memory difficulties. Additionally, TPM is associated with fatigue, dizziness, somnolence, mood changes, and suicidal ideation. Related to inhibition of carbonic anhydrase, TPM has been known to cause paresthesia, renal calculi, metabolic acidosis, hypokalemia, and taste disturbance. Cognitive side effects are more frequent in patients using TPM for migraine prophylaxis than in epilepsy patients.
Common Side Effects
Topiramate use for weight loss can cause many adverse effects, such as:
- Nervousness
- Drowsiness
- Numbness in feet or hands
- Shaking or tremors
- Nausea, stomach pain, and constipation
- Excessive menstrual bleeding
- Missed menstrual periods
- Bone pain
- Weight loss
Serious Side Effects
Serious side effects may include:
- Hyperthermia
- Suicidal ideation
- Impaired liver function and liver disease
- Bloody or cloudy urine
- Painful urination
- Unusual bruising or bleeding
- Intense side or back pain
- Fever
If you experience any troubling side effects of topiramate or an unusual or allergic reaction, call your doctor immediately. They may advise you to stop taking it or may adjust your dose.
Risk of Disordered Eating
Topamax has been used for weight loss in some individuals with binge eating disorder (BED), and though it can be effective in reducing weight, it doesn’t treat the underlying issues of BED. In fact, it can cause disordered eating patterns in people who take it.
Research indicates that taking Topamax can be risky to your health, especially for those who have a history of an eating disorder or are vulnerable to disordered eating. One case study assessed seven adolescents who developed disordered eating after taking topiramate. Three of the participants developed an eating disorder after starting Topamax, three had eating disorders prior to taking the medication, and one had been in eating disorder recovery. All of the teens had the same primary symptom of food restriction, while a few also engaged in purging and binging.
Although following a fad diet like the ketogenic diet doesn’t necessarily mean someone has an eating disorder, it can be considered disordered eating. And if an individual is following the keto diet to lose weight, taking Topamax for weight loss could be especially dangerous due to the severe body weight changes, as well as the risk of metabolic acidosis, which occurs when there’s a buildup of acid in the body.
Dangers of Rapid Weight Loss
Topamax can lead to rapid weight loss due to appetite suppression. However, losing weight quickly has many health risks, including:
- Vitamin and mineral deficiencies
- Muscle loss
- Malnourishment
- Decreased metabolism
Additionally, using Topamax for weight loss can increase the risk of disordered eating behaviors as well as the risk of developing full-blown eating disorders like anorexia nervosa (AN) and bulimia nervosa (BN). In fact, one study showed that teen girls who engaged in extreme dieting were 18 times more likely to develop an eating disorder than those who didn’t diet.
Further, rapid weight loss can lead to rebound weight gain, something known as weight cycling. Research indicates that weight cycling is worse for your health than never dieting at all and that it can increase your mortality rate or risk of death.
Overdose Information
It is possible to overdose on topiramate. Signs and symptoms of a topiramate overdose include:
- Vomiting
- Seizures
- Trouble speaking
- Blurred or double vision
- Loss of consciousness
- Agitation
- Shallow, fast breathing
- Irregular heartbeat
- Unresponsiveness
If you suspect that you or someone else has experienced a Topamax overdose, call 911 immediately. If you are a witness, stay with the overdosing person until first responders arrive to ensure their safety.
Important Precautions
It is very important that your doctor check your or your child's progress at regular visits to see if the medicine is working properly. Blood and urine tests may be needed to check for unwanted effects.
Using this medicine while you are pregnant can harm your unborn baby. Use an effective form of birth control to keep from getting pregnant. If you think you have become pregnant while using this medicine, tell your doctor right away. Birth control pills containing estrogen may not work properly if you take them with topiramate. To keep from getting pregnant, use an additional form of birth control (eg, condoms, spermicide) together with your birth control pill. If you have any questions about this, check with your doctor or pharmacist.
This medicine may cause vision changes, clumsiness or unsteadiness, dizziness, drowsiness, or trouble with thinking or speaking. Make sure you know how you or your child react to this medicine before you drive, use machines, climb in high places, swim, or do anything else that could be dangerous if you are not alert, well-coordinated, or able to think or see well.
Check with your doctor before using this medicine with alcohol or other medicines that affect the central nervous system. The use of alcohol or other medicines that affect the CNS with topiramate may worsen the side effects of this medicine, such as dizziness, poor concentration, drowsiness, unusual dreams, and trouble with sleeping. Some examples of medicines that affect the CNS are antihistamines or medicine for allergies or colds, sedatives, tranquilizers, or sleeping medicines, medicine for depression, medicine for anxiety, prescription pain medicine or narcotics, medicine for attention deficit and hyperactivity disorder, medicine for seizures or barbiturates, muscle relaxants, or anesthetics, including some dental anesthetics.
Check with your doctor right away if you or your child have changes in vision or pain around the eyes during and after treatment with this medicine. Your doctor may want your eyes to be checked by an ophthalmologist (eye doctor).
This medicine may make you sweat less which will cause your body temperature to increase. Use extra care not to become overheated during exercise or hot weather with this medicine. Overheating may result in heat stroke and hot baths or saunas may make you dizzy or feel faint.
Topiramate may cause some people to be agitated, irritable, or display other abnormal behaviors. It may also cause some people to have suicidal thoughts and tendencies or to become more depressed. Make sure the doctor knows if you have trouble sleeping, get upset easily, have a big increase in energy, or start to act reckless. Also tell the doctor if you have sudden or strong feelings, such as feeling nervous, angry, restless, violent, or scared. If you, your child, or your caregiver notice any of these side effects, tell your doctor right away.
This medicine may cause nausea, muscle tremors, breathing problems, eating problems, a fast heartbeat, restlessness, and stomach pain. Tell your doctor right away if you or your child have any of these symptoms. You might have a serious condition called metabolic acidosis (too much acid in the blood).
This medicine may decrease the density of bones, which can make your bones weak. Talk with your doctor if you have any concerns about this.
This medicine may cause slow growth. For children, the doctor will need to keep track of height and weight to make sure that the child is growing properly.
Do not suddenly stop using this medicine without checking first with your doctor. Stopping the medicine suddenly may cause your seizures to return or to occur more often. Your doctor may want you or your child to gradually reduce the amount you are using before stopping it completely.
Serious skin reactions (eg, Stevens-Johnson syndrome, toxic epidermal necrolysis) can occur with Topamax®, Trokendi XR®, and Eprontia®. Check with your doctor right away if you have blistering, peeling, or loosening of the skin, chills, cough, diarrhea, itching, joint or muscle pain, red irritated eyes, red skin lesions, often with a purple center, sore throat, sores, ulcers, or white spots in the mouth or on the lips, or unusual tiredness or weakness with this medicine.
Check with your doctor right away if you or your child are having unusual drowsiness, dullness, tiredness, weakness, feelings of sluggishness, mental depression or anxiety, nightmares or unusually vivid dreams, or vomiting. These may be symptoms of a serious condition called hyperammonemic encephalopathy.
Check with your doctor right away if you or your child have sudden back pain, stomach pain, pain while urinating, or bloody or dark urine. These may be symptoms of kidney stones.
Tell your doctor if your or your child's skin feels like it is burning, crawling, itching, or if you have numbness, prickling, "pins and needles", or tingling feeling after using topiramate.
Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.
Dispelling Diet Culture
People who decide to use medication like topiramate for weight loss are typically influenced by the insidious nature of diet culture. Most people aren’t even aware of how much diet culture affects us, our relationship to food, our movement, our bodies, and the decisions we make daily.
Diet culture is ever-present, in media, pop culture, advertisements, and marketing, at grocery stores, in conversations, at work and in doctor’s offices, on food labels and menus, and beyond. And diet culture, which tells us that body shape and weight are more important than well-being, leads to anxiety about weight gain, body shape, body size, and more.
Diet culture even influences medical decisions. In 2012, the Food and Drug Administration (FDA) approved a combination weight-loss medication consisting of phentermine and topiramate. These decisions come on the heels of the so-called “obesity epidemic,” which has pathologized living in a larger body, associating fatness with disease. However, weight isn’t an accurate indicator of health, and pathologizing fatness only reinforces fatphobia, diet culture, and healthism.
tags: #topiramate #100mg #for #weight #loss #information