Obesity has become a global epidemic with far-reaching health implications. When lifestyle changes like diet and exercise are insufficient, medical interventions such as Topamax may be considered. Topamax, known generically as topiramate, is an antiseizure drug initially approved by the FDA for treating epilepsy. However, its off-label use as a weight-loss aid has garnered attention due to weight loss being a common side effect observed during clinical trials. While Topamax has never received FDA approval specifically for weight loss, physicians are aware of its potential in this area and may prescribe it off-label.
History of Topamax and Weight Loss
Topamax, or topiramate, gained FDA approval for treating epilepsy. Significant weight loss was a common side effect during these trials. Despite this, topiramate has not been approved by the FDA for weight loss, making any such use off-label. The American Diabetes Association reported that clinical weight-loss trials were discontinued due to adverse effects associated with the drug's use in this manner.
Weight-Loss Success with Topamax
Weight loss was observed in between 11 and 26 percent of patients taking Topamax. Some patients lost as much as 15 to 20 percent of their body weight while taking between 100 and 200 mg of Topamax, often describing the weight loss as effortless.
How Topamax Works: Theories and Mechanisms
The specific mechanism by which topiramate induces weight loss remains not well-described. However, several theories attempt to explain this phenomenon. These include:
Loss of Taste Sensation
One theory suggests that Topamax alters taste sensations, making food less appealing. For some patients, this change in taste may be so severe that they lose the pleasure associated with eating, leading to decreased food intake and subsequent weight loss.
Read also: Comparing Qulipta and Topamax
Reduced Cortisol Production
Another theory proposes that Topamax may reduce leptin present in cortisol. Cortisol, a stress hormone, can lead to increased insulin production, which, according to Melissa Conrad Stoppler, MD, can increase appetite and cravings, significantly impacting weight gain or preventing weight loss.
Impact on Blood Glucose and Insulin Secretion
Topamax may also act on blood glucose and insulin secretion, potentially leading to weight loss through ketosis. This process is similar to how weight is lost on low-carbohydrate diets, where the body relies on fat stores as its primary energy source rather than dietary carbohydrates.
Other Physiological Mechanisms
Multiple physiological mechanisms are described for topiramate, enhancing 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.
It can lower calorie intake, decrease fat gain, and decrease 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.
Clinical Evidence Supporting Topiramate for Weight Loss
Multiple clinical studies have supported the use of topiramate as a weight-loss medication, demonstrating 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.
Read also: Lyrica, Topamax, and Body Weight
Domecq et al.’s meta-analysis also showed that patients on topiramate for over 3 months experienced 3.7 kg of weight loss.
Studies on Obese and Overweight Participants
Bray et al. evaluated the efficacy and safety of TPM for weight reduction in obese and healthy participants. 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.
Studies on Type 2 Diabetes Patients
Moradi et al. evaluated the effect of TPM on weight loss in patients with type 2 diabetes. 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).
Toplak et al. evaluated the safety and efficacy of TPM in obese patients with type 2 diabetes concurrently treated with metformin. 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.
Dosage of Topamax for Weight Loss
Since Topamax is not FDA-approved for weight loss, there are no official dosage recommendations for this purpose. A general guideline suggests that higher doses of Topamax may lead to greater weight loss, but this also increases the risk of side effects.
Read also: Does Topiramate Cause Weight Loss?
Reasons for Not Losing Weight on Topamax
Weight loss depends on many factors, and individual responses to medication vary. While many people lose weight on Topamax, others do not. Reasons for this include:
Dosage Issues
If you've been taking Topamax for a while without noticing weight changes, discuss your dosage with your doctor. Finding the correct dose is crucial, but remember that higher doses can lead to more pronounced side effects.
Alternative Medications
Newer medications specifically designed for weight management are now available. GLP-1 agonists like Wegovy (semaglutide) and Zepbound (tirzepatide) are developed with weight loss in mind. If Topamax isn't effective, discussing these alternatives with your doctor may be worthwhile, assuming insurance coverage.
Side Effects Counteracting Weight Loss
Topamax is linked to cognitive side effects, including fatigue, which can make consistency with lifestyle changes, such as increased movement or meal prep, more challenging.
Underlying Insulin Resistance Challenges
Topamax appears to help certain parts of the body-muscles, fat cells, and heart tissue-respond better to insulin. While helpful, it may not always be enough to keep the weight off long-term.
Lifestyle Changes Needed
All weight loss medications, including Topamax and semaglutide, work best in combination with a lifestyle approach. Nutrient balance, movement, sleep, and stress all play a significant role in weight regulation, as they affect hunger hormones and prevent metabolic adaptation.
Addressing Binge Eating
Sometimes Topamax is prescribed for binge eating disorder to reduce appetite and binges. But when emotional eating triggers are not addressed, they can overpower the appetite-reducing effects of medication.
Topamax Side Effects
Topamax (topiramate) side effects include:
- Weight loss
- Brain fog and cognitive function issues, including memory issues, trouble concentrating, and difficulty paying attention and focusing
- Nausea
- Dizziness
- Increased heart rate
- Suicidal behavior and thoughts
- Trouble with vision: harder to see things that are far away, or increased pressure in the eye (glaucoma)
- It is not safe for the unborn fetus in someone who is pregnant
- Trouble breathing
- Swelling in the face, mouth, and throat
- Allergic reactions on the skin, like itching, rash, or hives (pale red bumps on the skin)
- Hair loss (not a common side effect)
- Lower bone density
This is not a complete list of side effects. For more information on Topamax side effects, refer to the product label and consult a healthcare provider.
Topamax vs. Qysmia
Qysmia shows better weight loss results than Topamax (topiramate) alone. Qysmia is an FDA-approved combination pill of topiramate and phentermine, specifically approved for long-term weight loss. It takes about two months to experience weight loss on this drug.
How Fast Can You Lose Weight on Topamax?
Research shows that weight loss on Topamax may begin within four weeks of starting the medication.
Why Am I Gaining Weight on Topamax?
Weight gain is not a common side effect of Topamax, as the medication typically works by reducing appetite. If you’re experiencing weight gain on Topamax, consult your healthcare provider to explore potential reasons or alternative medications.
The Role of a Dietitian
A registered dietitian can help explore reasons why your weight loss has stalled on Topamax, including how satisfied you feel with the meals you are eating, any changes in your energy levels, sleep patterns, or stress levels.
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