Obesity, characterized by excess adipose tissue, is a widespread health concern. While pharmacotherapy is used in clinical medicine for obesity treatment, the efficacy and safety of specific drug combinations, such as topiramate and bupropion, warrant careful examination. This article explores the potential benefits and risks of using Topamax (topiramate) and Wellbutrin (bupropion) for weight loss, considering both clinical evidence and potential side effects.
Understanding Obesity and the Role of Medications
Obesity is a body condition characterized by the excess of adipose tissue in the body. The World Health Organization recognizes obesity as a global epidemic, highlighting the need for effective prevention and management strategies. While lifestyle interventions such as diet and exercise are fundamental, some individuals may require pharmacotherapy to achieve significant weight loss.
How Bupropion and Topiramate Work
Bupropion is an aminocetone antidepressant that inhibits the reuptake of dopamine and noradrenaline. Increased levels of these two catecholamines stimulate the activity of pro-opiomelanocortin (POMC) producing neurons, located in the arcuate nucleus in the hypothalamus. The POMC consists of a precursor polypeptide, and its cleavage gives rise to ∂-melanocyte-stimulating hormone (∂-MSH) and ß-endorphin, an endogenous opioid. Increased ∂-MSH promotes activation of melanocortin 4 receptor (MC4R) and the secondary signaling pathways coupled to them, leading to increased energy expenditure and decreased appetite.
Topiramate is an anticonvulsant drug considered a promising medication in the treatment of obesity and binge eating disorder (BED). Topiramate is currently used in the treatment of epilepsy and migraine, as it is an antagonist of the amino-3-hydroxy-5-methyl-isoxazol-4-propionic acid and kainate (AMPA/KA) receptor. This medication is also responsible for increasing gamma-aminobutyric acid (GABA) activity at GABA receptors by triggering stabilization of sodium and calcium channels. In animal models, topiramate has been shown to reduce appetite as well as to interfere with the efficiency of energy using, being the latter a consequence of increased thermogenesis and fat oxidation (due to stimulation of lipoprotein lipase in brown adipose tissue and skeletal muscle), which leads to weight loss.
Examining the Evidence: Clinical Studies
Several studies have investigated the efficacy of topiramate and bupropion, both individually and in combination, for weight loss.
Read also: Comparing Qulipta and Topamax
Topiramate
Topiramate's weight loss potential was first observed in patients treated for epilepsy. A study found that topiramate led to a mean weight loss of 7.3% over 56 weeks in patients with obesity (BMI ≥ 35 kg/m²).
Bupropion
Bupropion has been shown to promote weight loss through its effects on dopamine and norepinephrine levels. A study found that patients receiving bupropion experienced a mean weight loss of 7.2% over 24 weeks.
Naltrexone/Bupropion (Contrave)
The combination of naltrexone and bupropion has shown increased effectiveness compared to either drug alone. A study found that patients treated with naltrexone/bupropion experienced a mean weight loss of 5.0-9.3% over 56 weeks.
Animal Study Results
A study involving Wistar rats induced to obesity examined the effects of topiramate and bupropion, both alone and in combination, on weight loss. The study divided 40 male Wistar rats into eight groups:
- Ctr - control
- G0 - Sham
- G1 - oral saline solution (1.0mL/day)
- G2 - topiramate (20.0mg/kg) and bupropion (5.0mg/kg)
- G3 - naltrexone (20.0mg/kg)
- G4 - topiramate (20.0mg/kg)
- G5 - bupropion (5.0mg/kg)
- G6 - topiramate (20.0mg/kg), bupropion (5.0mg/kg) and naltrexone (20.0mg/kg)
The results showed that until the eighth week, all animals increased their weight by approximately 50%. After treatment, animals of all groups, except G3, increased their weight from 4% to 9% approximately. The medicines studied were not efficient in reducing weight in obese rats. The only group that presented a decrease in the volume of subcutaneous adipose tissue was G3, but this decrease was not significant when compared with the other groups. The G4, the G5 and the G6 presented increased adipose tissue volume. A fact to be considered in this study were the biochemical results, since the highest values of glucose and triglycerides were observed in the treated groups. We attributed the increase in these organic compounds to the weight gain that was observed in the animals. All the drugs studied were not effective in reducing weight, excepting the naltrexone.
Read also: Lyrica, Topamax, and Body Weight
These findings contrast with some clinical studies, highlighting the complexities of translating animal research to human outcomes. The study suggests that the treatment time of 30 days may have been insufficient to observe significant weight loss effects.
Potential Side Effects and Risks
While topiramate and bupropion can be effective for weight loss, they are associated with potential side effects and risks that must be carefully considered.
Topiramate 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 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
It is also possible to overdose on topiramate. Signs and symptoms of a topiramate overdose include:
Read also: Does Topiramate Cause Weight Loss?
- Vomiting
- Seizures
- Trouble speaking
- Blurred or double vision
- Loss of consciousness
- Agitation
- Shallow, fast breathing
- Irregular heartbeat
- Unresponsiveness
Bupropion Side Effects and Precautions
Using buPROPion with alcohol may increase the risk of uncommon side effects such as seizures, hallucinations, delusions, paranoia, mood and behavioral changes, depression, suicidal thoughts, anxiety, and panic attacks. On the other hand, sudden withdrawal from alcohol following regular or chronic use can also increase your risk of seizures during treatment with buPROPion. In general, you should avoid or limit the use of alcohol while being treated with buPROPion. Also avoid activities requiring mental alertness such as driving or operating hazardous machinery until you know how the medication affects you.
Both buPROPion and caffeine can increase blood pressure. And using them together may have additive effects. Talk to your doctor if you have any questions or concerns, particularly if you have a history of high blood pressure or heart disease.
Using buPROPion and nicotine together can cause an increase in blood pressure. This can cause dizziness, confusion, uneven heartbeats, and chest pain.
Bupropion is contraindicated in patients with a seizure disorder. Bupropion can cause seizure; the risk is dose-related. Bupropion is also contraindicated in patients with current/prior diagnosis of bulimia or anorexia nervosa and in patients undergoing abrupt discontinuation of alcohol, benzodiazepines, barbiturates, and antiepileptic drugs. Bupropion should be administered with caution in patients with conditions that increase the risk of seizure or who have other predisposing conditions.
Antidepressants increased the risk of suicidal thoughts and behavior in children, adolescents, and young adults in short-term trials; these trials did not show increased risk in patients older than 24 years and risk was reduced in patients 65 years and older. Patients of all ages treated with antidepressants for any indication should be monitored appropriately and observed closely for clinical worsening, suicidality, and unusual changes in behavior, especially during the first few months of drug therapy, and at times of dose changes.
Risks of Rapid Weight Loss with Topamax
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). 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.
Interactions
A total of 289 drugs are known to interact with topamax. A total of 522 drugs are known to interact with wellbutrin xl. There were no interactions found between topiramate and Wellbutrin XL. However, this does not necessarily mean no interactions exist. It is important to tell your doctor about all other medications you use, including vitamins and herbs.
The Influence of Diet Culture
People who decide to use medication like topiramate for weight loss are typically influenced by the insidious nature of diet culture. 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.
Just because a medication like Topamax has been approved for weight loss, that doesn’t mean using it is without its risks, both physical and psychological. When you choose to use a rapid weight-loss medication like topiramate, you’re subscribing to harmful beliefs about your body and self-worth. This may be an indication that you’re struggling with disordered eating patterns or even an eating disorder.
Alternative Approaches and Considerations
Given the potential risks associated with using topiramate and bupropion for weight loss, it's crucial to explore alternative approaches and consider individual circumstances.
Comprehensive Medical History and Evaluation
Before recommending weight loss medication, take a thorough medical history and order an upper gastrointestinal study. Patients meet criteria for weight loss medication if they have a body mass index ≥30, or ≥27 with a significant obesity-related disease such as type 2 diabetes, obstructive sleep apnea or hypertension.
Lifestyle Interventions
Lifestyle interventions such as diet and exercise are fundamental.
Weight Loss Medications after Bariatric Surgery
There is growing interest within the medical community in using weight loss medications after bariatric surgery.
Consider prescribing topiramate as the initial weight loss drug after bariatric surgery (off-label for this purpose). Notify patients of the possibility of cognitive changes (e.g., word-finding difficulty) and paresthesias. Follow-up should occur at least monthly after initiation of a weight loss agent or with dose adjustments. Titrate topiramate up by 25 mg at each monthly visit, but only if necessary (e.g., if weight loss has halted). Individualized dosing is important. If the patient has side effects but good weight loss response (5% to 10% total weight loss), consider switching to extended-release topiramate.
Additional Medications
For patients currently using psychotropic medication, consider adding metformin to topiramate. For weight loss, Stanford titrates most patients on metformin to 1000 mg by mouth twice daily.
If weight loss on topiramate is <5%, or if side effects are intolerable, consider an alternative agent such as zonisamide, whose mechanism of action is similar to that of topiramate.
A second agent might be added when the patient reaches weight stability or once a rebound occurs. To topiramate or zonisamide, Stanford and her colleagues typically add phentermine, 15 mg extended release in the morning with titration to 30 mg. They have the patient obtain blood pressure and pulse readings on Monday mornings, Wednesday afternoons, and Friday evenings at the start of the medication and whenever the dose is adjusted.
Addressing 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. There are plenty of options from in-person treatment at an inpatient or outpatient basis to online eating disorder treatment programs.