Zonisamide is an antiepileptic drug that has also been shown to promote weight loss. While primarily used to treat partial seizures in adults with epilepsy, healthcare providers sometimes prescribe it off-label for weight loss due to clinical research indicating its potential to enhance weight loss when combined with lifestyle changes. It is sold under the brand names Zonegran® and Zonisade®.
How Zonisamide Works
Zonisamide reduces abnormal electrical activity in the brain that can cause certain types of seizures. It is believed to support weight loss by reducing appetite and controlling cravings. This may be due to the drug targeting serotonin and dopamine, two key neurotransmitters that regulate appetite. However, more research is needed to fully understand the exact mechanism behind zonisamide’s influence on body weight.
Physicians might prescribe zonisamide alone or in combination with other medications to help target multiple mechanisms of weight loss. It may take three months or more to see body weight loss in the 3% to 5% range. For best results, pair this treatment with a fitness routine and nutritious diet.
Dosage and Administration
Zonisamide typically comes in capsule form, available in 25 mg, 50 mg, or 100 mg doses. The dosage is customized by a healthcare provider based on individual factors, including weight and tolerance to the medication. The dose may be gradually increased over time. It is typically taken daily, either as a single dose or divided into two doses. To help prevent kidney stones, each dose should be taken with a full glass of water, with or without food. The capsules should not be crushed, chewed, or divided.
If a dose is missed, the healthcare provider should be consulted for instructions. A double dose should not be taken to make up for a missed one. If you wish to stop taking this medication, talk to your provider so they can guide you on how to taper and discontinue zonisamide safely.
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Clinical Evidence for Weight Loss
A 1-year, randomized, double-blind, placebo-controlled trial was conducted in 225 nondiabetic obese men and women to assess the efficacy of zonisamide for weight loss. The participants were divided into three groups: a placebo group, a 200 mg zonisamide group, and a 400 mg zonisamide group. All participants received diet and lifestyle counseling from a dietitian, which included advice to decrease total caloric intake by 500 kcal and engage in regular exercise.
The results of the study showed that zonisamide at a daily dose of 400 mg moderately enhanced weight loss when combined with diet and lifestyle counseling. The mean weight change in the placebo group was -4.0 kg (mean -3.7%), while the 200 mg zonisamide group experienced a mean weight change of -4.4 kg (mean -3.9%; p = 0.79 vs. placebo), and the 400 mg zonisamide group had a mean weight change of -7.3 kg (mean -6.8%; p = 0.009 vs. placebo).
In the categorical analysis, 31.1% of participants in the placebo group, 34.2% in the 200 mg zonisamide group (p = 0.72), and 54.7% in the 400 mg zonisamide group (p = 0.007) achieved 5% or greater weight loss. For 10% or greater weight loss, the corresponding numbers were 8.1%, 22.4% (p = 0.02), and 32.0% (p < 0.001).
Expected weight loss depends on the dosage of zonisamide. In the clinical trial, people who took a 200 mg daily dose lost an average of 3.9% of their total body weight, while those who took 400 mg daily shed an average of 6.8%.
Potential Benefits Beyond Weight Loss
Zonisamide may offer additional benefits beyond treating certain seizures and promoting moderate weight loss. Studies suggest that this drug may support heart health by lowering blood pressure, triglyceride and blood sugar levels, and helping to improve sleep by reducing obstructive sleep apnea.
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Important Considerations and Precautions
It is very important that your doctor check your 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 during treatment with this medicine and for 1 month after the last dose. If you think you have become pregnant while using this medicine, tell your doctor right away.
This medicine 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. If you or your caregiver notice any of these side effects, tell your doctor right away.
Check with your doctor right away if you have sudden back pain, abdominal or stomach pain, pain while urinating, or bloody or dark urine. These may be symptoms of kidney stones.
Serious skin reactions (eg, Stevens-Johnson syndrome, toxic epidermal necrolysis) can occur with this medicine. 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.
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This medicine can temporarily lower the number of white blood cells in your blood, increasing the chance of getting an infection. If you can, avoid people with infections. Check with your doctor right away if you think you are getting an infection, or if you have a fever or chills, cough or hoarseness, lower back or side pain, or painful or difficult urination.
Zonisamide may cause a serious allergic reaction called drug reaction with eosinophilia and systemic symptoms (DRESS), which can be life-threatening and requires immediate medical attention. Check with your doctor right away if you have black, tarry stools, chest pain, chills, cough, fever, painful or difficult urination, sore throat, sores, ulcers, or white spots on the lips or in the mouth, swollen glands, trouble breathing, or unusual bleeding or bruising.
This medicine may make you sweat less, which causes your body temperature to increase. Use extra care not to become overheated during exercise or hot weather while you are taking this medicine. Overheating may result in heat stroke. Also, hot baths or saunas may make you dizzy or faint while you are taking this medicine.
Check with your doctor right away if eye pain or redness, blurred vision, difficulty with reading, or any other change in vision occurs during or after treatment. These could be symptoms of serious eye or vision problems (eg, acute myopia, secondary angle closure glaucoma). Your doctor may want your eyes be checked by an ophthalmologist (eye doctor).
Call your doctor right away if you have fast breathing, loss of appetite, fast, pounding, or uneven heartbeats, or unusual tiredness or weakness. These may be symptoms of a condition called metabolic acidosis.
This medicine may cause slow growth. If your child is using this medicine, the doctor will need to keep track of your child's height and weight to make sure that your child is growing properly.
Zonisamide may cause hyperammonemia (too much ammonia in the blood), which may damage the brain and can be life-threatening. Check with your doctor right away if you have nausea or vomiting that continues, an increase in the frequency of seizures, loss of appetite, swelling of the face, tiredness and weakness, or yellow eyes or skin.
Do not stop taking zonisamide without first checking with your doctor. Stopping the medicine suddenly may cause your seizures to return or to occur more often. Your doctor may want you to gradually reduce the amount of medicine you are taking before stopping it completely.
This medicine may cause some people to become dizzy, drowsy, or less alert than normal. Make sure you know how you react to this medicine before you drive, use machines, or do anything else that could be dangerous if you are dizzy or not alert.
This medicine will add to the effects of alcohol and other CNS depressants (medicines that make you drowsy or less alert). Some examples of CNS depressants are antihistamines, medicine for allergies or colds, sedatives, tranquilizers, sleeping medicine, prescription pain medicine, narcotics, medicine for seizures, muscle relaxants, or anesthetics, including some dental anesthetics. Check with your doctor or dentist before taking any of the above while you are taking this medicine.
Some women who use this medicine have become infertile (unable to have children). Talk with your doctor before using this medicine if you plan to have children.
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.
Common Side Effects
Many people experience no side effects while taking zonisamide. The most common side effects include:
- Dizziness and lightheadedness
- Fatigue and drowsiness
- Language and speech difficulty
- Metallic or unpleasant taste in the mouth
- Nausea
Other possible side effects include:
- Trouble sleeping
- Lack of coordination
- Loss of appetite and weight loss
- Diarrhea
- Double vision
- Mood changes, such as depression or irritability
- Difficulty concentrating
These symptoms may subside after your body adjusts to the medication.
Contraindications and Warnings
Do not take zonisamide if you have an allergy to sulfa drugs. A potentially fatal reaction can occur, including a life-threatening skin rash or a blood cell condition. Before using zonisamide, tell your health care provider about your medical history, especially if you have kidney disease, liver disease, long-term diarrhea, lung or breathing problems, metabolic acidosis or diabetic ketoacidosis, high ketone levels in your blood or urine, use insulin or other diabetes medications, and/or have a history of psychiatric disorders or suicidal thoughts. Talk to your health care provider if you are planning to become pregnant or if you are pregnant or breastfeeding.
Do not drive, operate heavy machinery or perform any hazardous task until you know the effects of this medication on you.
Drug Interactions
Some medications, herbal supplements, and foods can interact or interfere with zonisamide, including:
- Carbonic anhydrase inhibitors (such as acetazolamide)
- Orlistat
- Phenobarbital
- Primidone
- Rifamycins
- Glucocorticoids
- St. John's wort
- Grapefruit or grapefruit juice
You should not drink alcohol while taking zonisamide.
Zonisamide After Bariatric Surgery
There is growing interest within the medical community in using weight loss medications after bariatric surgery. Zonisamide can be considered as an alternative agent 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. Topiramate and zonisamide are antiepileptics, and rapid cessation may induce seizures.
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