Zonisamide: The Most Underrated Medication for Epilepsy

What is Zonisamide?

Despite being one of the finest treatments for epilepsy, Zonisamide is widely underused. It is administered once daily, aids in weight loss, eases headaches, lowers head pressure, and works wonders in reducing alcohol cravings and use. Additionally, it is fairly inexpensive and accessible.

What Type of Epilepsy Zonisamide Treat?

As a broad-spectrum medication, Zonisamide has been helpful in randomized-controlled trials as an adjunctive treatment for,

• Focal seizures

• Generalised seizures 

• Myoclonic epilepsy

It is also effective in monotherapy, according to observational studies and one randomised noninferiority trial that compared it to carbamazepine1. According to recent studies, we can now use it as the first line of treatment even though it is currently only approved as an adjunct therapy, or as a second agent.

What Additional Conditions Does Zonisamide Treat?

• Alcohol abuse disorder as it reduces alcohol craving and withdrawal symptoms.

• Weight loss, which makes it useful for treating eating disorders.

• Idiopathic intracranial hypertension as it lowers intracranial pressure.

How Does Zonisamide Work?

Zonisamide is a sulfonamide derivative that is unrelated to other anti-seizure drugs chemically and structurally. The voltage-dependent sodium and T-type calcium channels are thought to be its main targets for blockage. Inhibiting carbonic anhydrase also aids in the formation of cerebrospinal fluid.

How is Zonisamide Dosed?

Zonisamide is only seldom offered in liquid form and only in capsule form. Adults and children 5 years of age and older can use Zonisamide. Zonisamide dosage for adults is increased by 100 mg per week based on tolerability and seizure control after being begun at 100 mg per day for a week. The recommended dosage is 300 to 400 mg per day, given either once daily or twice daily. The daily maximum dose is divided into two doses of 600 mg in the long run. Zonisamide is administered to children at a dose of 1 mg/kg per day, which may be increased to 0.5 mg/kg per day after two weeks.

Zonisamide does not need to be adjusted in situations of liver failure. If you have modest renal problems, Zonisamide is fine, but it's advised that you avoid it if you have severe renal failure.

What If Zonisamide is not Helping Me?

There are numerous reasons why an anti-seizure medications could not be effective for you. Most often, people give up too soon or at a dose that is too low. The first is noncompliance; skipping doses of Zonisamide might result in breakthrough seizures; therefore, you should never skip a dosage; instead, you should make it up as soon as possible throughout the day or take twice as much at night. Contrary to other medications, which you can occasionally forget, anti-seizure medications must be continued and if missed needs to be replaced to avoid lower levels in the blood leading to seizures.

Additionally, give it time to work—roughly 3 to 6 months—and make sure you are taking a high enough dose. Another drug may be added, or you may choose another. Alternatively, you might have drug-resistant epilepsy, which affects 25% of epileptic patients and necessitates surgical intervention; this is covered in other article.

What are the Adverse effects of Zonisamide?

• Somnolence

• Ataxia

• Weight loss 

• Disorientation

• Aberrant thinking

• Anxiousness 

• Weariness

• Dizziness

• In children, decreased sweating and fever

• Kidney stones

• Allergies

The majority of these are self-limiting, and by titrating the dose gradually over four to eight weeks, the chance of side effects can be decreased. But in one study, cognitive abnormalities connected to the start of Zonisamide medication were dose-related and remained a year after the start of the treatment.

Another study found that cognitive and psychiatric adverse effects, such as 

• Depression, 

• Psychosis

• Violence, 

These side effects caused 5.8 and 6.9 per cent of patients to stop taking zonisamide, respectively. Risk factors for psychiatric side effects were a history of psychiatric symptoms and symptomatic generalised epilepsy.

While using Zonisamide, it's encouraged to drink lots of fluids because the medication alters the urine's acidity, which might cause kidney stones.

Can I use Zonisamide While Driving or Drinking Alcohol?

It is advised to avoid driving if you feel drowsy at first since Zonisamide can make you feel dizzy and sleepy until you grow acclimated to it. Zonisamide should not be taken with alcohol due to the aggravation of sleepiness and vertigo. Additionally, zonisamide is said to lessen the desire for alcohol.

How to Stop Zonisamide if it is Ineffective?

Like other anti-seizure medications, zonisamide should not be abruptly stopped. To avoid withdrawal seizures, they should be gradually tapered down over a few weeks. Only in cases of a severe allergic reaction do we cease it abruptly.

Is Zonisamide Safe in Pregnancy and Breastfeeding?

While the information on Zonisamide and pregnancy is sparse, it is comforting. Zonisamide is usually regarded as one of the moderately safe antiseizure drugs in pregnancy, according to previous studies. Newer studies, however, showed a little bit increased risk than the older studies. Zonisamide is safe for use while breastfeeding.

In Summary,

Now that we are aware of all the benefits of this wonderful drug, we utilise zonisamide in patients who prefer once-daily medicine, have a history of alcohol misuse, want to lose weight, have headaches associated with intracranial hypertension, or have generalised epilepsy.

References

1. Antiseizure medications: Mechanism of action, pharmacology, and adverse effects - UpToDate. Accessed October 12, 2022. https://www.uptodate.com/contents/antiseizure-medications-mechanism-of-action-pharmacology-and-adverse-effects?search=zonisamide&source=search_result&selectedTitle=2~47&usage_type=default&display_rank=1#H8