Most people who take Topamax (topiramate) have no side effects or only mild or moderate side effects without sequelae. No fatal reactions have been associated with its use.

Glaucoma
In 2001, doctors in the United States were notified of the development of glaucoma in 23 patients (including one child) out of over 825,000 who had used Topamax. These symptoms usually occurred during the first month of treatment. Patients should be advised to notify their doctor if they experience blurred vision or difficulty seeing that comes on quickly, with or without eye pain.

Metabolic acidosis
As mentioned in the page on common side effects, warnings about metabolic acidosis (decreased serum bicarbonate) in patients taking Topamax were issued in late 2003.

Certain circumstances predispose patients to acidosis:

• renal disease
• severe respiratory disorders
• status epilepticus
• diarrhea
• ketogenic diet
• other medications that inhibit carbonic anhydrase

Acidosis usually occurs early in treatment but can arise at any time. Physicians are advised to measure baseline serum bicarbonate before initiating treatment and to test levels periodically.

Metabolic acidosis can cause symptoms such as fatigue, loss of appetite, irregular heartbeat, and impaired consciousness. Patients should be advised to contact their doctor or other health care provider if these symptoms develop while taking topiramate.

Chronic, untreated acidosis may lead to conditions such as kidney stones, osteomalacia, or osteoporosis and may reduce growth rate (and maximal height) in pediatric patients.

If acidosis persists, discontinuation of Topamax or the addition of alkali treatment should be considered.

Kidney stones
About 1.5% of adults taking Topamax have developed kidney stones. They are more common in men and in those with a personal history. They also may be more likely if Diamox (acetazolamide) or Zonegran (zonisamide) is also taken or if the ketogenic diet is followed. Topamax therefore should be used cautiously in patients taking Diamox or Zonegran or using the ketogenic diet. To help prevent kidney stones, patients should be advised to drink plenty of water, juice, or other fluids (8 glasses every day for adults) and should be told what to do if they feel the onset of a kidney stone, such as sharp pains in their side or lower back.

Psychiatric side effects
Psychiatric side effects reported with Topamax include:

• depression
• psychosis, including delusions and hallucinations
• aggressive or hostile behavior
• agitated behavior

A study of 431 patients in England found that 103 (nearly 24%) had some kind of psychiatric effect (Mula 2003). This included 16 people (4%) with psychosis, 24 with aggressive behavior, 17 with other behavior abnormalities, and 46 with a mood disorder.

Another report of 91 patients in England found symptoms of psychosis in 12%, compared to less than 1% of patients who took Neurontin (gabapentin) or Lamictal (lamotrigine) (Crawford 1998). Seven patients (8%) were admitted to the hospital because of psychosis or depression.

Another group of doctors looking only for symptoms of psychosis found them in 5 (6%) of the first 80 patients they treated with Topamax (Khan 1999).

Most reports have indicated that people with a history of psychiatric illness are much more likely than others to experience psychiatric disorders while taking Topamax (Mula 2003, Trimble 2000). The disorder tends to be of the same type as before. That is, those who have had psychosis in the past are more likely to experience symptoms of psychosis again, and those with past mood disorders are more likely to have a similar mood disorder (Trimble 2000). People with no history of psychiatric disorders also can be affected, however (Khan 1999).

Other factors that have been implicated in the development of psychiatric side effects from Topamax are:

• high starting dose and rapid dose increases
• family history of psychiatric illness and epilepsy
• history of febrile seizures
• presence of tonic-atonic seizures (Mula 2003)

On the other hand, it has been reported that psychiatric side effects are less likely in people with a low frequency of seizures before starting Topamax and in those also taking Lamictal. (Mula 2003)

Osteopenia/osteoporosis
The effect of Topamax on bone health is not fully known. However, a person who has metabolic acidosis can develop osteopenia which could lead to osteoporosis if the acidosis is not treated properly. Patients taking Topamax should be instructed on the importance of regular exercise and diet to help bone health. Patients should talk to their doctor before taking calcium supplements, because too much calcium could increase the risk of kidney stones in some people who are taking topiramate.

On July 10, 2008, an advisory panel was convened by the Food and Drug Administration (FDA) to review data that the FDA had previously collected from drug studies showing an association between many of the antiepileptic drugs (AEDs) and suicidal ideation and behavior, which together are called suicidality. According to the FDA’s Alert, among the patients with epilepsy in these drug studies, 1 out of 1000 people taking the placebo (inactive substance) showed suicidality compared to approximately 3.5 out of 1000 people who took an AED. The FDA advisory panel voted to accept the FDA's data at its meeting on July 10. The FDA has provided the following information for patients, family members, and caregivers at www.fda.gov/cder/drug/InfoSheets/HCP/antiepilepticsHCP.htm.

• Taking antiepileptic medicines may increase the risk of having suicidal thoughts or actions;
• Do not make any changes to the medication regimen without first talking with the responsible healthcare professional;
• Pay close attention to any day-to-day changes in mood, behavior and actions. These changes can happen very quickly so it is important to be mindful of any sudden differences.
• Be aware of common warning signs that might be a signal for risk of suicide. Some of these are:
  • Talking or thinking about wanting to hurt yourself or end your life
  • Withdrawing from friends and family
  • Becoming depressed or having your depression get worse
  • Becoming preoccupied with death and dying
  • Giving away prized possessions

We again urge patients and families to contact their doctor before stopping an epilepsy medication because this may possibly lead to seizures and worsening of mood.

Reviewed July 2008 by Steven C. Schachter, MD, epilepsy.com Editorial Board.