Topiramate (TPM) has broad-spectrum antiepileptic properties. It was first approved by the U.S. Food and Drug Administration in 1995 for partial seizures in adults, but more recently has been approved for adults and children with partial or generalized seizures and for Lennox-Gastaut syndrome.

Attentional disturbances and psychomotor slowing have been reported commonly.116 In double-blind, placebo-controlled, and open label trials of TPM for partial seizures, the most common adverse effects observed in more than 10% of subjects included:

  • somnolence
  • psychomotor slowing
  • difficulty with memory
  • difficulty with concentration or attention
  • speech or language problems (Dr. Natalie Addi, Ortho-McNeil Pharmaceuticals, personal communication, November 1999)117

Slow escalation of TPM dose and reduction of polypharmacy may improve tolerance of the drug.118,119

Among healthy young adults randomly assigned in blinded fashion to receive TPM, gabapentin, or lamotrigine,74 only the TPM group demonstrated statistically significant declines in measures of attention and word fluency at acute doses and persisting at 2- and 4-week intervals. Although TPM acute dosing was higher and chronic administration was escalated more rapidly than in current clinical practice, this study supports previous experience with TPM. Self-reported ratings on the anger-hostility subscales of the Profile of Mood States inventory also were elevated in the TPM group.

A recent, double-blind, randomized trial of TPM in treating Lennox-Gastaut syndrome found that 33% of patients had at least a 50% reduction in seizures.120 In this study, adverse effects included

  • somnolence (42%)
  • anorexia (40%)
  • nervousness (21%)
  • behavioral problems (21%)

Although no patients discontinued therapy because of an adverse event, one wonders whether this population may have been too cognitively impaired to communicate about the severity of their distress from side effects. It remains unclear whether TPM's compromising effects on cognitive function in patients with developmental disability are mild or severe, and how much impact these effects have on the drug's risk-benefit ratio.

Anecdotal experience and several reports also suggest that TPM may cause symptoms of depression,121–124 although this may be partially a reaction to the cognitive side effects. Anxiety, irritability, behavioral problems, and even symptoms of psychosis also have been noted in patients treated with TPM.5,125 Acute psychotic symptoms have been shown to be associated with initiation of TPM.

In contrast, a few recent reports indicate that TPM may be useful in treating both the manic and depressive phases of bipolar disorder.126–128 Unlike other medications used to treat bipolar disorder, which tend to cause significant weight gain, TPM promotes weight loss.129

Patients using TPM should be advised to drink plenty of fluids, as TPM may be associated with a twofold to fourfold increased risk for nephrolithiasis.121,130

Adapted from: Ettinger AB, Barr WB, and Solomon SP. Psychotropic properties of antiepileptic drugs in patients with developmental disabilities. In: Devinsky O and Westbrook LE, eds. Epilepsy and Developmental Disabilities. Boston: Butterworth-Heinemann; 2001;219–230. With permission from Elsevier (www.elsevier.com).

Authored By: 
Sanford P. Solomon MD
William B. Barr MD
Alan B. Ettinger MD
I<
Reviewed By: 
Steven C. Schachter MD
on: 
Thursday, April 1, 2004