Is methylphenidate or atomoxetine to be preferred when treating patients with ADHD and an increased

Fråga: Is methylphenidate or atomoxetine to be preferred when treating patients with ADHD and an increased risk of seizures? The questioner is treating a 40-year-old woman who has problems with aggression and impulsivity. She does not fulfil the criterions for ADHD (attention-deficit hyperactivity disorder) diagnosis but the questioner considers treating her with methylphenidate (Concerta) or atomoxetine (Strattera). The patient has been operated on for hydrocephalus. She has no prior history of seizures but there are concerns for an increased propensity to seizures if she would start treatment with methylphenidate. She has not used this substance before.

Sammanfattning: The literature on the subject is not conclusive. Caution is advised when using methylphenidate in patients with seizure propensity. The effect of atomoxetine on the risk of seizures has been studied to an even more limited extent. However in a large cohort-study no significant association was seen with increased seizure tendencies in children. Much indicates that both of the substances can be used without a significantly increased risk of seizures, at least on a population level. Studies conducted so far on the matter have not been sufficiently statistically powered.

Svar: As a stimulant of the CNS methylphenidate is believed to lower the threshold for seizures. It has its effect through the blockade of reuptake of dopamine and noradrenaline in neurons and overdosing may lead to stimulation of the CNS or sympathomimetic system which could lead to seizures (1,2). Atomoxetine exerts its effect through blockade of norepinephrine reuptake. Based on the chemistry and pharmacology of atomoxetine there is no reason to believe it to be epileptogenic. However, in toxicology studies on animals given extremely large doses relative to those given to human patients seizures were seen, usually as an agonal event. Also increased levels of norepinephrine have been shown to increase the threshold for drug induced seizures in mice (3).

We conducted a literature search and found a number of articles concerning the propensity to seizures when medicating with methylphenidate for ADHD. There are no larger controlled studies on the subject but prospective and retrospective studies indicate that methylphenidate could be safe when given to patients with epilepsy or other types of seizure propensity with good seizure control (4). The literature is even more limited concerning atomoxetine and we could find no significant results indicating an increased risk of seizures. Literature in the field is based primarily on pediatric studies.

Methylphenidate has been thought to increase the risk of seizures but scientific support for this is limited and contradicted by some authors (2).

According to a review there has been no increased frequency of seizures in epilepsy patients also treated with methylphenidate in smaller trials (n=10-57). However, these trials are limited in statistical power. The literature concerning atomoxetine is also reviewed and no significant results are found indicating an increased risk of seizures (2).

The use of methylphenidate was studied in 30 patients with brain-damages and no increased seizure frequency was found. The authors recommend caution when using methylphenidate in these patients but do not advise against it (5).

A review of two company databases revealed no significant difference between methylphenidate, atomoxetine and placebo in seizure incidence as a side effect to pharmacological treatment in ADHD (3).

A retrospective cohort-study (n=34727, 22.3% on atomoxetine at any time during the study period) revealed no significant association between the use of atomoxetine and seizure tendencies in children ages 6-17 with ADHD and no prior seizure disorder (6).

There is no other approved indication for methylphenidate or atomoxetine in Sweden than ADHD (7).