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Clinical effects

Clinical effectsAlthough the psychometric studies generally show a tendency of cognitive impairments in polytherapy compared to monotherapy, this merely suggests a drug interaction effect. As previously mentioned evidence-based confirmation will be extremely difficult due to the methodological problems that occur when studying polytherapy and especially in the light of the many interfering factors, especially the seizure confound. Any study will have difficulties entangling the interfering factors of seizure effects and the effects of polytherapy, when typically polytherapy is used in the more refractory epilepsies.

Nonetheless, we may look at more anecdotal clinical information. In many drug trials a similar effect has been found as suggested by the psychometric studies: a higher incidence of side-effects in combination therapy when compared to the same drug in monotherapy. This is often observed in post-marketing studies. Many of the new drugs are first tested in add-on designs and monotherapy is only used later.

Table Percentage of side-effects for topiramate (topiramate) in polytherapy vs. monotherapy; potentiation of side-effects due to polytherapy?

Most common antiepileptic drugswith topiramate

adjunctive therapy*

% Patients
Adjunctive therapytopiramate 200-400

(N = 183)

Monotherapy(0 antiepileptic drugs at baseline)

topiramate 200/500

(N=71)

Somnolence 29 13
Dizziness 25 13
Ataxia 16 6
Nervousness 16 6
Abnormal vision 13 3
Psychomotor slowing 13 6
Speech disorders 13 1
Memory difficulty 12 8
Confusion 11 6
Paresthesia 11 38
Diplopia 10 1
Anorexia 10 15

Side-effects in combination therapy but also different types of dominant complaints when compared to monotherapy.

When inspecting this example we see cognitive impairments are reduced in monotherapy, but other impairments, especially paresthesia, are increased. This may lead to the hypothesis of potentiation of some tolerability problems and especially cognitive side-effects.

Of course, it is imperative to emphasize that the monotherapy studies typically include patients with other epilepsies compared to the initial add-on studies, which are done in refractory partial epilepsies with an associated risk of epilepsy-induced cognitive impairments. Moreover, in contrast with the former paragraph of this chapter, these side effects have not been established with formal psychometric or other objective measurements, but are based on clinician ratings of subjective patient complaints.

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