Neurotransmitters

known to primarily affect desire, whereas the

situation remains unclear for anxiolytics or

Mainly the neurotransmitters dopamine and

mood stabilizers.20

serotonin play an important role.

Treatment of sexual dysfunction, and mainly

the loss of sexual desire, is difficult, particularly

Dopamine

that associated with the use of antidepressants.

Popular management strategies, because they

Generally speaking, dopamine and dopamine

are considered

most effective

and most fre-

quently followed by experts, are dose reduction,

receptor agonists increase, whereas antagonists

antidepressant rotation, and co-medication with

decrease libido.19 In three central areas dopamine

is released before and/or during intercourse due

phosphodiesterase-5 inhibitors or testosterone

replacement in selected cases.21

to sexual stimulation: in the nigrostriatal sys-

SSRIs affect sexual functioning apparently

tem, the mesolimbic tract and the medial preop-

in a dose-related manner, also varying bet-

tic area.In the first one it facilitates somatomotor

ween different members of the group. This may

activity; in the mesolimbic tract it is beneficial

involve possible accumulation

together with

for different types of motivation, and in the

inhibition of

NO synthase,

anticholinergic

medial preoptic area it centers the motivation of

effects, modification of serotonin and dop-

the individual to sexual practice and controls

amine reuptake, and the amount of prolactin

frequency, sexual techniques, and genital refle-

release induced. Common policy is dosage

xes.6 By increasing NO synthase in the medial

preoptic area testosterone can stimulate pro-

reduction, drug holidays, antidepressant rota-

tion, waiting for development of tolerance, and

duction of NO, which results in heightened

therapy enhancement with certain serotonin

dopamine release. But also glutamate uses the

antagonists and a2-adrenoceptor antagonists,

same pathway to increase dopamine and is

extracellularly increased during copulation.

5-HT1A and dopamine receptor agonists, and

This means that this interaction together with

also PDE5 inhibitors.22 Flibanserin, a 5-HT1A

previous sexual experience is crucial to opti-

receptor agonist and 5-HT2A receptor antago-

mize intercourse and enhance future sexual

nist, is currently in late stage clinical develop-

ment for the treatment of hypoactive sexual

responsiveness.5

desire disorder (HHSD) in women.23 However,

very recently its approval has been denied by

Serotonin

the FDA.

Whereas dopamine enhances copulation faci-

Enzyme-inducing Antiepileptic Drugs

lities, serotonin acts chiefly inhibitory in res-

pect of sexual interest.Animal experiments with

Many antiepileptic drugs are inducers of the

microinjections of selective serotonin reuptake

cytochrome P450 enzymes (mostly CYP 3A4),

inhibitors showed a clear delay in beginning of

which metabolize testosterone. Moreover, sexual

the copulation,6 a finding possibly related to the

quality of life was observed to decline in men

use of SSRIs in the treatment of premature ejac-

with epilepsy, and that was related not only to

ulation (see below).

duration of epilepsy but also to an increase of sex

hormone-binding globulin levels.Both enhanced

Pharmacological Strategies

testosterone metabolism and sequestration by

sex hormone-binding globulin could contribute

CNS Drugs

to lower levels of free testosterone. A connection

could be drawn between the sex hormone-bind-

Sexual function can be hampered by adverse

ing globulin levels in those men, the enzyme-

effects of antidepressants, antipsychotics, mood

inducing capacity of the antiepileptic drugs, and

stabilizers, and anxiolytics, or patients can expe-

age of the patient. Surprisingly, in women this

rience worsening of preexistent sexual dysfunc-

was not the case.Therefore,the need for enzyme-

tion by psychotropics leading to increased

inducing antiepileptic drugs should be carefully

psychological difficulties culminating in discon-

weighed against their adverse effects on the

tinuation of the medication. Antipsychotics are

sexual quality of life in men with epilepsy.24