Can amitriptyline be used concomitantly with modafinil? If not, what alternative treatment of neura

Fråga: Can amitriptyline be used concomitantly with modafinil? If not, what alternative treatment of neuralgic pain could be used? A 50-year-old woman with multiple sclerosis (MS) is presently treated with modafinil, thyroxin and estrogen replacement, doses unknown. Non-sedative treatment of MS-associated neuralgic pain in the neck and arms is now required.

Sammanfattning: Modafinil can possibly interact with tricyclic antidepressants, by way of potentiated noradrenergic effects. Careful clinical and therapetic monitoring is recommended, should modafinil be combined with for example clomipramine, which is the only antidepressant approved for the treatment of neuralgia in Sweden. Alternative treatment in the present case may include a serotonin reuptake inhibitor, carbamazepine or gabapentin. Drug concentrations should be monitored, irrespectively of drug choice.

Svar: Modafinil is an alpha-1 receptor agonist, used to improve wakefulness in narcolepsy and idiopathic hypersomnia (which often occurs in patients with multiple sclerosis).

Tricyclic antidepressants, such as amitriptyline or clomipramine, are considered first line treatment of neuralgic pain (1). However, as all of these substances have noradrenergic properties, caution is advised in patients treated with modafinil, to avoid possible noradrenergic hyperstimulation (2). This caution is based on prudency and pharmacological reasoning, and no clinical data, supporting the caution, has been found in available literature. One case report describes the combined use of modafinil and clomipramine in the treatment of narcolepsy. The treatment was successful, but the clomipramine dose had to be reduced, probably due to inhibition by modafinil of the enzyme CYP2C19, which is responsible for clomipramine demethylation (3). Modafinil inhibition of CYP2C19 is supported by in vitro experiments, and by a reported pharmacokinetic interaction with clozapine (4, 5). According to in vitro data, modafinil can also cause induction of the enzymes CYP3A4, CYP1A2 and CYP2B6 (4). From a clinical point of view, carefully instituted and dose titrated amitriptyline can be tried in the present case, as both blood pressure and amitriptyline concentrations can easily be monitored.

Modafinil was given in combination (under steady-state conditions) with methylphenidate and dextroamphetamine, respectively, to 32 healthy volunteers, without signs of either pharmacokinetic or pharmacodynamic adverse interactions, despite the fact that both methylphenidate and dextroamphetamine have potent alpha-adrenergic effects (4, 5).

Alternative treatment for neuralgia in the present case may include for example citalopram, carbamazepine or gabapentin. Selective serotonine reuptake inhibitors (SSRIs) have been suggested in the treatment of neuralgia, but solid data concerning their effectiveness is lacking. Both carbamazepine and gabapentin may, but must not, cause sedation. Therapeutic drug monitoring (that is plasma drug concentrations) is recommended, irrespectively of drug choice.