A woman is treated with venlafaxine and risperidone due to a depression with additive psychosis. Wh

Fråga: A woman is treated with venlafaxine and risperidone due to a depression with additive psychosis. What will happen to the antidepressant effect when these drugs are combined?

Sammanfattning: Concomitant treatment with venlafaxine and risperidon may result in a pharmacokinetic interaction, however this has not been studied. Theoretically, an inhibition by risperidone of the postsynaptic 5HT-receptor may counteract the postsynaptic receptor stimulation produced by venlafaxine, following a possible decreased antidepressant activity. However, the clinical antidepressant effect is probably due to an inhibition of uptake of both norepinephrine and serotonin, hence the clinical outcome in this patient is not known. It could be advisable to monitor plasma levels of risperidone and if possible venlafaxine in order to avoid unexpected severe side effects. A future clinical study with these two drugs seems to be needed.

Svar: Risperidone is a neuroleptic drug used in treatment of acute and chronic schizophrenia (1). The drug is a potent serotonin 5-HT2A and dopamine D2 receptor antagonist (2). The new antidepressant drug venlafaxine, is a reuptake inhibitor of serotonin, norepinephrine, and to a lesser extent dopamine (1).

Despite a thorough literature search including Medline, common pharmacological handbooks and contact with the manufacturer, no study concerning a metabolic interaction between the two drugs could be found. However, it is known that both venlafaxine and risperidone are metabolised by the same enzyme, CYP2D6 and that venlafaxin is a weak inhibitor of this enzyme (3). Thus, a possible pharmacokinetic interaction could not be excluded during concomitant treatment with these drugs.

On a theoretical basis, treatment with venlafaxine, would result in an increased postsynaptic receptor stimulation because of the higher concentration of serotonin in the synaptic cleft. Then, by adding risperidone, a blockade of the postsynaptic 5-HT2A receptor would neutralise the effect of venlafaxine, thus decreasing the possible enhancement of serotonin transmission. If this putative interaction at the receptor level also will result in a clinical interaction is entirely unclear (4).

Inhibition of the uptake of norepinephrine seems to consistently yield antidepressant activity, while inhibition of serotonin uptake may provide antidepressant activity. However, inhibition of the uptake of norepinephrine or serotonin per se may not be a sufficient explanation for the antidepressant effect (2).

Thus, it is not known what the consequences of combined treatment with venlafaxine and risperidone will be with respect to the clinical antidepressant effect. 1 FASS 1997 (The Swedish catalog of approved medical products) 2 Goodman and Gilman, The pharmacological basis of therapeutics. 1996; 9th ed: 3 Drugline nr 14128 (year 1997) 4 Personal communication, Lars Ståhle, Department of Clinical Pharmacology, Huddinge Hospital