Hvilke antidepressiva bør seponeres før hudpriktest?
Bemærk at indholdet på denne side er mere end ét år gammel. Indholdet afspejler derfor ikke nødvendigvis IRFs nuværende holdning.
De fleste tricykliske antidepressiva og enkelte fra de nyere generationer af antidepressiva er histamin H1 antagonister. Interaktion til allergi hudtests er kun blevet demonstreret i kliniske studier for enkelte af de ældre antidepressiva. Der er ikke fundet kliniske undersøgelser, der ser på denne mulige interaktion for flertallet af de tilgængelige antidepressiva, selvom en interaktion er sandsynlig. Dette er mest sandsynligt for de anførte stoffer, som udviser udtalt in vitro H1 receptor blokade.
Det har været tilrådet at pausere doxepin mindst 7 dage før allergi hudtests. På grund af manglende litteratur på området kan der ikke gives tilsvarende specifikke råd for de øvrige antidepressiva. Klinikeren må derfor tage eliminationshastigheden og H1 antihistamin potensen for det givne antidepressiva med i overvejelserne. Desuden bør indikationen for en allergi hudtest sættes i relation til risikoen ved at pausere en behandling med antidepressiva.
When using skin prick tests (SPT) in evaluation of allergic patients, the use of antihistaminic drugs is usually discontinued some time before the test. This is to prevent a diminished allergic response in the skin and false negative result of the test. In the department of dermatology they are aware of the antihistaminic properties of mirtazapine and ask if an antihistaminic (H1) effect exists for other antidepressants.
Histamine is a transmitter in the brain where, like elsewhere in the body, it has at least three types of receptors, histamine H1, H2, and H3. In brain, H1 histamine receptors are thought to be involved with a number of functions including arousal and the regulation of appetite. Outside the nervous system, classically, histamine H1 receptors are involved with allergic reactions (1). The inhibitory effect of antihistamines on allergen-induced skin reactions is well described and can impair the results of allergen SPT, which are necessary for the diagnosis of atopic diseases (2,3).
Tricyclic antidepressants were originally developed as H1-antihistamines (4,5). In fact most tricyclic antidepressant compounds are in vitro more potent as antihistamines than as antagonists of the reuptake of biogenic amines (5). Some of the antidepressants are in fact more potent than any of the newer generation histamine H1-antagonists (6). We located only a few clinical trials investigating this antihistamine effect in vivo (4,7,8). The tricyclic antidepressant doxepin (Sinquan) is a potent antihistamine with an affinity for H1 receptor about 800 times greater than the classical antihistamine diphenhydramine (4,5). In vivo doxepin has been demonstrated to modulate the whealing response after percutaneous introduction of histamine (4,7). In a double-blinded study of 41 volunteers a 82.2 fold increase in the concentration of histamine were required to provoke responses equivalent to control reactions after a single dose of 25 mg doxepin (4). In another study of 33 healthy volunteers 25 mg desipramin suppressed the histamine induced wheal in the skin for two days and 25 mg doxepin for four days. It was therefore advised to withhold doxepin at least seven days before allergy skin testing (7).
In vitro studies of the potency of H1 receptor blockade list the antidepressants mirtazapine (Remeron mfl.), doxepin (Sinquan) and trimipramine (Surmotil) as the most potent. Amitriptyline (SAroten mfl.) and maprotiline (Ludiomil mfl.) also show very potent H1 receptor blockade. Imipramine (Imipramin) and nortriptyline (Noritren) are also potent. The following amoxapine, clomipramine (Anafranil), nefazodone, protriptyline and trazodone show some H1 receptor blockade. Desipramine have little potency, whereas citalopram show nearly no potency. Bupropion, fluoxetine, fluvoxamine, paroxetine, phenelzine, sertraline, tranylcypromine and venlafaxine are essentially inactive and have been classified as having no H1 receptor blockade potency (6,9). Apart from the mentioned clinical studies of the modulated whealing response after administration of doxepin and desipramine no studies have been found to support if this classification exists in vivo.
Clinicians are using some of the antidepressants to treat allergic and dermatological problems (6). Because sedation is the most common side effect of histamine H1 antagonists, they are used clinically as sedative hypnotics. The antihistaminic effect of the tricyclic antidepressants such as doxepin and amitriptyline are used to induce sleep and reduce pruritus (10). Recent case reports suggest that mirtazapine can be effective in the management of pruritus arising from cancer, cholestasis and renal failure (11).
This question regards antidepressants, but interaction on SPT results might also occur with other CNS active drugs which antagonize the histamine H1 receptor. Many antipsychotics are more potent than the classical antihistamine diphenhydramine at blocking histamine H1 receptors in vitro. This is in particular the case for olanzapine. In fact, olanzapine is by far the most potent H1 antagonist of all antipsychotics and may be the most potent histamine H1 antagonist known (1). However, we have located no clinical trials investigating the possible interaction to allergen skin testing.
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- Davis MP, Frandsen JL, Walsh D, Andresen S, Taylor S. Mirtazapine for pruritus. J Pain Symptom Manage. 2003 Mar;25(3):288-91.
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Institut for Rationel Farmakoterapi, 13. maj 2005