Dosisverhoging van SSRI'S bij depressie; niet aan te bevelen in richtlijnen

<span class="subtitle">summary </span> <span class="subtitle">background </span> In cases where patients with unipolar depression do not respond to a standard dose of selective serotonin reuptake inhibitors ( <span class="abbreviation">ssris </span>), treatment guidelines often recommend a higher dose. A systematic review of the literature revealed uncertainty about the efficacy of dose escalation and pointed to methodological weaknesses in earlier research. <span class="abbreviation subtitle">aim </span>To review current practice and results concerning dose-escalation of <span class="abbreviation">ssris </span>. <span class="subtitle">method </span> We made a summary of previously published English articles that systematically reviewed previous ssri-dose-escalation studies in depressed patients and present the results of a recent double-blind randomised dose-escalation study of paroxetine. By means of a 123I-β- <span class="abbreviation">cit-spect </span> study in a subgroup of the patients in the recent dose-escalation study it was possible to measure the amount of paroxetine bound to serotonin transporters. This provided combined clinical and pharmacological outcomes. <span class="subtitle">results </span> The study with paroxetine provided clinical evidence that dose-escalation of paroxetine in depression was not effective and that adverse effects increased. The occupancy of the serotonin-transporters did not increase significantly after dose-escalation, despite increases in paroxetine serum levels. <span class="subtitle">conclusion </span> Dose-escalation of ssris for patients with unipolar depression who did not respond to a standard dose, does not improve response or the chance of remission. The pharmacological explanation for this is that the occupancy of the serotonin-transporters does not increase following dose-escalation. <span class="abbreviation"> </span>