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Dosisverhoging SSRI’s bij depressie is niet zinvol

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Ruhé HG, Booij J, Van Weert HC, Reitsma JB, Franssen EJF, Michel MC, Schene AH. Dosisverhoging SSRI’s bij depressie is niet zinvol. Huisarts Wet 2009;52(6):289-96.

Achtergrond Depressieve patiënten die niet genoeg baat hebben bij een standaarddosering selectieve serotonineheropnameremmers (SSRI’s) krijgen vaak een hogere dosis voorgeschreven. In deze wetenschappelijke beschouwing becommentariëren we de werkzaamheid van deze strategie.

Methode We deden een systematisch literatuuronderzoek in vier databases naar gerandomiseerde, gecontroleerde onderzoeken en meta-analyses. Daarnaast voerden we een gerandomiseerd, placebogecontroleerd dosisverhogingsonderzoek uit bij unipolair depressieve patiënten van 18 tot 70 jaar (Hamilton Depression Rating Scale (HDRS17) > 18), met randomisatie (T0) van non-responders (HDRS17 daling < 50%; n= 60) na 6 weken paroxetine (20 mg/dag) naar dubbelblind verstrekte paroxetineverhoging (30-50 mg/dag) of placeboverhoging (paroxetine 20 mg/dag + placebo). De follow-up duurde zes weken (T1). We maakten op drie momenten serotonine-transporter (SERT) SPECT-scans: bij medicatievrije patiënten voorafgaand aan de behandeling, na zes weken behandeling met een standaarddosering en weer zes weken later na dosisverhoging. 
Resultaten De zeven dosisverhogingsonderzoeken en drie meta-analyses/beschouwingen die wij vonden, gaven geen eenduidige ondersteuning voor dosisverhoging. Wij staakten ons dosisverhogingsonderzoek na een interim-analyse (a priori stopregel voor futiliteit: p > 0,5). Van de 30 non-responders met paroxetineverhoging (46,7 ±5,5 mg/dag) reageerden er 10 (33,3%) alsnog op de dosisverhoging; datzelfde gold voor 10 van de 27 (37,0%) non-responders met placeboverhoging (p=0,788). Gedurende de follow-up was er geen significant effect van de dosisverhoging (p = 0,88). SPECT-scans toonden geen significante toename van de SERT-bezetting van het ‘midbrain’ (2,5 ±26,4% paroxetineverhoging; 3,1 ±25,8% placeboverhoging; p = 0,687) of het ‘diencephalon’ (p = 0,529).

Conclusie Dosisverhoging van SSRI’s bij depressieve patiënten is niet werkzaam omdat de hogere dosering niet leidt tot een significante toename van de SERT-bezetting.

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    Eric Ruhé

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  1. Eric Ruhé
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  2. Jan Booij
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  3. Henk van Weert
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  4. Johannes Reitsma
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  5. Eric Franssen
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  6. Martin Michel
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  7. Aart Schene
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Correspondence to Eric Ruhé.

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AMC, Zorgprogramma Stemmingsstoornissen, Afdeling Psychiatrie, Meibergdreef 5, 1105 AZ Amsterdam: dr. H.G. Ruhé, psychiater-epidemioloog, prof.dr. A.H. Schene, psychiater; AMC, Afdeling Nucleaire Geneeskunde: dr. J. Booij, nucleair geneeskundige; AMC, Afdeling Huisartsgeneeskunde: dr. H.C. van Weert, huisarts; AMC, Afdeling Klinische Epidemiologie, Biostatistiek en Bioinformatica: dr. J.B. Reitsma, arts-epidemioloog; Onze Lieve Vrouwe Gasthuis, Apotheek en Klinische Farmacologie: dr. E.J.F. Franssen, ziekenhuisapotheker-klinisch farmacoloog; AMC, Afdeling Farmacologie en Farmacotherapie: prof.dr. M.C. Michel, farmacoloog.

Mogelijke belangenverstrengeling: Dit onderzoek werd gefinancierd met een subsidie van het Academisch Medisch Centrum (SFA.07.012) en ZonMw, Geestkracht deelprogramma opleiding onderzoekers GGZ (OOG; #100-002-002). De auteurs hebben geen strijdige belangen.

Dit artikel is een bewerkte vertaling van: Ruhé HG, Huyser J, Swinkels JA, Schene AH. Dose escalation for insufficient response to standard-dose selective serotonin reuptake inhibitors in major depressive disorder: Systematic review. Br J Psychiatry 2006;189:309-16 en Ruhé HG, Booij J, Van Weert HC, Reitsma JB, Franssen EJF, Michel MC, et al. Evidence why dose-escalation of paroxetine in major depressive disorder is not effective: A 6-week, randomized-controlled trial with assessment of serotonin transporter occupancy. Neuropsychopharmacology 2009;34:999-1010. Publicatie gebeurt met toestemming van de uitgevers.

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Ruhé, E., Booij, J., van Weert, H. et al. Dosisverhoging SSRI’s bij depressie is niet zinvol. HUWE 52, 289–296 (2009). https://doi.org/10.1007/BF03085643

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