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This multicenter, observational drug utilization (DU) study ({"type":"clinical-trial","attrs":{"text":"NCT01594996","term_id":"NCT01594996"}}NCT01594996) investigated the profile of patients and specialist providers who prescribed extended release quetiapine fumarate (quetiapine XR) for treatment of major depressive disorder (MDD) across five European countries (Germany, Italy, Romania, Spain, and Sweden). A DU data abstraction form captured information on the characteristics of physicians, patients, and drugs utilized in the medical management of depressive episodes in MDD, where the therapeutic regimen included quetiapine XR. Data were reported descriptively. This analysis included 811 patients. Psychiatric histories indicated a burden of severe MDD in these patients. Patient demographics were similar across countries; however, those in Sweden had a younger mean age. Physicians’ ratings of the therapeutic effect of prior treatment with antidepressants suggested the need for an add-on treatment for most patients. Overall, 15.7% of patients initiated quetiapine XR treatment as monotherapy. Presence of psychotic symptoms during depressive episodes predicted treatment with higher than recommended doses of quetiapine XR (odds ratio=3.11; 95% confidence interval: 1.6–6.0). This analysis demonstrated similarities in DU across the countries analyzed, largely in accordance with the recommended dose of quetiapine XR as an adjunctive therapy to antidepressants in MDD (50–300 mg/day).

In this review is shown the analysis of clinical studies of the efficacy and safety of atypical antipsychotic extended release quetiapine, in the treatment of adult patients with major depressive disorder (MDD), as short-term monotherapy, short-term adjunctive treatment to on-going antidepressant and maintenance treatment or relapse prevention in major depressive episodes. Recommended dosing regimen was 50 to 300 mg daily. Six of seven studies were positive on the primary efficacy variable (MADRS, Montgomery Asberg Depression Rating Scale score) on at least one dose under investigation, whilst one study was not significant. None of the studies was positive on the secondary endpoint: improvement in the quality of life, by assessing the change in Q-LES-Q total score (Quality of Life Enjoyment and Satisfaction Questionnaire). Overall, the safety findings from the extended release quetiapine MDD clinical studies are consistent with known adverse event profile for quetiapine in other known indications: schizophrenia and bipolar disorder. However, during the short-term exposure in the extended release quetiapine MDD clinical studies, the long-term serious adverse events, in particular risk related to metabolic changes, and possibility of tardive dyskinesia and increased risk of sudden cardiac death, has not been adequately studied, therefore the risk benefit ratio, for now, can not be assessed as favorable, with high reliability. Despite that, the regulatory authorities in the U.S. (FDA - Food and Drug Administration) and EU (EMA - European Medicines Agency) have approved, however, reduced indication for extended release quetiapine in the treatment of major depressive disorder: add-on treatment of major depressive episodes in patients with MDD who had suboptimal response to antidepressant monotherapy, noting that, prior to initiating treatment, clinicians should consider the safety profile of extended release quetiapine. U radu je prikazana analiza kliničkih studija za procenu efikasnosti i bezbednosti atipičnog antipsihotika kvetiapina, u obliku tableta sa produženom brzinom oslobađanja kod odraslih pacijenata sa velikom depresijom, primenjenog kao: kratkotrajna monoterapija, kratkotrajna dodatna terapija na primenjivani antidepresiv i monoterapija održavanja u prevenciji relapsa epizode velike depresije. Preporučen opseg doza kvetiapina u ovim studijama bio je 50 do 300 mg/dan. Rezultati šest od sedam sprovedenih kliničkih studija pokazali su da je kvetiapin u obliku tableta sa produženom brzinom oslobađanja statistički značajno efikasniji u odnosu na placebo, s obzirom na primarni parametar efikasnosti, promenu ukupnog MADRS skora (Montgomery Asberg Depression Rating Scale Score) za bar jednu od doza koje su ispitivane u studijama, dok u jednoj od studija nije pokazana statistički značajna razlika između kvetiapina i placeba, u odnosu na ovaj parametar efikasnosti. Niti u jednoj od studija kvetiapin u obliku tableta sa produženim oslobađanjem nije bio statistički značajno efikasniji od placeba u odnosu na sekundarni parametar efikasnosti: poboljšanje kvaliteta života procenjeno na osnovu promene ukupnog skora Q-LES-Q upitnika (Quality of Life Enjoyment and Satisfaction Questionnaire total score). Profil neželjenih efekata kvetiapina u obliku tableta sa produženim oslobađanjem u sprovedenim kliničkim studijama na pacijentima sa velikom depresijom nije se razlikovao od poznatog bezbednosnog profila kvetiapina ustanovljenog u ranije odobrenim indikacijama za ovaj lek (shizofrenija i bipolarni poremećaj). Međutim, kratkotrajna izloženost pacijenata sa velikom depresijom kvetiapinu u sprovedenim kliničkim studijama, nije dovoljna za procenu rizika od njegovih dugoročnih ozbiljnih neželjenih efekata kao što su: metabolički poremećaji, potencijalni rizik za razvoj tardivne diskinezije i mogućnost povećanja rizika od iznenadne srčane smrti, tako da se odnos korist/rizik primene ovog leka kod pacijenata sa velikom depresijom, još uvek ne može, sa velikom pouzdanošću, proceniti kao povoljan. Uprkos tome, regulatorna tela u SAD (FDA - Food and Drug Administration) i EU (EMA - European Medicines Agency) odobrila su, doduše, suženu indikaciju za kvetiapin u obliku tableta sa produženim oslobađanjem u terapiji velike depresije: dodatna terapija (add-on) kod pacijenata sa velikom depresijom, koji su imali suboptimalan odgovor na monoterapiju antidepresivom, uz napomenu da, pre započinjanja terapije, lekari treba da razmotre profil bezbednosti ovog leka.