Criticisms of drugs in early development for the treatment of depression: what can be improved?

A Pharmacogenomic-based Antidepressant Treatment for Patients with Major Depressive Disorder: Results from an 8-week, Randomized, Single-blinded Clinical Trial

“…Currently, the main biological treatment for MDD is various antidepressants such as selective serotonin reuptake inhibitors (SSRIs), dopamine-norepinephrine reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, and noradrenergic and specific serotonin antagonists, and multimodal antidepressant which were mainly developed under a monoamine hypothesis. [1][2][3] Despite the ultimate goal of antidepressant treatment for patients with MDD is to achieve full resolution of symptoms leading to the restoration of functional impairment and wellness of quality of life, it is very difficult to achieve this optimal goal in routine practice. 2,4) For instance, according to the results from the most largest and longest practical clinical study for MDD, "the Sequenced Treatment Alternatives to Relieve Depression (STAR*D)" trial, 5) the overall remission rates for the treatment steps were 28% after level 1 treatment, while it was decreased to 10% at level 4 treatment; the unadjusted cumulative remission rate was 67%.…”

“…[1][2][3] Despite the ultimate goal of antidepressant treatment for patients with MDD is to achieve full resolution of symptoms leading to the restoration of functional impairment and wellness of quality of life, it is very difficult to achieve this optimal goal in routine practice. 2,4) For instance, according to the results from the most largest and longest practical clinical study for MDD, "the Sequenced Treatment Alternatives to Relieve Depression (STAR*D)" trial, 5) the overall remission rates for the treatment steps were 28% after level 1 treatment, while it was decreased to 10% at level 4 treatment; the unadjusted cumulative remission rate was 67%. 6,7) Inadequate clinical outcomes as remission and response as well as higher relapse rates were reported in those who needed additional treatment levels during the naturalistic follow-up phase.…”

Morbidity in Depressive Disorders

“…Progress to more effective biomedical and psychosocial treatments for MDD (aimed at reducing the substantial remaining morbidity) has been slow but includes some promising developments, as reviewed elsewhere [68,69]. Alternatives to antidepressants also are emerging for depression in BD [70,71].…”

Zukünftige Therapieansätze der Depressionsbehandlung

“…In einem Delphi-Panel zur Therapiepräferenz deutscher Ärzte in der antidepressiven Therapie wurden Parameter identifiziert, die für die Behandlung der Patienten relevant sind (Gründer et al, 2016b In den letzten Jahren wurden nunmehr bevorzugt Substanzen mit pharmakologischer Wirkung an mehreren Neurotransmittersystemen entwickelt. Beispielhaft können hier Wirkstoffe mit neuen Wirkmechanismen aufgeführt werden wie Vilazodon und Vortioxetin, die unmet needs in der antidepressiven Wirksamkeit adressieren (Wang et al, 2015). Vilazodon repräsentiert einen Serotonin-Reuptake Inhibi-tor mit zusätzlicher agonistischer Wirkung auf den 5-HT 1a -Rezeptor (Hughes et al, 2005).…”

“…Ein schneller Wirkeintritt ist in der antidepressiven Therapie ein therapeutischer Bedarf, der primär durch Ketamin adressiert werden könnte (Überblick: Wang et al, 2015). Ketamin repräsentiert einen glutaminergen Modulator und NMDA-Rezeptoragonisten, der intensiv untersucht wurde (Rot et al, 2012).…”