Title : Comparative efficacy of typical and atypical antidepressants with olanzapine in acute and chronic models of depression
Abstract:
Depression is a chronic disease afflicting ~245 million individuals worldwide, of which 30-40% patients remain dissatisfied despite 70 years of research, >5 antidepressant drug classes, and 3 trillion healthcare-budget. Fluoxetine, an SSRI alone and with Olanzapine, is the first-line therapy but patient profile, poor efficacy, and tachyphylaxis, apart from tolerability, many times warrant switching/starting to/with other drug classes and augmentation therapies. However, there are no head-to-head preclinical/ clinical studies within and across drug classes unequivocally supporting prescription changes. This study in immobilized and dark cycle-induced acute and chronic SD rat models of depression was conducted to assess if Fluoxetine/Olanzapine efficacy is a class effect. The forced swimming test (FST) conducted in acute and chronic models treated with typical antidepressants (SSRI- Fluoxetine, SNRI- Duloxetine, TCA- Amitriptyline) or atypical antidepressants (Bupropion) alone and in combination with Olanzapine indicated that all drugs showed statistically significant antidepressant effect and that synergistic efficacy seen with Fluoxetine/Olanzapine is not a class effect and other drugs, except Bupropion, can also yield similar efficacy. Additionally, Amitriptyline showed the highest Anhedonia reversal effects, as assessed by the sucrose preference test (SPT). These insights could help physicians augment the primary drug chosen based on patient disease/risk profile and preference with Olanzapine rather than switching to SSRI to attain Olanzapine effects through the only FDA-approved combination. The data also equips physicians to choose alternate drug classes during tachyphylaxis with SSRIs and lastly positions Amitriptyline as an additional anhedonia reversal drug for patients without cardiovascular risk factors.
Audience Take Away Notes:
- Patients are increasingly taking charge of their health and expect data driven conversations with physicians on their prescriptions and this study outcomes equip physicians both in regulated and developing markets
- Slow onset of action combined with titration and efficacy/tolerability concerns, 30-40% of patients are dissatisfied with their first line antidepressant. This data is expected to accelerate the switching or augmentation therapies thereby combatting compliance
- Uniquely the data identifies Amitriptyline as a superior drug for Anhedonia again helping physicians make the choice for their niche segment of severe anhedonia patients
- Help transition from hit and trial AE driven therapeutic regimen to ‘right drug for right patient’ yielding better efficacy and thus delay/prevent TRD
