Thread by @psycheureka

Which antidepressants work most effectively, and which barely beat placebo?

The largest meta-analysis (Cipriani et al., 2018) compared 21 antidepressants in 116,477 patients, revealing striking differences in efficacy and tolerability.

Here’s how this data can transform your prescribing practice 🧵👇

Most ‘Effective’ Antidepressants (Head-to-Head)

In the largest network meta-analysis to date, the following antidepressants consistently outperformed others in head-to-head comparisons for efficacy (odds ratio range: 1.19–1.96):

● Agomelatine
● Amitriptyline
● Escitalopram
● Mirtazapine
● Paroxetine

These consistently outperformed others.

Note: Just because a drug ranks high in efficacy doesn’t mean it’s the best choice for every patient.

The Numbers Behind Antidepressant’s Efficacy

Odds ratios (OR) provide a clearer picture.

● Amitriptyline: OR = 2.13 (113% higher odds vs. placebo)
● Reboxetine: OR = 1.37 (37% higher odds)

All drugs beat the placebo, but not equally.

Higher OR = greater efficacy.

Well-Tolerated Antidepressants (Lower Dropout Rates)

Patients are more likely to stick with well-tolerated treatments.

Cipriani et al. (2018) found:

● Agomelatine, citalopram, escitalopram, fluoxetine, sertraline, and vortioxetine → better acceptability than many other antidepressants.

● Only agomelatine & fluoxetine had fewer dropouts than placebo.

● The others were not superior to placebo on this metric.

Balancing Efficacy and Tolerability

No drug is perfect. Clinicians must balance efficacy with tolerability:

● Amitriptyline: Highly effective but poorly tolerated.
● Escitalopram & Agomelatine: Offer a strong balance of both.

This is the cornerstone of personalised prescribing.

Best/Worst Overview

Efficacy leaders: 

Agomelatine, Amitriptyline, Escitalopram, Mirtazapine, Paroxetine, Venlafaxine, Vortioxetine.

Tolerability leaders: 

Agomelatine, Citalopram, Escitalopram, Fluoxetine, Sertraline, Vortioxetine.

Caution: 
● Least efficacy— Fluoxetine, Fluvoxamine, Reboxetine, Trazodone. 

● High dropout— Amitriptyline, Clomipramine, Duloxetine, Fluvoxamine, Reboxetine, Trazodone, Venlafaxine.

Why This Study Stands Out

This network meta-analysis was groundbreaking, including:

● Data from 522 trials (published + unpublished).
● Direct and indirect comparisons of 21 drugs.

Strengths: Largest antidepressant dataset, reduced publication bias.

Limitations: Short trial durations (<12 weeks) and exclusion of treatment-resistant/psychotic depression.

Practical Prescribing Tips

Use these insights to refine your practice:

● Prioritise efficacy leaders when maximising response.

● Choose tolerability leaders for side-effect-sensitive patients.

● Use shared decision-making to align choice with patient needs.

Personalised Treatment Improves Outcomes

STAR*D showed that after first-line antidepressant treatment:

●~47% respond (~1 in 2)

●~27–37% remit (~1 in 3, scale-dependent)

Balancing efficacy, tolerability, and patient preferences is key to improving outcomes.

Learn more about antidepressant medications and delve deep into their intricate mechanisms of action below 👇

Refine Your Prescribing Expertise

Our course, ‘Antidepressant Mechanisms & Management: Advanced Training for Psychiatrists’, equips you with the tools to refine your decision-making and improve patient outcomes.

Access the full course on The Academy.

psychscene.co/4jjdnZb