What are the most effective medications for treating major depressive disorder (MDD)?

From the Guidelines

The most effective medications for depression are selective serotonin reuptake inhibitors (SSRIs) like fluoxetine (Prozac), sertraline (Zoloft), or escitalopram (Lexapro), which are often prescribed as first-line treatments due to their effectiveness and relatively mild side effect profiles. These medications usually start at low doses (e.g., fluoxetine 10-20mg daily, sertraline 25-50mg daily, escitalopram 5-10mg daily) and may take 4-6 weeks to reach full effectiveness 1. If SSRIs aren't effective, doctors might recommend serotonin-norepinephrine reuptake inhibitors (SNRIs) like venlafaxine (Effexor) or duloxetine (Cymbalta), or other classes such as bupropion (Wellbutrin), mirtazapine (Remeron), or tricyclic antidepressants.

Key Considerations

• Medication choice depends on individual symptoms, medical history, and potential side effects 1.
• These medications work by increasing levels of neurotransmitters like serotonin and norepinephrine in the brain, which help regulate mood.
• It's essential to take these medications consistently, even after feeling better, and to work closely with a healthcare provider to monitor effectiveness and adjust treatment as needed.
• Medication works best when combined with psychotherapy, regular exercise, good sleep habits, and social support.

Treatment Duration

• Treatment for a first episode of major depression should last at least four months 1.
• Patients with recurrent depression may benefit from prolonged treatment.

Special Considerations

• For older patients with depression, preferred agents include citalopram (Celexa), escitalopram (Lexapro), sertraline (Zoloft), mirtazapine (Remeron), venlafaxine, and bupropion (Wellbutrin) 1.
• Paroxetine (Paxil) and fluoxetine (Prozac) should generally be avoided in older adults due to higher rates of adverse effects.

From the FDA Drug Label

The FDA drug label does not answer the question.

From the Research

Medications for Depression

The following medications are commonly used to treat depression:

• Selective serotonin reuptake inhibitors (SSRIs)
• Venlafaxine
• Mirtazapine
• Selective norepinephrine reuptake inhibitors (SNRIs)

Dose-Response Relationship

Studies have investigated the dose-response relationship of these medications:

• A systematic review and dose-response meta-analysis found that the lower range of the licensed dose of SSRIs achieves the optimal balance between efficacy, tolerability, and acceptability in the acute treatment of major depression 2
• A meta-analysis of randomized, double-blind, placebo-controlled, dose-finding studies found that initiating treatment with SSRIs at doses higher than those typically used is associated with higher response rates but also higher rates of discontinuation due to intolerance 3
• A systematic review of reviews and meta-narrative synthesis found that standard daily doses of SSRIs provide a favourable balance between efficacy, acceptability, and tolerability 4
• A meta-analysis and network meta-analysis of randomized controlled trials found no evidence of a dose-response relationship in SNRIs, and recommended prescribing medium doses 5

Switching Medications

If a patient does not respond to a first SSRI, switching to another medication may be considered:

• A systematic review found that switching to venlafaxine showed a modest and clinically equivocal benefit over SSRIs 6
• The review also found that any switch within or between classes of antidepressants appears legitimate, but more guidance by randomized empirical studies is needed 6