What is the first-line medication for major depressive disorder (MDD)?

From the Guidelines

Second-generation antidepressants, specifically selective serotonin reuptake inhibitors (SSRIs), should be used as the first-line treatment for depression due to their effectiveness and favorable side effect profile. When choosing a pharmacologic therapy, clinicians should select second-generation antidepressants based on adverse effect profiles, cost, and patient preferences 1. Common SSRIs include fluoxetine (Prozac) 20-80 mg daily, sertraline (Zoloft) 50-200 mg daily, escitalopram (Lexapro) 10-20 mg daily, and citalopram (Celexa) 20-40 mg daily. Some key points to consider when prescribing these medications include:

• Bupropion is associated with a lower rate of sexual adverse events than fluoxetine or sertraline, whereas paroxetine has higher rates of sexual dysfunction than fluoxetine, fluvoxamine, nefazodone, or sertraline 1
• SSRIs are associated with an increased risk for suicide attempts compared with placebo, and patients should be closely monitored on a regular basis for increases in suicidal thoughts and behaviors 1
• Treatment should typically continue for at least 6-12 months after symptom resolution to prevent relapse
• Patients should be aware that these medications usually take 2-4 weeks to show initial benefits, with full effects often requiring 6-8 weeks
• Common side effects include nausea, headache, sleep disturbances, and sexual dysfunction, which often improve with time
• Regular follow-up is important to monitor response and adjust dosage if needed, beginning within 1 to 2 weeks of initiation of therapy 1

From the FDA Drug Label

1 INDICATIONS AND USAGE

1. 1 Major Depressive Disorder (MDD) Bupropion hydrochloride extended-release tablets (XL) are indicated for the treatment of major depressive disorder (MDD), as defined by the Diagnostic and Statistical Manual (DSM) The efficacy of the immediate-release formulation of bupropion was established in two 4-week controlled inpatient trials and one 6-week controlled outpatient trial of adult patients with MDD The efficacy of the sustained-release formulation of bupropion in the maintenance treatment of MDD was established in a long-term (up to 44 weeks), placebo-controlled trial in patients who had responded to bupropion in an 8-week study of acute treatment [see Clinical Studies (14.1)].

Bupropion is indicated for the treatment of Major Depressive Disorder (MDD).

• The recommended starting dose for MDD is 150 mg once daily in the morning.
• After 4 days of dosing, the dose may be increased to the target dose of 300 mg once daily in the morning 2.

From the Research

First-Line Medications for Depression

The following medications are commonly used as first-line treatments for depression:

• Selective serotonin reuptake inhibitors (SSRIs) such as citalopram, escitalopram, fluoxetine, paroxetine, and sertraline 3, 4, 5, 6
• Serotonin and norepinephrine reuptake inhibitors (SNRIs) such as venlafaxine and duloxetine 4, 7
• Norepinephrine-dopamine reuptake inhibitors (NDRIs) such as bupropion 4, 7

Efficacy and Tolerability of First-Line Medications

Studies have shown that:

• SSRIs have a gradual increase in efficacy up to doses between 20 mg and 40 mg fluoxetine equivalents, and a flat to decreasing trend through the higher licensed doses up to 80 mg fluoxetine equivalents 3
• Venlafaxine has an initially increasing dose-efficacy relationship up to around 75-150 mg, followed by a more modest increase 3
• Mirtazapine has an increasing dose-efficacy relationship up to a dose of about 30 mg and then decreases 3
• SSRIs have the best benefit-risk profile, making them suitable as first-line treatments, while tricyclics are highly effective but less tolerated than SSRIs and placebo 5

Comparison of First-Line Medications

Comparative studies have found that:

• Escitalopram is significantly more effective than citalopram in achieving acute response and remission 6
• Escitalopram is also more effective than citalopram in terms of remission 6
• Sertraline and paroxetine are effective for the largest number of ICD-11 disease subgroups (four out of seven) 5
• There is limited evidence guiding the selection of an SGA based on accompanying symptoms of depression, such as anxiety, insomnia, and pain 7