What is the first line Selective Serotonin Reuptake Inhibitor (SSRI)?

From the Guidelines

The first-line SSRI for depression treatment is typically sertraline (Zoloft), starting at 50mg daily and titrating up to 200mg daily as needed, based on the most recent evidence from 2015 1. When starting an SSRI, patients should be informed that therapeutic effects may take 2-6 weeks to appear, while side effects like nausea, headache, and sexual dysfunction may occur earlier.

Key Considerations

• Treatment should continue for at least 6-12 months after symptom resolution to prevent relapse, as suggested by clinical guidelines 1.
• SSRIs work by increasing serotonin levels in the brain by blocking its reuptake, which helps regulate mood, anxiety, and other emotional states.
• Regular follow-up is important to monitor response and adjust dosing as needed.
• If the first SSRI is ineffective or poorly tolerated after an adequate trial (usually 4-6 weeks at therapeutic dose), switching to another SSRI or a different class of antidepressant may be appropriate.

Additional Options

• Other common first-line options include fluoxetine (Prozac), escitalopram (Lexapro), and citalopram (Celexa) 1.
• For older patients, preferred agents include citalopram, escitalopram, sertraline, mirtazapine, and venlafaxine, while paroxetine and fluoxetine should generally be avoided due to higher rates of adverse effects 1.

Recent Guidelines

• A recent guideline from 2023 suggests SSRIs as a recommended treatment option for social anxiety disorder, although with a weak strength of recommendation and low certainty of evidence 1.
• However, for depression treatment, the 2015 guidelines from the American Academy of Family Physicians provide more relevant and stronger evidence 1.

From the FDA Drug Label

The mechanism of action of citalopram HBr as an antidepressant is presumed to be linked to potentiation of serotonergic activity in the central nervous system (CNS) resulting from its inhibition of CNS neuronal reuptake of serotonin (5-HT) The mechanism of antidepressant action of escitalopram, the S-enantiomer of racemic citalopram, is presumed to be linked to potentiation of serotonergic activity in the central nervous system (CNS) resulting from its inhibition of CNS neuronal reuptake of serotonin (5-HT). Sertraline hydrochloride is a selective serotonin reuptake inhibitor (SSRI) for oral administration.

First line SSRI options include:

• Citalopram 2
• Escitalopram 3
• Sertraline 4

These are all considered selective serotonin reuptake inhibitors (SSRIs).

From the Research

First-Line SSRI Treatment

The selection of a first-line SSRI (Selective Serotonin Reuptake Inhibitor) for the treatment of depression and other disorders involves considering the pharmacokinetic properties, efficacy, and tolerability of the available options.

• The five commonly used SSRIs are fluoxetine, fluvoxamine, paroxetine, sertraline, and citalopram, which have similar antidepressant efficacy but differ in their pharmacokinetic properties 5.
• Escitalopram, a newer SSRI, has been shown to have a more favorable tolerability profile and potentially greater efficacy compared to paroxetine and sertraline 6.
• A systematic review of second-generation antidepressants found that SSRIs do not differ significantly in their effectiveness for treating accompanying anxiety, insomnia, and pain in patients with major depressive disorder 7.

Factors Influencing SSRI Selection

Several factors can influence the selection of a first-line SSRI, including:

• Pharmacokinetic properties, such as half-life and metabolism 5
• Efficacy and tolerability profiles 6, 8
• Potential for drug-drug interactions 5, 8
• Patient-specific factors, such as history of overdose or adverse reactions 8

Comparative Efficacy of SSRIs

Studies have compared the efficacy of different SSRIs, with some findings suggesting that:

• Escitalopram may be more effective than paroxetine and sertraline 6
• Fluoxetine may have a slower onset of action and more adverse effects compared to other SSRIs 8
• Citalopram and sertraline may have a lower risk of drug interactions compared to other SSRIs 8

Long-Term Prophylactic Efficacy

The long-term prophylactic efficacy of SSRIs in preventing recurrence of major depressive disorder has been examined, with findings suggesting that:

• Escitalopram and fluoxetine may have a numerically higher prophylactic efficacy than paroxetine and sertraline, although the difference was not statistically significant 9
• Concomitant cognitive behavioral therapy (CBT) may improve the prophylactic efficacy of SSRIs 9