From the Guidelines
The best evidence for SSRIs in depression supports their use as first-line pharmacological treatment for moderate to severe major depressive disorder, with escitalopram showing benefits over citalopram, although the clinical significance is doubtful 1. When considering treatment options, it's essential to evaluate the effectiveness, quality of life, and speed of response for acute phase treatment.
- Effectiveness for Acute Phase: No significant differences were found among different SSRIs for the treatment of major depressive disorder (MDD) 1.
- Quality of Life: Evidence from 18 fair-quality efficacy trials showed no differences among second-generation antidepressants, including SSRIs, in terms of quality of life or functional capacity 1.
- Speed of Response for Acute Phase: Mirtazapine had a statistically significantly faster onset of action than some SSRIs, such as citalopram, fluoxetine, paroxetine, or sertraline, although response rates were similar after 4 weeks 1. Commonly prescribed SSRIs include fluoxetine (20-80mg daily), sertraline (50-200mg daily), escitalopram (10-20mg daily), citalopram (20-40mg daily), and paroxetine (20-50mg daily). Treatment should typically continue for at least 6-12 months after symptom resolution to prevent relapse, with full therapeutic effects often taking 4-6 weeks to develop. SSRIs work by blocking serotonin reuptake in the brain, increasing serotonin availability at synapses, which helps regulate mood, emotion, and sleep patterns disrupted in depression. They generally have better tolerability than older antidepressants, though side effects may include nausea, headache, insomnia, sexual dysfunction, and initial anxiety. Response rates in clinical trials show approximately 50-60% of patients experience significant improvement compared to 30-40% with placebo. For optimal outcomes, medication should be combined with psychotherapy such as cognitive behavioral therapy, and patients should be monitored regularly for side effects, suicidal ideation (particularly in young adults and adolescents), and treatment response.
From the FDA Drug Label
The efficacy of sertraline in the treatment of a major depressive episode was established in six to eight week controlled trials of adult outpatients whose diagnoses corresponded most closely to the DSM-III category of major depressive disorder A major depressive episode implies a prominent and relatively persistent depressed or dysphoric mood that usually interferes with daily functioning (nearly every day for at least 2 weeks); it should include at least 4 of the following 8 symptoms: change in appetite, change in sleep, psychomotor agitation or retardation, loss of interest in usual activities or decrease in sexual drive, increased fatigue, feelings of guilt or worthlessness, slowed thinking or impaired concentration, and a suicide attempt or suicidal ideation. The efficacy of sertraline in maintaining an antidepressant response for up to 44 weeks following 8 weeks of open-label acute treatment (52 weeks total) was demonstrated in a placebo-controlled trial.
The best evidence for SSRI in depression is that sertraline has been shown to be effective in the treatment of major depressive disorder in adults, with efficacy established in six to eight week controlled trials. The drug has also been shown to be effective in maintaining an antidepressant response for up to 44 weeks following initial treatment 2. Key symptoms of major depressive disorder that may be improved with sertraline include:
- Change in appetite
- Change in sleep
- Psychomotor agitation or retardation
- Loss of interest in usual activities or decrease in sexual drive
- Increased fatigue
- Feelings of guilt or worthlessness
- Slowed thinking or impaired concentration
- Suicide attempt or suicidal ideation
From the Research
Efficacy of SSRIs in Depression
- SSRIs are considered the treatment of choice for many indications, including major depression, due to their efficacy, good side-effect profile, tolerability, and safety in overdose, as well as patient compliance 3.
- A systematic review and meta-analysis found that escitalopram was more effective than other SSRIs in terms of response rate, remission rate, and withdrawal rate in the acute-phase treatment for adults with major depressive disorder 4.
- Another study found that both SSRIs and tricyclic antidepressants (TCAs) are efficacious in terms of response rates when compared to placebo, with no statistically significant differences between the active drugs and placebo in terms of dropout rates 5.
Comparison of SSRIs
- A comparative analysis of SSRIs found that escitalopram was the better choice in terms of remission rate and withdrawal rate, and was more effective than other defined SSRIs in terms of response rate, remission rate, and withdrawal rate 4.
- SSRIs differ in terms of pharmacokinetics and effects on CYP450 enzymes, which can impact their safety and efficacy 6.
Safety and Adverse Effects
- SSRIs have a unique side effect profile, with common adverse effects including gastrointestinal disturbances, headache, sedation, insomnia, activation, weight gain, impaired memory, excessive perspiration, paresthesia, and sexual dysfunction 3.
- A narrative review found that SSRIs can have adverse effects, including an increased risk of suicidality in children and young adults aged 18-24, and emphasized the importance of a risk-benefit analysis when prescribing SSRIs 7.
- SSRIs were designed to be safer and more tolerable than previous antidepressants, with a specific mechanism of action and minimal adverse effects 6.