From the Guidelines
Sertraline (Zoloft) is often considered a good first choice for SSRI treatment due to its balanced efficacy and tolerability profile. This recommendation is based on the most recent and highest quality study available, which suggests that all second-generation antidepressants, including SSRIs, are equally effective for the treatment of acute-phase major depressive disorder (MDD) 1.
Key Considerations
- The available evidence does not support clinically significant differences in efficacy, effectiveness, or quality of life among SSRIs, SNRIs, SSNRIs, or other second-generation antidepressants for the treatment of acute-phase MDD 1.
- Sertraline is typically started at 25-50mg daily and gradually increased to 50-200mg daily as needed.
- Other commonly prescribed SSRIs include fluoxetine (Prozac), escitalopram (Lexapro), citalopram (Celexa), and paroxetine (Paxil), each with slightly different side effect profiles and half-lives.
- SSRIs generally take 4-6 weeks to reach full effectiveness, and treatment should continue for at least 6-12 months after symptom improvement for depression, or longer for anxiety disorders.
Common Side Effects
- Nausea
- Headache
- Sleep disturbances
- Sexual dysfunction
- These medications work by increasing serotonin levels in the brain by blocking its reuptake, which helps regulate mood, anxiety, and other psychological functions.
Patient-Specific Factors
- The best SSRI is ultimately the one that provides symptom relief with minimal side effects for the individual patient, often requiring trial and adjustment under medical supervision.
- Patient preferences, adverse effect profiles, cost, and dosing frequency should be taken into consideration when choosing an SSRI 1.
From the FDA Drug Label
The mechanism of action of sertraline is presumed to be linked to its inhibition of CNS neuronal uptake of serotonin (5HT). 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 FDA drug label does not answer the question.
From the Research
Effectiveness of Selective Serotonin Reuptake Inhibitors (SSRIs)
The effectiveness of SSRIs is a subject of extensive research, with various studies comparing the efficacy of different SSRIs.
- According to 2, the five selective serotonin reuptake inhibitors (SSRIs), fluoxetine, fluvoxamine, paroxetine, sertraline, and citalopram, have similar antidepressant efficacy and a similar side effect profile.
- A study published in 3 found that fluoxetine has a more favorable tolerability profile for a similar efficacy in comparison to tricyclic antidepressants.
- However, as noted in 3, 4, 5, there is no scientific evidence to suggest that any one SSRI is more effective than another, but not all patients respond to the same agent.
- A randomized trial published in 6 compared the effectiveness of paroxetine, fluoxetine, and sertraline in primary care and found that the three SSRIs were similar in effectiveness for depressive symptoms as well as multiple domains of health-related quality of life over the entire 9 months of the trial.
Pharmacokinetic Properties of SSRIs
The pharmacokinetic properties of SSRIs differ significantly, which can affect their efficacy and safety.
- As mentioned in 2, SSRIs differ in their pharmacokinetic properties, including half-life and metabolism pathways.
- According to 4, the half-life of fluoxetine and its active metabolite norfluoxetine is more extended than other SSRIs, which may be an advantage in poorly compliant patients but also requires a long period of wash-out before introducing other drugs.
- The study in 2 also notes that SSRIs are potent inhibitors of the hepatic isoenzyme P450-2D6, which can affect the clearance of other drugs.
Clinical Implications
The choice of SSRI depends on various factors, including the patient's medical history, comorbidities, and potential drug interactions.
- As noted in 3, 5, SSRIs are generally well-tolerated and safe, but can cause side effects such as gastrointestinal disturbances, headache, and sexual dysfunction.
- The study in 6 found that the three SSRIs (paroxetine, fluoxetine, and sertraline) were associated with similar incidences of adverse effects and discontinuation rates.
- According to 5, SSRIs are the treatment of choice for many indications, including major depression, dysthymia, panic disorder, obsessive-compulsive disorder, eating disorders, and premenstrual dysphoric disorder, due to their efficacy, good side-effect profile, tolerability, and safety in overdose.