What is the list of Selective Serotonin Reuptake Inhibitors (SSRIs)?

List of Selective Serotonin Reuptake Inhibitors (SSRIs)

The six FDA-approved Selective Serotonin Reuptake Inhibitors (SSRIs) available in clinical practice are fluoxetine, paroxetine, sertraline, fluvoxamine, citalopram, and escitalopram. 1

Mechanism of Action

• SSRIs work by selectively inhibiting the reuptake of serotonin (5-HT) in the central nervous system, resulting in increased serotonergic activity 2, 3
• They have minimal effects on norepinephrine and dopamine neuronal reuptake compared to other antidepressant classes 2, 3
• SSRIs have low affinity for muscarinic, histaminergic, and adrenergic receptors, which explains their more favorable side effect profile compared to older antidepressants 3

Complete List of SSRIs

Fluoxetine

• Brand names include Prozac, Sarafem 4
• Most activating SSRI with significant stimulating effects 5
• Has the longest half-life (1-4 days for parent compound, 7-15 days for active metabolite norfluoxetine) 6
• Recommended dosage: 5-20 mg/day 4

Sertraline

• Brand name: Zoloft 4
• Moderate activation profile 5
• Dosage range: 25-200 mg/day or 50 mg 4-8 hours pre-intercourse (for premature ejaculation) 4

Citalopram

• Brand name not specified in evidence 4
• Well-tolerated with balanced activation profile 5
• Maximum recommended dose is 20 mg/day for patients over 60 years due to risk of QT prolongation 2
• Starting dose typically 10 mg with increments of 10 mg 4

Escitalopram

• Active S-enantiomer of racemic citalopram 3
• Well-tolerated with balanced activation profile 5
• At least 100-fold more potent than the R-enantiomer in inhibiting 5-HT reuptake 3

Paroxetine

• Brand name: Paxil 4
• Least activating SSRI with more sedating properties 5
• Dosage: 10,20,40 mg/day or 20 mg 3-4 hours pre-intercourse (for premature ejaculation) 4
• Has been associated with discontinuation syndrome 4

Fluvoxamine

• Less clear activation profile but may require twice-daily dosing due to shorter half-life 5
• Chemically designated as 5-methoxy-4'-(trifluoromethyl)valerophenone-(E)-O-(2-aminoethyl)oxime maleate 7
• Has greater potential for drug-drug interactions compared to other SSRIs 4

Pharmacokinetic Differences

• Half-lives range from approximately 21 hours (paroxetine) to 36 hours (citalopram) for most SSRIs, with fluoxetine being the exception with a much longer half-life 6
• Sertraline and citalopram show linear pharmacokinetics, while fluoxetine, fluvoxamine, and paroxetine show nonlinear pharmacokinetics 6
• All SSRIs undergo extensive hepatic metabolism with high interindividual variability 6

Clinical Considerations

• SSRIs are used for multiple conditions including major depression, dysthymia, panic disorder, obsessive-compulsive disorder, eating disorders, and premenstrual dysphoric disorder 8
• Common side effects include gastrointestinal disturbances, headache, sedation, insomnia, activation, weight gain, impaired memory, excessive perspiration, paresthesia, and sexual dysfunction 8
• SSRIs vary in their potential for drug-drug interactions, with fluvoxamine having greater potential for interactions 4
• Citalopram/escitalopram may have the least effect on CYP450 isoenzymes compared to other SSRIs 4

Safety Considerations

• All SSRIs should be slowly tapered when discontinued because of risk of withdrawal effects 4
• Concomitant administration of any SSRI with monoamine oxidase inhibitors (MAOIs) is contraindicated due to risk of serotonin syndrome 4
• Serotonin syndrome symptoms include mental status changes, neuromuscular hyperactivity, and autonomic hyperactivity 4