What are the recommended selective serotonin reuptake inhibitors (SSRIs)?

List of Selective Serotonin Reuptake Inhibitors (SSRIs)

The primary SSRIs currently available include fluoxetine, sertraline, citalopram, escitalopram, paroxetine, and fluvoxamine.

Commonly Prescribed SSRIs

FDA-Approved SSRIs

1. Fluoxetine (Prozac)

   • Initial dose: 10-20 mg daily
   • Maximum dose: 60 mg daily
   • Notable for long half-life and activating properties 1

2. Sertraline (Zoloft)

   • Initial dose: 25-50 mg daily
   • Maximum dose: 200 mg daily
   • Well-tolerated with less effect on metabolism of other medications 1, 2
   • Mechanism: Potent and selective inhibitor of neuronal serotonin reuptake 2

3. Citalopram (Celexa)

   • Initial dose: 10 mg daily
   • Maximum dose: 40 mg daily (20 mg maximum in elderly due to QT prolongation risk)
   • Well-tolerated with some patients experiencing nausea and sleep disturbances 1, 3
   • Highly selective serotonin reuptake inhibitor with minimal effects on norepinephrine and dopamine 3

4. Escitalopram (Lexapro)

   • Initial dose: 10 mg daily
   • Maximum dose: 20 mg daily
   • S-enantiomer of racemic citalopram, at least 100-fold more potent than R-enantiomer 4
   • FDA-approved for adolescents aged 12 years and older 1

5. Paroxetine (Paxil)

   • Initial dose: 10 mg daily
   • Maximum dose: 40-60 mg daily
   • Less activating but more anticholinergic than other SSRIs 1

6. Fluvoxamine (Luvox)

   • Initial dose: 50 mg twice daily
   • Maximum dose: 150 mg twice daily
   • May require twice-daily dosing in youths 1
   • Exercise caution when using with alprazolam or triazolam 1

Pharmacological Properties

Mechanism of Action

• All SSRIs inhibit the presynaptic reuptake of serotonin in the brain, increasing serotonin availability at the synaptic cleft 1, 2, 3, 4
• This blockade leads to downregulation of inhibitory serotonin autoreceptors, heightening serotonergic neuronal firing rate 1
• The multistep process explains the delay in onset of therapeutic effects 1

Pharmacokinetics

• Most SSRIs have sufficiently long elimination half-lives to permit once-daily dosing 1
• Half-lives range from approximately 21-36 hours for most SSRIs, with fluoxetine having a longer half-life of 1-4 days (and its active metabolite norfluoxetine 7-15 days) 5
• Sertraline, citalopram, and escitalopram show linear pharmacokinetics, while fluoxetine, fluvoxamine, and paroxetine show nonlinear pharmacokinetics 5

Clinical Considerations

Common Side Effects

• Dry mouth, nausea, diarrhea, headache, somnolence, insomnia, dizziness
• Vivid dreams, changes in appetite, weight changes, fatigue, nervousness
• Sexual dysfunction, diaphoresis 1, 6

Serious Adverse Effects

• Suicidal thinking and behavior (particularly in children and adolescents)
• Behavioral activation/agitation
• Hypomania or mania
• Serotonin syndrome
• Abnormal bleeding 1

Drug Interactions

• SSRIs may inhibit various cytochrome P450 isoenzymes, potentially affecting metabolism of other medications 2, 3
• Paroxetine and fluoxetine are potent inhibitors of CYP2D6
• Fluvoxamine strongly inhibits CYP1A2 and CYP2C19 5

Special Populations

Children and Adolescents

• Only fluoxetine is FDA-approved for depression in children and adolescents
• Only escitalopram is FDA-approved for adolescents aged 12 years and older 1
• SSRIs are recommended for anxiety disorders in children and adolescents 6-18 years old 1

Elderly Patients

• Lower maximum doses are recommended, particularly for citalopram (20 mg maximum due to QT prolongation risk) 3
• Sertraline, citalopram, and escitalopram are often preferred due to favorable side effect profiles and lower risk of drug interactions 7

SSRIs represent an important class of medications with demonstrated efficacy across multiple psychiatric conditions, including depression, anxiety disorders, obsessive-compulsive disorder, and others 8. Their relatively favorable side effect profile compared to older antidepressants has made them first-line agents for many conditions.