Educational Guide on Antidepressants: Pros, Cons, and Special Considerations

Brexanolone (Zulresso)

Bottom Line: A novel, fastacting option for severe postpartum depression administered intravenously over 60 hours in a healthcare setting.

Pros: Effective for postpartum depression with rapid onset of action.

Cons: Requires 60hour infusion with close monitoring, very high cost, limited followup data beyond 30 days.

Special Considerations: Patients must be monitored for excessive sedation, hypoxia, and loss of consciousness throughout treatment. Requires enrollment in the Zulresso REMS program. Limited data on breastfeeding safety, but transfer to breast milk appears minimal.

Bupropion (Wellbutrin)

Bottom Line: Often chosen for patients with depression associated with fatigue and poor concentration, with the added benefit of no sexual side effects or weight gain.

Pros: Energizing; helps with focus; no sexual side effects or weight gain.

Cons: Increases seizure risk in high doses, not effective for anxiety.

Special Considerations: Avoid in patients with a history of seizures or eating disorders. May cause insomnia, so it's usually taken in the morning.

Citalopram (Celexa)

Bottom Line: An SSRI with fewer drug interactions but a higher risk of QT prolongation, which limits its use.

Pros: Generally welltolerated with low potential for drug interactions.

Cons: QT prolongation risk, especially at higher doses; fewer FDAapproved uses compared to other SSRIs.

Special Considerations: Avoid in patients with cardiac issues or those on CYP2C19 inhibitors. Maximum dose is 20 mg/day in patients over 60.

Clomipramine (Anafranil)

Bottom Line: Primarily used for OCD, this tricyclic antidepressant has more side effects compared to SSRIs but is effective for treatmentresistant cases.

Pros: Effective for OCD and other conditions where SSRIs are ineffective.

Cons: Sedation, weight gain, sexual dysfunction, overdose risk.

Special Considerations: ECG monitoring is recommended for patients on higher doses or with cardiac history.

Desvenlafaxine (Pristiq)

Bottom Line: An SNRI similar to venlafaxine, but with fewer drug interactions and easier dosing.

Pros: Effective for depression with fewer interactions than venlafaxine.

Cons: Limited efficacy for anxiety; doserelated increases in blood pressure.

Special Considerations: Regular blood pressure monitoring is recommended.

Duloxetine (Cymbalta)

Bottom Line: Another SNRI, duloxetine is effective for both depression and various pain syndromes.

Pros: Effective for depression, anxiety, and pain conditions.

Cons: Potential liver toxicity; sexual side effects; nausea.

Special Considerations: Monitor liver function in patients with liver disease or heavy alcohol use.

Escitalopram (Lexapro)

Bottom Line: A firstline SSRI with minimal side effects and drug interactions.

Pros: Welltolerated; effective for both depression and anxiety; fewer QT prolongation concerns than citalopram.

Cons: May cause sexual side effects; nausea; headache.

Special Considerations: Safe in elderly patients but monitor for hyponatremia.

Esketamine (Spravato)

Bottom Line: A nasal spray version of ketamine for treatmentresistant depression and suicidality with rapid onset of action.

Pros: Fastacting, with relief often within 24 hours.

Cons: Requires administration in a healthcare setting; high cost; dissociation and elevated blood pressure.

Special Considerations: Monitor blood pressure and mental status during and after administration. Requires observation for two hours after dosing.

Fluoxetine (Prozac)

Bottom Line: A longestablished SSRI with multiple FDA indications, commonly used for patients needing an activating antidepressant.

Pros: Long halflife reduces withdrawal symptoms; activating, making it useful for patients with fatigue or low energy.

Cons: Higher potential for drug interactions; can cause agitation or insomnia.

Special Considerations: May not be the best choice for bipolar patients due to the risk of inducing mania.

Levomilnacipran (Fetzima)

Bottom Line: An SNRI that focuses more on norepinephrine reuptake inhibition, making it a secondline option after other SNRIs.

Pros: Effective for depression; less prone to drug interactions than some other options.

Cons: Can cause nausea, urinary hesitation, and increased heart rate; higher cost.

Special Considerations: Monitor blood pressure and pulse due to the risk of cardiovascular effects.

Monoamine Oxidase Inhibitors (MAOIs)

Bottom Line: Effective for treatmentresistant depression but less commonly used due to side effects and dietary restrictions.

Pros: Highly effective for atypical depression.

Cons: Requires strict dietary restrictions to avoid hypertensive crisis; many drug interactions.

Special Considerations: Avoid foods high in tyramine and many common medications. Regular blood pressure monitoring is crucial.

Nefazodone (Serzone)

Bottom Line: A rarely used antidepressant due to the risk of serious liver damage, but it may be an option for patients with sexual side effects from other medications.

Pros: Minimal sexual side effects.

Cons: Black box warning for hepatotoxicity; requires liver function monitoring.

Special Considerations: Avoid in patients with liver disease or elevated liver enzymes.

Paroxetine (Paxil)

Bottom Line: Effective for depression and anxiety but has a higher likelihood of causing sedation, weight gain, and sexual dysfunction.

Pros: Effective for anxiety disorders.

Cons: High risk of sexual side effects, weight gain, and sedation; significant withdrawal symptoms.

Special Considerations: Avoid during pregnancy due to the risk of fetal malformations. Best taken at night due to sedative effects.

Selegiline Transdermal (Emsam)

Bottom Line: A transdermal MAOI with fewer dietary restrictions at lower doses and fewer side effects than oral MAOIs.

Pros: Easier to tolerate than oral MAOIs; fewer dietary restrictions at 6 mg dose.

Cons: Higher doses require dietary restrictions; risk of orthostatic hypotension.

Special Considerations: Avoid applying external heat to the patch site, as it may increase drug absorption.

Sertraline (Zoloft)

Bottom Line: A wellestablished SSRI, effective for depression and anxiety with flexible dosing and few drug interactions.

Pros: Effective for depression, anxiety, OCD; welltolerated with few drug interactions.

Cons: Sexual side effects, nausea, and diarrhea are common.

Special Considerations: Safe during pregnancy and breastfeeding. Monitor sodium levels in elderly patients.

Thyroid (Cytomel, Synthroid)

Bottom Line: Often used as an augmentation strategy in patients with depression and fatigue, especially those on tricyclics.

Pros: Inexpensive and welltolerated; can boost energy and mood.

Cons: Risk of hyperthyroidism and reduced bone density at higher doses.

Special Considerations: Regular thyroid function tests (TSH) are required.

Trazodone (Desyrel)

Bottom Line: Commonly used as a sleep aid at low doses but effective for depression at higher doses with fewer sexual side effects.

Pros: Useful for insomnia; less risk of sexual dysfunction and weight gain.

Cons: Sedating at higher doses; risk of orthostatic hypotension.

Special Considerations: Best taken at bedtime due to sedative effects.

Tricyclic Antidepressants (TCAs)

Bottom Line: Not commonly used due to side effects and overdose risk but highly effective for depression, anxiety, and chronic pain.

Pros: Effective for depression and chronic pain.

Cons: Sedating, weight gain, sexual dysfunction, and risk of cardiac issues in overdose.

Special Considerations: Requires ECG monitoring in patients with a cardiac history. Caution with overdose risk.

Venlafaxine (Effexor)

Bottom Line: An SNRI more effective than SSRIs for some patients but with more side effects, such as increased blood pressure and withdrawal symptoms.

Pros: Effective for severe depression and anxiety.

Cons: Increases blood pressure at higher doses; significant withdrawal symptoms.

Special Considerations: Blood pressure monitoring is recommended, and the medication should be tapered slowly to avoid withdrawal.

Vilazodone (Viibryd)

Bottom Line: An SSRI with added buspironelike effects, often marketed as having fewer sexual side effects, though the evidence is not strong.

Pros: May be beneficial for anxious depression.

Cons: Common gastrointestinal side effects; must be taken with food;