Antidepressants

Key takeaways

• Antidepressants treat depression and anxiety by adjusting brain chemical signaling: SSRIs (sertraline, fluoxetine, escitalopram) come first, SNRIs (venlafaxine, duloxetine) add pain relief, and older TCAs (amitriptyline) are reserved for non-responders.
• The real difference is mechanism and side effects, not strength: bupropion skips SSRI-type sexual side effects but carries a seizure risk, and TCAs are far more dangerous in overdose.
• Every antidepressant carries a warning for increased suicidal thinking in people under 25, especially in the first weeks of treatment or after a dose change.

How antidepressants work

Most antidepressants raise serotonin, norepinephrine or dopamine levels at nerve connections in the brain, gradually changing mood-regulating circuits over several weeks. SSRIs act mainly on serotonin, SNRIs add norepinephrine, and bupropion works through norepinephrine and dopamine instead.

Choosing between sertraline, fluoxetine, paroxetine, duloxetine, venlafaxine, bupropion, mirtazapine and amitriptyline

• Sertraline is a first-line SSRI for depression, panic disorder and several anxiety conditions, with fewer drug interactions than some other SSRIs.
• Fluoxetine treats depression, panic disorder and bulimia; its long half-life makes a missed dose matter less but keeps it in your system for weeks.
• Paroxetine works well for social anxiety and panic disorder but has the highest discontinuation-symptom rate among the SSRIs, so it needs a slower taper.
• Duloxetine, an SNRI, treats depression and generalized anxiety, also approved for diabetic nerve pain and fibromyalgia.
• Venlafaxine behaves like an SSRI at low doses and adds norepinephrine effects at higher ones, raising blood pressure enough to need monitoring.
• Bupropion works through norepinephrine and dopamine, avoiding SSRI-type sexual side effects and weight gain, but its dose-dependent seizure risk rules it out in seizure disorders and eating disorders.
• Mirtazapine is sedating and increases appetite, often taken at night for depression with insomnia and poor appetite.
• Amitriptyline, an older TCA, treats depression and nerve pain but is far more dangerous in overdose, capable of causing life-threatening heart rhythm problems.

Escitalopram, citalopram and fluvoxamine are other first-line SSRIs; fluvoxamine treats obsessive-compulsive disorder mainly. Vortioxetine and vilazodone are newer antidepressants marketed for fewer sexual side effects. Clomipramine, imipramine, doxepin and nortriptyline are older TCAs sharing amitriptyline's overdose danger, now used for obsessive-compulsive disorder (clomipramine), bedwetting (imipramine) or nerve pain (doxepin, nortriptyline). Trazodone sedates at low doses for insomnia and works as a full antidepressant at higher doses. Milnacipran is an SNRI used more for fibromyalgia than depression.

Common questions

Why do doctors warn about suicide risk in the first few weeks?

Antidepressants can lift energy before mood improves, briefly raising the risk of acting on suicidal thoughts, especially in people under 25. Close monitoring matters most early on and after any dose change.

Can I just stop taking mine once I feel fine?

Stopping suddenly can trigger dizziness, electric-shock sensations, irritability and flu-like symptoms, especially with paroxetine and venlafaxine. Doses are tapered down over weeks instead.

Safety essentials

• Everyone under 25 needs close monitoring for new or worsening suicidal thoughts, especially early in treatment or after a dose change; this warning applies class-wide.
• Bupropion is avoided in seizure disorders and eating disorders because it lowers the seizure threshold in a dose-dependent way.
• TCAs (amitriptyline, clomipramine, imipramine, doxepin, nortriptyline) are dangerous in overdose due to heart rhythm toxicity; prescribers often limit the quantity dispensed to anyone at risk of self-harm.
• Never combine an SSRI, SNRI or TCA with an MAOI antidepressant; the combination can cause a life-threatening serotonin reaction.
• Contact a doctor urgently for chest pain, seizures, severe agitation, or thoughts of self-harm.

This page is educational and does not replace advice from a doctor or pharmacist who knows your health history.