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Antidepressant Medications Comparison

Comparative Benefits and Harms Chart

Medication Advantages Disadvantages Points to consider
SSRIs (Selective Serotonin Reuptake Inhibitors)
Citalopram (Celexa) Low potential for drug interactions.

Helpful for anxiety disorders.
Dose-dependent QT interval prolongation.

Not recommended for persons with congenital long QT syndrome, bradycardia, hypokalemia, or hypomagnesemia.
Not an ideal choice for patients with renal impairment because of the potential for accumulation.

Avoid in persons prone to overdose.
Escitalopram (Lexapro) Low potential for drug interactions

Easy to titrate.
Significantly more expensive than generic SSRIs.

Not perfect choice for persons with renal impairment.
Should not be used to treat depression failed to respond to other SSRIs, but may be considered for people with severe depression who responded to other SSRIs but have been unable to tolerate side effects.
Fluoxetine (Prozac) Less likely than other SSRIs to cause discontinuation syndrome. Basically, fluoxetine self-tapers.

Good choice for patients with comorbid eating disorders
CYP 450 drug interactions.

Delayed onset of antidepressant action.
May cause more agitation and sleep disturbances than the other SSRIs.

Should normally be taken in the morning.
Paroxetine (Paxil) Effective for anxiety disorders. Worst side effects profile: weight gain, sexual dysfunction, sedation, and anticholinergic side effects!

CYP 450 drug interactions.

Significantly more problems on discontinuation than with other SSRIs.
Pregnancy caregory D:
studies have linked paroxetine to an increased risk of cardiovascular malformations in babies who were exposed to it during the first trimester.
Sertraline (Zoloft) Favourable balance of safety, efficacy, and cost.

Highest incidence of diarrhea.

Multiple titrations.
Sertraline is the preferred SSRI in patients with ischemic heart disease.

Relatively few drug interactions.
Serotonin and Noradrenaline Reuptake Inhibitors (SNRIs)
Duloxetine (Cymbalta) Improves painful symptoms of depression

Lower risk of sexual problems that with SSRIs.
High acquisition cost - Cymbalta is still in patent.

Higher discontinuation rates due to adverse effects compared with most SSRIs.

May elevate liver enyzmes, worsen narrow angle glaucoma, and cause urinary hesitancy.

May increase blood pressure.
Can help with fibromyalgia.

May aggravate liver disease.
Venlafaxine (Effexor) Slightly higher response rate.

Usually no effect on weight.
Marked discontinuation syndrome.

Highest rate of nausea and vomiting.

Increases blood pressure.

More toxic than the SSRIs in overdose.
Useful for treatment-resistant depression.

Poor tolerability: patients on venlafaxine are more likely to discontinue treatment early due to side effects, than those on other antidepressants.
Norepinephrine and dopamine reuptake inhibitors (NDRIs)
Bupropion (Wellbutrin) Favorable side effect profile!

Free of sexual side effects.

Does not cause weight gain.

Useful in smoking cessation and ADHD.

"Energizing" or stimulating effect.
Can worsen anxiety.

Increases seizure risk.

Less robust antidepressant effect.
Unique antidepressant - most closely resembles the action of psychostimulants.

Avoid in persons with history of epilepsy, seizures, head trauma, alcohol dependence.

Useful augmentation therapy for SSRI’s.
Norepinephrine and Dopamine Reuptake Inhibitors (NDRIs)
Remeron (mirtazapine) Faster onset of antidepressant action.

Lack of anticholinergic activity.

No sexual dysfunction, no nausea or gastrointestinal problems.
Weight gain and sedation!

Higher weight gain than with any of the SSRIs or SNRIs.
Starts to work more quickly than other medications for depression.


Appetite stimulation.
Other Antidepressants
Trazodone (Desyrel) Particularly useful for insomnia.

May help with anxiety, agitation, hostility.

No anticholinergic effects.
Frequently causes somnolence.

Risk of priaprism.

Postural hypotension.
Marked sedative and hypnotic effects may be of particular benefit in people with insomnia, although disadvantageous to others.

The Best Antidepressant

First of all, antidepressant that is universally effective for everyone does not exist: many depressed patients do not experience a satisfactory clinical benefit from the initial treatment. It is impossible to recommend antidepressant effective for all patients.

Sertraline (Zoloft) and escitalopram (Lexapro) are considered to have the best combination of efficacy and acceptability [1]. Sertraline may be the best choice when starting treatment for moderate to severe major depression in adults because it has the most favourable balance between benefits, adverse effects, and acquisition cost.

Side Effects

Sexual Issues

  • Decreased libido, difficulty getting an erection: Paroxetine, Venlafaxine, Sertraline
  • Improved libido: Bupropion
  • Priapism: Trazodone

Weight Change

  • Weigt gain: Mirtazapine, Paroxetine
  • Weigt loss: Bupropion, Fluoxetine


  • Most activating: Bupropion, Fluoxetine
  • Most sedating: Trazodone, Mirtazapine, Paroxetine

Discontinuation syndrom

  • Highest rates of withdrawal symptoms: Paroxetine, Venlafaxine
  • Lowest rate of withdrawal symptoms: Fluoxetine

Further reading:

Best Antidepressants for various conditions.


  • 1. Cipriani A, Funkawa TA, Salanti G, et al. Lancet. 2009;373:746–758.
  • 2. Using second-generation antidepressants to treat depressive disorders: a clinical practice guideline from the American College of Physicians.
  • 3. Clinical guidelines for antidepressant use in primary and secondary care. February 2010

Last Updated: March 27, 2013

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