Your activity: 2 p.v.
< Back

Side effects of antidepressant medications[1-7]

Side effects of antidepressant medications[1-7]
Drug Anticholinergic Drowsiness Insomnia/agitation Orthostatic hypotension QTc prolongation* Gastrointestinal toxicity Weight gain Sexual dysfunction
Selective serotonin reuptake inhibitors
Citalopram 0 0 1+ 1+ 3+Δ 1+ 1+ 3+
Escitalopram 0 0 1+ 1+ 2+ 1+ 1+ 3+
Fluoxetine 0 0 2+ 1+ 1+ 1+ 0 3+
Fluvoxamine 0 1+ 1+ 1+ 1+ 1+ 1+ 3+
Paroxetine 1+ 1+ 1+ 2+ 0 to 1+ 1+ 2+ 4+
Sertraline 0 0 2+ 1+ 1 to 2+ 2+◊ 1+ 3+
Atypical agents
Agomelatine§ (not available in United States) 0 1+ 1+ 0 0 1+ 0 0 to 1+
Bupropion 0 0

2+ (immediate release)

1+ (sustained release) 		0 1+ 1+ 0 0
Mirtazapine 1+ 4+ 0 0 1+ 0 4+ 1+
Serotonin-norepinephrine reuptake inhibitors,¥
Desvenlafaxine‡ 0 0 1+ 0 0 2+ Unknown 1+
Duloxetine 0 0 1+ 0 0 2+ 0 to 1+ 1+
Levomilnacipran‡ 0† 0 0 to 1+ 0 to 1+ 0 2+ 0 1+
Milnacipran‡ 0 1+ 0 0 0 2+ 0 1+
Venlafaxine‡ 0 1+ 1+ 0 1 to 2+ 2+ 0 to 1+ 3+
Serotonin modulators
Nefazodone** 1+ 2+ 0 1+ 0 2+ 0 0
Trazodone 0 4+ 0

1+ (hypnotic dose)

3+ (antidepressant dose) 		1 to 2+

1+ (hypnotic dose)

3+ (antidepressant dose)

0 (hypnotic dose)

1+ (antidepressant dose) 		1+¶¶
Vilazodone 0 0 2+ 0 0 4+ΔΔ 0 2+
Vortioxetine 0 0 0 0 0 3+ 0 1+
Tricyclic and tetracyclic antidepressants
Amitriptyline 4+ 4+ 0 3+ 1 to 2+ 1+◊◊ 4+ 3 to 4+
Amoxapine 2+ 2+ 2+ 2+ 1+ 0◊◊ 2+ ND
Clomipramine 4+ 4+ 1+ 2+ 3+ 1+◊◊ 4+ 4+
Desipramine 1+ 2+ 1+ 2+ 1 to 2+ 0◊◊ 1+ ND
Doxepin 3+ 3+ 0 2+ 3+ 0◊◊ 4+ 3+
Imipramine 3+ 3+ 1+ 4+ 3+ 1+◊◊ 4+ 3+
Maprotiline 2+ 3+ 0 2+ 1+ 0◊◊ 2+ ND
Nortriptyline 2+ 2+ 0 1+ 1 to 2+ 0◊◊ 1+ ND
Protriptyline 2+ 1+ 1+ 2+ 1+ 1+◊◊ 1+ 3 to 4+
Trimipramine 4+ 4+ 1+ 3+ 1+ 0◊◊ 4+ ND
Monoamine oxidase inhibitors
Isocarboxazid 1+ 1+ 2+ 2+ 0 1+ 1+ 4+
Phenelzine 1+ 2+ 1+ 3+ 0 1+ 2+ 4+
Selegiline 1+ 0 1+ 1+ 0 0 0 0
Tranylcypromine 1+ 1+ 2+ 2+ 0 1+ 1+ 4+
Scale: 0 = none; 1+ = slight; 2+ = low; 3+ = moderate; 4+ = high; ND = inadequate data.
SSRI: selective serotonin reuptake inhibitors; SNRI: serotonin-norepinephrine reuptake inhibitor.
* Relative mean QTc prolongation at therapeutic doses; arrhythmogenic potential can be significantly increased in overdose (eg, for cyclic antidepressants, bupropion, citalopram, duloxetine, venlafaxine, and some others). QTc prolongation classifications are based upon US Food and Drug Administration guidance.[6] The use of other classification criteria may lead to some agents being classified differently by other sources. Refer to UpToDate topics on acquired long QT syndrome and acute antidepressant poisonings.
¶ All SSRIs and SNRIs can cause transient nausea and gastrointestinal discomfort when starting therapy or increasing dose.
Δ Based upon reports of dose-related QTc prolongation and arrhythmia, the maximum recommended dose of citalopram is 40 mg/day in most patients; for patients at increased risk of elevated serum concentrations (eg, age >60 years, significant hepatic impairment, receiving interacting medications), the maximum daily dose is 20 mg.
◊ Sertraline is associated with higher rates of diarrhea.
§ Agomelatine may be hepatotoxic and is contraindicated in any degree of liver impairment. Transaminase monitoring is required.
¥ SNRIs do not have significant anticholinergic effects. However, SNRIs can produce anticholinergic-like effects (which appear to be mediated by noradrenergic stimulation) such as dry mouth and constipation, and they should be used with caution in narrow angle glaucoma. Levomilnacipran is associated with urinary hesitancy.
‡ May cause persistent dose-related increases in blood pressure (primarily diastolic) and heart rate. Monitor blood pressure regularly.
† Levomilnacipran can cause dose-dependent urinary hesitancy.
** Caution: can cause liver failure; transaminase monitoring is required. Withdrawn from market due to hepatotoxicity in many countries.
¶¶ Trazodone is associated rarely with priapism, which is considered a medical emergency. Refer to UpToDate topic on serotonin modulators.
ΔΔ Gastrointestinal effects include nausea, vomiting, and diarrhea.
◊◊ Gastrointestinal forms of anticholinergic side effects include: dry mouth, constipation, epigastric distress, decreased esophagogastric tone. Refer to "Anticholinergic" data column for frequency rankings.
References:
  1. Wenzel-Seifert K, Wittmann M, Haen E: QTc prolongation by psychotropic drugs and the risk of torsade de pointes. Dtsch Arztebl Int 2011; 108:687.
  2. Reichenpfader U, Gartlehner G, Morgan LC, et al. Sexual dysfunction associated with second generation antidepressants in patients with major depressive disorder: Results from a systematic review with network meta-analysis. Drug Saf 2014; 37:19.
  3. Howland RH. A benefit-risk assessment of agomelatine in the treatment of major depression. Drug Saf 2011; 34:709.
  4. Lexicomp Online. Copyright © 1978-2023 Lexicomp, Inc. All Rights Reserved.
  5. Baldwin DS, Chrones L, Florea I, et al. The safety and tolerability of vortioxetine: Analysis of data from randomized placebo-controlled trials and open-label extension studies. J Psychopharmacol 2016; 30:242.
  6. Clinical Evaluation of QT/QTc Interval Prolongation and Proarrhythic Potential for Non-Antiarrhythmic Drugs – Questions and Answers; Guidance for Industry US Food and Drug Administration, June 2017. Available at: https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM073161.pdf.
  7. The American Psychiatric Association Publishing Textbook of Psychopharmacology, 5th ed, Schatzberg AF, Nemeroff CB (Eds), American Psychiatric Association Publishing 2017.
Graphic 62488 Version 25.0