Selective serotonin reuptake inhibitors (SSRIs) are the most popularly prescribed antidepressants they all work by selectively increasing the levels of serotonin in the body, especially the brain.


SSRIs include citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine and sertraline.

Medical usesEdit

They are primarily used to treat depression, although they may also be used to treat anxiety disorders (including generalized anxiety disorder and obsessive-compulsive disorder).

Drug Flag of the United States
FDA-approved indications
Flag of Australia
TGA-approved indications
Flag of the United Kingdom
MHRA-approved indications
Other indications; notes
Citalopram Depression Major depression Depression and panic disorder Alcoholism, binge-eating disorder, cocaine dependence, generalized anxiety disorder, hot flashes, obsessive-compulsive disorder and premenstrual dysphoric disorder.
Escitalopram Major depressive disorder and generalized anxiety disorder Major depression, generalized anxiety disorder, obsessive-compulsive disorder and social phobia. Depression, panic disorder and social anxiety disorder. None notable.
Fluoxetine Major depressive disorder (including paediatric), obsessive-compulsive disorder, bulimia nervosa and premenstrual dysphoric disorder. Major depression, obsessive-compulsive disorder and premenstrual dysphoric disorder. Major depression, bulimia nervosa and obsessive-compulsive disorder. Post-traumatic stress disorder.
Fluvoxamine Obsessive-compulsive disorder and panic disorder Major depression and obsessive-compulsive disorder. Depression and obsessive-compulsive disorder. None notable. It is the only one that is dosed up to twice a day.
Paroxetine Depression, obsessive-compulsive disorder, panic disorder, social phobia, generalized anxiety disorder, post-traumatic stress disorder, premenstrual dysphoric disorder and menopausal vasomotor symptoms. Major depression, obsessive-compulsive disorder, panic disorder, generalized anxiety disorder, post-traumatic stress disorder and social phobia. Major depression, obsessive-compulsive disorder, panic disorder, social anxiety disorder, post-traumatic stress disorder and generalized anxiety disorder. Stuttering, bipolar depression, diabetic neuropathy and vasovagal syncope.
Sertraline Major depressive disorder, obsessive-compulsive disorder, panic disorder, post-traumatic stress disorder, social anxiety disorder and premenstrual dysphoric disorder. Major depression, obsessive-compulsive disorder, panic disorder, social phobia and premenstrual dysphoric disorder. Depression, obsessive-compulsive disorder and panic disorder. Itchiness.

Side effectsEdit

SSRIs are usually defined as agents with minimal affinity towards the mAChRs, H1 and α-adrenergic receptors; although paroxetine does antagonize the mAChRs, weakly. Consequently they produces little of the side effects associated with the previous generation of antidepressants the TCAs. They usually have minimal effects on blood pressure, heart rate and metabolic parameters (like the levels and composition of fats and sugar in one's blood).

Their principal side effects include: digestive complaints,[note 1] orthostatic hypotension,[note 2] psychiatric/neurologic side effects,[note 3] sleep changes,[note 4] weight gain or loss,[note 5] sexual dysfunction,[note 6] sweating, muscle aches and rashes. Less common, yet serious side effects include: seizures, syndrome of inappropriate secretion of antidiuretic hormone (SIADH), bleeding problems, blood disorders and liver dysfunction.[1]

Citalopram and escitalopram may prolong the QT interval of the heart's electrical cycle, hence predisposing one to heart rhythm anomalies that may be fatal. Their dosage ranges are significantly more limited than are the other SSRIs, most likely due to the potential for this side effect. Escitalopram is believed to be less likely than citalopram to cause this side effect. Many physicians regularly monitor their patients that are prescribed these agents due to the potential for QT interval prolongation. Citalopram is also the most toxic of SSRIs in overdose, likely due to its potential for causing this side effect.


Compared to other antidepressants, especially the previous generation of antidepressants the TCAs and MAOIs they are comparatively non-toxic in cases of overdose. Of them citalopram and fluvoxamine are believed to be the most toxic in cases of overdose.[2]

Mechanism of actionEdit

Binding profile (Kis) of SSRIs[note 7][3][4]
Drug SERT NET DAT mAChRs H1 α1
Citalopram 1.4 5100 28000 1800 1800 1550
Escitalopram 1.1 7840 >10000 1240 1970 3870
Fluoxetine 0.8 244 3600 2000 6250 5900
Fluvoxamine 2.2 1300 9100 24000 >100000 7700
Norfluoxetine 25 410 1100 810 >10000 3900
Paroxetine 0.1 40 500 108 22000 >100000
Sertraline 0.3 417 25 625 24000 370


Drug Bioavailability Plasma protein binding Half-life Metabolizing enzymes Enzymes inhibited[5][6]
Citalopram 80% 80% 24-48 hours CYP2C19, CYP2D6 (minor) and CYP3A4. None.
Escitalopram 80% 56% 27-32 hours CYP2C19, CYP2D6 (minor) and CYP3A4. CYP2D6 (weak).
Fluoxetine 90% >95% 1-4 days, 7-15 days (norfluoxetine metabolite) CYP2D6 (major), lesser contributions from CYP2C9 and CYP3A4. CYP2D6 (potently) and CYP3A4.
Fluvoxamine 53% 80% 15.6 hours None. CYP1A2 (strong), CYP2C19 (strong), CYP2C9 (moderate), CYP2D6 (moderate) and CYP3A4 (moderate).
Paroxetine  ? 93-95% 21 hours CYP2D6 CYP2D6 (strong).
Sertraline  ? 98% 26 hours CYP2D6 CYP2D6 (moderate).

Special populationsEdit

Only fluoxetine and escitalopram (only FDA approved for the treatment of adolescents over the age of 12, however) have been proven effective in treating children and/or adolescents; mostly because the others have not been sufficiently studied in well-designed clinical trials.[7] They may be associated with a slighter higher risk of suicide in people under the age of 25 years. This potential danger was added to the labelling of every antidepressant in the United States (as a black box warning) and while one might expect that suicide rates would be on the decline in this population as a result, a recent observational study found that since the FDA required this additional labelling, prescription rates have been on the decline (as one would expect, by up to 30%) while suicide rates in this population have been on the incline.[8]

In pregnant women the SSRIs are considered fairly safe, with regards to pregnancy outcomes, with the exception of paroxetine (which seems to increase the risk of congenital heart defects).[9] Sertraline may be the best choice in this population as it crosses the placenta to the least extent.[10] Untreated major depression, during pregnancy, is also associated with poorer pregnancy outcomes in itself, hence in some cases SSRIs may even improve pregnancy outcomes.[10]

See alsoEdit

External linksEdit


  1. Like constipation, diarrhoea, dry mouth, indigestion, nausea/vomiting, etc. Diarrhoea is more frequent with sertraline; digestive complaints, on average, are more frequent with fluvoxamine.
  2. Drops in blood pressure that occur upon standing up, leading, potentially, to dizziness and fainting. Far less problematic with the SSRIs than with the MAOIs and TCAs
  3. Agitation, tremor, weakness, dizziness, anxiety and less commonly (occurring in fewer than 1% of patients taking them) worsening depression, suicidal thoughts and mania. These side effects are believed to be more frequent with fluoxetine than the other SSRIs.
  4. This includes difficulty falling and staying asleep (more common with sertraline and fluoxetine, especially fluoxetine), daytime drowsiness (more problematic with paroxetine), etc. Usually significantly less problematic than with the MAOIs, SARIs, NaSSAs and TCAs. It is worth noting, however, that depression itself often causes sleep changes, hence any changes in sleep patterns could just be the antidepressants correcting this symptom.
  5. Weight changes are usually pretty minimal in people prescribed SSRIs, as opposed to TCAs and NaSSAs. Weight gain is more problematic with paroxetine; whereas weight loss is more frequent with fluoxetine.
  6. Occurs in about 60%-70% of patients treated with them; includes impotence, loss of desire, inability/difficulty in achieving an orgasm, etc. More problematic with paroxetine, especially in females.
  7. Kis are a numerical way of stating how potently drugs bind to their respective receptor/transporter sites; the lower the Ki the more potently the drug binds to the protein in question. All in nanomolars (nM).

Reference listEdit

  1. Rossi, S, ed. (July 2014). "Sertraline". Australian Medicines Handbook. Adelaide, Australia: Australian Medicines Handbook Pty Ltd. Retrieved 15 August 2014. 
  2. White, N; Litovitz, T; Clancy, C (December 2008). "Suicidal antidepressant overdoses: a comparative analysis by antidepressant type.". Journal of Medical Toxicology 4 (4): 238–50. PMC 3550116. PMID 19031375. doi:10.1007/BF03161207. 
  3. Roth, BL; Driscol, J (12 January 2011). "PDSP Ki Database". Psychoactive Drug Screening Program (PDSP). University of North Carolina at Chapel Hill and the United States National Institute of Mental Health. Retrieved 12 August 2014. 
  4. Brunton, L; Chabner, B; Knollman, B (2010). Goodman and Gilman's The Pharmacological Basis of Therapeutics (12th ed.). New York, USA: McGraw-Hill Professional. ISBN 978-0-07-162442-8. 
  5. Hemeryck, A; Belpaire, FM (February 2002). "Selective serotonin reuptake inhibitors and cytochrome P-450 mediated drug-drug interactions: an update.". Current Drug Metabolism 3 (1): 13–37. PMID 11876575. doi:10.2174/1389200023338017. 
  6. Brunton, L; Chabner, B; Knollman, B (2010). Goodman and Gilman's The Pharmacological Basis of Therapeutics (12th ed.). New York, USA: McGraw-Hill Professional. ISBN 978-0-07-162442-8. 
  7. Cheung, AH; Kozloff, N; Sacks, D (August 2013). "Pediatric depression: an evidence-based update on treatment interventions.". Current Psychiatry Reports 15 (8): 381. PMC 3744276. PMID 23881712. doi:10.1007/s11920-013-0381-4. 
  8. Lu, CY; Zhang, F; Lakoma, MD; Madden, JM; Rusinak, D; Penfold, RB; Simon, G; Ahmedani, BK; Clarke, G; Hunkeler, EM; Waitzfelder, B; Owen-Smith, A; Raebel, MA; Rossom, R; Coleman, KJ; Copeland, LA; Soumerai, SB (18 June 2014). "Changes in antidepressant use by young people and suicidal behavior after FDA warnings and media coverage: quasi-experimental study". BMJ 348 (jun18 24): g3596–g3596. doi:10.1136/bmj.g3596. 
  9. "Is it safe to use SSRIs during pregnancy?". Health News and Evidence. Strawberry Hills, Australia: NPS MedicineWise. 8 March 2013. Retrieved 15 August 2014. 
  10. 10.0 10.1 Taylor, D; Paton, C; Shitij, K (2012). Maudsley Prescribing Guidelines in Psychiatry (11th ed.). West Sussex: Wiley-Blackwell. ISBN 978-0-47-097948-8. 

Ad blocker interference detected!

Wikia is a free-to-use site that makes money from advertising. We have a modified experience for viewers using ad blockers

Wikia is not accessible if you’ve made further modifications. Remove the custom ad blocker rule(s) and the page will load as expected.