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Serotonin Uptake Inhibitors

Serotonin Uptake Inhibitors, Antidepressive Agents


Arketis, Euplix, Paroxetin 2care4, Paroxetin Actavis, Paroxetin Alpharma, Paroxetin Amneal, Paroxetin Aurobindo, Paroxetin EQL Pharma, Paroxetin Ebb, Paroxetin HEXAL, Paroxetin Hexal, Paroxetin Mylan, Paroxetin Orifarm, Paroxetin Orion, Paroxetin Sandoz, Paroxetin Teva, Paroxetin ratiopharm, Paroxiflex, Seroxat, Seroxat®


paroxetine, paroxetine hydrochloride, paroxetine hydrochloride hemihydrate, paroxetine mesylate

Paroxetine hydrochloride and paroxetine mesylate belong to a class of antidepressant agents known as selective serotonin-reuptake inhibitors (SSRIs). Despite distinct structural differences between compounds in this class, SSRIs possess similar pharmacological activity. As with other antidepressant agents, several weeks of therapy may be required before a clinical effect is seen. SSRIs are potent inhibitors of neuronal serotonin reuptake. They have little to no effect on norepinephrine or dopamine reuptake and do not antagonize α- or β-adrenergic, dopamine D2 or histamine H1 receptors. During acute use, SSRIs block serotonin reuptake and increase serotonin stimulation of somatodendritic 5-HT1A and terminal autoreceptors. Chronic use leads to desensitization of somatodendritic 5-HT1A and terminal autoreceptors. The overall clinical effect of increased mood and decreased anxiety is thought to be due to adaptive changes in neuronal function that leads to enhanced serotonergic neurotransmission. Side effects include dry mouth, nausea, dizziness, drowsiness, sexual dysfunction and headache (see Toxicity section below for a complete listing of side effects). Side effects generally occur during the first two weeks of therapy and are usually less severe and frequent than those observed with tricyclic antidepressants. Paroxetine hydrochloride and mesylate are considered therapeutic alternatives rather than generic equivalents by the US Food and Drug Administration (FDA); both agents contain the same active moiety (i.e. paroxetine), but are formulated as different salt forms. Clinical studies establishing the efficacy of paroxetine in various conditions were performed using paroxetine hydrochloride. Since both agents contain the same active moiety, the clinical efficacy of both agents is thought to be similar. Paroxetine may be used to treat major depressive disorder (MDD), panic disorder with or without agoraphobia, obsessive-compulsive disorder (OCD), social anxiety disorder (social phobia), generalized anxiety disorder (GAD), post-traumatic stress disorder (PTSD) and premenstrual dysphoric disorder (PMDD). Paroxetine has the most evidence supporting its use for anxiety-related disorders of the SSRIs. It has the greatest anticholinergic activity of the agents in this class and compared to other SSRIs, paroxetine may cause greater weight gain, sexual dysfunction, sedation and constipation.

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The T-value in the score for hazard refers to acute toxicity. Underlying data for P, B and T are from Fass.

Below is Hazard and Risk from Fass environmental information for Seroxat (paroxetine) (downloaded 2018-10-01)

Persistence: "Ready degradability: <1% degradation in 28 days (TAD 3.11). [---] Primary metabolite (BRL36610): 50% primary degradation in 23 hrs. [---] Paroxetine is not readily degradable or inherently degradable. This substance degrades rapidly via photlysis but fate and effects data is not available for photo degradents. The phrase “paroxetine is potentially persistent in the environment” is thus chosen."

Bioaccumulation: Log Dow at pH 7 = 1.30.

Acute toxicity: There are data for 3 trophic levels, lowest for green algae (Scenedesmus subspicatus) "IC50 96h (growth)" = 140 microg/L.

PEC/PNEC is based on sales data in Sweden in year 2016. PEC/PNEC = 0.2 which gives the risk low.

Pharmaceutical analyses of water and fish
Paroxetine has been detected in purified wastewater, surface and drinking water. In the Swedish surveillance program, paroxetine was detected up to 44 ng/L in single samples of purified wastewater.

Paroxetine has been found in wild Swedish fish, perch, at a concentration of 17 microg/kg.

Comparative assessment of environmental risk in the use of citalopram, escitalopram, sertraline, fluoxetine, venlafaxine, paroxetine and clomipramine in Sweden (Report Goodpoint 2018)
Overall, there is a risk profile for the studied antidepressants.


  1. Fass.se för vårdpersonal
  2. Stockholm Vatten. Läkemedelsrester i Stockholms vattenmiljö. 2010. ISBN 978-91-633-6642-0.
  3. IVL Swedish Environmental Research Institute Ltd. Fick J, Lindberg RH, Kaj L, Brorström-Lundén E. Results from the Swedish National Screening Programme 2010. Subreport 3, B 2014 Pharmaceuticals.
  4. IVL Swedish Environmental Research Institute Ltd Fick J, Lindberg RH, Fång J, Magnér J, Kaj L, Brorström-Lundén E. Screening 2014. Analysis of pharmaceuticals and hormones in samples from WWTPs and receiving waters. Rapport C 135.
  5. Goodpoint. Jämförande bedömning av miljörisk vid användning av citalopram, escitalopram, sertralin, fluoxetin, venlafaxin, paroxetin och klomipramin. Stockholm: Goodpoint; 2018.