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Antidepressive Agents, Second-Generation

Antidepressive Agents, Second-Generation, Serotonin Uptake Inhibitors, Antidepressive Agents


Cipramil, Cipramil®, Citalopram 2care4, Citalopram ACO, Citalopram Actavis, Citalopram Alternova, Citalopram Arrow, Citalopram BMM Pharma, Citalopram Bluefish, Citalopram GEA, Citalopram Hydrobromide, Citalopram IVAX, Citalopram Jubilant, Citalopram Lundbeck, Citalopram Mylan, Citalopram Orifarm, Citalopram Orion, Citalopram STADA®, Citalopram Sandoz, Citalopram Teva, Citalopram Vitabalans, Citalopram ratiopharm, Citalopram® CNSpharma, Citavie, Talam, Talohexal, Temperax, Vodelax, Zentius, Zetalo


citalopram, citalopram hydrobromide, citalopram hydrochloride

Citalopram hydrobromide belongs to a class of antidepressant agents known as selective serotonin-reuptake inhibitors (SSRIs). Citalopram and its N-demethylated metabolites exist as a racemic mixture but its effects are largely due to the S-enantiomer, S-citalopram and S-demthylcitalopram. 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. Side effects generally occur within the first two weeks of therapy and are usually less severe and frequent than those observed with tricyclic antidepressants. Citalopram is approved for treatment of depression. Unlabeled indications include mild dementia-associated agitation in nonpsychotic patients, smoking cessation, ethanol abuse, obsessive-compulsive disorder (OCD) in children, and diabetic neuropathy. Citalopram has the fewest drug-drug interactions of the SSRIs.

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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.se, see below.

Citalopram is a racemate of which one of the enantiomers, escitalopram (S-form), has the pharmacological effect. Therefore, see also the information about escitalopram.

Concentrations in the environment in Sweden for several SSRI/SNRIs exceed concentrations with reported effect on the aquatic environment, especially for invertebrates. However, studies with the very lowest effect concentrations are questioned. Levels of citalopram in fish exposed to treated wastewater are equivalent with therapeutic levels in humans.

Citalopram is included in the Stockholm County Council's table of pharmaceuticals with a negative environmental impact according to the environmental programme 2017-2021 based on lowest effect concentration, LOEC = 150 ng/L, and concentrations found in the environment. Citalopram has been detected in treated wastewater and surface water in Stockholm County in the last five years (2012-2016). The method for analysis does not distinguish between the different enantiomers.

In the Wise List escitalopram is recommended. Environmental classification of pharmaceuticals is taken into consideration, sometimes with other environmental aspects, when selecting pharmaceuticals for the Wise List. When comparable pharmaceuticals are equivalent to medical effects, safety and pharmaceutical efficacy, environmental impact and price are considered.

Below is Hazard and Risk from Fass environmental information for Cipramil (citalopram) (downloaded 2018-07-10)

Persistence: "The potential for persistence of Citalopram cannot be excluded, due to lack of data."

Bioaccumulation: Log Kow = 1.39

Acute toxicity: There are data for 2 trophic levels, lowest for alae (Pseudokirchneriella subcapita) 1.6 mg/L.

Sales data are available for Sweden in the year 2013. PEC/PNEC: "As the base set is not complete, it is not possible to determine the most sensitive specie, and a PNEC cannot be derived." Risk of environmental impact of citalopram cannot be excluded, since there is not sufficient ecotoxicity data available.

Suggestions on how to reduce the release of citalopram and escitalopram
Concrete proposals on how to work to reduce emissions of environmentally harmful pharmaceuticals on the list have been developed in close cooperation with the Stockholm Drug and Therapeutics Committee's expert advice. The action proposals were developed from an environmental perspective. The patient's best always goes first and several pharmaceuticals on the list are also included in the Wise List. However, for such pharmaceuticals, there may be measures that could reduce the environmental impact.

Concrete proposal for citalopram and escitalopram:
•  In the first place, non pharmacological treatment and / or measures (eg, CBT and physical activity) alone or in combination with pharmaceuticals for the treatment of depression. Avoid overconsumption of alcohol.
• Citalopram is not recommended in the Wise List. Instead, escitalopram is recommended.
• Avoid randomized prescribing of SSRIs (eg escitalopram / citalopram). Evaluate and reconsider the treatment with SSRIs. Can the pharmaceutical be de-prescribed?
• Starter pack for escitalopram is available within the reimbursement system.

The risk assessment can not be excluded, according to Fass.se, is due to persistence and toxicity studies being incomplete, why a risk calculation has not been possible. It is voluntary for manufacturers to provide information on the environmental impact.

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. Goodpoint. Prioritering av läkemedel med miljörisk inom SLL. Stockholm: Goodpoint; 2016. Rapport LS 2016–0634.
  2. Kellner M, Porseryd T, Porsch-Hällström I, Hansen SH, Olsén KH. Environmentally relevant concentrations of citalopram partially inhibit feeding in the three-spine stickleback (Gasterosteus aculeatus). Aquat Toxicol. 2015;158:165-70.
  3. Grabicova K, Lindberg RH, Ostman M, Grabic R, Randak T, Larsson DG et al. Tissue-specific bioconcentration of antidepressants in fish exposed to effluent from a municipal sewage treatment plant. Sci Total Environ. 2014;488-489:46-50.
  4. 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. Pharmaceuticals.
  5. Fick J, Lindberg RH, Tysklind M, Larsson DG. Predicted critical environmental concentrations for 500 pharmaceuticals. Regul Toxicol Pharmacol. 2010;58:516-23.
  6. SLL. Sammanställning av läkemedelsprovtagningar - Bearbetning av regional försäljningsstatistik av läkemedel samt datamaterial från Stockholms läns landstings mätprogram för läkemedelssubstanser i vattenmiljö, 2012–2016.
  7. Stockholms läns landsting. Förteckning över miljöbelastande läkemedel med åtgärdsförslag framtagen inom ramen för SLL:s miljöprogram 2017–2021.
  8. Goodpoint. Jämförande bedömning av miljörisk vid användning av citalopram, escitalopram, sertralin, fluoxetin, venlafaxin, paroxetin och klomipramin. Stockholm: Goodpoint; 2018.
  9. Fass.se för vårdpersonal
  10. Stockholms läns landsting. Kloka Listan 2018.
  11. Stockholm County Council. The Wise List 2015.