Sertraline

Template:Short description Template:Redirect Template:Pp-move Template:Use dmy dates Template:Cs1 config Template:Main other {{#invoke:Infobox|infobox}}Template:Template other{{#invoke:TemplatePar |check |template=Template:Infobox_drug |all= |opt= pronounce= pronounce_ref= pronounce_comment= ATC_prefix= ATC_suffix= ATC_supplemental= ATCvet= biosimilars= CAS_number_Ref= CAS_number= CAS_supplemental= ChEBI= ChEBI_Ref= ChEMBL_Ref= ChEMBL= ChemSpiderID= ChemSpiderID_Ref= chirality= class= container_only= DailyMedID= data_page= DrugBank_Ref= DrugBank= Drugs.com= duration_of_action= INN= INN_EMA= IUPAC_name= IUPHAR_ligand= KEGG_Ref= KEGG= MedlinePlus= NIAID_ChemDB= PDB_ligand= PubChemSubstance= PubChem= StdInChIKey_Ref= StdInChIKey= StdInChI_Ref= StdInChI_comment= StdInChI= UNII_Ref= UNII= DTXSID= Verifiedfields= Watchedfields= addiction_liability= alt2= altL= altR= alt= bioavailability= boiling_high= boiling_notes= boiling_point= captionLR= caption= caption2= charge= chemical_formula= chemical_formula_ref= chemical_formula_comment= class1= class2= class3= class4= class5= class6= component1= component2= component3= component4= component5= component6= density= density_notes= dependency_liability= drug_name= elimination_half-life= engvar= excretion= image2= imageL= imageR= image= image_class= image_class2= image_classL= image_classR= Jmol= legal_AU= legal_BR= legal_CA= legal_DE= legal_EU= legal_NZ= legal_UK= legal_UN= legal_US= legal_AU_comment= legal_BR_comment= legal_CA_comment= legal_DE_comment= legal_UK_comment= legal_NZ_comment= legal_US_comment= legal_UN_comment= legal_EU_comment= legal_status= licence_CA= licence_EU= licence_US= license_CA= license_EU= license_US= mab_type= melting_high= melting_notes= melting_point= metabolism= metabolites= molecular_weight= molecular_weight_round= molecular_weight_unit= molecular_weight_ref= molecular_weight_comment= onset= pregnancy_AU= pregnancy_AU_comment= pregnancy_category= protein_bound= routes_of_administration= SMILES= smiles= solubility= sol_units= source= specific_rotation= synonyms= target= tradename= type= vaccine_type= verifiedrevid= width2= widthL= widthR= width= AAN= BAN= JAN= USAN= source_tissues= target_tissues= receptors= agonists= antagonists= precursor= biosynthesis= gt_target_gene= gt_vector= gt_nucleic_acid_type= gt_editing_method= gt_delivery_method= sec_combustion= Ac=Ag=Al=Am=Ar=As=At=Au=B=Ba=Be=Bh=Bi=Bk=Br=C=Ca=Cd=Ce=Cf=Cl=Cm=Cn=Co=Cr=Cs=Cu= D=Db=Ds=Dy=Er=Es=Eu=F=Fe=Fl=Fm=Fr=Ga=Gd=Ge=H=He=Hf=Hg=Ho=Hs=I=In=Ir=K=Kr=La=Li=Lr=Lu=Lv= Mc=Md=Mg=Mn=Mo=Mt=N=Na=Nb=Nd=Ne=Nh=Ni=No=Np=O=Og=Os=P=Pa=Pb=Pd=Pm=Po=Pr=Pt=Pu=Ra=Rb=Re=Rf=Rg=Rh=Rn=Ru=S=Sb=Sc=Se=Sg=Si=Sm=Sn=Sr=Ta=Tb=Tc=Te=Th=Ti=Tl=Tm=Ts=U=V=W=Xe=Y=Yb=Zn=Zr= index_label= index2_label= index_comment= index2_comment= CAS_number2= CAS_supplemental2= ATC_prefix2= ATC_suffix2= ATC_supplemental2= PubChem2= PubChemSubstance2= IUPHAR_ligand2= DrugBank2= ChemSpiderID2= UNII2= KEGG2= ChEBI2= ChEMBL2= PDB_ligand2= NIAID_ChemDB2= SMILES2= smiles2= StdInChI2= StdInChIKey2= CAS_number2_Ref= ChEBI2_Ref= ChEMBL2_Ref= ChemSpiderID2_Ref= DrugBank2_Ref= KEGG2_Ref= StdInChI2_Ref= StdInChIKey2_Ref= UNII2_Ref= DTXSID2= QID= QID2=PLLR= pregnancy_US= pregnancy_US_comment= |cat=Pages using infobox drug with unknown parameters |format=0|errNS=0

|preview=

}}{{Infobox drug/maintenance categoriesTemplate:Yesno | drug_name = | INN = | _drugtype =

| _has_physiological_data= | _has_gene_therapy=

| vaccine_type= | mab_type= | _number_of_combo_chemicals={{#invoke:ParameterCount |main |component1 |component2 |component3 |component4|component5|component6 }} | _vaccine_data= | _mab_data= | _mab_vaccine_data= | _mab_other_data=17171ClC1=CC=C([C@H]2C3=C([C@H](CC2)NC)C=CC=C3)C=C1Cl1S/C17H17NCl2/c1-20-17-9-7-12(13-4-2-3-5-14(13)17)11-6-8-15(18)16(19)10-11/h2-6,8,10,12,17,20H,7,9H2,1H3/t12-,17-/m0/s1VGKDLMBJGBXTGI-SJCJKPOMSA-NTemplate:StdinchiciteTemplate:Stdinchicite | _combo_data= | _physiological_data= | _clinical_data=Template:Drugs.coma697048None<ref name=Hub2001>Template:Cite book</ref>Sertraline <ref name="Drugs.com pregnancy">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>CBy mouthZoloft, Lustral, Setrona, others<ref name=Brand2015/>Selective serotonin reuptake inhibitor (SSRI)N06 | _legal_data=S4<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>C1Rx-onlyPrescription onlyPOMRx-onlyRx-only

| _other_data=(1S,4S)-4-(3,4-Dichlorophenyl)-N-methyl-1,2,3,4-tetrahydronaphthalen-1-amine

| _image_0_or_2 = Sertraline.svgSertraline-A-3D-balls.png | _image_LR =

| _datapage = Sertraline (data page) | _vaccine_target={{#ifeq: | vaccine | | _type_not_vaccine }} | _legal_all=S4C1Rx-onlyPOMRx-onlyRx-only | _ATC_prefix_supplemental=N06 | _has_EMA_link = | CAS_number=79617-96-2 | PubChem=68617 | ChemSpiderID=61881 | ChEBI=9123 | ChEMBL=809 | DrugBank=DB01104 | KEGG=D02360 | _hasInChI_or_Key={{#if:1S/C17H17NCl2/c1-20-17-9-7-12(13-4-2-3-5-14(13)17)11-6-8-15(18)16(19)10-11/h2-6,8,10,12,17,20H,7,9H2,1H3/t12-,17-/m0/s1VGKDLMBJGBXTGI-SJCJKPOMSA-N |yes}} | UNII=QUC7NX6WMB | _hasJmol02 = |_hasMultipleCASnumbers = |_hasMultiplePubChemCIDs = |_hasMultipleChEBIs =

| _countSecondIDs={{#invoke:ParameterCount |main |CAS_number2 |ATC_prefix2 |PubChem2 |PubChemStructure2 |IUPHAR_ligand2 |DrugBank2 |ChemSpiderID2 |UNII2 |KEGG2 |ChEBI2 |ChEMBL2 |PDB_ligand2 |NIAID_ChemDB2 |SMILES2 |smiles2 |StdInChI2 |StdInChIKey2 |DTXCID2}} | _countIndexlabels={{#invoke:ParameterCount |main |index_label |index2_label}} | _trackListSortletter= |QID = |QID2 = |Verifiedfields= |Watchedfields=changed |verifiedrevid=464389436}} Sertraline, sold under the brand name Zoloft among others, is an antidepressant medication of the selective serotonin reuptake inhibitor (SSRI) class<ref name=AHFS2018/> used to treat major depressive disorder, generalized anxiety disorder, social anxiety disorder, obsessive–compulsive disorder (OCD), panic disorder, and premenstrual dysphoric disorder.<ref>Template:Cite journal</ref> Although also having approval for post-traumatic stress disorder (PTSD), findings indicate it leads to only modest improvements in symptoms associated with this condition.<ref name="pmid25644881"/><ref name="pmid27126398"/>

The drug shares the common side effects and contraindications of other SSRIs, with high rates of nausea, diarrhea, headache, insomnia, mild sedation, dry mouth, and sexual dysfunction, but it appears not to lead to much weight gain, and its effects on cognitive performance are mild. Similar to other antidepressants, the use of sertraline for depression may be associated with a mildly elevated rate of suicidal thoughts in people under the age of 25 years old. It should not be used together with monoamine oxidase inhibitors (MAOIs): this combination may cause serotonin syndrome, which can be life-threatening in some cases. Sertraline taken during pregnancy is associated with an increase in congenital heart defects in newborns.<ref name="pmid30415641"/><ref name="pmid33354752"/>

Sertraline was developed by scientists at Pfizer and approved for medical use in the United States in 1991. It is on the World Health Organization's List of Essential Medicines<ref name="WHO23rd">Template:Cite book</ref> and available as a generic medication.<ref name=AHFS2018>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> In 2016, sertraline was the most commonly prescribed psychotropic medication in the United States.<ref name=PsychCentral2>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> It was also the eleventh most commonly prescribed medication in the United States, with more than 39Template:Nbspmillion prescriptions in 2022,<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> and sertraline ranks among the top 10 most prescribed medications in Australia between 2017 and 2023.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

For alleviating the symptoms of depression, the drug is usually second in potency to another SSRI, escitalopram. Sertraline's effectiveness is similar to that of other antidepressants in its class, such as fluoxetine and paroxetine, which are also considered first-line treatments and are better tolerated than the older tricyclic antidepressants.

Medical uses

Sertraline has been approved for major depressive disorder, obsessive–compulsive disorder (OCD), post-traumatic stress disorder (PTSD), premenstrual dysphoric disorder, panic disorder, social anxiety disorder (SAD), and generalized anxiety disorder (GAD). Sertraline is approved for use in children with OCD.<ref name="DailyMed">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Depression

In meta-analyses, sertraline displays similar efficacy to other SSRI antidepressants, with an odds ratio for response in clinical depression of between 1.44 and 1.67.<ref name="Jakobsen2017">Template:Cite journal</ref><ref name="CiprianiFurukawa2018">Template:Cite journal</ref> However, as with other antidepressants, the nature and clinical significance of this effect remain disputed.<ref name="Moncrieff2018">Template:Cite journal</ref><ref name="BMJ2019">Template:Cite journal</ref> A major study of sertraline in a broad primary care population found improvements in general mental health, quality of life, and anxiety.<ref name="Lewis2019">Template:Cite journal</ref> However, it failed to find significant effects on depression in either the mildly or severely depressed, and the clinical relevance and accuracy of the positive effects found have been questioned.<ref name="Hengartner2020">Template:Cite journal</ref><ref name="Paludan202020">Template:Cite journal</ref>

In several double-blind studies, sertraline was consistently more effective than placebo for dysthymia, a more chronic variety of depression, and comparable to imipramine in that respect. Sertraline also improves the functional impairments of dysthymia to a similar degree whether group Cognitive-Behavioral Therapy is undergone or not.<ref name="pmid21456103">Template:Cite journal</ref>

Limited pediatric data also demonstrates a reduction in depressive symptoms in the pediatric population though remains a second-line therapy after fluoxetine.<ref>Template:Cite journal</ref><ref>Template:Cite book</ref>

Comparison with other antidepressants

In general, sertraline efficacy is similar to that of other antidepressants.<ref name="pmid11420570">Template:Cite journal</ref> For example, a meta-analysis of 12 new-generation antidepressants showed that sertraline and escitalopram are the best in terms of efficacy and acceptability in the acute-phase treatment of adults with depression.<ref name=cipriani>Template:Cite journal; Template:Lay source</ref> Comparative clinical trials demonstrated that sertraline is similar in efficacy against depression to moclobemide,<ref name="pmid17168253">Template:Cite journal</ref> nefazodone,<ref name="pmid8626364">Template:Cite journal</ref> escitalopram, bupropion,<ref name="pmid9448656">Template:Cite journal</ref> citalopram, fluvoxamine, paroxetine,<ref name=cipriani /> venlafaxine,<ref name="pmid16870212"/> and mirtazapine.<ref name="pmid16172440">For the review, see:Template:Cite journal</ref> Sertraline may be more efficacious for the treatment of depression in the acute phase (first four weeks) than fluoxetine.<ref>Template:Cite journal</ref>

There are differences between sertraline and some other antidepressants in their efficacy in the treatment of different subtypes of depression and in their adverse effects. For severe depression, sertraline is as good as clomipramine but is better tolerated.<ref name="pmid16870212">Template:Cite journal</ref> Sertraline appears to work better in melancholic depression than fluoxetine, paroxetine, and mianserin and is similar to the tricyclic antidepressants such as amitriptyline and clomipramine.<ref name="pmid11420570"/> In the treatment of depression accompanied by OCD, sertraline performs significantly better than desipramine on the measures of both OCD and depression.<ref name="pmid21456103"/><ref name="pmid25969470">Template:Cite journal</ref> Sertraline is equivalent to imipramine for the treatment of depression with co-morbid panic disorder, but it is better tolerated.<ref name="pmid12516310">Template:Cite journal</ref> Compared with amitriptyline, sertraline offered a greater overall improvement in quality of life of depressed patients.<ref name="pmid11420570" />

Depression in elderly

Sertraline used for the treatment of depression in elderly (older than 60) patients is superior to placebo and comparable to another SSRI fluoxetine, and tricyclic antidepressants (TCAs) amitriptyline, nortriptyline and imipramine. Sertraline has much lower rates of adverse effects than these TCAs, with the exception of nausea, which occurs more frequently with sertraline. In addition, sertraline appears to be more effective than fluoxetine or nortriptyline in the older-than-70 subgroup.<ref name="pmid12093324">Template:Cite journal</ref> Accordingly, a meta-analysis of antidepressants in older adults found that sertraline, paroxetine and duloxetine were better than placebo.<ref>Template:Cite journal</ref> However, in a 2003 trial the effect size was modest, and there was no improvement in quality of life as compared to placebo.<ref name="pmid12832242">Template:Cite journal</ref> With depression in dementia, there is no benefit of sertraline treatment compared to either placebo or mirtazapine.<ref name="Banerjee2013">Template:Cite journal</ref>

Obsessive–compulsive disorder

Sertraline is effective for the treatment of OCD in adults,<ref name="DailyMed" /> adolescents and children.<ref name="NIHR_Evidence_2022">Template:Cite journal</ref><ref name="Boaden_2020">Template:Cite journal</ref><ref name="Correll_2021">Template:Cite journal</ref> It was better tolerated and, based on intention-to-treat analysis, performed better than the gold standard of OCD treatment clomipramine.<ref name="pmid9393392">Template:Cite journal</ref> Continuing sertraline treatment helps prevent relapses of OCD with long-term data supporting its use for up to 24 months.<ref name="pmid25081580">Template:Cite journal</ref> The sertraline dosages necessary for the effective treatment of OCD are higher than the usual dosage for depression.<ref name="medscape">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> The onset of action is also slower for OCD than for depression. The treatment recommendation is to start treatment with half of the maximal recommended dose for at least two months. After that, the dose can be raised to the maximal recommended in the cases of unsatisfactory response.<ref name="pmid16838823">Template:Cite journal</ref>

Cognitive behavioral therapy alone is not more effective than sertraline in adolescents and children; however, a combination of these treatments is effective.<ref name="Correll_2021" />

Panic disorder

Sertraline is superior to placebo for the treatment of panic disorder.<ref name="DailyMed"/> The response rate was independent of the dose. In addition to decreasing the frequency of panic attacks by about 80% (vs. 45% for placebo) and decreasing general anxiety, sertraline resulted in an improvement in quality of life on most parameters. The patients rated as "improved" on sertraline reported better quality of life than the ones who "improved" on placebo. The authors of the study argued that the improvement achieved with sertraline is different and of a better quality than the improvement achieved with a placebo.<ref name="pmid10945134">Template:Cite journal</ref><ref name="pmid16292466">Template:Cite journal</ref> Sertraline is equally effective for men and women,<ref name="pmid16292466" /> and for patients with or without agoraphobia.<ref name="pmid11206597">Template:Cite journal</ref> Previous unsuccessful treatment with benzodiazepines does not diminish its efficacy.<ref name="pmid11199932">Template:Cite journal</ref> However, the response rate was lower for the patients with more severe panic.<ref name="pmid11206597"/> Starting treatment simultaneously with sertraline and clonazepam, with subsequent gradual discontinuation of clonazepam, may accelerate the response.<ref name=Amrein>Template:Cite book</ref>

Double-blind comparative studies found sertraline to have the same effect on panic disorder as paroxetine or imipramine.<ref name="pmid21342080">Template:Cite journal</ref> While imprecise, comparison of the results of trials of sertraline with separate trials of other anti-panic agents (clomipramine, imipramine, clonazepam, alprazolam, and fluvoxamine) indicates approximate equivalence of these medications.<ref name="pmid10945134" />

Other anxiety disorders

Sertraline has been successfully used for the treatment of social anxiety disorder.<ref>Template:Cite journal</ref><ref name="pmid17092192">Template:Cite journal</ref> All three major domains of the disorder (fear, avoidance, and physiological symptoms) respond to sertraline.<ref name="pmid21456103" /> Maintenance treatment, after the response is achieved, prevents the return of the symptoms.<ref name="pmid18374843">Template:Cite journal</ref> The improvement is greater among the patients with later, adult onset of the disorder.<ref name="pmid17963189">Template:Cite journal</ref> In a comparison trial, sertraline was superior to exposure therapy, but patients treated with the psychological intervention continued to improve during a year-long follow-up, while those treated with sertraline deteriorated after treatment termination.<ref name="pmid16318597">Template:Cite journal</ref> The combination of sertraline and cognitive behavioral therapy appears to be more effective in children and young people than either treatment alone.<ref name="pmid23834458">Template:Cite journal</ref>

Sertraline has not been approved for the treatment of generalized anxiety disorder; however, several guidelines recommend it as a first-line medication referring to good quality controlled clinical trials.<ref name="nice-gad">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref name="pmid12516310"/><ref name="pmid25081580"/>

Premenstrual dysphoric disorder

Sertraline is effective in alleviating the symptoms of premenstrual dysphoric disorder, a severe form of premenstrual syndrome.<ref name="Jespersen_2024">Template:Cite journal</ref> Significant improvement was observed in 50–60% of cases treated with sertraline vs. 20–30% of cases on placebo. The improvement began during the first week of treatment, and in addition to mood, irritability, and anxiety, improvement was reflected in better family functioning, social activity, and general quality of life. Work functioning and physical symptoms, such as swelling, bloating, and breast tenderness, were less responsive to sertraline.<ref name="pmid12215058">Template:Cite journal</ref><ref name="pmid11972726">Template:Cite journal</ref> Taking sertraline only during the luteal phase, that is, the 12–14 days before menses is not as effective as continuous treatment.<ref name="Jespersen_2024" /> Continuous treatment with sub-therapeutic doses of sertraline (25 mg vs. usual 50–100 mg) is also effective.<ref name="pmid26377947">Template:Cite journal</ref>

Other indications

Sertraline is approved for the treatment of post-traumatic stress disorder (PTSD).<ref name="DailyMed"/> The National Institute for Clinical Excellence recommends it for patients who prefer drug treatment to a psychological one.<ref name="NICE-PTSD">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> Other guidelines also suggest sertraline as a first-line option for pharmacological therapy.<ref name="pmid16734498"/><ref name="pmid12516310"/> When necessary, long-term pharmacotherapy can be beneficial.<ref name="pmid16734498">Template:Cite journal</ref> There are both negative and positive clinical trial results for sertraline, which may be explained by the types of psychological traumas, symptoms, and comorbidities included in the various studies.<ref name="pmid25081580"/> Positive results were obtained in trials that included predominantly women (75%) with a majority (60%) having physical or sexual assault as the traumatic event.<ref name="pmid16734498"/> Somewhat contrary to the above suggestions, a meta-analysis of sertraline clinical trials for PTSD found it to be statistically superior to placebo in the reduction of PTSD symptoms but the effect size was small.<ref name="pmid25644881">Template:Cite journal</ref> Another meta-analysis relegated sertraline to the second line, proposing trauma focused psychotherapy as a first-line intervention. The authors noted that Pfizer had declined to submit the results of a negative trial for inclusion in the meta-analysis making the results unreliable.<ref name="pmid27126398">Template:Cite journal</ref>

Sertraline, when taken daily, can be useful for the treatment of premature ejaculation.<ref>Template:Cite journal</ref> A disadvantage of sertraline is that it requires continuous daily treatment to delay ejaculation significantly.<ref name="pmid17983899">Template:Cite journal</ref>

A 2019 systematic review suggested that sertraline may be a good way to control anger, irritability, and hostility in depressed patients and patients with other comorbidities.<ref name="pmid31126061">Template:Cite journal</ref>

Contraindications

Sertraline is contraindicated in individuals taking monoamine oxidase inhibitors or the antipsychotic pimozide. Sertraline concentrate contains ethanol and is therefore contraindicated with disulfiram. The prescribing information recommends that treatment of the elderly and patients with liver impairment "must be approached with caution". Due to the slower elimination of sertraline in these groups, their exposure to sertraline may be as high as three times the average exposure for the same dose.<ref name="DailyMed"/>

Side effects

Nausea, ejaculation failure, insomnia, diarrhea, dry mouth, somnolence, dizziness, tremor, headache, excessive sweating, fatigue, restless legs syndrome and decreased libido are the common adverse effects associated with sertraline with the greatest difference from placebo. Those that most often result in interruption of the treatment are nausea, diarrhea, and insomnia.<ref name="DailyMed"/> The incidence of diarrhea is higher with sertraline – especially when prescribed at higher doses – in comparison with other SSRIs.<ref name=ICP2014>Template:Cite journal</ref>

Over more than six months of sertraline therapy for depression, people showed no significant weight increase.<ref name="pmid11105740">Template:Cite journal</ref> A 30-month-long treatment with sertraline for OCD also resulted in no significant weight gain.<ref name="pmid15491240">Template:Cite journal</ref> Although the difference did not reach statistical significance, the average weight gain was lower for fluoxetine (1%) but higher for citalopram, fluvoxamine and paroxetine (2.5%). Of the sertraline group, 4.5% gained a large amount of weight (defined as more than 7% gain). This result compares favorably with placebo, where, according to the literature, 3–6% of patients gained more than 7% of their initial weight. The large weight gain was observed only among female members of the sertraline group; the significance of this finding is unclear because of the small size of the group.<ref name="pmid15491240" />

Over a two-week treatment of healthy volunteers, sertraline slightly improved verbal fluency but did not affect word learning, short-term memory, vigilance, flicker fusion time, choice reaction time, memory span, or psychomotor coordination.<ref name="pmid11565624">Template:Cite journal</ref><ref name="pmid12692706">Template:Cite journal</ref> In spite of lower subjective rating, that is, feeling that they performed worse, no clinically relevant differences were observed in the objective cognitive performance in a group of people treated for depression with sertraline for 1.5 years as compared to healthy controls.<ref name="pmid16485140">Template:Cite journal</ref> In children and adolescents taking sertraline for six weeks for anxiety disorders, 18 out of 20 measures of memory, attention, and alertness stayed unchanged. Divided attention was improved and verbal memory under interference conditions decreased marginally. Because of the large number of measures taken, it is possible that these changes were still due to chance.<ref name="pmid16190792">Template:Cite journal</ref> The unique effect of sertraline on dopaminergic neurotransmission may be related to these effects on cognition and vigilance.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>

Sertraline has a low level of exposure of an infant through the breast milk and is recommended as the preferred option for the antidepressant therapy of breast-feeding mothers.<ref>Template:Cite journal</ref><ref name="pmid28440103">Template:Cite journal</ref> There is 29–42% increase in congenital heart defects among children whose mothers were prescribed sertraline during pregnancy,<ref name="pmid30415641"/><ref name="pmid33354752">Template:Cite journal</ref> with sertraline use in the first trimester associated with 2.7-fold increase in septal heart defects.<ref name="pmid30415641">Template:Cite journal</ref>

Abrupt interruption of sertraline treatment may result in withdrawal or discontinuation syndrome. Dizziness, insomnia, anxiety, agitation, and irritability are common symptoms.<ref name="pmid23596418">Template:Cite journal</ref> It typically occurs within a few days from drug discontinuation and lasts a few weeks.<ref name="pmid25721705"/> The withdrawal symptoms for sertraline are less severe and frequent than for paroxetine, and more frequent than for fluoxetine.<ref name="pmid23596418"/><ref name="pmid25721705">Template:Cite journal</ref> In most cases symptoms are mild, short-lived, and resolve without treatment. More severe cases are often successfully treated by temporary reintroduction of the drug with a slower tapering-off rate.<ref name ="WarnerAFP">Template:Cite journal</ref>

Sertraline and SSRI antidepressants in general may be associated with bruxism and other movement disorders.<ref name="pmid32546134">Template:Cite journal</ref><ref>Template:Cite journal</ref> Sertraline appears to be associated with microscopic colitis, a rare condition of unknown etiology.<ref name="pmid30881078">Template:Cite journal</ref>

Sexual

Like other SSRIs, sertraline is associated with sexual side effects, including sexual arousal disorder, erectile dysfunction and difficulty achieving orgasm. While nefazodone and bupropion do not have negative effects on sexual functioning, 67% of men on sertraline experienced ejaculation difficulties versus 18% before the treatment.<ref name="pmid11229450">Template:Cite journal</ref> Sexual arousal disorder, defined as "inadequate lubrication and swelling for women and erectile difficulties for men", occurred in 12% of people on sertraline as compared with 1% of patients on placebo. The mood improvement resulting from the treatment with sertraline sometimes counteracted these side effects, so that sexual desire and overall satisfaction with sex stayed the same as before the sertraline treatment. However, under the action of placebo the desire and satisfaction slightly improved.<ref name="pmid10363731">Template:Cite journal</ref> Some people continue experiencing sexual side effects after they stop taking SSRIs.<ref>Template:Cite journal</ref>

Suicide

The US Food and Drug Administration (FDA) requires all antidepressants, including sertraline, to carry a boxed warning stating that antidepressants increase the risk of suicide in persons younger than 25 years.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref><ref>Template:Cite journal</ref> This warning is based on statistical analyses conducted by two independent groups of FDA experts that found a 100% increase of suicidal thoughts and behavior in children and adolescents, and a 50% increase in the 18–24 age group.<ref name=FDA>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref name="FDA2">Template:Cite Q</ref><ref name="FDA3">Template:Cite Q</ref>

Suicidal ideation and behavior in clinical trials are rare. For the above analysis, the FDA combined the results of 295 trials of 11 antidepressants for psychiatric indications to obtain statistically significant results. Considered separately, sertraline use in adults decreased the odds of suicidal behavior with a marginal statistical significance of 37%<ref name =FDA3 /> or 50%<ref name =FDA2 /> depending on the statistical technique used. The authors of the FDA analysis note that "given the large number of comparisons made in this review, chance is a very plausible explanation for this difference".<ref name =FDA2 /> The more complete data submitted later by the sertraline manufacturer Pfizer indicated increased suicidal behavior.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> Similarly, the analysis conducted by the UK MHRA found a 50% increase of odds of suicide-related events, not reaching statistical significance, in the patients on sertraline as compared to the ones on placebo.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref name="pmid15718537">Template:Cite journal</ref>

Overdose

Acute overdosage is often manifested by emesis, lethargy, ataxia, tachycardia and seizures. Plasma, serum or blood concentrations of sertraline and norsertraline, its major active metabolite, may be measured to confirm a diagnosis of poisoning in hospitalized patients or to aid in the medicolegal investigation of fatalities.<ref>Template:Cite book</ref> As with most other SSRIs its toxicity in overdose is considered relatively low.<ref name = Maudsley>Template:Cite book</ref><ref>Template:Cite journal</ref>

Interactions

As with other SSRIs, sertraline may increase the risk of bleeding with NSAIDs (ibuprofen, naproxen, mefenamic acid), antiplatelet drugs, anticoagulants, omega-3 fatty acids, vitamin E, and garlic supplements due to sertraline's inhibitory effects on platelet aggregation via blocking serotonin transporters on platelets.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> Sertraline, in particular, may potentially diminish the efficacy of levothyroxine.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Sertraline is a moderate inhibitor of CYP2D6 and CYP2B6 in vitro.<ref name="pmid16192315">Template:Cite journal</ref> Accordingly, in human trials it caused increased blood levels of CYP2D6 substrates such as metoprolol, dextromethorphan, desipramine, imipramine and nortriptyline, as well as the CYP3A4/CYP2D6 substrate haloperidol.<ref name="pmid9472843">Template:Cite journal</ref><ref name="pmid10211917">Template:Cite journal</ref><ref name="pmid10631623">Template:Cite journal</ref> This effect is dose-dependent; for example, co-administration with 50 mg of sertraline resulted in 20% greater exposure to desipramine, while 150 mg of sertraline led to a 70% increase.<ref name="pmid12452737" /><ref name="pmid17224709">Template:Cite journal</ref> In a placebo-controlled study, the concomitant administration of sertraline and methadone caused a 40% increase in blood levels of the latter, which is primarily metabolized by CYP2B6.<ref name="pmid10914294">Template:Cite journal</ref> Bupropion is metabolized by CYP2B6, which is inhibited by sertraline, and this may result in an interaction between sertraline and bupropion.<ref name="TurpeinenZanger2012">Template:Cite journal</ref><ref name="SchatzbergHemeroff2024">Template:Cite book</ref><ref name="MolnariHassanMyers2012">Template:Cite journal</ref>

Sertraline had a slight inhibitory effect on the metabolism of diazepam, tolbutamide, and warfarin, which are CYP2C9 or CYP2C19 substrates; the clinical relevance of this effect was unclear.<ref name="pmid12452737" /> As expected from in vitro data, sertraline did not alter the human metabolism of the CYP3A4 substrates erythromycin, alprazolam, carbamazepine, clonazepam, and terfenadine; neither did it affect metabolism of the CYP1A2 substrate clozapine.<ref name="pmid12452737" /><ref name="DailyMed" /><ref name="pmid14709940">Template:Cite journal</ref><ref name="pmid16192315" />

Sertraline did not affect the actions of digoxin and atenolol, which are not metabolized in the liver.<ref name=FDALabel>Sertraline FDA Label Last updated May 2014</ref> Case reports suggest that taking sertraline with phenytoin or zolpidem may induce sertraline metabolism and decrease its efficacy,<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref> and that taking sertraline with lamotrigine may increase the blood level of lamotrigine, possibly by inhibition of glucuronidation.<ref name="pmid9627209">Template:Cite journal</ref>

CYP2C19 inhibitor esomeprazole increased sertraline concentrations in blood plasma by approximately 40%.<ref name="pmid24887634">Template:Cite journal</ref>

Clinical reports indicate that interaction between sertraline and the MAOIs isocarboxazid and tranylcypromine may cause serotonin syndrome. In a placebo-controlled study in which sertraline was co-administered with lithium, 35% of the subjects experienced tremors, while none of those taking placebo did.<ref name="pmid12452737" />

Pharmacology

Pharmacodynamics

citation

CitationClass=web }}</ref>
Site	Ki (nM)	Species	References
Template:Abbrlink	0.15–3.3	Human	<ref name="pmid9537821">Template:Cite journal</ref><ref name="pmid9400006">Template:Cite journal</ref><ref name="pmid11543737">Template:Cite journal</ref>
Template:Abbrlink	420–925	Human	<ref name="pmid9537821" /><ref name="pmid9400006" /><ref name="pmid11543737" />
Template:Abbrlink	22–315	Human	<ref name="pmid9537821" /><ref name="pmid9400006" /><ref name="pmid11543737" />
5-HT1A	35000+	Human	<ref name="pmid7855217">Template:Cite journal</ref>
5-HT2A	2207	Rat	<ref name="pmid11543737" />
5-HT2C	2298	Pig	<ref name="pmid11543737" />
α1A	1900	Human	<ref name="pmid32608144">Template:Cite journal</ref>
α1B	3500	Human	<ref name="pmid32608144"/>
α1D	2500	Human	<ref name="pmid32608144"/>
α2	477–4100	Human	<ref name="pmid9400006" /><ref name="pmid7855217" />
D2	10700	Human	<ref name="pmid7855217" />
H1	24000	Human	<ref name="pmid7855217" />
Template:Abbrlink	427–2100	Human	<ref name="pmid11543737" /><ref name="pmid7855217" /><ref name="pmid8100134">Template:Cite journal</ref>
σ1	32–57	Rat	<ref name="AlbayrakHashimoto2017">Template:Cite book</ref><ref name="pmid20373470">Template:Cite journal</ref>
σ2	5297	Rat	<ref name="pmid20373470" />
Values are Ki (nM), unless otherwise noted. The smaller the value, the more strongly the drug binds to or inhibits the site.

Sertraline is a selective serotonin reuptake inhibitor (SSRI). By binding to the serotonin transporter (SERT) it inhibits neuronal reuptake of serotonin and potentiates serotonergic activity in the central nervous system.<ref name="DailyMed" /> Over time, this leads to a downregulation of pre-synaptic 5-HT_1A receptors, which is associated with an improvement in passive stress tolerance, and delayed downstream increase in expression of brain-derived neurotrophic factor (BDNF), which may contribute to a reduction in negative affective biases.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref> It does not significantly affect histamine, acetylcholine, GABA or benzodiazepine receptors.<ref name="DailyMed" />

Sertraline also shows relatively high activity as an inhibitor of the dopamine transporter (DAT) occupying ~20% of DAT receptors at doses 200mg and above, <ref name="pmid9537821" /><ref name="pmid11357798">Template:Cite journal</ref><ref name="HemmingsEgan2012">Template:Cite book</ref> and antagonist of the sigma σ₁ receptor (but not the σ₂ receptor).<ref name="AlbayrakHashimoto2017" /><ref name="pmid20373470" /><ref name="pmid20021354">Template:Cite journal</ref> However, sertraline affinity for its main target (SERT) is much greater than its affinity for σ₁ receptor and DAT.<ref name="PDSP" /><ref name="pmid9537821" /><ref name="pmid20373470" /><ref name="AlbayrakHashimoto2017" /> Although there could be a role for the σ₁ receptor in the pharmacology of sertraline, the significance of this receptor in its actions is unclear.<ref name="pmid11420570" /> Similarly, the clinical relevance of sertraline's blockade of the dopamine transporter is uncertain.<ref name="pmid9537821" />

Pharmacokinetics

File:Desmethylsertraline skeletal.svg

Desmethylsertraline, the major metabolite of sertaline

Absorption

Following a single oral dose of sertraline, mean peak blood levels of sertraline occur between 4.5 and 8.4 hours.<ref name="FDALabel" /> Bioavailability is likely linear and dose-proportional over a dose range of 150 to 200 mg.<ref name="FDALabel" /> Concomitant intake of sertraline with food slightly increases sertraline peak levels and total exposure.<ref name="FDALabel" /> There is an approximate 2-fold accumulation of sertraline with continuous administration and steady-state levels are reached within one week.<ref name="FDALabel" />

Distribution

Sertraline is highly plasma protein bound (98.5%) across a concentration range of 20 to 500 ng/mL.<ref name="FDALabel" /> Despite the high plasma protein binding, sertraline and its metabolite desmethylsertraline at respective tested concentrations of 300 ng/mL and 200 ng/mL were found not to interfere with the plasma protein binding of warfarin and propranolol, two other highly plasma protein-bound drugs.<ref name="FDALabel" />

Metabolism

Sertraline is subject to extensive first-pass metabolism, as indicated by a small study of radiolabeled sertraline in which less than 5% of plasma radioactivity was unchanged sertraline in two males.<ref name="FDALabel" /> The principal metabolic pathway for sertraline is N-demethylation into desmethylsertraline (N-desmethylsertraline) mainly by CYP2B6.<ref name="FDALabel" /><ref name="pmid15547048" /> Reduction, hydroxylation, and glucuronide conjugation of both sertraline and desmethylsertraline also occur.<ref name="FDALabel" /> Desmethylsertraline, while pharmacologically active, is substantially (50-fold) weaker than sertraline as a serotonin reuptake inhibitor and its influence on the clinical effects of sertraline is thought to be negligible.<ref name="FDALabel" /><ref name="pmid9400006" /><ref name="In Vivo SERT binding">Template:Cite journal</ref> Based on in vitro studies, sertraline is metabolized by multiple cytochrome 450 isoforms;<ref name="pmid15547048" >Template:Cite journal</ref><ref name="pmid10383917">Template:Cite journal</ref> however, it appears that in the human body CYP2C19 plays the most important role, followed by CYP2B6.<ref name="pmid29136336">Template:Cite journal</ref> In addition to the cytochrome P450 system, sertraline can be oxidatively deaminated in vitro by monoamine oxidases;<ref name="FDALabel" /> however, this metabolic pathway has never been studied in vivo.<ref name="pmid15547048" />

Elimination

The elimination half-life of sertraline is on average 26 hours, with a range of 13 to 45 hours.<ref name="FDALabel" /><ref name="pmid12452737">Template:Cite journal</ref> The elimination half-life of desmethylsertraline is 62 to 104 hours.<ref name="FDALabel" />

In a small study of two males, sertraline was excreted to similar degrees in urine and feces (40 to 45% each within 9 days).<ref name="FDALabel" /> Unchanged sertraline was not detectable in urine, whereas 12 to 14% of unchanged sertraline was present in feces.<ref name="FDALabel" />

Pharmacogenomics

CYP2C19 and CYP2B6 are thought to be the key cytochrome P450 enzymes involved in the metabolism of sertraline.<ref name="pmid29136336" /> Relative to CYP2C19 normal (extensive) metabolizers, poor metabolizers have 2.7-fold higher levels of sertraline<ref name="pmid31649299">Template:Cite journal</ref> and intermediate metabolizers have 1.4-fold higher levels.<ref name="pmid33237321">Template:Cite journal</ref> In contrast, CYP2B6 poor metabolizers have 1.6-fold higher levels of sertraline and intermediate metabolizers have 1.2-fold higher levels.<ref name="pmid29136336" />

History

File:Sertraline precursors.svg

Skeletal formulae of thiothixene, lometraline and tametraline, from which sertraline was derived. Commonalities to the structure of sertraline are highlighted in red.

The history of sertraline dates back to the early 1970s when Pfizer chemist Reinhard Sarges invented a novel series of psychoactive compounds, including lometraline, based on the structures of the neuroleptics thiothixene and pinoxepin.<ref name=Welch /><ref>Template:Cite journal</ref> Further work on these compounds led to tametraline, a norepinephrine and weaker dopamine reuptake inhibitor. Development of tametraline was soon stopped because of undesired stimulant effects observed in animals. A few years later, in 1977, pharmacologist Kenneth Koe, after comparing the structural features of a variety of reuptake inhibitors, became interested in the tametraline series. He asked another Pfizer chemist, Willard Welch, to synthesize some previously unexplored tametraline derivatives. Welch generated several potent norepinephrine and triple reuptake inhibitors, but to the surprise of the scientists, one representative of the generally inactive cis-analogs was a serotonin reuptake inhibitor. Welch then prepared stereoisomers of this compound, which were tested in vivo by animal behavioral scientist Albert Weissman. The most potent and selective (+)-isomerTemplate:Efn was taken into further development and eventually named sertraline. Weissman and Koe recalled that the group did not set up to produce an antidepressant of the SSRI type—in that sense their inquiry was not "very goal driven", and the invention of the sertraline molecule was serendipitous. According to Welch, they worked outside the mainstream at Pfizer, and even "did not have a formal project team". The group had to overcome initial bureaucratic reluctance to pursue sertraline development, as Pfizer was considering licensing an antidepressant candidate from another company.<ref name=Welch>Template:Cite book</ref><ref>See also: Template:Cite journal</ref><ref>A short blurb on the history of sertraline, see: Template:Cite journal</ref>

Sertraline was approved by the US Food and Drug Administration (FDA) in 1991 based on the recommendation of the Psychopharmacological Drugs Advisory Committee; it had already become available in the United Kingdom the previous year.<ref name=He168>Template:Cite book</ref> The FDA committee achieved a consensus that sertraline was safe and effective for the treatment of major depression. During the discussion, Paul Leber, the director of the FDA Division of Neuropharmacological Drug Products, noted that granting approval was a "tough decision", since the treatment effect on outpatients with depression had been "modest to minimal". Other experts emphasized that the drug's effect on inpatients had not differed from placebo and criticized the poor design of the clinical trials by Pfizer.<ref name=pdac>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> For example, 40% of participants dropped out of the trials, significantly decreasing their validity.<ref name="pmid8573661">See also:Template:Cite journal</ref>

Until 2002, sertraline was only approved for use in adults ages 18 and over; that year, it was approved by the FDA for use in treating children aged 6 or older with severe OCD. In 2003, the UK Medicines and Healthcare products Regulatory Agency issued guidance that, apart from fluoxetine (Prozac), SSRIs are not suitable for the treatment of depression in patients under 18.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref>Template:Cite news</ref> However, sertraline can still be used in the UK for the treatment of OCD in children and adolescents.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> In 2005, the FDA added a boxed warning concerning pediatric suicidal behavior to all antidepressants, including sertraline. In 2007, labeling was again changed to add a warning regarding suicidal behavior in young adults ages 18 to 24.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Society and culture

Generic availability

The US patent for Zoloft expired in 2006,<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> and sertraline is available in generic form and is marketed under many brand names worldwide.<ref name=Brand2015>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Brand names

In the US, Zoloft is marketed by Viatris after Upjohn was spun off from Pfizer.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Interest during COVID-19 pandemic

Sertraline has been the most sought-after antidepressant worldwide before, during, and after the COVID-19 pandemic, according to Google Trends data. The pandemic has led to an increase in searches for antidepressants, with sertraline, fluoxetine, duloxetine, and venlafaxine showing the highest search volumes, whereas searches of citalopram decreased during the pandemic.<ref name="pmid37731683">Template:Cite journal</ref>

Other uses

Sertraline may be useful to treat murine Zaire ebolavirus (murine EBOV).<ref name="Ebola-treatment" /> The World Health Organization (WHO) considers this a promising area of research.<ref name="Ebola-treatment">

  Template:Unbulleted list citebundle

</ref>

Lass-Flörl et al., 2003 finds it significantly inhibits phospholipase B in the fungal genus Candida, reducing virulence.<ref name="Phospholipase-B">

  Template:Unbulleted list citebundle

</ref>

Sertraline is also a very effective leishmanicide.<ref name="Chamber-of-Secrets" /> Specifically, Palit & Ali 2008 find that sertraline kills almost all promastigotes of Leishmania donovani.<ref name="Chamber-of-Secrets" />

Sertraline is strongly antibacterial against some species.<ref name="Chamber-of-Secrets">Template:Cite journal</ref> It is also known to act as a photosensitizer of bacterial surfaces.<ref name = "Photosensitizers" /> In combination with antibacterials its photosensitization effect reverses antibacterial resistance.<ref name = "Photosensitizers" /> As such sertraline shows promise for food preservation.<ref name = "Photosensitizers" >Template:Cite journal</ref>

Lass-Flörl et al., 2003 finds this compound acts as a fungicide against Candida parapsilosis.<ref name = "Immunomodulation" /> Its anti-Cp effect is indeed due to its serotonergic activity and not its other effects.<ref name = "Immunomodulation" >

Template:Cite journal

</ref>

Sertraline is a promising trypanocide.<ref name="tcruz"/> It acts at several different life stages and against several strains.<ref name="tcruz"/> Sertraline's trypanocidal mechanism of action is by way of interference with bioenergetics.<ref name="tcruz"> Template:Cite journal

This review cites this study: Template:Cite journal </ref>

See also

• List of antidepressants

External links

Template:Navbox with collapsible groups {{#invoke:navbox|navbox | name = Anxiolytics | title = Anxiolytics (N05B) | state = collapsed | groupstyle = text-align:center; | listclass = hlist

 | group1 = Template:Abbrlink agonists
 |  list1 =

• Buspirone
• Gepirone
• Tandospirone

 | group2 = Template:Abbrlink Template:Abbrlink
 |  list2 = 

• Benzodiazepines: Adinazolam
• Alprazolam
• Bromazepam
• Camazepam
• Chlordiazepoxide
• Clobazam
• Clonazepam
• Clorazepate
• Clotiazepam
• Cloxazolam
• Diazepam^#
• Ethyl loflazepate
• Etizolam
• Fludiazepam
• Halazepam
• Ketazolam
• Lorazepam^#
• Medazepam
• Nordazepam
• Oxazepam
• Pinazepam
• Prazepam; Others: Alpidem^‡
• Barbiturates (e.g., phenobarbital)
• Carbamates (e.g., meprobamate)
• Carisoprodol
• Chlormezanone^‡
• Ethanol (alcohol)
• Etifoxine

 | group3 = Hypnotics
 | list3 =

• Zopiclone

 | group4 = Gabapentinoids
([[Voltage-dependent calcium channel#.CE.B12.CE.B4_Subunit|Template:Abbr Template:Abbr]] blockers)
 |  list4 =

• Gabapentin
• Gabapentin enacarbil
• Phenibut
• Pregabalin

 | group5 = Antidepressants
 | list5 = 

• Template:Abbrlink (e.g., escitalopram)
• Template:Abbrlink (e.g., duloxetine)
• Template:Abbrlink (e.g., trazodone)
• Template:Abbrlink (e.g., clomipramine^#)
• Template:Abbrlink (e.g., mirtazapine)
• Template:Abbrlink (e.g., phenelzine); Others: Agomelatine
• Bupropion
• Tianeptine
• Vilazodone
• Vortioxetine

 | group6 = Antipsychotics
 | list6 =

• Quetiapine
• Flupentixol

 | group7 = Sympatholytics
(Antiadrenergics)
 |  list7 =

• Alpha-1 blockers (e.g., prazosin)
• Alpha-2 agonists (e.g., clonidine, dexmedetomidine, guanfacine)
• Beta blockers (e.g., propranolol)

 | group8 = Others
 |  list8 =

• Benzoctamine
• Cycloserine
• Fabomotizole
• Hydroxyzine
• Lorpiprazole
• Mebicar
• Mepiprazole
• Nicotine
• Opipramol
• Oxaflozane^‡
• Phenaglycodol
• Phenibut
• Picamilon
• Selank
• Tiagabine
• Tofisopam
• Validolum

| list9 = Template:PharmNavFootnote

}} Template:OCD pharmacotherapies Template:Monoamine reuptake inhibitors Template:Sigma receptor modulators Template:Portal bar Template:Authority control