Sertraline, sold under the brand name Zoloft among others, is an

antidepressant medication Antidepressants are a class of medications used to treat major depressive disorder, anxiety disorders, chronic pain, and addiction. Common side effects of antidepressants include dry mouth, weight gain, dizziness, headaches, akathisia, sex ...

of the

selective serotonin reuptake inhibitor Selective serotonin reuptake inhibitors (SSRIs) are a class of drugs that are typically used as antidepressants in the treatment of major depressive disorder, anxiety disorders, and other psychological conditions. SSRIs primarily work by blo ...

(SSRI) class used to treat

major depressive disorder Major depressive disorder (MDD), also known as clinical depression, is a mental disorder characterized by at least two weeks of pervasive depression (mood), low mood, low self-esteem, and anhedonia, loss of interest or pleasure in normally ...

generalized anxiety disorder Generalized anxiety disorder (GAD) is an anxiety disorder characterized by excessive, uncontrollable and often irrational worry about events or activities. Worry often interferes with daily functioning. Individuals with GAD are often overly con ...

social anxiety disorder Social anxiety disorder (SAD), also known as social phobia, is an anxiety disorder characterized by sentiments of fear and anxiety in social situations, causing considerable distress and impairing ability to function in at least some asp ...

obsessive–compulsive disorder Obsessive–compulsive disorder (OCD) is a mental disorder in which an individual has intrusive thoughts (an ''obsession'') and feels the need to perform certain routines (''Compulsive behavior, compulsions'') repeatedly to relieve the dis ...

(OCD),

panic disorder Panic disorder is a mental disorder, specifically an anxiety disorder, characterized by reoccurring unexpected panic attacks. Panic attacks are sudden periods of intense fear that may include palpitations, sweating, shaking, shortness of breath ...

, and

premenstrual dysphoric disorder Premenstrual dysphoric disorder (PMDD) is a mood disorder characterized by emotional, cognitive, and physical symptoms. PMDD causes significant distress or impairment in menstruating women during the luteal phase of the menstrual cycle. The symp ...

. Although also having approval for

post-traumatic stress disorder Post-traumatic stress disorder (PTSD) is a mental disorder that develops from experiencing a Psychological trauma, traumatic event, such as sexual assault, domestic violence, child abuse, warfare and its associated traumas, natural disaster ...

(PTSD), findings indicate it leads to only modest improvements in symptoms associated with this condition. The drug shares the common

side effects In medicine, a side effect is an effect of the use of a medicinal drug or other treatment, usually adverse but sometimes beneficial, that is unintended. Herbal and traditional medicines also have side effects. A drug or procedure usually used ...

and

contraindication In medicine, a contraindication is a condition (a situation or factor) that serves as a reason not to take a certain medical treatment due to the harm that it would cause the patient. Contraindication is the opposite of indication, which is a rea ...

s of other SSRIs, with high rates of

nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. It can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the throat. Over 30 d ...

diarrhea Diarrhea (American English), also spelled diarrhoea or diarrhœa (British English), is the condition of having at least three loose, liquid, or watery bowel movements in a day. It often lasts for a few days and can result in dehydration d ...

headache A headache, also known as cephalalgia, is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of Depression (mood), depression in those with severe ...

insomnia Insomnia, also known as sleeplessness, is a sleep disorder where people have difficulty sleeping. They may have difficulty falling asleep, or staying asleep for as long as desired. Insomnia is typically followed by daytime sleepiness, low ene ...

, mild

sedation Sedation is the reduction of irritability or agitation by administration of sedative drugs, generally to facilitate a medical procedure or diagnostic procedure. Examples of drugs which can be used for sedation include isoflurane, diethyl ether, ...

, dry mouth, and

sexual dysfunction Sexual dysfunction is difficulty experienced by an individual or partners during any stage of normal sexual activity, including physical pleasure, desire, preference, arousal, or orgasm. The World Health Organization defines sexual dysfunction ...

, but it appears not to lead to much

weight gain Weight gain is an increase in body weight. This can involve an increase in muscle mass, fat deposits, excess fluids such as water or other factors. Weight gain can be a symptom of a serious medical condition. Description Weight gain occurs ...

, 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 inhibitor Monoamine oxidase inhibitors (MAOIs) are a drug class, class of drugs that inhibit the activity of one or both monoamine oxidase enzymes: monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B). They are best known as effective antidepressa ...

s (MAOIs): this combination may cause

serotonin syndrome Serotonin syndrome (SS) is a group of symptoms that may occur with the use of certain Serotonin, serotonergic medications or Recreational drug use, drugs. The symptoms can range from mild to severe, and are potentially fatal. Symptoms in mild c ...

, which can be life-threatening in some cases. Sertraline taken during pregnancy is associated with an increase in

congenital heart defect A congenital heart defect (CHD), also known as a congenital heart anomaly, congenital cardiovascular malformation, and congenital heart disease, is a defect in the structure of the heart or great vessels that is present at birth. A congenital h ...

s in newborns. Sertraline was developed by scientists at

Pfizer Pfizer Inc. ( ) is an American Multinational corporation, multinational Pharmaceutical industry, pharmaceutical and biotechnology corporation headquartered at The Spiral (New York City), The Spiral in Manhattan, New York City. Founded in 184 ...

and approved for medical use in the United States in 1991. It is on the

World Health Organization's List of Essential Medicines The WHO Model List of Essential Medicines (aka Essential Medicines List or EML), published by the World Health Organization (WHO), contains the medications considered to be most effective and safe to meet the most important needs in a health s ...

and available as a

generic medication A generic drug is a pharmaceutical drug that contains the same chemical substance as a drug that was originally protected by chemical patents. Generic drugs are allowed for sale after the patents on the original drugs expire. Because the active ch ...

. In 2016, sertraline was the most commonly prescribed psychotropic medication in the United States. It was also the eleventh most commonly prescribed medication in the United States, with more than 39million prescriptions in 2022, and sertraline ranks among the top 10 most prescribed medications in Australia between 2017 and 2023. For alleviating the symptoms of depression, the drug is usually second in potency to another SSRI,

escitalopram Escitalopram ( ), sold under the brand names Lexapro and Cipralex, among others, is an antidepressant medication of the selective serotonin reuptake inhibitor (SSRI) class. It is mainly used to treat major depressive disorder, generalized ...

. Sertraline's

effectiveness Effectiveness or effectivity is the capability of producing a desired result or the ability to produce desired output. When something is deemed effective, it means it has an intended or expected outcome, or produces a deep, vivid impression. Et ...

is similar to that of other antidepressants in its class, such as

fluoxetine Fluoxetine, sold under the brand name Prozac, among others, is an Antidepressant, antidepressant medication of the selective serotonin reuptake inhibitor (SSRI) class used for the treatment of major depressive disorder, Anxiety disorder, anx ...

and

paroxetine Paroxetine ( ), sold under the brand name Paxil among others, is an Antidepressant, antidepressant medication of the selective serotonin reuptake inhibitor (SSRI) class used to treat major depressive disorder, obsessive-compulsive disorder, o ...

, which are also considered first-line treatments and are better tolerated than the older tricyclic antidepressants.

Medical uses

Sertraline has been approved for

(OCD),

(PTSD),

(SAD), and

(GAD). Sertraline is approved for use in children with OCD.

Depression

meta-analyses Meta-analysis is a method of synthesis of quantitative data from multiple independent studies addressing a common research question. An important part of this method involves computing a combined effect size across all of the studies. As such, th ...

, sertraline displays similar efficacy to other SSRI antidepressants, with an

odds ratio An odds ratio (OR) is a statistic that quantifies the strength of the association between two events, A and B. The odds ratio is defined as the ratio of the odds of event A taking place in the presence of B, and the odds of A in the absence of B ...

for response in clinical depression of between 1.44 and 1.67. However, as with other antidepressants, the nature and clinical significance of this effect remain disputed. A major study of sertraline in a broad primary care population found improvements in general mental health, quality of life, and anxiety. 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. In several

double-blind In a blind or blinded experiment, information which may influence the participants of the experiment is withheld until after the experiment is complete. Good blinding can reduce or eliminate experimental biases that arise from a participants' expec ...

studies, sertraline was consistently more effective than

placebo A placebo ( ) can be roughly defined as a sham medical treatment. Common placebos include inert tablets (like sugar pills), inert injections (like saline), sham surgery, and other procedures. Placebos are used in randomized clinical trials ...

for

dysthymia Dysthymia ( ), known as persistent depressive disorder (PDD) in the DSM-5-TR and dysthymic disorder in ICD-11, is a psychiatric condition marked by symptoms that are similar to those of major depressive disorder, but which persist for at leas ...

, a more chronic variety of depression, and comparable to

imipramine Imipramine, sold under the brand name Tofranil, among others, is a tricyclic antidepressant (TCA) mainly used in the treatment of depression. It is also effective in treating anxiety and panic disorder. Imipramine is taken by mouth. Common s ...

in that respect. Sertraline also improves the functional impairments of dysthymia to a similar degree whether group Cognitive-Behavioral Therapy is undergone or not. Limited pediatric data also demonstrates a reduction in depressive symptoms in the pediatric population though remains a second-line therapy after fluoxetine.

Comparison with other antidepressants

In general, sertraline efficacy is similar to that of other antidepressants. For example, a meta-analysis of 12 new-generation antidepressants showed that sertraline and

are the best in terms of efficacy and acceptability in the acute-phase treatment of adults with depression.; Comparative clinical trials demonstrated that sertraline is similar in efficacy against depression to

moclobemide Moclobemide, sold under the brand names Amira, Aurorix, Clobemix, Depnil and Manerix among others, is a reversible inhibitor of monoamine oxidase A (RIMA) drug primarily used to treat Clinical depression, depression and social anxiety. It is not ...

, nefazodone,

, bupropion,

citalopram Citalopram, sold under the brand name Celexa among others, is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is used to treat major depressive disorder, obsessive compulsive disorder, panic disorder, and soci ...

fluvoxamine Fluvoxamine, sold under the brand name Luvox among others, is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is primarily used to treat major depressive disorder and, perhaps more-especially, obsessive–compu ...

venlafaxine Venlafaxine, sold under the brand name Effexor among others, is an antidepressant medication of the serotonin–norepinephrine reuptake inhibitor (SNRI) class. It is used to treat major depressive disorder, generalized anxiety disorder, pani ...

, and

mirtazapine Mirtazapine, sold under the brand name Remeron among others, is an atypical antidepressant, atypical tetracyclic antidepressant, and as such is used primarily to treat Depression (mood), depression. Its effects may take up to four weeks but ca ...

.For the review, see: Sertraline may be more efficacious for the treatment of depression in the acute phase (first four weeks) than

. 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. Sertraline appears to work better in melancholic depression than fluoxetine,

, and mianserin and is similar to the tricyclic antidepressants such as amitriptyline and clomipramine. In the treatment of depression accompanied by OCD, sertraline performs significantly better than desipramine on the measures of both OCD and depression. Sertraline is equivalent to imipramine for the treatment of depression with co-morbid panic disorder, but it is better tolerated. Compared with amitriptyline, sertraline offered a greater overall improvement in

quality of life Quality of life (QOL) is defined by the World Health Organization as "an individual's perception of their position in life in the context of the culture and value systems in which they live and in relation to their goals, expectations, standards ...

of depressed patients.

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

. 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. Accordingly, a meta-analysis of antidepressants in older adults found that sertraline,

and duloxetine were better than placebo. However, in a 2003 trial the

effect size In statistics, an effect size is a value measuring the strength of the relationship between two variables in a population, or a sample-based estimate of that quantity. It can refer to the value of a statistic calculated from a sample of data, the ...

was modest, and there was no improvement in

as compared to

. With depression in dementia, there is no benefit of sertraline treatment compared to either placebo or

Obsessive–compulsive disorder

Sertraline is effective for the treatment of OCD in adults, adolescents and children. It was better tolerated and, based on

intention-to-treat analysis In medicine an intention-to-treat (ITT) analysis of the results of a randomized controlled trial is based on the initial treatment assignment and not on the treatment eventually received. ITT analysis is intended to avoid various misleading artifac ...

, performed better than the gold standard of OCD treatment clomipramine. Continuing sertraline treatment helps prevent relapses of OCD with long-term data supporting its use for up to 24 months. The sertraline dosages necessary for the effective treatment of OCD are higher than the usual dosage for depression. 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.

Cognitive behavioral therapy Cognitive behavioral therapy (CBT) is a form of psychotherapy that aims to reduce symptoms of various mental health conditions, primarily depression, PTSD, and anxiety disorders. Cognitive behavioral therapy focuses on challenging and chang ...

alone is not more effective than sertraline in adolescents and children; however, a combination of these treatments is effective.

Panic disorder

Sertraline is superior to placebo for the treatment of

. 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. Sertraline is equally effective for men and women, and for patients with or without agoraphobia. Previous unsuccessful treatment with

benzodiazepines Benzodiazepines (BZD, BDZ, BZs), colloquially known as "benzos", are a class of central nervous system (CNS) depressant drugs whose core chemical structure is the fusion of a benzene ring and a diazepine ring. They are prescribed to treat co ...

does not diminish its efficacy. However, the response rate was lower for the patients with more severe panic. Starting treatment simultaneously with sertraline and clonazepam, with subsequent gradual discontinuation of clonazepam, may accelerate the response. Double-blind comparative studies found sertraline to have the same effect on panic disorder as

. While imprecise, comparison of the results of trials of sertraline with separate trials of other anti-panic agents ( clomipramine,

, clonazepam,

alprazolam Alprazolam, sold under the brand name Xanax among others, is a fast-acting, potent tranquilizer of moderate duration within the triazolobenzodiazepine group of chemicals called benzodiazepines. Alprazolam is most commonly prescribed in the ...

, and

) indicates approximate equivalence of these medications.

Other anxiety disorders

Sertraline has been successfully used for the treatment of

. All three major domains of the disorder (fear, avoidance, and physiological symptoms) respond to sertraline. Maintenance treatment, after the response is achieved, prevents the return of the symptoms. The improvement is greater among the patients with later, adult onset of the disorder. In a comparison trial, sertraline was superior to

exposure therapy Exposure therapy is a technique in behavior therapy to treat anxiety disorders. Exposure therapy involves exposing the patient to the anxiety source or its context (without the intention to cause any danger). Doing so is thought to help them overc ...

, 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. The combination of sertraline and

cognitive behavioral therapy Cognitive behavioral therapy (CBT) is a form of psychotherapy that aims to reduce symptoms of various mental health conditions, primarily depression, PTSD, and anxiety disorders. Cognitive behavioral therapy focuses on challenging and chang ...

appears to be more effective in children and young people than either treatment alone. Sertraline has not been approved for the treatment of

; however, several guidelines recommend it as a first-line medication referring to good quality controlled clinical trials.

Premenstrual dysphoric disorder

Sertraline is effective in alleviating the symptoms of

, a severe form of

premenstrual syndrome Premenstrual syndrome (PMS) is a disruptive set of emotional and physical symptoms that regularly occur in the one to two weeks before the start of each menstrual period. Symptoms resolve around the time menstrual bleeding begins. Symptoms v ...

. 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. Taking sertraline only during the

luteal phase The menstrual cycle is on average 28 days in length. It begins with Menstruation, menses (day 1–7) during the follicular phase (day 1–14), followed by ovulation (day 14) and ending with the luteal phase (day 14–28). While historically, medi ...

, that is, the 12–14 days before menses is not as effective as continuous treatment. Continuous treatment with sub-therapeutic doses of sertraline (25 mg vs. usual 50–100 mg) is also effective.

Other indications

Sertraline is approved for the treatment of

(PTSD). The National Institute for Clinical Excellence recommends it for patients who prefer drug treatment to a psychological one. Other guidelines also suggest sertraline as a first-line option for pharmacological therapy. When necessary, long-term pharmacotherapy can be beneficial. There are both negative and positive clinical trial results for sertraline, which may be explained by the types of

psychological trauma Psychological trauma (also known as mental trauma, psychiatric trauma, emotional damage, or psychotrauma) is an emotional response caused by severe distressing events, such as Major trauma, bodily injury, Sexual assault, sexual violence, or ot ...

s, symptoms, and comorbidities included in the various studies. Positive results were obtained in trials that included predominantly women (75%) with a majority (60%) having physical or sexual assault as the traumatic event. 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. Another meta-analysis relegated sertraline to the second line, proposing trauma focused psychotherapy as a first-line intervention. The authors noted that

had declined to submit the results of a negative trial for inclusion in the meta-analysis making the results unreliable. Sertraline, when taken daily, can be useful for the treatment of

premature ejaculation Premature ejaculation (PE) is a male sexual dysfunction that occurs when a male Ejaculation, expels semen (and most likely experiences orgasm) soon after beginning sexual activity, and with minimal penile stimulation. It has also been called ''e ...

. A disadvantage of sertraline is that it requires continuous daily treatment to delay ejaculation significantly. A 2019

systematic review A systematic review is a scholarly synthesis of the evidence on a clearly presented topic using critical methods to identify, define and assess research on the topic. A systematic review extracts and interprets data from published studies on ...

suggested that sertraline may be a good way to control

anger Anger, also known as wrath ( ; ) or rage (emotion), rage, is an intense emotional state involving a strong, uncomfortable and non-cooperative response to a perceived provocation, hurt, or threat. A person experiencing anger will often experie ...

irritability Irritability is the excitatory ability that living organisms have to respond to changes in their environment. The term is used for both the physiological reaction to stimuli and for the pathological, abnormal or excessive sensitivity to stimul ...

, and

hostility Hostility is seen as a form of emotionally charged aggressive behavior. In everyday speech, it is more commonly used as a synonym for anger and aggression. It appears in several psychological theories. For instance it is a Facet (psychology), f ...

in depressed patients and patients with other comorbidities.

Contraindications

Sertraline is contraindicated in individuals taking

s or the antipsychotic

pimozide Pimozide (sold under the brand name Orap) is a neuroleptic medication, drug of the diphenylbutylpiperidine class. It was discovered at Janssen Pharmaceutica in 1963. It has a high potency compared to chlorpromazine (ratio 50-70:1). On a weigh ...

. Sertraline concentrate contains

ethanol Ethanol (also called ethyl alcohol, grain alcohol, drinking alcohol, or simply alcohol) is an organic compound with the chemical formula . It is an Alcohol (chemistry), alcohol, with its formula also written as , or EtOH, where Et is the ps ...

and is therefore contraindicated with

disulfiram Disulfiram is a medication used to support the treatment of chronic alcoholism by producing an acute sensitivity to ethanol (drinking alcohol). Disulfiram works by Enzyme inhibition, inhibiting the enzyme aldehyde dehydrogenase (specifically ALD ...

. 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.

Side effects

Nausea, ejaculation failure, insomnia, diarrhea, dry mouth, somnolence, dizziness, tremor, headache, excessive sweating, fatigue,

restless legs syndrome Restless legs syndrome (RLS), also known as Willis–Ekbom disease (WED), is a neurological disorder, usually chronic, that causes an overwhelming urge to move one's legs. There is often an unpleasant feeling in the legs that improves temporaril ...

and decreased

libido In psychology, libido (; ) is psychic drive or energy, usually conceived of as sexual in nature, but sometimes conceived of as including other forms of desire. The term ''libido'' was originally developed by Sigmund Freud, the pioneering origin ...

are the common adverse effects associated with sertraline with the greatest difference from

. Those that most often result in interruption of the treatment are nausea, diarrhea, and insomnia. The incidence of diarrhea is higher with sertraline – especially when prescribed at higher doses – in comparison with other SSRIs. Over more than six months of sertraline therapy for depression, people showed no significant weight increase. A 30-month-long treatment with sertraline for OCD also resulted in no significant weight gain. Although the difference did not reach

statistical significance In statistical hypothesis testing, a result has statistical significance when a result at least as "extreme" would be very infrequent if the null hypothesis were true. More precisely, a study's defined significance level, denoted by \alpha, is the ...

, the average weight gain was lower for

(1%) but higher for

and

(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. Over a two-week treatment of healthy volunteers, sertraline slightly improved verbal

fluency Fluency (also called volubility and eloquency) refers to continuity, smoothness, rate, and effort in speech production. It is also used to characterize language production, language ability or language proficiency. In speech language patholog ...

but did not affect word learning,

short-term memory Short-term memory (or "primary" or "active memory") is the capacity for holding a small amount of information in an active, readily available state for a short interval. For example, short-term memory holds a phone number that has just been recit ...

, vigilance, flicker fusion time, choice

reaction time Mental chronometry is the scientific study of processing speed or reaction time on cognitive tasks to infer the content, duration, and temporal sequencing of mental operations. Reaction time (RT; also referred to as "response time") is measured ...

, memory span, or psychomotor coordination. 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. 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. The unique effect of sertraline on

dopaminergic Dopaminergic means "related to dopamine" (literally, "working on dopamine"), a common neurotransmitter. Dopaminergic substances or actions increase dopamine-related activity in the brain. Dopaminergic pathways, Dopaminergic brain pathways facil ...

neurotransmission may be related to these effects on cognition and vigilance. 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. There is 29–42% increase in

s among children whose mothers were prescribed sertraline during pregnancy, with sertraline use in the first trimester associated with 2.7-fold increase in septal heart defects. Abrupt interruption of sertraline treatment may result in withdrawal or discontinuation syndrome. Dizziness, insomnia, anxiety, agitation, and irritability are common symptoms. It typically occurs within a few days from drug discontinuation and lasts a few weeks. The withdrawal symptoms for sertraline are less severe and frequent than for paroxetine, and more frequent than for

. 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. Sertraline and SSRI antidepressants in general may be associated with

bruxism Bruxism is excessive teeth grinding or jaw clenching. It is an oral Parafunctional habit, parafunctional activity; i.e., it is unrelated to normal function such as eating or talking. Bruxism is a common behavior; the global prevalence of brux ...

and other movement disorders. Sertraline appears to be associated with microscopic colitis, a rare condition of unknown

etiology Etiology (; alternatively spelled aetiology or ætiology) is the study of causation or origination. The word is derived from the Greek word ''()'', meaning "giving a reason for" (). More completely, etiology is the study of the causes, origins ...

Sexual

Like other SSRIs, sertraline is associated with sexual side effects, including sexual arousal disorder,

erectile dysfunction Erectile dysfunction (ED), also referred to as impotence, is a form of sexual dysfunction in males characterized by the persistent or recurring inability to achieve or maintain a Human penis, penile erection with sufficient rigidity and durat ...

and difficulty achieving

orgasm Orgasm (from Greek , ; "excitement, swelling"), sexual climax, or simply climax, is the sudden release of accumulated sexual excitement during the sexual response cycle, characterized by intense sexual pleasure resulting in rhythmic, involu ...

. 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.

Sexual arousal Sexual arousal (also known as sexual excitement) describes the Physiology, physiological and psychological responses in preparation for sexual intercourse or when exposed to Sexual stimulation, sexual stimuli. A number of physiological response ...

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. Some people continue experiencing sexual side effects after they stop taking SSRIs.

Suicide

The US

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...

(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. 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.

Suicidal ideation Suicidal ideation, or suicidal thoughts, is the thought process of having ideas or ruminations about the possibility of dying by suicide.World Health Organization, ''ICD-11 for Mortality and Morbidity Statistics'', ver. 09/2020MB26.A Suicidal i ...

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% or 50% 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". The more complete data submitted later by the sertraline manufacturer Pfizer indicated increased suicidal behavior. 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.

Overdose

Acute overdosage is often manifested by

emesis Vomiting (also known as emesis, puking and throwing up) is the forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose. Vomiting can be the result of ailments like food poisoning, gastroenteritis, pregna ...

lethargy Lethargy is a state of tiredness, sleepiness, weariness, fatigue, sluggishness, or lack of energy. It can be accompanied by depression, decreased motivation, or apathy. Lethargy can be a normal response to inadequate sleep, overexertion, overw ...

ataxia Ataxia (from Greek α- negative prefix+ -τάξις rder= "lack of order") is a neurological sign consisting of lack of voluntary coordination of muscle movements that can include gait abnormality, speech changes, and abnormalities in e ...

tachycardia Tachycardia, also called tachyarrhythmia, is a heart rate that exceeds the normal resting rate. In general, a resting heart rate over 100 beats per minute is accepted as tachycardia in adults. Heart rates above the resting rate may be normal ...

and

seizures A seizure is a sudden, brief disruption of brain activity caused by abnormal, excessive, or synchronous neuronal firing. Depending on the regions of the brain involved, seizures can lead to changes in movement, sensation, behavior, awareness, o ...

. 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. As with most other SSRIs its toxicity in overdose is considered relatively low.

Interactions

As with other SSRIs, sertraline may increase the risk of bleeding with NSAIDs (

ibuprofen Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) that is used to relieve pain, fever, and inflammation. This includes dysmenorrhea, painful menstrual periods, migraines, and rheumatoid arthritis. It can be taken oral administration, ...

naproxen Naproxen, sold under the brand name Aleve among others, is a nonsteroidal anti-inflammatory drug (NSAID) used to treat pain, menstrual cramps, and inflammatory diseases such as rheumatoid arthritis, gout and fever. It is taken orally. It ...

mefenamic acid Mefenamic acid is a member of the Nonsteroidal anti-inflammatory drug#Anthranilic acid derivatives .28fenamates.29, anthranilic acid derivatives (or fenamate) class of nonsteroidal anti-inflammatory drugs (NSAIDs), and is used to treat mild to m ...

antiplatelet drug An antiplatelet drug (antiaggregant), also known as a platelet agglutination inhibitor or platelet aggregation inhibitor, is a member of a class of pharmaceuticals that decrease platelet aggregation and inhibit thrombus formation. They are effectiv ...

anticoagulant An anticoagulant, commonly known as a blood thinner, is a chemical substance that prevents or reduces the coagulation of blood, prolonging the clotting time. Some occur naturally in blood-eating animals, such as leeches and mosquitoes, which ...

omega-3 fatty acid Omega−3 fatty acids, also called omega−3 oils, ω−3 fatty acids or ''n''−3 fatty acids, are polyunsaturated fatty acids (PUFAs) characterized by the presence of a double bond three atoms away from the terminal methyl group in their ...

vitamin E Vitamin E is a group of eight compounds related in molecular structure that includes four tocopherols and four tocotrienols. The tocopherols function as fat-soluble antioxidants which may help protect cell membranes from reactive oxygen speci ...

, and garlic supplements due to sertraline's inhibitory effects on

platelet aggregation Platelets or thrombocytes () are a part of blood whose function (along with the coagulation factors) is to react to bleeding from blood vessel injury by clumping to form a blood clot. Platelets have no cell nucleus; they are fragments of cytop ...

via blocking serotonin transporters on platelets. Sertraline, in particular, may potentially diminish the efficacy of levothyroxine. Sertraline is a moderate

inhibitor Inhibitor or inhibition may refer to: Biology * Enzyme inhibitor, a substance that binds to an enzyme and decreases the enzyme's activity * Reuptake inhibitor, a substance that increases neurotransmission by blocking the reuptake of a neurotransmi ...

CYP2D6 Cytochrome P450 2D6 (CYP2D6) is an enzyme that in humans is encoded by the ''CYP2D6'' gene. ''CYP2D6'' is primarily expressed in the liver. It is also highly expressed in areas of the central nervous system, including the substantia nigra. CYP2 ...

and CYP2B6 ''

in vitro ''In vitro'' (meaning ''in glass'', or ''in the glass'') Research, studies are performed with Cell (biology), cells or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in ...

''. Accordingly, in human trials it caused increased blood levels of CYP2D6 substrates such as metoprolol,

dextromethorphan Dextromethorphan, sold under the brand name Robitussin among others, is a cough suppressant used in many cough and Common cold, cold medicines. In 2022, the US Food and Drug Administration (FDA) approved the combination dextromethorphan/bupropi ...

, desipramine,

and nortriptyline, as well as the

CYP3A4 Cytochrome P450 3A4 (abbreviated CYP3A4) () is an important enzyme in the body, mainly found in the liver and in the intestine, which in humans is encoded by ''CYP3A4'' gene. It organic redox reaction, oxidizes small foreign organic molecules ( ...

/CYP2D6 substrate

haloperidol Haloperidol, sold under the brand name Haldol among others, is a typical antipsychotic medication. Haloperidol is used in the treatment of schizophrenia, tics in Tourette syndrome, mania in bipolar disorder, delirium, agitation, acute psychos ...

. 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. In a placebo-controlled study, the concomitant administration of sertraline and

methadone Methadone, sold under the brand names Dolophine and Methadose among others, is a synthetic opioid used medically to treat chronic pain and opioid use disorder. Prescribed for daily use, the medicine relieves cravings and opioid withdrawal sym ...

caused a 40% increase in blood levels of the latter, which is primarily metabolized by CYP2B6. Bupropion is metabolized by CYP2B6, which is inhibited by sertraline, and this may result in an interaction between sertraline and bupropion. Sertraline had a slight inhibitory effect on the metabolism of

diazepam Diazepam, sold under the brand name Valium among others, is a medicine of the benzodiazepine family that acts as an anxiolytic. It is used to treat a range of conditions, including anxiety disorder, anxiety, seizures, alcohol withdrawal syndr ...

, tolbutamide, and

warfarin Warfarin, sold under the brand name Coumadin among others. It is used as an anticoagulant, anticoagulant medication. It is commonly used to prevent deep vein thrombosis and pulmonary embolism, and to protect against stroke in people who ha ...

, which are

CYP2C9 Cytochrome P450 family 2 subfamily C member 9 (abbreviated CYP2C9) is an enzyme protein. The enzyme is involved in the metabolism, by oxidation, of both xenobiotics, including drugs, and endogenous compounds, including fatty acids. In humans, t ...

or CYP2C19 substrates; the clinical relevance of this effect was unclear. As expected from ''in vitro'' data, sertraline did not alter the human metabolism of the CYP3A4 substrates

erythromycin Erythromycin is an antibiotic used for the treatment of a number of bacterial infections. This includes respiratory tract infections, skin infections, chlamydia infections, pelvic inflammatory disease, and syphilis. It may also be used ...

, carbamazepine, clonazepam, and

terfenadine Terfenadine is an antihistamine formerly used for the treatment of allergic conditions. It was brought to market by Hoechst Marion Roussel (now Sanofi) and was marketed under various brand names, including Seldane in the United States, Triluda ...

; neither did it affect metabolism of the

CYP1A2 Cytochrome P450 1A2 (abbreviated CYP1A2), a member of the cytochrome P450 mixed-function oxidase system, is involved in the metabolism of xenobiotics in the human body. In humans, the CYP1A2 enzyme is encoded by the ''CYP1A2'' gene. Function ...

substrate clozapine. Sertraline did not affect the actions of

digoxin Digoxin (better known as digitalis), sold under the brand name Lanoxin among others, is a medication used to treat various heart disease, heart conditions. Most frequently it is used for atrial fibrillation, atrial flutter, and heart failure. ...

and

atenolol Atenolol is a beta blocker medication primarily used to treat high blood pressure and angina, heart-associated chest pain. Although used to treat high blood pressure, it does not seem to improve mortality rate, mortality in those with the condi ...

, which are not metabolized in the liver.Sertraline FDA Label
Last updated May 2014

Case report In medicine, a case report is a detailed report of the symptoms, signs, diagnosis, treatment, and follow-up of an individual patient. Case reports may contain a demographic profile of the patient, but usually describe an unusual or novel occurrenc ...

s suggest that taking sertraline with phenytoin or

zolpidem Zolpidem, sold under the brand name Ambien among others, is a medication primarily used for the short-term treatment of sleeping problems. Guidelines recommend that it be used only after cognitive behavioral therapy for insomnia and after beh ...

may induce sertraline metabolism and decrease its efficacy, and that taking sertraline with lamotrigine may increase the blood level of lamotrigine, possibly by inhibition of glucuronidation. CYP2C19 inhibitor esomeprazole increased sertraline concentrations in blood plasma by approximately 40%. Clinical reports indicate that interaction between sertraline and the MAOIs isocarboxazid and

tranylcypromine Tranylcypromine, sold under the brand name Parnate among others, is a monoamine oxidase inhibitor (MAOI). More specifically, tranylcypromine acts as nonselective and irreversible inhibitor of the enzyme monoamine oxidase (MAO). It is used a ...

may cause

. In a placebo-controlled study in which sertraline was co-administered with

lithium Lithium (from , , ) is a chemical element; it has chemical symbol, symbol Li and atomic number 3. It is a soft, silvery-white alkali metal. Under standard temperature and pressure, standard conditions, it is the least dense metal and the ...

, 35% of the subjects experienced tremors, while none of those taking placebo did.

Pharmacology

Pharmacodynamics

Sertraline is a

(SSRI). By binding to the serotonin transporter (SERT) it inhibits neuronal reuptake of

serotonin Serotonin (), also known as 5-hydroxytryptamine (5-HT), is a monoamine neurotransmitter with a wide range of functions in both the central nervous system (CNS) and also peripheral tissues. It is involved in mood, cognition, reward, learning, ...

and potentiates serotonergic activity in the

central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain, spinal cord and retina. The CNS is so named because the brain integrates the received information and coordinates and influences the activity o ...

. 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 Brain-derived neurotrophic factor (BDNF), or abrineurin, is a protein found in the and the periphery. that, in humans, is encoded by the ''BDNF'' gene. BDNF is a member of the neurotrophin family of growth factors, which are related to the can ...

(BDNF), which may contribute to a reduction in negative affective biases. It does not significantly affect

histamine Histamine is an organic nitrogenous compound involved in local immune responses communication, as well as regulating physiological functions in the gut and acting as a neurotransmitter for the brain, spinal cord, and uterus. Discovered in 19 ...

acetylcholine Acetylcholine (ACh) is an organic compound that functions in the brain and body of many types of animals (including humans) as a neurotransmitter. Its name is derived from its chemical structure: it is an ester of acetic acid and choline. Par ...

GABA GABA (gamma-aminobutyric acid, γ-aminobutyric acid) is the chief inhibitory neurotransmitter in the developmentally mature mammalian central nervous system. Its principal role is reducing neuronal excitability throughout the nervous system. GA ...

benzodiazepine Benzodiazepines (BZD, BDZ, BZs), colloquially known as "benzos", are a class of central nervous system (CNS) depressant, depressant drugs whose core chemical structure is the fusion of a benzene ring and a diazepine ring. They are prescribed t ...

receptors. However, it does raise acetylcholine levels through inhibition of

acetylcholinesterase Acetylcholinesterase (HUGO Gene Nomenclature Committee, HGNC symbol ACHE; EC 3.1.1.7; systematic name acetylcholine acetylhydrolase), also known as AChE, AChase or acetylhydrolase, is the primary cholinesterase in the body. It is an enzyme th ...

. Sertraline also shows relatively high activity as an inhibitor of the

dopamine transporter The dopamine transporter (DAT, also sodium-dependent dopamine transporter) is a membrane-spanning protein coded for in humans by the ''SLC6A3'' gene (also known as ''DAT1''), that pumps the neurotransmitter dopamine out of the synaptic cleft ba ...

(DAT) occupying ~20% of DAT receptors at doses 200mg and above, and antagonist of the

sigma Sigma ( ; uppercase Σ, lowercase σ, lowercase in word-final position ς; ) is the eighteenth letter of the Greek alphabet. In the system of Greek numerals, it has a value of 200. In general mathematics, uppercase Σ is used as an operator ...

σ₁ receptor (but not the σ₂ receptor). However, sertraline affinity for its main target (SERT) is much greater than its affinity for σ₁ receptor and DAT. Although there could be a role for the σ₁ receptor in the

pharmacology Pharmacology is the science of drugs and medications, including a substance's origin, composition, pharmacokinetics, pharmacodynamics, therapeutic use, and toxicology. More specifically, it is the study of the interactions that occur betwee ...

of sertraline, the significance of this receptor in its actions is unclear. Similarly, the clinical relevance of sertraline's blockade of the dopamine transporter is uncertain.

Pharmacokinetics

Absorption

Following a single oral dose of sertraline, mean peak blood levels of sertraline occur between 4.5 and 8.4 hours.

Bioavailability In pharmacology, bioavailability is a subcategory of absorption and is the fraction (%) of an administered drug that reaches the systemic circulation. By definition, when a medication is administered intravenously, its bioavailability is 100%. H ...

is likely linear and dose-proportional over a dose range of 150 to 200 mg. Concomitant intake of sertraline with food slightly increases sertraline peak levels and total exposure. There is an approximate 2-fold accumulation of sertraline with continuous administration and steady-state levels are reached within one week.

Distribution

Sertraline is highly plasma protein bound (98.5%) across a concentration range of 20 to 500 ng/mL. Despite the high plasma protein binding, sertraline and its

metabolite In biochemistry, a metabolite is an intermediate or end product of metabolism. The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, c ...

desmethylsertraline Desmethylsertraline (DMS), also known as norsertraline, is an active metabolite of the antidepressant drug sertraline. Like sertraline, desmethylsertraline acts as a monoamine reuptake inhibitor, and may be responsible for some of its parent's th ...

at respective tested concentrations of 300 ng/mL and 200 ng/mL were found not to interfere with the plasma protein binding of

and

propranolol Propranolol is a medication of the beta blocker class. It is used to treat hypertension, high blood pressure, some types of cardiac dysrhythmia, irregular heart rate, thyrotoxicosis, capillary hemangiomas, akathisia, performance anxiety, and ...

, two other highly plasma protein-bound drugs.

Metabolism

Sertraline is subject to extensive

first-pass metabolism The first pass effect (also known as first-pass metabolism or presystemic metabolism) is a phenomenon of drug metabolism at a specific location in the body which leads to a reduction in the concentration of the active drug before it reaches the ...

, as indicated by a small study of radiolabeled sertraline in which less than 5% of plasma

radioactivity Radioactive decay (also known as nuclear decay, radioactivity, radioactive disintegration, or nuclear disintegration) is the process by which an unstable atomic nucleus loses energy by radiation. A material containing unstable nuclei is conside ...

was unchanged sertraline in two males. The principal

metabolic pathway In biochemistry, a metabolic pathway is a linked series of chemical reactions occurring within a cell (biology), cell. The reactants, products, and Metabolic intermediate, intermediates of an enzymatic reaction are known as metabolites, which are ...

for sertraline is ''N''-demethylation into

(''N''-desmethylsertraline) mainly by CYP2B6. Reduction, hydroxylation, and glucuronide

conjugation Conjugation or conjugate may refer to: Linguistics *Grammatical conjugation, the modification of a verb from its basic form *Emotive conjugation or Russell's conjugation, the use of loaded language Mathematics *Complex conjugation, the change o ...

of both sertraline and desmethylsertraline also occur. Desmethylsertraline, while pharmacologically active, is substantially (50-fold) weaker than sertraline as a

serotonin reuptake inhibitor A serotonin reuptake inhibitor (SRI) is a type of drug which acts as a reuptake inhibitor of the neurotransmitter serotonin (5-hydroxytryptamine, or 5-HT) by blocking the drug action, action of the serotonin transporter (SERT). This in turn lea ...

and its influence on the clinical effects of sertraline is thought to be negligible. Based on ''

'' studies, sertraline is metabolized by multiple cytochrome 450 isoforms; however, it appears that in the human body CYP2C19 plays the most important role, followed by CYP2B6. In addition to the cytochrome P450 system, sertraline can be oxidatively deaminated ''

'' by

monoamine oxidase Monoamine oxidases (MAO) () are a family of enzymes that catalyze the oxidation of monoamines, employing oxygen to clip off their amine group. They are found bound to the outer membrane of mitochondria in most cell types of the body. The fi ...

s; however, this

has never been studied ''

in vivo Studies that are ''in vivo'' (Latin for "within the living"; often not italicized in English) are those in which the effects of various biological entities are tested on whole, living organisms or cells, usually animals, including humans, an ...

''.

Elimination

The

elimination half-life Biological half-life (elimination half-life, pharmacological half-life) is the time taken for concentration of a biological substance (such as a medication) to decrease from its maximum concentration ( Cmax) to half of Cmax in the blood plasma. ...

of sertraline is on average 26 hours, with a range of 13 to 45 hours. The elimination half-life of desmethylsertraline is 62 to 104 hours. In a small study of two males, sertraline was excreted to similar degrees in

urine Urine is a liquid by-product of metabolism in humans and many other animals. In placental mammals, urine flows from the Kidney (vertebrates), kidneys through the ureters to the urinary bladder and exits the urethra through the penile meatus (mal ...

and

feces Feces (also known as faeces American and British English spelling differences#ae and oe, or fæces; : faex) are the solid or semi-solid remains of food that was not digested in the small intestine, and has been broken down by bacteria in the ...

(40 to 45% each within 9 days). Unchanged sertraline was not detectable in urine, whereas 12 to 14% of unchanged sertraline was present in feces.

Pharmacogenomics

CYP2C19 and CYP2B6 are thought to be the key

cytochrome P450 Cytochromes P450 (P450s or CYPs) are a Protein superfamily, superfamily of enzymes containing heme as a cofactor (biochemistry), cofactor that mostly, but not exclusively, function as monooxygenases. However, they are not omnipresent; for examp ...

enzyme An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...

s involved in the

metabolism Metabolism (, from ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cellular processes; the co ...

of sertraline. Relative to CYP2C19 normal (extensive) metabolizers, poor metabolizers have 2.7-fold higher levels of sertraline and

intermediate metabolizer Pharmacogenomics, often abbreviated "PGx," is the study of the role of the genome in drug response. Its name ('' pharmaco-'' + ''genomics'') reflects its combining of pharmacology and genomics. Pharmacogenomics analyzes how the genetic makeup o ...

s have 1.4-fold higher levels. In contrast, CYP2B6 poor metabolizers have 1.6-fold higher levels of sertraline and intermediate metabolizers have 1.2-fold higher levels.

Chemistry

In terms of

chemical structure A chemical structure of a molecule is a spatial arrangement of its atoms and their chemical bonds. Its determination includes a chemist's specifying the molecular geometry and, when feasible and necessary, the electronic structure of the target m ...

, sertraline is a 1-aminotetralin. Several notable analogues sertraline are known, including

, dasotraline, tametraline, and lometraline.

History

The history of sertraline dates back to the early 1970s when

chemist Reinhard Sarges invented a novel series of psychoactive compounds, including lometraline, based on the structures of the neuroleptics thiothixene and pinoxepin. Further work on these compounds led to tametraline, a

norepinephrine Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic compound, organic chemical in the catecholamine family that functions in the brain and human body, body as a hormone, neurotransmitter and neuromodulator. The ...

and weaker dopamine reuptake inhibitor. Development of tametraline was soon stopped because of undesired

stimulant Stimulants (also known as central nervous system stimulants, or psychostimulants, or colloquially as uppers) are a class of drugs that increase alertness. They are used for various purposes, such as enhancing attention, motivation, cognition, ...

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 ''

'' by animal behavioral scientist Albert Weissman. The most potent and selective (+)-isomer 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. Sertraline was approved by the US

(FDA) in 1991 based on the recommendation of the Psychopharmacological Drugs Advisory Committee; it had already become available in the

United Kingdom The United Kingdom of Great Britain and Northern Ireland, commonly known as the United Kingdom (UK) or Britain, is a country in Northwestern Europe, off the coast of European mainland, the continental mainland. It comprises England, Scotlan ...

the previous year. The FDA committee achieved a consensus that sertraline was safe and effective for the treatment of

major depression Major depressive disorder (MDD), also known as clinical depression, is a mental disorder characterized by at least two weeks of pervasive low mood, low self-esteem, and loss of interest or pleasure in normally enjoyable activities. Intro ...

. 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

and criticized the poor design of the clinical trials by Pfizer. For example, 40% of participants dropped out of the trials, significantly decreasing their validity.See also: 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 The Medicines and Healthcare products Regulatory Agency (MHRA) is an executive agency of the Department of Health and Social Care in the United Kingdom which is responsible for ensuring that medicines and medical devices work and are accepta ...

issued guidance that, apart from

(Prozac), SSRIs are not suitable for the treatment of depression in patients under 18. However, sertraline can still be used in the UK for the treatment of OCD in children and adolescents. In 2005, the FDA added a boxed warning concerning pediatric suicidal behavior to all

antidepressant Antidepressants are a class of medications used to treat major depressive disorder, anxiety disorders, chronic pain, and addiction. Common side effects of antidepressants include Xerostomia, dry mouth, weight gain, dizziness, headaches, akathi ...

s, including sertraline. In 2007, labeling was again changed to add a warning regarding suicidal behavior in young adults ages 18 to 24.

Society and culture

Generic availability

The US patent for Zoloft expired in 2006, and sertraline is available in generic form and is marketed under many brand names worldwide.

Brand names

In the US, Zoloft is marketed by Viatris after Upjohn was spun off from Pfizer.

Interest during COVID-19 pandemic

Sertraline has been the most sought-after antidepressant worldwide before, during, and after the

COVID-19 pandemic The COVID-19 pandemic (also known as the coronavirus pandemic and COVID pandemic), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), began with an disease outbreak, outbreak of COVID-19 in Wuhan, China, in December ...

, according to Google Trends data. The pandemic has led to an increase in searches for antidepressants, with sertraline,

, duloxetine, and

showing the highest search volumes, whereas searches of

decreased during the pandemic.

Other uses

Sertraline may be useful to treat murine Zaire ebolavirus (murine EBOV). The

World Health Organization The World Health Organization (WHO) is a list of specialized agencies of the United Nations, specialized agency of the United Nations which coordinates responses to international public health issues and emergencies. It is headquartered in Gen ...

(WHO) considers this a promising area of research. Lass-Flörl ''et al.'', 2003 finds it significantly inhibits phospholipase B in the fungal genus '' Candida'', reducing

virulence Virulence is a pathogen's or microorganism's ability to cause damage to a host. In most cases, especially in animal systems, virulence refers to the degree of damage caused by a microbe to its host. The pathogenicity of an organism—its abili ...

. Sertraline is also a very effective leishmanicide. Specifically, Palit & Ali 2008 find that sertraline kills almost all promastigotes of ''

Leishmania donovani ''Leishmania donovani'' is a species of intracellular parasites belonging to the genus ''Leishmania'', a group of haemoflagellate kinetoplastids that cause the disease leishmaniasis. It is a human blood parasite responsible for visceral leishm ...

''. Sertraline is strongly

antibacterial An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention ...

against some species. It is also known to act as a photosensitizer of bacterial surfaces. In combination with antibacterials its photosensitization effect reverses antibacterial resistance. As such sertraline shows promise for

food preservation Food preservation includes processes that make food more resistant to microorganism growth and slow the redox, oxidation of fats. This slows down the decomposition and rancidification process. Food preservation may also include processes that in ...

. Lass-Flörl ''et al.'', 2003 finds this compound acts as a

fungicide Fungicides are pesticides used to kill parasitic fungi or their spores. Fungi can cause serious damage in agriculture, resulting in losses of yield and quality. Fungicides are used both in agriculture and to fight fungal infections in animals, ...

against '' Candida parapsilosis''. Its anti-''Cp'' effect is indeed due to its serotonergic activity and not its other effects. Sertraline is a promising trypanocide. It acts at several different life stages and against several strains. Sertraline's trypanocidal

mechanism of action In pharmacology, the term mechanism of action (MOA) refers to the specific biochemical Drug interaction, interaction through which a Medication, drug substance produces its pharmacological effect. A mechanism of action usually includes mention o ...

is by way of interference with bioenergetics. This review cites this study:

References

External links

{{Authority control 1-Aminotetralins Secondary amines Antidepressants Chlorobenzene derivatives CYP2D6 inhibitors Dopamine reuptake inhibitors Drugs developed by Pfizer Selective serotonin reuptake inhibitors Sigma antagonists Wikipedia medicine articles ready to translate