Definition
A selective serotonin uptake inhibitor that is used in the treatment of depression.
A selective serotonin uptake inhibitor that is used in the treatment of depression.; Sertraline hydrochloride (also labeled under numerous brand names: Zoloft, Sertralin, Lustral, Apo-Sertral, Asentra, Gladem, Serlift, Stimuloton, Xydep, Serlain, Concorz) is an orally administered antidepressant of the selective serotonin reuptake inhibitor (SSRI) type. It was first approved by the Food and Drug Administration (FDA) in 1991.; Sertraline is an odorless, white, sparingly soluble crystalline solid. The minimum effective dose is usually 50 mg per day (it can be still effective at 25 mg or 37.5 mg), but lower doses may be used in the initial weeks of treatment to acclimate the patient's body, especially the liver, to the drug and to minimize the severity of any side effects. Patients who do not experience relief of symptoms at 50 mg a day may have their dose increased, up to 200 mg a day.; Sertraline (HCl) is used medically mainly to treat the symptoms of depression and anxiety. It is also prescribed for the treatment of obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), premenstrual dysphoric disorder (PMDD), panic disorder (PD) and social phobia/social anxiety disorder.; A study has shown that sertraline is an effective treatment for impulsive aggressive behavior in personality disordered patients. [HMDB]
Description
Sertraline hydrochloride belongs to a class of antidepressant agents known as selective serotonin-reuptake inhibitors (SSRIs). Despite distinct structural differences between compounds in this class, SSRIs possess similar pharmacological activity. As with other antidepressant agents, several weeks of therapy may be required before a clinical effect is seen. SSRIs are potent inhibitors of neuronal serotonin reuptake. They have little to no effect on norepinephrine or dopamine reuptake and do not antagonize α- or β-adrenergic, dopamine D2 or histamine H1 receptors. During acute use, SSRIs block serotonin reuptake and increase serotonin stimulation of somatodendritic 5-HT1A and terminal autoreceptors. Chronic use leads to desensitization of somatodendritic 5-HT1A and terminal autoreceptors. The overall clinical effect of increased mood and decreased anxiety is thought to be due to adaptive changes in neuronal function that leads to enhanced serotonergic neurotransmission. Side effects include dry mouth, nausea, dizziness, drowsiness, sexual dysfunction and headache (see Toxicity section below for a more detailed listing of side effects). Compared to other agents in this class, sertraline may cause greater diarrheal and male sexual dysfunction effects. Side effects generally occur within the first two weeks of therapy and are usually less severe and frequent than those observed with tricyclic antidepressants. Sertraline may be used to treat major depressive disorder, obsessive-compulsive disorder (OCD), panic disorder, post-traumatic stress disorder (PTSD), premenstrual dysphoric disorder (PMDD) and social anxiety disorder (social phobia).
Top Gene Interactions
Related Pathways
General Information
- Metabolism: Extensively metabolized in the liver. Sertraline metabolism involves N-demethylation, N-hydroxylation, oxidative deamination, and glucuronidation of sertraline carbamic acid. Sertraline undergoes N-demethylation primarily catalyzed by cytochrome P450 (CYP) 2B6, with CYP2C19, CYP3A4 and CYP2D6 contributing to a lesser extent. Deamination occurs via CYP3A4 and CYP2C19. In vitro studies have shown that monoamine oxidase A and B may also catalyze sertraline deamination. Sertraline N-carbamoyl glucuronidation has also been observed in human liver microsomes. Route of Elimination: Sertraline is extensively metabolized and excretion of unchanged drug in urine is a minor route of elimination. Half Life: The elimination half-life of sertraline is approximately 25-26 hours. The elimination half-life of desmethylsertraline is approximately 62-104 hours.
- Uses/Sources: For the management of major depressive disorder, posttraumatic stress disorder, obsessive-compulsive disorder, panic disorder with or without agoraphobia, premenstrual dysphoric disorder, social phobia, premature ejaculation, and vascular headaches.
- Symptoms: Symptoms of toxicity include alopecia, decreased libido, diarrhea, ejaculation disorder, fatigue, insomnia, somnolence and serotonin syndrome.
- Treatment: Treatment should consist of those general measures employed in the management of overdosage with any antidepressant. Ensure an adequate airway, oxygenation and ventilation. Monitor cardiac rhythm and vital signs. General supportive and symptomatic measures are also recommended. Induction of emesis is not recommended. Gastric lavage with a large-bore orogastric tube with appropriate airway protection, if needed, may be indicated if performed soon after ingestion, or in symptomatic patients. Activated charcoal should be administered. Due to large volume of distribution of this drug, forced diuresis, dialysis, hemoperfusion and exchange transfusion are unlikely to be of benefit. No specific antidotes for sertraline are known. (L1712)
- Route of Exposure: The effects of food on the bioavailability of the sertraline tablet and oral concentrate were studied in subjects administered a single dose with and without food. For the tablet, AUC was slightly increased when drug was administered with food but the Cmax was 25% greater, while the time to reach peak plasma concentration (Tmax) decreased from 8 hours post-dosing to 5.5 hours. For the oral concentrate, Tmax was slightly prolonged from 5.9 hours to 7.0 hours with food.
Mechanism of Action
| Target Name | Mechanism of Action | References |
|---|---|---|
|
Cytochrome P450 3A4 Sodium-dependent dopamine transporter Sodium-dependent noradrenaline transporter Cytochrome P450 2D6 Cytochrome P450 2C9 Cytochrome P450 2C19 |
21093273 9537821 15181382 16314097 9871604 18664165 17187269 9808077 |
|
|
5-hydroxytryptamine receptor 1A Sodium-dependent serotonin transporter Cytochrome P450 3A3 |
It is believed that sertraline inhibits reuptake of serotonin at the neuronal membrane. SSRIs have less sedative, anticholinergic, and cardiovascular effects than the tricyclic antidepressant drugs because of decreased binding to histamine, acetylcholine, and norepinephrine receptors. |
21093273 12955294 11750179 11243491 8951980 12143142 16154484 14709940 15606893 16963794 12151556 10774624 12647451 10575045 16314097 9871604 16035959 15547048 |
Sertraline Interacts with Diseases
| Disease | Inference Score | References/Inference Genes |
| Lipidoses | 57.11 | |
| Prostatic Neoplasms | 32.85 |
References/Inference Genes
|
| Brain Ischemia | 30.57 | |
| Arthritis, Juvenile | 26.93 | |
| Reperfusion Injury | 25.32 | |
| Stomach Neoplasms | 22.33 | |
| Breast carcinoma | 21.14 |
References/Inference Genes
|
| Autism | 20.49 | |
| Heat Stroke | 20.39 |
|
| Neoplasm Metastasis | 19.33 | |
| Endometriosis | 18.45 | |
| Status Epilepticus | 18.42 | |
| Trigeminal Neuralgia | 17.77 |
|
| Kidney Failure, Chronic | 17.61 | |
| Squamous cell carcinoma | 17.08 | |
| Hepatocellular carcinoma | 16.7 | |
| Colonic neoplasm | 16.07 | |
| Parkinson's disease | 16.06 | |
| Liver Cirrhosis, Experimental | 16.02 | |
| Diabetes Mellitus, Type 2 | 15.86 |