Sertraline, sold under the brand name Zoloft among others, is an antidepressant medication of the selective serotonin reuptake inhibitor (SSRI) class used to treat major depressive disorder, generalized anxiety disorder, social anxiety disorder, obsessive–compulsive disorder (OCD), panic disorder, and premenstrual dysphoric disorder.[5] Although also having approval for post-traumatic stress disorder (PTSD), findings indicate it leads to only modest improvements in symptoms associated with this condition.
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. In some patients, sexual dysfunction may persist even after the drug is discontinued, a condition known as post-SSRI sexual dysfunction; regulatory agencies including the European Medicines Agency and Health Canada have recommended that sertraline's product labeling warn of this risk. 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.
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[6] and available as a generic medication.[7] In 2016, sertraline was the most commonly prescribed psychotropic medication in the United States.[8] It was also the eleventh most commonly prescribed medication in the United States, with more than 42million prescriptions in 2023,[9][10] and sertraline ranks among the top 10 most prescribed medications in Australia between 2017 and 2023.[11]
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.[12]
Contraindications
Sertraline is contraindicated in individuals taking monoamine oxidase inhibitors or the antipsychotic pimozide. Liquid formulations of sertraline contain ethanol and are 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.[12]
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.[12] The incidence of diarrhea is higher with sertraline – especially when prescribed at higher doses – in comparison with other SSRIs.[68]
Over more than six months of sertraline therapy for depression, people showed no significant weight increase.[69] A 30-month-long treatment with sertraline for OCD also resulted in no significant weight gain.[70] 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).
Therapeutic dosage
The therapeutic dosage varies according to the patient's age and/or clinical condition, but for all treatments with sertraline, it is recommended to start with lower dosages (25 to 50 mg/daily) and adjust according to the patient's therapeutic response, with a maximum maintenance dose of up to 200 mg per day.[106]
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.[107] As with most other SSRIs its toxicity in overdose is considered relatively low.[108][109]
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.[110] Sertraline, in particular, may potentially diminish the efficacy of levothyroxine.[111]
Sertraline is a moderate inhibitor of CYP2D6 and CYP2B6 in vitro.[112] 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
Pharmacology
Pharmacodynamics
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.[12] Over time, this leads to a downregulation of pre-synaptic 5-HT1A 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.[136][137] It does not significantly affect histamine, acetylcholine, GABA or benzodiazepine receptors.[12]
Chemistry
In terms of chemical structure, sertraline is a 1-aminotetralin.[152] Several notable analogues sertraline are known, including desmethylsertraline, dasotraline, tametraline, and lometraline.[152]
History
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.[153] 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 (+)-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".
Society and culture
Research
Sertraline may be useful to treat murine Zaire ebolavirus (murine EBOV). The World Health Organization (WHO) considers this a promising area of research.[172]
Lass-Flörl et al., 2003 finds it significantly inhibits phospholipase B in the fungal genus Candida, reducing virulence.[173]
Sertraline is also a very effective leishmanicide. Specifically, Palit & Ali 2008 find that sertraline kills almost all promastigotes of Leishmania donovani.
Sertraline is strongly antibacterial against some species.[174] 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.[175]
See also
- List of antidepressants
External links
References
- Sertraline (Zoloft) Use During Pregnancy Drugs.com, 4 May 2020, retrieved 17 May 2020^
- Substance Abuse in the Mentally and Physically Disabled CRC Press, 2001^
- Anvisa. RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial