Sertraline Trade names Zoloft.
Pregnancy category AU: C
Routes of administration By mouth
Drug class Selective serotonin reuptake inhibitor (SSRI)
Bioavailability 44%
Protein binding 98.5%
Metabolism Liver mainly by CYP2B6; also metabolism by CYP2C19
Elimination half-life • Sertraline: 26 hours (32 hours in females, 22 hours in males; range 13–45 hours)
Metabolite: Desmethylsertraline: 62–104 hours
Excretion Urine (40–45%)
Feces (40–45%)
Sertraline, sold under the brand name Zoloft among others, is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class.
The effectiveness of sertraline for depression is similar to that of other antidepressants, and the differences are mostly confined to side effects.
Sertraline is better tolerated than the older tricyclic antidepressants, and is effective for panic disorder, social anxiety disorder, generalized anxiety disorder (GAD), and obsessive–compulsive disorder (OCD).
Sertraline leads to only modest improvement in post-traumatic stress disorder (PTSD).
Sertraline also alleviates the symptoms of premenstrual dysphoric disorder (PMDD) and can be used in sub-therapeutic doses or intermittently for its treatment.
Sertraline shares the common side effects and contraindications of other SSRIs: high rates of diarrhea, nausea, insomnia, and sexual dysfunction.
Sertraline appears not to lead to much weight gain, and its effects on cognitive performance are mild.
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 has been approved for major depressive disorder (MDD), obsessive–compulsive disorder (OCD), post-traumatic stress disorder (PTSD), premenstrual dysphoric disorder (PMDD), panic disorder, and social anxiety disorder (SAD).
Sertraline displays similar efficacy to other SSRI antidepressants.
It fails 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.
Sertraline is consistently more effective than placebo for dysthymia, a more chronic variety of depression, and comparable to imipramine in that respect.
It improves the functional impairments of dysthymia to a similar degree whether group Cognitive-Behavioural Therapy is undergone or not.
Sertraline’s efficacy is similar to that of other antidepressants.
Sertraline and escitalopram are the best in terms of efficacy and acceptability in the acute-phase treatment of adults with depression.
Sertraline is similar in efficacy against depression to moclobemide, nefazodone, escitalopram, bupropion, citalopram, fluvoxamine, paroxetine, venlafaxine, and mirtazapine.
It may be more efficacious for the treatment of depression in the acute phase (than fluoxetine.
For severe depression, sertraline is as good as clomipramine but is better tolerated.
Sertraline appears to work better in depression than fluoxetine, paroxetine, 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.
Compared with amitriptyline, sertraline offered a greater overall improvement in quality of life of depressed patients.
Sertraline used for the treatment of depression in elderly patients is superior to placebo and comparable to another SSRI fluoxetine, and tricyclic antidepressants (TCAs) amitriptyline, nortriptyline and imipramine.
Sertraline has lower rates of adverse effects than tricyclic antidepressants with the exception of nausea, which occurs more frequently with sertraline.
Sertraline is more effective than fluoxetine or nortriptyline in the older-than-70 subgroup..
A meta-analysis of antidepressants in older adults found that sertraline, paroxetine and duloxetine were better than placebo: the effect size was modest, and there was no improvement in quality of life as compared to placebo.
With depression in dementia, there is no benefit of sertraline treatment compared to either placebo or mirtazapine.
Sertraline is effective for the treatment of OCD, performing better than the gold standard of OCD treatment clomipramine.
Sertraline treatment helps prevent relapses of OCD with data supporting its use for up to 24 months.
The sertraline dosages necessary for the effective treatment of OCD are higher than for depression.
Cognitive behavioral therapy alone is not more effective than sertraline however, a combination of these treatments is effective.
Sertraline is superior to placebo for the treatment of panic disorder, decreasing the frequency of panic attacks by about 80% (vs. 45% for placebo) and decreasing general anxiety, sertraline resulted in improvement of quality of life on most parameters.
The response rate was lower for the patients with more severe panic.
Starting treatment together with sertraline and clonazepam, with subsequent gradual discontinuation of clonazepam, may accelerate the response.
Studies have found sertraline to have the same effect on panic disorder as paroxetine, imipramine, clomipramine,, clonazepam, alprazolam, and fluvoxamine.
Sertraline has been successfully used for the treatment of social anxiety disorder, with fear, avoidance, and physiological symptoms:
Fear, avoidance, and physiological symptoms of social anxiety respond to sertraline.
Maintenance treatment for social anxiety, 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.[
The combination of sertraline and cognitive behavioral therapy appears to be more effective in children and young people than either treatment alone.
Sertraline is effective in alleviating the symptoms of premenstrual dysphoric disorder.
Significant improvement was observed in 50–60% of cases treated with sertraline vs. 20–30% of cases on placebo, with improvement during the first week of treatment in 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, are less responsive to sertraline.
Taking sertraline only during the luteal phase, that is, the 12–14 days before menses, was shown to work as well as continuous treatment.
Continuous treatment with sub-therapeutic doses of sertraline (25 mg vs. usual 50–100 mg) is also effective alleviating the symptoms of premenstrual dysphoric disorder.
Sertraline is approved for the treatment of post-traumatic stress disorder (PTSD).
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.
Sertraline when taken daily can be useful for the treatment of premature ejaculation, but it requires continuous daily treatment to delay ejaculation significantly.
Sertraline may be a good way to control anger, irritability and hostility in depressed patients and patients with other comorbidities.
Sertraline is contraindicated in individuals taking monoamine oxidase inhibitors, the antipsychotic pimozide, and disulfiram.
Treatment of the elderly and patients with liver impairment require caution.
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 .
Symptoms most often resulted 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 show no significant weight increase.
Treatment of healthy volunteers with 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.
In spite of lower 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.
Sertraline has a low level of exposure 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 congenital heart defects among children whose mothers were prescribed sertraline during pregnancy.
Sertraline use in the first trimester associated with 2.7-fold increase in septal heart defects.
Abrupt interruption of sertraline use may result in withdrawal or discontinuation syndrome: Dizziness, insomnia, anxiety, agitation, and irritability are its common symptoms.
Withdrawal typically occurs within a few days from drug discontinuation and lasts a few weeks.
Withdrawal symptoms for sertraline are less severe and frequent than with paroxetine, and more frequent than for fluoxetine.
In most cases withdrawal symptoms are mild, short-lived, and resolve without treatment.
Sertraline and SSRI antidepressants in general may be associated with bruxism and other movement disorders.
Sertraline appears to be associated with microscopic colitis, a rare condition of unknown etiology.
Like other SSRIs, sertraline is associated with sexual side effects, including sexual arousal disorder, erectile dysfunction and difficulty achieving orgasm.
67% of men on sertraline experienced ejaculation difficulties versus 18% before the treatment.
Sexual arousal disorder, is defined as inadequate lubrication and swelling for women and erectile difficulties for men, occurs in 12% of people on sertraline as compared with 1% of patients on placebo.
The mood improvement resulting from sertraline sometimes counteracted these side effects, so that sexual desire and overall satisfaction with sex stayed the same as before the sertraline treatment.
Some people continue experiencing sexual side effects after they stop taking SSRIs.
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.
There is a 100% increase of suicidal thoughts and behavior in children and adolescents, and a 50% increase in the 18–24 age group.
Suicidal ideation and behavior in clinical trials are rare.
Acute overdosage is often manifested by emesis, lethargy, ataxia, tachycardia and seizures.
Plasma, serum or blood concentrations of sertraline 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.
As with other SSRIs, sertraline may increase the risk of bleeding with NSAIDs, 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.
Sertraline, in particular, may potentially diminish the efficacy of levothyroxine.
Sertraline is a moderate inhibitor of CYP2D6 and CYP2B6.
It causes increased blood levels of CYP2D6 substrates such as metoprolol, dextromethorphan, desipramine, methadone,imipramine and nortriptyline, as well as the CYP3A4/CYP2D6 substrate haloperidol:This effect is dose-dependent.
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, tolbutamide and warfarin, which are CYP2C9 or CYP2C19 substrates; the clinical relevance of this effect was unclear.
Phenytoin or zolpidem may induce sertraline metabolism and decrease its efficacy.
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 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.
Sertraline is a selective serotonin reuptake inhibitor (SSRI), that binding to the serotonin transporter (SERT) it inhibits neuronal reuptake of serotonin and potentiates serotonergic activity in the central nervous system.
This leads to a downregulation of pre-synaptic 5-HT1A receptors, associated with an improvement in passive stress tolerance.
The delayed downstream increase in expression of brain-derived neurotrophic factor (BDNF), which may contribute to a reduction in negative affect.
Sertraline does not significantly affect histamine, acetylcholine, GABA or benzodiazepine receptors.
Sertraline also shows relatively high activity as an inhibitor of the dopamine transporter.
Following a single oral dose of sertraline, mean peak blood levels of sertraline occur between 4.5 and 8.4 hours.
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.
Sertraline is highly plasma protein bound (98.5%) across a concentration range of 20 to 500 ng/mL.
Sertraline is subject to extensive first-pass metabolism.
The principal metabolic pathway for sertraline is N-demethylation into desmethylsertraline (N-desmethylsertraline) mainly by CYP2B6.
Reduction, hydroxylation, and glucuronide conjugation of both sertraline and desmethylsertraline also occur.
Desmethylsertraline, while pharmacologically active, is substantially (50-fold) weaker than sertraline as a serotonin reuptake inhibitor.
The elimination half-life of sertraline is on average 26 hours.
Its half-life has a range of 13 to 45 hours.
The half-life of sertraline is longer in women (32 hours) than in men (22 hours).
There is 1.5-fold higher exposure to sertraline in women compared to men.
Sertraline is excreted to similar degrees in urine and feces.
Unchanged sertraline was not detectable in urine, whereas 12 to 14% unchanged sertraline was present in feces.
CYP2C19 and CYP2B6 are thought to be the key cytochrome P450 enzymes involved in the metabolism of sertraline.
Relative to CYP2C19 normal (extensive) metabolizers, poor metabolizers have 2.7-fold higher levels of sertraline.
Intermediate metabolizers 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.