Question explored with the scientific record
Sertraline side effects
The short version: sertraline helps some people but the evidence on its harms is incomplete, especially in children, and the risk of suicidality in youth is real.
The evidence here comes from manufacturer-funded or academic trials, none independently replicated. The largest observational study found nearly three out of four patients reported adverse events [1]. Nausea (24%), headache (19%), and diarrhea (14%) were most common [1]. In children, 84% reported at least one adverse event, with headache, nausea, and insomnia each at 21% [9]. The pediatric suicidality signal is the most serious: one analysis found 2.65% of children on sertraline reported suicidality versus 1.09% on placebo, giving a number needed to harm of 64 [15]. A separate Danish study found overall suicidality decreased after SSRI initiation, but prior suicidality was the strongest predictor of post-treatment events [16]. The evidence does not include a single long-term safety study comparing sertraline users to untreated controls. The overdose case report shows that psychiatric symptoms can emerge hours after physical symptoms resolve [19], a pattern the system does not monitor in routine use.
| Adverse event | Sertraline rate | Comparator rate | Source |
|---|---|---|---|
| Any adverse event | ~74% | similar to other SSRIs | [1] |
| Nausea | 24.3% | 27.0% (other SSRIs) | [1] |
| Diarrhea | 14.0% | 6.8% (other SSRIs) | [1] |
| Pediatric suicidality | 1.6% | 1.0% (placebo) | [15] |
| Pediatric any AE | 84% | no placebo comparator | [9] |
My call: sertraline has a real adverse event burden and a documented suicidality risk in children that the evidence does not fully quantify. The long-term safety data does not exist. Confidence: moderate for common side effects, low for long-term and pediatric safety.
Sources examined 20
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Adverse events in users of sertraline: results from an observational study in psychiatric practice in The Netherlands
This observational study evaluates the safety profile of sertraline compared to other SSRIs in psychiatric practice in The Netherlands, finding that nearly three out of four patients reported adverse events, with a similar distribution of common adverse events across both groups.
DOI: 10.1002/pds.752 -
Un estudio multicéntrico doble ciego controlado con placebo de sertralina en el tratamiento agudo y de continuación de la depresión mayor
Sertraline demonstrates superior efficacy to placebo in the acute treatment (6 weeks) of major depressive disorder in outpatients, with higher response rates and lower discontinuation due to inefficacy; continuation among acute responders shows persistent improvement more often …
DOI: 10.1017/s1134066500002769 -
A double-blind comparison of sertraline and fluoxetine in the treatment of major depressive episode in outpatients
Sertraline and fluoxetine both yielded significant depression relief over six months in outpatients with major depressive disorder, with sertraline showing a non-significant trend toward greater efficacy and QoL gains and comparable tolerability to fluoxetine.
DOI: 10.1016/s0924-9338(99)80714-7 -
Major Depression and Its Response to Sertraline in Primary Care vs. Psychiatric Office Practice Patients
Open-label sertraline (50 mg/day with possible escalation to 100 mg/day) for 8 weeks produced substantial depressive-symptom reduction in adults with major depression in both primary care and psychiatric office settings in Argentina, with similar outcomes, high adherence, and so…
DOI: 10.1016/s0033-3182(99)71274-0 -
Effectiveness and acceptability of sertraline and citalopram in major depressive disorder: pragmatic randomized open‐label comparison
This study compares the effectiveness and acceptability of citalopram and sertraline in treating major depressive disorder in Indian patients, finding that citalopram is more effective with an earlier onset of action.
DOI: 10.1002/hup.864 -
Efficacy of Sertraline in Preventing Relapse of Posttraumatic Stress Disorder: Results of a 28-Week Double-Blind, Placebo-Controlled Study
This randomized, 28-week double-blind, placebo-controlled maintenance trial shows sertraline significantly reduces relapse and prolongs remission in PTSD patients who had previously responded to acute and continuation treatment, compared with placebo.
DOI: 10.1176/APPI.AJP.158.12.1974 -
Comparing escitaloipram with sertraline for obsessive and compulsive symptoms in patients with obsessive compulsive disorder: A comparative double blind clinical trial
In this randomized, double-blind clinical trial conducted at a single center in Iran, escitalopram and sertraline showed comparable efficacy and safety for obsessive-compulsive symptoms in OCD over 12 weeks, with no significant differences in Y-BOCS or CGI-2 outcomes.
DOI: 10.1016/j.ajp.2017.11.004 -
Does oral administration of ketamine accelerate response to treatment in major depressive disorder? Results of a double-blind controlled trial
A randomized, double-blind trial shows that adding a fixed low-dose oral ketamine to sertraline accelerates and enhances antidepressant response in adults with moderate-to-severe major depressive disorder over six weeks, with early improvement and higher response and a favorable…
DOI: 10.1016/j.jad.2018.02.056 -
Sertraline Treatment of Children and Adolescents With Obsessive‐Compulsive Disorder or Depression: Pharmacokinetics, Tolerability, and Efficacy
An open-label pediatric study of sertraline in children (6–12) and adolescents (13–17) with major depression and/or OCD found adult-like pharmacokinetics and overall good tolerability, with efficacy signals for depression and OCD and support for using the standard adult titratio…
DOI: 10.1097/00004583-199804000-00016 -
0807 Sleep-related hiccups: A case report of antidepressant associated hypnic jerks
This paper reports a single case of antidepressant-associated sleep-related hiccups and hypnic jerks, with video/audio documentation and polysomnography confirming severe sleep events and leading to CPAP intervention, highlighting a potential adverse effect of antidepressants on…
DOI: 10.1093/sleep/zsac079.803 -
P321 Neuronal activity correlates with treatment response to transcranial magnetic stimulation (TMS) in auditory verbal hallucinations (AVH)
This randomized sham-controlled trial evaluated whether 10 daily sessions of transcranial micropolarization (TCMP) combined with sertraline improve depressive symptoms more than 20-minute TCMP or sham, finding the 30-minute TCMP protocol yields greater improvement and acceptable…
DOI: 10.1016/j.clinph.2016.10.391 -
A Double-Blind, Placebo-Controlled Study of Sertraline in the Prevention of Depression in Stroke Patients
This study demonstrates that sertraline significantly reduces the incidence of poststroke depression in nondepressed patients following an acute ischemic stroke compared to placebo over a 12-month period.
DOI: 10.1176/appi.psy.44.3.216 -
Quetiapine augmentation for depression
A retrospective EMR study of 977 patients with major depressive disorder treated with quetiapine augmentation found real-world dosing is lower than FDA/RCT doses, with mean initial 23.6 mg/day and maintenance 40.7 mg/day over about six months, and common adverse events including…
DOI: 10.1097/yic.0000000000000055 -
Childhood trauma predicts antidepressant response in adults with major depression: data from the randomized international study to predict optimized treatment for depression
Abuse in childhood, especially during ages 4–7, predicts poorer acute antidepressant response and remission in adults with major depressive disorder, with sertraline showing the strongest disadvantage for those with that history.
DOI: 10.1038/tp.2016.61 -
Treatment Benefit and the Risk of Suicidality in Multicenter, Randomized, Controlled Trials of Sertraline in Children and Adolescents
This study evaluates the balance between the treatment benefits of sertraline and the associated risk of suicidality in children and adolescents through a review of multicenter, randomized, controlled trials.
DOI: 10.1089/cap.2006.16.91 -
Suicidality and self‐injury with selective serotonin reuptake inhibitors in youth: Occurrence, predictors and timing
A retrospective, observational within-subject study of 365 children and adolescents treated with SSRIs in Danish CAMHS, describing the occurrence, timing, and predictors of suicidality and non-suicidal self-injury, and finding that overall suicidality decreased after SSRI initia…
DOI: 10.1111/acps.13360 -
Sertraline-induced pseudocholinesterase enzyme deficiency
A case report of acquired pseudocholinesterase deficiency likely linked to chronic sertraline use, causing prolonged mivacurium-induced neuromuscular blockade during laparoscopic cholecystectomy, with recovery after sertraline withdrawal and supportive care.
DOI: 10.2147/ijgm.s14365 -
Ginsenoside Rg1 fails to rescue PTSD-like behaviors in a mice model of single-prolonged stress
Using a mouse model of PTSD induced by single-prolonged stress (SPS), the study shows that ginsenoside Rg1 at 10 mg/kg fails to rescue SPS-induced anxiety- and despair-like behaviors, contextual fear memory, hippocampal neurogenesis deficits, or SPS-elevated serum ACTH, whereas …
DOI: 10.1016/j.bbrc.2020.05.159 - Asynchronicity of Organic and Psychiatric Symptoms in a Case of Sertraline Intoxication DOI: 10.1097/wnf.0000000000000169
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Obsessive-compulsive disorder after long-term cannabis use – case report
A single-patient case report examining the dual role of cannabis/cannabinoids in OCD, showing symptom improvement after cannabis abstinence with sertraline but also suggesting cannabis derivatives could trigger OCD, thereby highlighting the need for further research.
DOI: 10.1192/j.eurpsy.2023.1369