What are the long-term risks of using sertraline (Selective Serotonin Reuptake Inhibitor - SSRI)?

From the Guidelines

Sertraline, a commonly prescribed selective serotonin reuptake inhibitor (SSRI), carries several potential long-term risks, including sexual dysfunction, weight gain, emotional blunting, physical dependence, and increased risk of suicidal thinking and behavior, particularly in youths under 24 years old, as reported in the most recent study 1.

Common Long-term Side Effects

• Sexual dysfunction, affecting 30-50% of users, which may include decreased libido, delayed orgasm, or erectile dysfunction
• Weight gain, typically modest at 1-2 kg but potentially more significant for some individuals
• Emotional blunting or feeling emotionally "flat," which can persist throughout treatment
• Physical dependence, leading to withdrawal symptoms if the medication is stopped abruptly rather than tapered gradually

Severe Adverse Events

• Suicidality, with a pooled absolute rate of 1% for suicidal ideation in youths treated with an antidepressant, and a number needed to harm (NNH) of 143, as reported in 1
• Behavioral activation/agitation, more common in younger children than adolescents, which may occur early in SSRI treatment, with dose increases, or with concomitant administration of drugs that inhibit the metabolism of SSRIs
• Serotonin syndrome, a potentially life-threatening condition caused by elevated brain serotonin levels, which can be triggered when serotonergic medications are combined, as warned in 1

Recommendations

• Close monitoring for suicidality is recommended, especially in the first months of treatment and following dosage adjustments, as advised in 1
• Patients should discuss any persistent side effects with their healthcare provider rather than discontinuing the medication suddenly
• The benefits of treating depression or anxiety disorders with sertraline should be carefully weighed against the potential long-term risks, and alternative treatments should be considered if necessary, as suggested in 1

From the FDA Drug Label

The risks, if any, that may be associated with sertraline’s use beyond 1 year in children and adolescents with OCD or major depressive disorder have not been systematically assessed In particular, there are no studies that directly evaluate the effects of long-term sertraline use on the growth, development, and maturation of children and adolescents Although there is no affirmative finding to suggest that sertraline possesses a capacity to adversely affect growth, development or maturation, the absence of such findings is not compelling evidence of the absence of the potential of sertraline to have adverse effects in chronic use Sertraline therapy was associated with small mean increases in total cholesterol (approximately 3%) and triglycerides (approximately 5%), and a small mean decrease in serum uric acid (approximately 7%) of no apparent clinical importance The safety profile observed with sertraline treatment in patients with major depressive disorder, OCD, panic disorder, PTSD, PMDD and social anxiety disorder is similar (including Torsade de Pointes arrhythmias) (including reversible cerebral vasoconstriction syndrome and Call-Fleming syndrome) hypothyroidism, agranulocytosis, aplastic anemia and pancytopenia, leukopenia, thrombocytopenia, lupus-like syndrome, serum sickness, diabetes mellitus, hyperglycemia, galactorrhea, hyperprolactinemia, extrapyramidal symptoms, oculogyric crisis, serotonin syndrome, psychosis, pulmonary hypertension, severe skin reactions, which potentially can be fatal, such as Stevens-Johnson syndrome, vasculitis, photosensitivity and other severe cutaneous disorders, rare reports of pancreatitis, and liver events-clinical features (which in the majority of cases appeared to be reversible with discontinuation of sertraline) occurring in one or more patients include: elevated enzymes, increased bilirubin, hepatomegaly, hepatitis, jaundice, abdominal pain, vomiting, liver failure and death.

The long-term risks of using sertraline include:

• Potential effects on growth, development, and maturation in children and adolescents that have not been systematically assessed 2
• Increased risk of hyponatremia in elderly patients 2
• Small mean increases in total cholesterol and triglycerides 2
• Severe skin reactions, such as Stevens-Johnson syndrome 2
• Liver events, including elevated enzymes, hepatitis, and liver failure 2
• Other rare but potentially serious adverse events, such as agranulocytosis, aplastic anemia, and pancytopenia 2

From the Research

Long-term Risks of Sertraline

The long-term risks of using sertraline, a Selective Serotonin Reuptake Inhibitor (SSRI), include:

• Increased risk of tachyphylaxis and discontinuation syndrome 3
• Potential impact on bone mineral density (BMD) and increased risk of osteoporosis 4
• Risk of adverse events (AEs), including psychiatric and gastrointestinal disorders, particularly in children and adolescents 5
• Possible long-term harms that persist after end of drug intake, although current evidence is limited and inconclusive 6

Specific Risks

Some specific risks associated with long-term sertraline use include:

• Relapse prevention as a major benefit, but also increased risk of tachyphylaxis and discontinuation syndrome 3
• Decreased BMD and increased fracture risk, particularly in the early stages of treatment 4
• Higher rates of AEs, including psychiatric and gastrointestinal disorders, in children and adolescents 5
• Potential for long-term harms, including mortality, functional outcomes, quality of life, and core psychiatric events, although evidence is limited 6

Considerations for Long-term Use

When considering long-term use of sertraline, the following factors should be taken into account:

• The decision to continue or discontinue sertraline should be an active one, involving both the patient and prescriber, and should be revisited periodically 3
• Patients who remain on sertraline for the long-term should have periodic monitoring to reassess the risk-benefit ratio of remaining on the SSRI, as well as to assess the safety, tolerability, and efficacy of the medication 3
• The safety profile of sertraline in a long-term, real-world setting is similar to that of prior pediatric sertraline studies, but AEs and suicidal ideation/behavior should be closely monitored 5