Sertraline drug interactions
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Sertraline Drug Interactions: A Comprehensive Overview
Introduction to Sertraline and Its Pharmacokinetics
Sertraline, a selective serotonin reuptake inhibitor (SSRI), is widely used to treat major depressive disorder, panic disorder, obsessive-compulsive disorder, and post-traumatic stress disorder (PTSD) 28. It is slowly absorbed after oral administration, with peak plasma concentrations occurring 6-8 hours post-dose. The drug undergoes extensive first-pass metabolism, primarily through the cytochrome P450 enzyme CYP3A4, forming N-desmethyl-sertraline, a weakly active metabolite 29.
Minimal Inhibitory Effects on Cytochrome P450 Enzymes
Sertraline has minimal inhibitory effects on major cytochrome P450 enzymes, which reduces the likelihood of significant drug-drug interactions. This characteristic makes it relatively safe for use in combination with other medications 28. However, certain interactions can still occur, particularly with drugs metabolized by the same enzymes.
Interaction with Erythromycin: Increased Genotoxicity
A notable interaction occurs between sertraline and erythromycin, an antibiotic also metabolized by CYP3A4. Concurrent administration of these drugs has been shown to increase genotoxicity in mice, likely due to prolonged drug retention in the body caused by mutual inhibition of CYP3A4 3. This interaction underscores the importance of monitoring for potential toxic effects when these drugs are co-administered.
Interaction with Clozapine: Reduced Sertraline Plasma Concentrations
In patients with schizophrenia, co-administration of sertraline and clozapine can lead to significantly lower sertraline plasma concentrations. This reduction is attributed to clozapine-induced gastrointestinal hypomotility and its CYP3A4 inducing properties at higher doses 6. Clinicians should consider therapeutic drug monitoring (TDM) to ensure effective sertraline plasma levels when these drugs are used together.
Interaction with Antipsychotics: No Significant Adverse Effects
Despite the potential for pharmacokinetic interactions, studies have shown that the addition of sertraline to antipsychotic medications in patients with schizophrenia does not result in clinically significant adverse effects. This finding suggests that sertraline can be safely used to treat depression in these patients without major concerns about drug interactions 7.
Safety in the Frail Elderly: Better Tolerability Compared to Venlafaxine
In a study involving frail elderly nursing home residents, sertraline was found to be better tolerated than venlafaxine, with fewer serious adverse events and side effects 1. This finding highlights sertraline's relative safety in populations that are particularly vulnerable to drug-drug and drug-disease interactions.
Conclusion
Sertraline is a well-tolerated SSRI with a relatively low potential for significant drug-drug interactions, making it a suitable option for treating various psychiatric conditions. However, certain interactions, such as those with erythromycin and clozapine, require careful monitoring and consideration of therapeutic drug levels. Overall, sertraline's pharmacokinetic profile supports its use in diverse patient populations, including the frail elderly and those with comorbid conditions requiring multiple medications.
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Most relevant research papers on this topic
Probing the safety of medications in the frail elderly: evidence from a randomized clinical trial of sertraline and venlafaxine in depressed nursing home residents.
In frail elderly nursing home residents, venlafaxine was less well tolerated and possibly less safe than sertraline for treating depression without evidence of an increase in efficacy.
RCT
Highly CitedClinical Pharmacokinetics of Sertraline
Sertraline is a well-tolerated and relatively safe antidepressant with minimal inhibitory effects on major cytochrome P450 enzymes and few drug-drug interactions.
Highly CitedGenotoxicity induced by drug-drug interaction between the antidepressant sertraline and the antibiotic erythromycin in mice bone marrow cells.
Concurrent treatment with sertraline and erythromycin may increase genotoxicity in mice bone marrow cells, potentially due to their inhibition of CYP3A4 activity.
Non-RCT
Animal StudyExploring binding properties of sertraline with human serum albumin: Combination of spectroscopic and molecular modeling studies.
Sertraline binds to human serum albumin in subdomain IIA, with hydrophobic interactions playing a crucial role in binding, and does not alter the protein's secondary structure.
In Vitro StudyRandomized, placebo-controlled trial of sertraline and contingency management for the treatment of methamphetamine dependence.
Sertraline is not effective for treating methamphetamine dependence, but contingency management shows promise in achieving three consecutive weeks of abstinence.
RCTHighly CitedLower sertraline plasma concentration in patients co‐medicated with clozapine—Implications for pharmacological augmentation strategies in schizophrenia
Co-medicating with clozapine may lead to reduced sertraline plasma concentrations, potentially due to clozapine-induced gastrointestinal hypo-mobility and cytochrome P450 3A4 inducing properties at high doses.
RCTSerum Monitoring of Antipsychotic Drug Levels during Concomitant Administration of Sertraline and Antipsychotic Medication
Sertraline does not cause clinically significant adverse effects when added to antipsychotic medications for depression in individuals with schizophrenia.
RCTClinical Implications of the Pharmacology of Sertraline
Sertraline has generally favorable pharmacokinetics and pharmacodynamics, but caution is needed when it is combined with lithium or low therapeutic ratio drugs.
Fetal cardiac safety of sertraline use during pregnancy
Sertraline use during pregnancy is associated with septal heart malformations, but not severe heart malformations, and fetal heart function studies do not indicate major cardiac problems later in life.
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