What is the interaction between Sertraline (Selective Serotonin Reuptake Inhibitor) and Zolpidem (Nonbenzodiazepine Hypnotic)?

From the Guidelines

Sertraline and zolpidem should be prescribed with caution and under medical supervision due to potential interactions and increased risk of cognitive impairment and fall risk. Sertraline, an SSRI, is considered safe for patients with cardiovascular disease, with a lower risk of QTc prolongation compared to other SSRIs like citalopram or escitalopram 1. However, when combined with zolpidem, a sedative-hypnotic medication, the risk of central nervous system depression increases, potentially causing excessive sedation, dizziness, confusion, and impaired coordination.

Some key points to consider when prescribing sertraline and zolpidem together include:

• Sertraline is typically taken in the morning, with a daily dose of 50-200mg, while zolpidem is taken at bedtime, with a usual dose of 5-10mg 1.
• Cognitive behavioral therapy for insomnia is recommended as first-line treatment before initiating sedating antidepressants or melatonin receptor agonists, and hypnotics like zolpidem should be prescribed with caution due to the risk of cognitive impairment and fall risk 1.
• The effect of SSRIs like sertraline may take up to 6 weeks, making them less suitable for managing depressive symptoms at the immediate end of life, and alternative treatments like psychostimulants may be considered in select populations with monitoring for cardiovascular risks 1.

It is essential to inform all healthcare providers about all medications being taken to prevent potential drug interactions and to seek medical attention immediately if unusual drowsiness, confusion, or breathing difficulties occur while taking these medications.

From the FDA Drug Label

Concomitant administration of zolpidem and sertraline increases exposure to zolpidem [see CLINICAL PHARMACOLOGY (12. 3)]. Following five consecutive nightly doses at bedtime of oral zolpidem tartrate 10 mg in the presence of sertraline 50 mg (17 consecutive daily doses, at 7:00 am, in healthy female volunteers), zolpidem Cmax was significantly higher (43%) and Tmax was significantly decreased (-53%).

The concomitant use of sertraline and zolpidem may increase the exposure to zolpidem, with a significant increase in Cmax (43%) and a decrease in Tmax (-53%). This may lead to increased drowsiness and psychomotor impairment. Key points to consider:

• Increased exposure: Concomitant administration of zolpidem and sertraline increases exposure to zolpidem.
• Pharmacokinetic interactions: Zolpidem Cmax was significantly higher and Tmax was significantly decreased when administered with sertraline.
• Clinical implications: The increased exposure to zolpidem may lead to increased drowsiness and psychomotor impairment, which can impact daily activities, such as driving 2.

From the Research

Sertaline and Zolpidem Interaction

• There is no direct evidence of the interaction between sertaline and zolpidem in the provided studies.
• However, study 3 compared the effectiveness of second-generation antidepressants, including sertraline, for accompanying anxiety, insomnia, and pain in depressed patients.
• The study found that selective serotonin reuptake inhibitors (SSRIs), which include sertraline, do not differ in their effectiveness for treating anxiety, insomnia, and pain, with moderate evidence.

Zolpidem and Insomnia

• Study 4 found that cognitive-behavioral therapy (CBT) for insomnia, when delivered alone or in combination with zolpidem, produces durable sleep improvements up to two years after completion of treatment.
• Study 5 examined the relationship of age to insomnia and the impact of age on the treatment of insomnia with zolpidem extended-release (zolpidem-ER) in depressed suicidal patients.
• The study found that older age at baseline was associated with worse middle and late insomnia, but not with early insomnia, and that treatment with zolpidem-ER produced superior improvement in early and middle insomnia, but not late insomnia.

Sertaline and Insomnia

• Study 6 found that cognitive-behavioral therapy for insomnia (CBT-I) presents a promising treatment for depression comorbid with insomnia, and that insomnia improvement due to CBT-I may mediate the improvement in depressive symptoms.
• Study 7 reviewed the literature on cognitive-behavioral therapy for insomnia in adults and adolescents with depression, and found that sleep problems are an important predictor of depression and that sleep problems are associated with more severe depression, more suicidality, and worse outcomes for treatment of depression.
• However, there is no direct evidence of the effectiveness of sertraline for insomnia in the provided studies.