Are mirtazapine (Remeron) 15 mg at bedtime and sertraline (Zoloft) 100 mg daily safe in a 57‑year‑old man with mildly elevated alkaline phosphatase (~142 U/L) and aspartate aminotransferase (~47 U/L)?

Safety of Mirtazapine and Sertraline in a 57-Year-Old Man with Mildly Elevated Liver Enzymes

Yes, mirtazapine 15 mg at bedtime and sertraline 100 mg daily are safe choices in this patient with mildly elevated alkaline phosphatase (142 U/L) and AST (47 U/L), as these elevations are mild (<5× upper limit of normal) and do not represent contraindications to either medication. 1

Assessment of Liver Enzyme Elevations

Your patient's liver enzyme pattern shows:

• Alkaline phosphatase ~142 U/L represents a mild elevation, likely <2× the upper limit of normal 1
• AST ~47 U/L is minimally elevated, well below the threshold of concern for drug-induced liver injury 1
• These elevations are classified as mild (<5× upper reference limit), which does not preclude antidepressant therapy 1

The American Gastroenterological Association recommends that mild aminotransferase elevations warrant initial evaluation but do not automatically require drug discontinuation, particularly when the clinical context suggests the medications are not the cause 1.

Safety Profile of Mirtazapine

Mirtazapine has an excellent hepatic safety profile:

• Clinical trials demonstrate very low incidences of clinically relevant changes in liver enzymes (ALT and AST) with mirtazapine treatment, comparable to placebo 2
• The 15 mg starting dose is appropriate and recommended by the American Academy of Family Physicians, balancing efficacy with tolerability 3
• Mirtazapine is extensively metabolized in the liver, but hepatotoxicity is rare 4
• In overdose situations (up to 975 mg), mirtazapine caused only sedation without hepatic complications 5

Important monitoring consideration: The FDA label notes that mirtazapine should be used cautiously in patients with hepatic impairment, but mild enzyme elevations do not constitute a contraindication 6. Regular monitoring is prudent but not emergent.

Safety Profile of Sertraline

While sertraline (Zoloft) safety data is not extensively detailed in the provided evidence, SSRIs as a class have well-established safety profiles in patients with mild liver enzyme elevations. The key consideration is that:

• Drug-induced liver injury typically presents with ALT/AST >3-5× upper limit of normal as a threshold for concern 7
• Your patient's values fall well below this threshold 1

Recommended Monitoring Approach

Before attributing liver enzyme elevations to medications, complete the diagnostic workup:

• Confirm hepatobiliary origin of the elevated alkaline phosphatase by measuring GGT and/or alkaline phosphatase isoenzyme fractionation 8, 9
• Review medication history for other potential hepatotoxic agents 1
• Obtain viral hepatitis markers (HAV-IgM, HBsAg, HCV antibody) if not already done 8
• Consider abdominal ultrasound to evaluate for biliary obstruction or parenchymal liver disease if the alkaline phosphatase is confirmed to be of hepatobiliary origin 8

Ongoing monitoring while on antidepressants:

• Repeat liver function tests (ALT, AST, alkaline phosphatase, bilirubin) in 4-6 weeks after starting or adjusting doses 1
• If enzyme elevations worsen significantly (>3-5× upper limit of normal) or if jaundice develops, discontinue the suspected offending agent immediately 1, 7
• Close clinical follow-up is appropriate for asymptomatic patients with mild elevations and intact hepatic function 8

Clinical Advantages of This Regimen

Mirtazapine at bedtime offers specific benefits:

• Sedating properties improve sleep disturbances commonly associated with depression 3, 5
• Anxiolytic effects from dual noradrenergic and serotonergic enhancement 3, 4
• Earlier response than SSRIs, with improvements noted as early as 1 week 3
• Minimal cardiovascular and anticholinergic effects, making it safe in this 57-year-old patient 5, 2

Common Pitfalls to Avoid

• Do not automatically discontinue antidepressants for mild enzyme elevations without completing the diagnostic workup to identify the actual cause 1
• Do not confuse mild enzyme elevations with drug-induced liver injury, which typically requires ALT/AST >3-5× upper limit of normal with or without symptoms 7
• Monitor for weight gain and increased appetite with mirtazapine, which occurs in ~10-11% of patients 6, 2
• Avoid concurrent benzodiazepines with mirtazapine when possible, as this combination may impair cognitive and motor performance 6, 4
• Watch for serotonin syndrome given the combination of mirtazapine and sertraline, though this is rare; symptoms include agitation, confusion, fast heart rate, tremors, and hyperthermia 6

Contraindications and Precautions

The FDA label specifies that mirtazapine should not be used in patients taking MAOIs or within 14 days of MAOI discontinuation 6. Your patient's regimen does not include MAOIs, so this is not a concern.

The combination of mirtazapine and sertraline is commonly used in clinical practice and does not represent a contraindication, though monitoring for serotonin syndrome is warranted 6.