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Case Studies_ Stahl's Essential - Stephen M. Stahl.docx
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Current medications

Zolpidem-CR (Ambien-CR) 12.5mg/d (BZRA)

Zolpidem (Ambien) 5 mg/d as needed for severe breakthrough insomnia (BZRA)

Alprazolam (Xanax) 0.25 mg/d as needed for panic attacks (BZ)

Mirtazapine (Remeron) 15 mg/d (NaSSA)

Ibuprofen (Motrin) 1200 mg/d

Tramadol (Ultram) 50 mg/d as needed for severe pain

Question

Should interferon-induced depression respond to antidepressant monotherapy?

Yes

No

Attending physician’s mental notes: initial evaluation

This patient has her first MDE now

This seems superimposed upon GAD, which was likely pre-existing

She is remarkably agitated and looks horribly withdrawn and fatigued

It is acute and precipitated by a medication (Interferon) known to induce MDD in patients being treated for hepatitis

There is some evidence that SSRI and TCA treat interferon-induced depression

  • – Sometimes SSRIs are used prophylactically as a pretreatment

  • – She could respond to initial monotherapies

Her initial failure to a subtherapeutic SSRI and SNRI is possibly alarming, but her issue has been intolerance, not inefficacy

She was recently started on a minimally therapeutic dose of a third antidepressant in a novel class

  • – Mirtazapine (Remeron) is an NaSSA antidepressant

  • – It is unlikely to be problematic

    • She has known CYP450 2D6 and 2C19 genetic enzyme deficiencies

    • Mirtazapine pharmacokinetics include

      • Approximately 100% of the orally administered dose is excreted via urine and feces within four days

      • Biotransformation is mainly mediated by the CYP2D6 and CYP3A4 isoenzymes

      • Inhibitors of these isoenzymes (or those with genetic enzyme deficiencies) cause modest increases in mirtazapine plasma concentrations (17% and 32%, respectively) usually without leading to clinically relevant consequences as mirtazapine has multiple routes of metabolism and clearance

    • Mirtazapine has little inhibitory effects on CYP isoenzymes and, therefore, the pharmacokinetics of co-administered drugs are usually unaffected

However, her documented CYP450 2D6 liver enzyme deficiency will predispose her to side effects of many drugs and many psychotropics will need to be dose-modified during her care

  • – Her first two reactions (to an SSRI and SNRI) and side effects clearly worsened her agitation and her trust of psychotropics

    • Escitalopram (Lexapro) requires CYP450 2C19 and 3A4 enzymes

      • Her 3A4 system should have been able to metabolize the escitalopram

      • However, 2C19-deficient patients can show a 1.8-fold increase in escitalopram, making her initial SSRI side effects possibly related to her 2C19 enzyme deficiency

    • Desvenlafaxine (Pristiq) requires no CYP450 metabolism and is renally excreted; it should not have caused side effects based upon her CYP450 genetic deficiencies

      • Her side effects appear to be either usual activating side effects or hypochondriacal responses

  • – She seems convinced and determined that she will be hurt by all interventions

Her clear isoenzyme deficiencies, anxiety, and hypochondriacal thought processes make her prognosis difficult to determine

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