Lexette
Lexette
Generic Name
Lexette
Mechanism
- Selective norepinephrine reuptake inhibition: Blocks the norepinephrine transporter (NET) in presynaptic neurons, increasing synaptic NE levels.
- Minimal dopaminergic action: Limited dopamine reuptake inhibition differentiates it from other TCAs and reduces extrapyramidal side effects.
- Anticholinergic, antihistaminic, and α1‑adrenergic blockade: Contributes to side‑effect profile (dry mouth, orthostatic hypotension, sedation).
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Pharmacokinetics
| Parameter | Details |
| Absorption | Oral bioavailability ~65–70%; peak plasma concentration 4–6 h post‑dose. |
| Distribution | Highly lipophilic; protein binding 70–80% (primarily albumin, α1‑acid glycoprotein). |
| Metabolism | Extensive first‑pass hepatic metabolism via CYP2D6 → active metabolites; secondary pathways via CYP3A4. |
| Elimination | Renal excretion of metabolites; half‑life 12–15 h (may extend to 20 h in CYP2D6 poor metabolizers). |
| Drug interactions | Strong inhibitors or inducers of CYP2D6 or CYP3A4 alter serum levels; combined use with MAO inhibitors increases risk of serotonin syndrome. |
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Indications
- Major depressive disorder (adult patients).
- Anxiety disorders (off‑label).
- Chronic neuropathic pain (low‑dose, off‑label).
- Note: Not first‑line due to anticholinergic burden; reserved for patients refractory to SSRIs/SNRIs.
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Contraindications
- Contraindicated:
- Acute myocardial infarction, uncontrolled hypertension, severe cardiac disease (especially arrhythmias, congestive heart failure).
- Known hypersensitivity to TCAs or desipramine.
- Concomitant use of monoamine oxidase inhibitors (MAOIs) unless a 14‑day washout period has elapsed.
- Warnings:
- Cardiotoxicity: Monitor ECG; avoid in QT prolongation or Brugada syndrome.
- Anticholinergic toxicity: Watch for delirium, urinary retention, and vision changes in elderly.
- Seizure threshold: Lower seizure threshold; caution in patients with epilepsy.
- Drug interactions: Potentiation with CYP2D6 inhibitors (e.g., fluoxetine) or CYP3A4 inducers (e.g., rifampin).
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Dosing
- Initial dose: 50 mg PO once daily, either before bedtime (to reduce tremor) or in the morning (to avoid insomnia).
- Titration: Increase by 25–50 mg every 4–7 days as tolerated, max 400 mg/day (high‑dose for pain, lower for depression).
- Maintenance: 150–300 mg/day, divided or as a single nightly dose.
- Therapeutic monitoring: Not routinely required but measure plasma levels if treatment failure or toxicity suspected.
- Abrupt discontinuation: May precipitate withdrawal (dizziness, flu‑like symptoms); taper over 2–4 weeks.
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Adverse Effects
| Category | Examples |
| Common | Dry mouth, blurred vision, sedation, orthostatic hypotension, constipation, weight gain. |
| Serious | Cardiac arrhythmias (QT prolongation, Torsades), orthostatic syncope, severe anticholinergic toxicity, seizures, serotonin syndrome (when combined with serotonergic agents). |
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Monitoring
- Baseline: ECG (QTc), CBC, CMP, fasting lipids if >12 weeks therapy.
- Follow‑up:
- CBC/CMP for hepatic/renal function at 3 months and annually.
- ECG if new cardiovascular symptoms or QT‑prolonging drugs co‑administered.
- Weight, BMI, and metabolic panel if >6 months or >2 years of use.
- Psychological: Monitor for suicidal ideation, especially in adolescents or new users.
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Clinical Pearls
- CYP2D6 Phenotyping Matters: Poor metabolizers may reach therapeutic levels faster but at risk of toxicity; consider lower starting doses.
- Elderly Use: Anticholinergic burden can precipitate delirium; dose titration should be slower, and start at the lowest effective dose.
- IOP Monitoring: Desipramine increases intraocular pressure; avoid in patients with glaucoma or use with caution.
- Pain Syndromes: Low doses (25–75 mg/day) can be effective for neuropathic pain with minimal mood alterations.
- Drug‑Drug Interaction Cheat Sheet:
- Fluoxetine, paroxetine ↑ desipramine levels → lower desipramine or increase monitoring.
- Rifampin, carbamazepine ↓ desipramine levels → consider higher dose or alternative agents.
- Take‑home Message: Despite superior antidepressant efficacy over several other TCAs, Lexette’s side‑effect profile warrants careful patient selection, robust monitoring, and clear education about signs of toxicity.
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• Lexette remains a useful tool for clinicians dealing with refractory depression or specific pain conditions, provided its pharmacological nuances and safety considerations are rigorously applied.