Trintellix
Trintellix
Generic Name
Trintellix
Mechanism
- Trintellix (vortioxetine) is a multimodal serotonin modulator.
- It functions as:
* 5‑HT1A partial agonist – stimulates serotonergic activity while dampening hyperactivity.
* 5‑HT3, 5‑HT1D, 5‑HT2C antagonist – blocks these receptors, reducing side effects such as nausea and improving mood.
* 5‑HT1B partial agonist and 5‑HT7 antagonist – further modulates serotonergic tone and neuroplasticity.
• The combined action enhances cortical serotonergic neurotransmission and improves synaptic plasticity.
Pharmacokinetics
| Parameter | Typical Value | Clinical Implication |
| Absorption | Rapid, peak plasma concentration at 1–2 h post‑dose | Can be taken with or without food |
| Bioavailability | ~88 % | Mildly variable; unaffected by food or CYP2D6 genotype |
| Distribution | 85 % plasma protein bound; crosses the blood‑brain barrier | Achieves therapeutic CNS levels |
| Metabolism | Primarily hepatic via CYP2D6 and CYP3A4 | Dose adjustments in severe hepatic impairment |
| Elimination Half‑Life | ~66 h (steady state ~5‑7 days) | Steady‑state achieved after 5‑7 days |
| Excretion | Renal (≈30 %) and fecal (≈70 %) | No dose adjustment needed for moderate CKD |
> Note: Vortioxetine therapy is not recommended with potent CYP2D6 inhibitors (e.g., fluoxetine) or inducers (e.g., carbamazepine) due to potential level changes.
Indications
- Major Depressive Disorder (MDD) – adults, adults with anxiety comorbidity.
- Off‑label: Post‑traumatic stress disorder, bipolar depression (with caution), and certain anxiety disorders, though evidence is limited.
Contraindications
- Contraindications
* Known hypersensitivity to vortioxetine or any excipients.
* Use with monoamine oxidase inhibitors (MAOIs) within 14 days.
• Warnings
* Serotonin syndrome risk when combined with other serotonergic agents.
* Suicidal ideation – monitoring in first 12 weeks (FDA boxed warning).
* Hepatic impairment – caution; monitor liver function.
* Pregnancy & Lactation – limited data; consider risk/benefit.
* QT prolongation – minimal clinically significant effect, but avoid in QT‑prolonging drugs.
Dosing
| Population | Typical Initial Dose | Maintenance Dose | Titration | Max Daily Dose |
| Adults (MDD) | 5 mg daily | 20–40 mg daily (titrated over 2–3 weeks) | Increase by 10 mg increments | 40 mg |
| Adolescents (¹) | 5 mg daily | 20 mg daily | Titrate by 10 mg | 20 mg |
| Special | ¹ FDA approved for patients 12‑17 years old with MDD (labeling considerations).
Adverse Effects
| System | Common (≤10 %) | Serious (≤1 %) |
| GI | Nausea, diarrhea, constipation | Vomiting, severe dehydration |
| Neurologic | Headache, dizziness, insomnia | Syncope, seizures (rare) |
| Genitourinary | Sexual dysfunction (reduced libido, delayed ejaculation) | None |
| Metabolic | Weight loss (inc. 10 % at 2 yrs) | Hypoglycemia (in diabetics) |
| Cardiac | Palpitations | QT prolongation (rare) |
| Psychiatric | Anxiety, mania onset (in bipolar) | Suicidal thoughts, serotonin syndrome |
• Weight loss: Notable in 20–40 % of patients at 20 mg daily.
• Sexual dysfunction: ~35 % incidence; may limit adherence.
Monitoring
- Baseline:
* Depression severity (HAM-D, PHQ‑9).
* BMI and weight trend.
* Liver function tests.
* QT interval (if risk factors).
• Follow‑up:
* Reassess depression scores at 2–4 weeks, then monthly until improvement > 50 %.
* Weight monitoring at each visit.
* Monitor for suicidal ideation ≤12 weeks.
* If concomitant serotonergic agents, check for serotonin syndrome early.
• Lab testing: Routine labs unnecessary; monitor liver function if hepatic disease.
Clinical Pearls
- Steep, slow titration: Low starting dose (5 mg) reduces nausea; 10 mg increments avoid serotonin syndrome.
- Weight Advantage: Unlike many SSRIs, vortioxetine frequently promotes modest weight loss – a benefit for obese patients or those intolerant to weight gain.
- CYP2D6: While primarily metabolized by CYP2D6, many patients remain therapeutic because the drug is active in itself. Genotype data rarely alter dosing.
- Sexual Side Effects: Lower incidence compared to pure SSRI therapy; discuss proactively with patients concerned about sexual function.
- Rapid Onset of Action: Clinical benefit may be seen as early as 2–3 weeks, earlier than typical SSRIs.
- Qatar: In patients with known QT prolongation, a monitoring ECG at baseline and at 3 days post‑start is sufficient because QT changes are transient and clinically insignificant.
- Pregnancy: Category C – data suggest low teratogenicity; still consider non-pharmacologic options first.
- Rehabilitation Setting: Dose 5 mg can be used safely—no interactions with benzodiazepines; may help momentum in motivational enhancement therapy.
--
• *Always refer to prescribing information and practice guidelines for the most current recommendations.*