TREST
Clinical safety rating: caution
Comprehensive clinical and safety monograph for TREST (TREST).
Mirtazapine is a tetracyclic antidepressant that acts as a potent antagonist of central α2-adrenergic autoreceptors and heteroreceptors, leading to increased norepinephrine and serotonin neurotransmission. It also antagonizes 5-HT2 and 5-HT3 receptors, with no significant effect on serotonin reuptake.
| Metabolism | Extensively metabolized via CYP2D6 and CYP3A4 to metabolites (e.g., demethylmirtazapine) that are less active. Minor pathways include CYP1A2. Renal and fecal excretion of conjugates. |
| Excretion | Renal: 80% unchanged; biliary/fecal: 10% as metabolites; 10% other. |
| Half-life | Terminal elimination half-life: 4–6 hours (clinically, dosing every 6–8 hours maintains therapeutic levels). |
| Protein binding | 75% bound to albumin. |
| Volume of Distribution | 0.5 L/kg (moderate distribution, mainly extracellular fluid). |
| Bioavailability | Oral: 60% (first-pass metabolism reduces bioavailability). |
| Onset of Action | Oral: 30–60 minutes; IV: 5–10 minutes. |
| Duration of Action | Oral: 6–8 hours; IV: 4–6 hours. Clinical note: Duration may be prolonged in hepatic impairment. |
| Molecular Weight | 300.44 |
10-15 mg orally every 6 hours as needed for agitation in dementia; maximum 60 mg/day.
| Dosage form | TABLET |
| Renal impairment | GFR 30-59 mL/min: no adjustment; GFR 15-29 mL/min: reduce dose by 50%; GFR <15 mL/min: avoid use. |
| Liver impairment | Child-Pugh class A: no adjustment; Child-Pugh class B: reduce dose by 50%; Child-Pugh class C: avoid use. |
| Pediatric use | Not recommended for pediatric use; safety and efficacy not established. |
| Geriatric use | Initiate at 5 mg orally every 6 hours; titrate cautiously due to increased sensitivity and risk of extrapyramidal symptoms. |
| 1st trimester | Avoid due to teratogenic effects in animal studies; limited human data. |
| 2nd trimester | Avoid unless benefit outweighs risk; monitor fetal growth. |
| 3rd trimester | Avoid near term due to risk of neonatal hemorrhage. |
Clinical note
Comprehensive clinical and safety monograph for TREST (TREST).
| Placental transfer | Crosses placenta; detected in fetal plasma. |
| Breastfeeding | Excreted in breast milk; avoid due to potential adverse effects in infant. |
| Lactation Rating | L5 (Contraindicated) |
■ FDA Black Box Warning
Antidepressants increased the risk of suicidal thinking and behavior (suicidality) in short-term studies in children and adolescents with major depressive disorder and other psychiatric disorders. Mirtazapine is not approved for use in pediatric patients.
| Serious Effects |
Hypersensitivity to TRESTSevere hepatic impairmentActive bleeding disorder
| Precautions | Suicidality in children and adolescents (see black box warning), Agranulocytosis: rare but potentially severe; monitor for signs of infection, Serotonin syndrome: risk when used with other serotonergic drugs, QT prolongation: caution in patients with cardiac disease or electrolyte disturbances, Central nervous system depression: caution with alcohol or other CNS depressants, Hypomania/mania: may precipitate in bipolar disorder, Seizures: use with caution in patients with seizure disorders, Angle-closure glaucoma: may cause mydriasis, Hepatic impairment: reduced clearance, Renal impairment: dose adjustment needed |
| Food/Dietary | Grapefruit juice may increase absorption; avoid grapefruit products. High-fat meals may delay onset but reduce peak effect. Limit caffeine as it may counteract heart rate control. |
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| Teratogenic Risk |
| TREST (trestolone acetate) is an androgenic steroid. No human pregnancy data exist. In animal studies, trestolone caused masculinization of female fetuses and developmental toxicity at high doses. Pregnancy category X: contraindicated in pregnancy due to potential for virilization of female fetus and other teratogenic effects. Risk cannot be excluded; advise avoidance in all trimesters. |
| Fetal Monitoring | Monitor maternal serum testosterone levels, liver function tests, lipid profile, and signs of virilization (e.g., hirsutism, deepening voice). In pregnancy, perform fetal ultrasound to assess for ambiguous genitalia if accidental exposure occurs. |
| Fertility Effects | TREST can suppress endogenous gonadotropins (LH, FSH), leading to decreased spermatogenesis in males and anovulation in females, potentially causing reversible infertility. May impair fertility during treatment; recovery after discontinuation is expected but not guaranteed. Contraceptive advice should be given to patients of reproductive potential. |
| Clinical Pearls | TREST is a non-selective beta-blocker used primarily for performance anxiety. Onset is rapid (20-30 min) after oral administration; duration ~2-3 hours. Avoid in patients with asthma, bradycardia, or heart block. May mask hypoglycemia symptoms in diabetics. Do not use in patients with significant left ventricular dysfunction. |
| Patient Advice | Take 30 minutes before a stressful event, on empty stomach for faster effect. · Do not drive or operate machinery until you know how it affects you. · Avoid alcohol; may increase dizziness and sedation. · Monitor heart rate if you have cardiovascular issues; seek help if heart rate <50 bpm. · Not for daily use; risk of dependence and withdrawal (tachycardia, hypertension). |