TREST

Clinical safety rating: caution

Comprehensive clinical and safety monograph for TREST (TREST).

How it works

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.

What the body does with it

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.

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for TREST (TREST).

Breastfeeding	It is unknown if trestolone or its metabolites are excreted in human milk. No M/P ratio available. Due to potential for adverse effects in the nursing infant (e.g., hormonal disruption, virilization), breast-feeding is not recommended during therapy. Discontinue nursing or discontinue drug.
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.

Warnings & precautions

■ 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.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Hypersensitivity to mirtazapine or any excipients","Concurrent use of MAOIs or within 14 days of stopping MAOI therapy","Use in patients with known QT prolongation or with other drugs that prolong QT interval"]

Clinical Precautions

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"]

Clinical Tips & Counseling

Drug interactions

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TREST

Clinical safety rating: caution

Comprehensive clinical and safety monograph for TREST (TREST).

How it works

What the body does with it

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.

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for TREST (TREST).

Breastfeeding	It is unknown if trestolone or its metabolites are excreted in human milk. No M/P ratio available. Due to potential for adverse effects in the nursing infant (e.g., hormonal disruption, virilization), breast-feeding is not recommended during therapy. Discontinue nursing or discontinue drug.
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.