II. Indications
-
Major Depression
- Unresponsive to other Antidepressants
- Comorbid Anxiety Disorder
- Comorbid Insomnia
- Other indications
- Cachectic or chronically ill patients
- Antipsychotic induced Akathisia
III. Mechanism
- Tetracyclic piperazinoazepine
- Norepinephrine Antagonist Serotonin Antagonist
- Blocks Pre-synaptic Alpha 2 Adrenergic Receptors
- Enhances central noradrenergic activity
- Blocks Post-synaptic 5-HT2, 5-HT3 Serotonin Receptors
- Enhances central Serotoninergic activity at 5-HT-1
- Blocks Pre-synaptic Alpha 2 Adrenergic Receptors
- Significant Antihistamine activity
- Dose dependent effect
- Dose 15 mg: Antihistamine effects predominate
- Dose 45 mg: Noradrenergic effects predominate
- Antihistamine Symptoms
- Weight gain
- Sedation
- Dose dependent effect
IV. Pharmacokinetics
- Half-Life: 20 to 40 hours
- Primarily Hepatic metabolism
V. Dosing
-
Major Depression
- Start: 15 mg orally at bedtime
- May titrate dose every 1-2 weeks
- Effective dose: 15 to 30 mg orally at bedtime (maximum dose 45 mg/day)
-
Antipsychotic induced Akathisia
- Dose: 15 mg orally daily each morning
VI. Efficacy: Effective in treating Major Depression
VII. Adverse Effects
-
Somnolence (54%)
- Consider dosing at bedtime to improve sleep
- Dry Mouth (25%)
- Increased appetite (17%)
- Weight gain (12%) may be significant
- Dizziness (7%)
- Agranulocytosis (0.1% cases)
VIII. Precautions
-
Agranulocytosis (occurs in 0.1% cases)
- Similar Incidence to other Antidepressants
- Does not warrant routine CBC monitoring
- Do not use within 14 days of MAO Inhibitor
- Serotonin Syndrome risk
- Do not use with drugs causing excessive sedation
IX. Advantages
- No cardiac effects
- No or minimal Orthostatic Hypotension
- Low incidence Antidepressant Induced Sexual Dysfunction
- No deaths have occurred in overdosage
- Available as a solutab (dissolves)
X. Safety
- Pregnancy Category C
- Unknown safety in Lactation
XI. Drug Interactions
- Minimal Cytochrome P450 inhibition
XII. Resources
XIII. References
- (2023) Med Lett Drugs Ther 62(1592): 25-32
- Olson (2020) Clinical Pharmacology, Medmaster Miami, p. 38-9
- Hamilton (2020) Tarascon Pocket Pharmacopoeia
- Burrows (1997) Psychopharmacol 17:34S-39S [PubMed]
- Hartmann (1999) Am Fam Physician 59(1): 159-61 [PubMed]
- Majeroni (1998) J Am Board Fam Pract 11:127-39 [PubMed]
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