Tricyclic Antidepressant

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Contents 1 More Specific Terms 2 Indications 3 Contraindications 4 Dosage 5 Pharmacokinetics 6 Adverse-effects 7 Drug-interactions 8 Mechanism-of-action 9 More General Terms 10 Additional Terms 11 References

More Specific Terms

• amitriptyline (Elavil, Endep)
• amoxapine (Asendin)
• clomipramine (Anafranil)
• cyclobenzaprine (Flexeril)
• desipramine (Norpramin, Pertofrane)
• dothiepin (Prothiaden)
• doxepin (Sinequan, Adapin, Zonalon, Silenor)
• imipramine (Tofranil, Janimine)
• maprotiline (Ludiomil)
• nortriptyline (Aventyl, Pamelor)
• protriptyline (Vivactil, Concordin)
• trimipramine (Surmontil)

Indications

• depression
• neuropathic pain syndromes

Contraindications

• avoid use within 6 months of coronary syndrome

Dosage

• low-dose (< 100 mg/day) may be effective, with reduced risk of adverse effects [1]

Pharmacokinetics

• metabolism by cyt P450 2D6 > 2C9, 2C10, 2C19

Adverse-effects

• anticholinergic effects

• tinnitus
• constipation
• confusion
• tachycardia

• amitriptyline > doxepin > nortriptyline > desipramine

• in general, NOT a good class of agents for the elderly

• arrhythmic effects

• overdose results in prolongation of the QT interval
• patients with a bundle branch block are at higher risk
• risk of torsades de pointes
• avoid use within 6 months of coronary syndrome

• cholinergic symptoms with abrupt withdrawal

• abdominal cramping & diarrhea

• increased risk of seizures [2]
• orthostatic hypotension

• doxepin = amitriptyline > imipramine = nortriptyline > desipramine

• galactorrhea, hyperprolactinemia [3]
  

• Overdose:

• early endotracheal intubation, hyperventilation
• fluid resustitaion
• gastric lavage followed by activated charcoal even with delayed presentation
• EKG monitoring: QRS complex > 100 msec predicts seizures
• bicarbonate

• bolus 1-2 meq/kg every 3-5 minutes until QRS complex narrows or blood pressure improves
• bicarbonate drip titrated to QRS & blood pressure
• monitor serum K+, signs of fluid overload

• norepinephrine for hypotension not responsive to bicarbonate
• lidocaine for ventricular arrhythmias
• benzodiazepines for seizures

• avoid phenytoin
• propafol or barbiturates for refractory seizures
  

• drug adverse effects of tricyclic antidepressants
• drug adverse effects of antidepressants

Drug-interactions

• TCA may potentiate adverse effects of opiate agonists
• flumazenil ( Romazicon) may potentiate toxic effects of TCA
• TCA block the uptake of guanethidine, guanadrel
• TCA inhibit the action of centrally-acting antihypertensives:

• clonidine

• alpha-methyldopa
• SSRI: paroxetine, fluoxetine ( metabolized by same P450s)
• class 1A antiarrhythmic agents
• effects additive with EtOH
  
• drug interaction(s) of antidepressants with benzodiazepines

Mechanism-of-action

• Histamine H1 antagonist

• doxepin >> amitriptyline >> nortriptyline = imipramine >> nortriptyline = desipramine

• alpha-1-adrenergic receptor antagonism

• doxepin = amitriptyline > nortriptyline = imipramine = desipramine

More General Terms

• dibenzazepine; iminostilbene
• antidepressant

Additional Terms

• amitriptyline/chlordiazepoxide (Limbitrol)
• amitriptyline/perphenazine (Etrafon, Triavil)
• cytochrome P450 2D6 (cytochrome P450 2D, cytochrome P450 DB1, debrisoquine-4-hydroxylase, CYP2D6)
• tricyclic antidepressants (TCA) in serum/plasma

References

1. Journal Watch 23(1):11, 2003 Furukawa TA et al, Meta-analysis of effects and side effects of low dosage tricyclic antidepressants in depression: systematic review BMJ 325:991, 2002 <PubMed> PMID: &dopt=Abstract <Internet> [1]
2. Medications Can Cause Seizures Prescriber's Letter 10(3):16 2003 Detail-Document#: [2] (subscription needed) [3]
3. Medical Knowledge Self Assessment Program (MKSAP) 14, 14, American College of Physicians, Philadelphia 2006, 2009
4. The Washington Manual of Medical Therapeutics, 33rd edition Foster C et al (eds) Lippincott, Williams & Wilkins, Philadelphia, 2010, pg 957

tricyclic antidepressant (TCA)