What are the names of tricyclic antidepressants (TCAs)?

Tricyclic Antidepressants (TCAs)

The common tricyclic antidepressants include amitriptyline, amoxapine, clomipramine, desipramine, doxepin, imipramine, maprotiline, nortriptyline, protriptyline, and trimipramine. 1

Primary TCAs and Their Classification

TCAs can be categorized based on their chemical structure and pharmacological properties:

Tertiary Amines

• Amitriptyline
• Clomipramine
• Doxepin
• Imipramine
• Trimipramine

Secondary Amines

• Desipramine
• Nortriptyline
• Protriptyline

Tetracyclic Antidepressants (sometimes grouped with TCAs)

• Amoxapine
• Maprotiline

Clinical Applications

TCAs have several therapeutic applications beyond depression:

1. Neuropathic Pain Management: TCAs are considered first-line medications for neuropathic pain conditions 1

   • Particularly effective for diabetic neuropathy, postherpetic neuralgia, and other chronic pain syndromes

2. Irritable Bowel Syndrome: The American Gastroenterological Association suggests using TCAs for IBS management 1

   • Particularly beneficial for IBS with diarrhea (IBS-D) due to anticholinergic effects
   • Secondary amines like desipramine and nortriptyline may be better tolerated in IBS with constipation due to lower anticholinergic effects 1

3. Sodium Channel Blockade: TCAs function as sodium channel blockers, which contributes to their analgesic properties and potential cardiac effects 1

Pharmacological Properties

TCAs have multiple mechanisms of action:

• Inhibition of serotonin and norepinephrine reuptake
• Blockade of muscarinic-1, α1-adrenergic, and histamine-1 receptors 1
• Sodium channel blocking properties similar to class Ia or Ic antiarrhythmics 1

Safety Considerations

1. Cardiovascular Effects: TCAs can cause QRS prolongation, hypotension, and ventricular dysrhythmias 1

   • Sodium bicarbonate is recommended for treating life-threatening cardiotoxicity from TCA poisoning 1
   • TCAs have quinidine-like activity that can affect cardiac function 2

2. Drug Interactions:

   • TCAs are primarily metabolized by CYP2D6 3
   • Interactions with SSRIs, cimetidine, and other CYP2D6 inhibitors can increase TCA plasma levels 3, 4
   • Dangerous additive effects may occur with quinidine or procainamide 2

3. Suicide Risk: TCAs should be dispensed in the least possible quantities to depressed outpatients due to overdose risk 4

Dosing Considerations

• TCAs are often used at lower doses for pain management than for depression 5
• Therapeutic drug monitoring can improve efficacy and safety, particularly for nortriptyline, desipramine, amitriptyline, and imipramine 6
• Desipramine may have a higher case fatality rate in overdose compared to other TCAs, suggesting the need for careful dosing 7

Clinical Pearls

• Secondary amine TCAs (desipramine, nortriptyline) generally have fewer anticholinergic side effects than tertiary amines 1
• TCAs with tertiary amines appear more effective in penetrating membrane barriers than those with secondary amines when used as local anesthetics 8
• TCAs are considered first-generation antidepressants and have been largely replaced by second-generation agents (SSRIs, SNRIs) for depression treatment due to better safety profiles 1