Tricyclic Antidepressants

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Tricyclic antidepressants are used for depression and neuropathic pain. They are inhibitors of reuptake of norepinephrine and serotonin in the descending projections from the brain to the dorsal horn of the spinal cord resulting in modulation of the incoming nociceptive signals. Norepinephrine seems to be more important for analgesia whereas serotonin is more important for antidepressant effects. The sedating effects may be helpful with sleep. Usually these agents are initiated as an evening dose, escalating every 3-5 days. Beneficial effects may not be noticed, however, for 1-3 weeks. There are common side effects of all of the tricyclic antidepressants, although to varying degrees. Dry mouth, blurred vision, urinary retention, constipation and reflux (anticholinergic), weakness, lethargy, and fatigue can occur. Secondary amines tend to be better tolerated than the tertiary amines. A comparison of the most common TCAs can be found in Table 34.6. Caution must be taken with these agents to evaluate for exacerbation of psychiatric symptoms, postural hypotension, benign prostate hypertrophy, urinary retention, and closed-angle glaucoma. Cardiac dysrhythmias are more common than with the specific serotonin reuptake inhibitors (SSRIs).

Table 34.6 Tricyclic Antidepressants with Dosing and Common Side Effect Profiles.

Tricyclic antidepressants

Name Anticholinergic



Initial dose

Max dose

Tertiary amines

Imipramine ++ + (Tofranil®)

++ +

• First TCA introduced (1957)

10-25 mg qhs

300 mg/day

Clomipramine ++++ (Anafranil®)

++ +

• Especially effective for OCD

• Most serotonergic TCA

10-25 mg qhs

300 mg/day

Amitriptyline ++++ + (Elavil®®)

++++ +

• 10-30 mg qhs for sleep disorders and chronic pain

10-25 mg qhs

300 mg/day

Doxepin ++ + (Sinequan®)


• Most histamine block

10-25 mg qhs

300 mg/day

Secondary amines

Nortriptyline + (Aventyl®)

• Lower maximum dose compared to other TCAs

10 mg qhs

150 mg/day

Desipramine +


• Most NE activity

10-25 mg qhs

300 mg/day


• Least anticholinergic TCA

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