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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).
Tricyclic antidepressants | ||||
Name Anticholinergic |
Sedation |
Comments |
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 |
(Norpramin®®) |
• Least anticholinergic TCA |
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