Beyond depression: Other uses for tricyclic antidepressants

Article Figures & Data

TABLE 1

Dosing and adverse effects of commonly prescribed tricyclic antidepressants

	Reuptake mechanism^b	Adverse effects^a					Initial/maximum dosing (for MDD)
	Reuptake mechanism^b	Sedation	Hypotension	Seizures	Weight gain	Cardiac	Initial/maximum dosing (for MDD)
Tertiary amine tricyclic antidepressants (TCAs)
Amitriptyline	5-HT > NE	+++	+++	++	++	+++	25–75 mg/200 mg daily
Clomipramine	5-HT > NE	++	++	+++	+	++	25 mg/250 mg daily
Doxepin	5-HT = NE	++++	+	++	++	+	50–75 mg/300 mg nightly
Imipramine	5-HT = NE	++	+++	++	++	+++	50–100 mg/200 mg daily
Secondary amine TCAs
Despiramine	NE > 5-HT	+	+	+	+	++	100–200 mg/300 mg daily
Maprotiline	NE > 5-HT	++	+	+	++	+	25–50 mg/225 mg nightly
Nortriptyline	NE > 5-HT	+	+	+	+	++	25–50 mg/150 mg daily

↵a Plus sign indicates potential severity of adverse effects.
↵b Tertiary amine TCAs tend to preferentially inhibit serotonin reuptake, resulting in greater synaptic serotonin levels, whereas secondary amine TCAs tend to preferentially inhibit norepinephrine reuptake, resulting in greater synaptic norepinephrine levels.
MDD = major depressive disorder; NE = norepinephrine; 5-HT = serotonin

TABLE 2

Dosing guide for tricyclic antidepressants in conditions other than depression

Indication	Medications	Initial/maximum dosing	Dose escalation	Adverse effect management
Headache or migraine	Amitriptyline	10–25 mg/100 mg nightly	Individualized: Increase by 10–25 mg every 5–14 days, assess for tolerability and adverse effects Amitriptyline side effects (dry mouth, orthostasis) often limit dose escalation above 100 mg; nortriptyline or maprotiline may be considered (better tolerated at higher doses)	Dry mouth and secretions: Pilocarpine 5 mg 2–3/day Constipation: Stool softeners, eg, docusate sodium, senna glycoside Weight gain: Consider augmenting with metformin 500–1,000 mg/day or topiramate 50–100 mg/day Seizures, QT interval prolongation, active suicidal risk, orthostasis, or falls: Discontinue the agent
Neuropathic pain	Amitriptyline	25–50 mg/150 mg nightly (or divided into twice-daily doses if frequent pain or symptom flares)
Chronic low back pain	Amitriptyline, maprotiline	25–50 mg/150 mg nightly
Fibromyalgia or chronic widespread pain	Amitriptyline, nortriptyline, maprotiline	25–50 mg/150 mg nightly (or divided into twice-daily doses if frequent pain or symptom flares)
Irritable bowel syndrome	Amitriptyline, nortriptyline	10–25 mg/100 mg nightly
Cyclic vomiting syndrome	Amitriptyline, nortriptyline	25–50 mg/100 mg nightly
Chronic pelvic pain, interstitial cystitis, nocturia	Amitriptyline, nortriptyline, imipramine	10–25 mg/100 mg nightly
Insomnia	Amitriptyline, maprotiline, doxepin	25–50 mg/150 mg nightly