Nortriptyline; Uses, Side Effects, Interactions, Pregnancy


Nortriptyline is a tricyclic antidepressant agent used for short-term treatment of various forms of depression. Nortriptyline blocks the norepinephrine presynaptic receptors, thereby blocking the reuptake of this neurotransmitter and raising the concentration in the synaptic cleft in the CNS. Nortriptyline also binds to alpha-adrenergic, histaminergic and cholinergic receptors. Long-term treatment with nortriptyline produces a downregulation of adrenergic receptors due to the increased stimulation of these receptors.

Nortriptyline hydrochloride, the N-demethylated active metabolite of amitriptyline, is a dibenzocycloheptene-derivative tricyclic antidepressant (TCA). TCAs are structurally similar to phenothiazines. They contain a tricyclic ring system with an alkyl amine substituent on the central ring. In non-depressed individuals, nortriptyline does not affect mood or arousal but may cause sedation. It is used to treat clinical depression, childhood bedwetting. Off-label uses include chronic pain and migraine and labile affect in some neurological disorders. Chemically, it is a secondary amine dibenzocycloheptene and pharmacologically it is classed as a second-generation TCA. It affects chemicals in the brain that may be unbalanced in people with depression.

Mechanism of Action of Nortriptyline

TCAs are structurally similar to phenothiazines. They contain a tricyclic ring system with an alkyl amine substituent on the central ring. In non-depressed individuals, nortriptyline does not affect mood or arousal but may cause sedation. In depressed individuals, nortriptyline exerts a positive effect on mood. TCAs are potent inhibitors of serotonin and norepinephrine reuptake. Secondary amine TCAs, such as nortriptyline, are more potent inhibitors of norepinephrine reuptake than tertiary amine TCAs, such as amitriptyline. TCAs also down-regulate cerebral cortical β-adrenergic receptors and sensitize post-synaptic serotonergic receptors with chronic use. The antidepressant effects of TCAs are thought to be due to an overall increase in serotonergic neurotransmission. TCAs also block histamine-H1receptors, α1-adrenergic receptors, and muscarinic receptors, which accounts for their sedative, hypotensive and anticholinergic effects (e.g. blurred vision, dry mouth, constipation, urinary retention), respectively. See toxicity section below for a complete listing of side effects. Nortriptyline exerts less anticholinergic and sedative side effects compared to the tertiary amine TCAs, amitriptyline, and clomipramine. Nortriptyline may be used to treat depression, chronic pain (unlabeled use), irritable bowel syndrome (unlabeled use), diabetic neuropathy (unlabeled use), post-traumatic stress disorder (unlabeled use), and for migraine prophylaxis

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Indications of Nortriptyline

Contra Indications of Nortriptyline

Dosages of Nortriptyline

Strengths: 10 mg; 25 mg;  50 mg; 75 mg; 10 mg/5 mL;


  • 25 mg orally three or four times per day
  • Maximum dose: 150 mg orally per day

Nocturnal enuresis

Pediatric population

The recommended doses for

  • Children aged 6 to 10 years: 10 mg – 20 mg. A suitable dosage form should be used for this age group.
  • Children aged 11 years and above: 25 mg – 50 mg daily
  • The dose should be increased gradually.
  • Dose to be administered 1-1½ hours before bedtime.
  • The maximum period of treatment course should not exceed 3 months. If repeated courses of

nortriptyline is needed, a medical review should be conducted every 3 months.

Chronic Urticaria, Nocturnal Pruritus, Angioedema

  • 75mg/day Post Operative

Smoking Cessation

  • 25 mg PO qDay; start 1-2 weeks before quit date; may titrate to 75-100 mg/day 10-28 days prior to selected quit date; titrate dose to 75-100 mg/day; continue therapy for 12 weeks or more after quit day
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ADHD (Off-label)

  • 25 mg PO q6-8hr

Postherpetic Neuralgia

  • 10-25 mg PO qHS; may increase q3-5days in 10 mg increments qDay up to 160 mg qHS or divided q12hr if tolerated

Side Effects of Nortriptyline

The most common



Drug Interaction of Nortriptyline

Nortriptyline may interact with the following drugs, supplements, & may change the mode of action of drugs.

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Pregnancy & Lactations of Nortriptyline

FDA Pregnancy Category C


This medication should not be used during pregnancy unless the benefits outweigh the risks. If you become pregnant while taking this medication, contact your doctor immediately.


This medication passes into breast milk. If the breastfeeding-feeding mother and are taking nortriptyline, it may affect your baby. Talk to your doctor about whether you should continue breast-feeding.



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