Nortriptyline
Class: antidepressant – tricyclic
Indications (NB some may be unlicensed): depression, smoking cessation, neuropathic pain, itch
Contraindications/cautions: arrhythmias (particularly heart block), recent MI, epilepsy (lowers seizure threshold), urinary retention; use of MAOI within 14 days; manic phase of bipolar disorder. Caution in cardiovascular disease, QT prolongation, hyperthyroidism, prostatic hypertrophy; concommittant serotonergic drugs and drugs that prolong QT
Adverse reactions: common: anticholinergic – dry mouth, blurred vision, urinary retention, constipation, drowsiness (tolerance to these may develop except dry mouth) less common: sweating, confusion, arrhythmias, tachycardia, postural hypotension
Metabolism/clearance: metabolised by the metabolising enzyme CYP2D6 (major) mainly in the liver to active metabolites; increased sedative effects in hepatic impairment
Interactions:
- increased clinical effect/toxicity of nortriptyline (due to increased blood concentrations) may occur with some CYP metabolising enzyme inhibitors (see above) e.g. bupropion, fluoxetine, paroxetine, quinine
- additive risk of serotonin syndrome (potentially fatal syndrome – symptoms include sweating, diarrhoea, confusion) with other serotonergic drugs e.g. carbamazepine, fluoxetine (SSRIs; SNRIs)
- additive drowsiness may occur with alcohol, benzodiazepines (e.g. clonazepam)
- increased risk of seizures in epileptics may occur with nortriptyline so interacts with anticonvulsants e.g. phenytoin
- additive CNS effects with other CNS depressants e.g. benzodiazepines (e.g. lorazepam), phenothiazines (e.g. chlorpromazine), opioids, alcohol
- additive increased risk of QT interval prolongation (cardiac adverse effect which may lead to arrhythmias) with other drugs that prolong the QT interval e.g. lignocaine, lithium, haloperidol, domperidone
| Dosing: | ||
|---|---|---|
| depression | pain | |
| oral: | 25 to 100 mg at night | 10 to 50 mg at night (max. of 50 mg in elderly) (start 10 mg; increase gradually) |
| subcut: | not available | not available |
| rectal: | not available | not available |
Syringe driver: not available
Mechanism of action: not really understood but thought to be through noradrenaline and serotonin in the CNS
Onset: depression: 2 to 6 weeks pain: several days
Notes:
- metabolite of amitriptyline, less adverse reactions (including sedation) than amitriptyline
- 25 mg nortriptyline Ξ 75 mg amitriptyline (approx)
- nortriptyline may be better tolerated than amitriptyline. It is less likely to cause postural hypotension and has fewer troublesome antimuscarinic effects. At least 4 to 8 weeks of treatment with a first-line medicine is necessary to allow for dose titration and sufficient duration of treatment at a therapeutic dose to assess efficacy. For patients who experience a partial response but feel that response is inadequate, increasing the dose or switching to another first-line medicine may be considered. Amitriptyline (or other tricyclic antidepressants) and either gabapentin or pregabalin can be used in combination if the patient has an inadequate response to either drug at the maximum tolerated dose (NZF)