Tricyclic antidepressants

Tricyclic antidepressants (TCAs) can be used under the supervision of a psychiatrist for patients with treatment-resistant major depression, or if the patient has responded well to them previously. TCAs have a role in the management of patients with severe or melancholic depression.

Some people are unable to tolerate the adverse effects of TCAs. Nortriptyline has a lower incidence of anticholinergic effects, orthostatic hypotension and sedation than the other TCAs. Nortriptyline is the only TCA shown to have a dose-response curve based on blood concentrations, which is useful for titration or when adherence issues are suspected12. TCAs are potentially lethal in overdose (see Tricyclic antidepressants in the Toxicology and Toxinology guidelines).

TCAs are generally less well tolerated in older people. However, if a TCA is well tolerated and effective in an older person, it is unnecessary to switch to another antidepressant; switching may cause a relapse, and is of particular concern in patients with a history of severe episodes, hospitalisation or suicide attempt.

A baseline electrocardiogram (ECG) and close monitoring for postural dizziness using lying and standing blood pressure in the first 2 weeks and after dosage changes is recommended.

An appropriate regimen in adults or young people is:

1 amitriptyline 25 to 75 mg orally, at night, increasing as tolerated by 25 to 50 mg every 2 to 3 days to a target dose of 150 mg. If response is inadequate, further dose increases may be needed to a maximum daily dose of 300 mg major depression amitriptyline amitriptyline amitriptyline

OR

1 clomipramine 25 to 75 mg orally, at night, increasing as tolerated by 25 to 50 mg every 2 to 3 days to a target dose of 150 mg. If response is inadequate, further dose increases may be needed to a maximum daily dose of 300 mg major depression clomipramine clomipramine clomipramine

OR

1 dosulepin (dothiepin) 25 to 75 mg orally, at night, increasing as tolerated by 25 to 50 mg every 2 to 3 days to a target dose of 150 mg. If response is inadequate, further dose increases may be needed to a maximum daily dose of 300 mg major depression dosulepin (dothiepin) dosulepin (dothiepin) dosulepin (dothiepin)

OR

1 doxepin 25 to 75 mg orally, at night, increasing as tolerated by 25 to 50 mg every 2 to 3 days to a target dose of 150 mg. If response is inadequate, further dose increases may be needed to a maximum daily dose of 300 mg major depression doxepin doxepin doxepin

OR

1 imipramine 25 to 75 mg orally, at night, increasing as tolerated by 25 to 50 mg every 2 to 3 days to a target dose of 150 mg. If response is inadequate, further dose increases may be needed to a maximum daily dose of 300 mg major depression imipramine imipramine imipramine

OR

1 nortriptyline 25 to 75 mg orally, at night, increasing as tolerated by 25 to 50 mg every 2 to 3 days to a target dose of 100 mg. If response is inadequate, further dose increases may be needed to a maximum daily dose of 150 mg12 . major depression nortriptyline nortriptyline nortriptyline

1 A list of Australian laboratory test databases is available at the Australasian Association for Clinical Biochemistry and Laboratory Medicine (AACB) ‘Testing for health’ website.Return
2 For information on therapeutic reference ranges of psychotropics, see Hiemke C, Bergemann N, Clement HW, Conca A, Deckert J, Domschke K, et al. Consensus guidelines for therapeutic drug monitoring in neuropsychopharmacology: update 2017. Pharmacopsychiatry 2018;51(1-02):9-62. [URL]Return