Due to the risk of toxicity in overdose and the potential for suicide attempts or self-harm, consider limiting the quantity prescribed on each prescription (see Suicide risk, here).

Tricyclic antidepressants (TCAs) are associated with the greatest risk in overdose; lofepramine is associated with fewer anticholinergic side effects, is less sedating and is considered to be safer in overdose. Amitriptyline, imipramine and clomipramine should be avoided where there is a suicide risk. It is accepted that Selective Serotonin Re-uptake Inhibitors (SSRIs) are better tolerated and are safer in overdose than other classes of antidepressants and should be considered first-line for treating depression. Refer to formulary guidance on the management of unipolar depression here.

Elderly patients are particularly susceptible to many of the side-effects of tricyclic antidepressants; low initial doses should be used, with close monitoring, particularly for psychiatric and cardiac side-effects.

Healthcare professionals should be aware of the small increased risk of fractures in patients taking, or starting to take TCAs (MHRA, 2014).

Amitriptyline

• Tablets 10mg, 25mg, 50mg (£0.63 = 10mg at night)

Indications

• Neuropathic pain (unlicensed indication)
• Diabetic neuropathy (unlicensed indication)
• Irritable bowel syndrome (unlicensed indication)
• Prophylaxis of migraine (unlicensed indication)
• No longer recommended for the treatment of depression but may be continued for established patients

Dose

• Neuropathic pain, initially 10mg daily at night, gradually increased if necessary to 75mg daily; higher doses under specialist supervision

Clomipramine

• Capsules 10mg, 25mg, 50mg (£4.55 = 25mg daily)

Indications

• Panic disorder (unlicensed indication)

Imipramine

• Tablets 10mg, 25mg (£1.18 = 25mg daily)

Indications

• Irritable bowel syndrome (unlicensed indication)
• Neuropathic pain (unlicensed indication)

Lofepramine

• Tablets 70mg (£16.81 = 140mg daily)

Indications

• Unipolar depression

Dose

• 140–210mg daily in divided doses; elderly may respond to lower doses

Nortriptyline

• Tablet 10mg, 25mg (£0.47 = 10mg daily)

Indications

• No longer recommended for the treatment depression, but may be continued for established patients; see Treatment of unipolar depression, for further guidance
• Nortriptyline remains an option as a tertiary tricyclic drug if imipramine is not tolerated by a patient with neuropathic pain; see Management of neuropathic pain for further guidance

Dosulepin

Following national guidance from NHS England, dosulepin is not recommended for use due to significant safety concerns. It is more toxic than other tricyclic antidepressants due to its pro-convulsive and cardiac arrhythmic effects and it is very dangerous in overdose. Click here for more information. Prescribers should not initiate dosulepin for any new patient. If, in exceptional circumstances, there is a clinical need for dosulepin to be initiated, this should be undertaken in a cooperation arrangement with a multi-disciplinary team and/or other healthcare professional. Patients currently prescribed dosulepin should be regularly reviewed, and alternative treatments considered. Click the following link for a patient information leaflet to support deprescribing.

Trimipramine

Following national guidance from NHS England, trimipramine is not recommended for use due to significantly higher costs; more cost-effective tricyclic antidepressants are available. Click here for more information . Prescribers should not initiate trimipramine for any new patient. Click the following link for a patient information leaflet to support deprescribing.

Tricyclic-related antidepressants

Trazodone

• Capsules 50mg, 100mg (£2.09 = 150mg daily (28 x 50mg plus 28 x 100mg))
• Tablets 150mg (£2.30 = 150mg daily)
• Oral solution sugar free 50mg/5ml (£8.88 = 120ml)

Indications

• Depression, particularly where sedation is required

Dose

• Initially 150mg (elderly 100mg) daily in divided doses after food or as a single dose at bedtime; may be increased to 300mg daily; hospital patients up to maximum 600mg daily in divided doses