ENDEP

What it is

ENDEP is a tricyclic antidepressant with sedative properties. It contains amitriptyline hydrochloride and is available in 10 mg, 25 mg or 50 mg tablet strengths.

Approved indications

— Treatment of major depression. — Nocturnal enuresis where organic pathology has been excluded.

Dosing overview

Dosage should be initiated at a low level and increased gradually, noting carefully the clinical response and any evidence of intolerance.

Key safety warnings

**Suicide risk in depression.** The risk of suicide attempt is inherent in depression and may persist until significant remission occurs. Patients with depression, both adult and paediatric, may experience worsening of their depressive symptoms and/or the emergence of suicidal ideation and behaviour, whether or not they are taking antidepressant medications, and this risk may persist until significant remission occurs. As improvement may not occur during the first few weeks or more of treatment, patients should be closely monitored for clinical worsening and suicidality, especially at the beginning of a course of treatment, or at the time of dose changes. Pooled analyses of short-term placebo-controlled trials showed that antidepressant drugs increase the risk of suicidal thinking and behaviour in children, adolescents and young adults (ages 18–24) with major depressive disorder and other psychiatric disorders. Short-term studies did not show an increase in risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction with antidepressants compared to placebo in adults aged 65 and older. **Cardiovascular effects.** Tricyclic antidepressant medicines, including amitriptyline hydrochloride, particularly when given in high doses, have been reported to produce arrhythmias, sinus tachycardia, and prolongation of the conduction time. Myocardial infarction and stroke have been reported with medicines of this class. **Severe cutaneous reactions.** Severe cutaneous adverse reactions (SCARs) including drug reaction with eosinophilia and systemic symptoms (DRESS), which can be life-threatening or fatal, have been reported in association with amitriptyline treatment. Most of these reactions occurred within 2 to 6 weeks. At the time of prescription patients should be advised of the signs and symptoms and monitored closely for cutaneous reactions. If signs and symptoms suggestive of these reactions appear, ENDEP should be withdrawn immediately, treatment with ENDEP must not be restarted in this patient at any time and an alternative treatment should be considered. **ENDEP 50 mg tablets.** The 50 mg tablets are indicated only for the maintenance treatment of major depression. The 50 mg tablets should not be used in acutely ill patients where there is a risk of suicide. There is an increased risk of completed suicide by overdose with the 50 mg tablet compared with the 25 mg tablet.

Contraindications

ENDEP is contraindicated in patients who have shown prior hypersensitivity to it. ENDEP should not be given concurrently with monoamine oxidase inhibitors, including selegiline. The combination of amitriptyline with a monoamine oxidase inhibitor has caused severe convulsions, hyperpyretic crises and death. When it is desired to substitute ENDEP for a monoamine oxidase inhibitor, a minimum of 14 days should be allowed to elapse after the latter is discontinued. ENDEP is contraindicated in patients taking cisapride due to the possibility of adverse cardiac interactions including prolongation of the QT interval, cardiac arrhythmias and conduction system disturbances.

Regulatory history

ENDEP 25 mg was first listed on the ARTG on 2 May 1997. ENDEP 50 mg was first listed on 19 May 1998. ENDEP 10 mg was first listed on 20 September 1999.