PROTHIADEN Capsule, hard Ref.[11083] Active ingredients: Dosulepin

It may be two to four weeks from the start of treatment before there is an improvement in the patient’s depression; the subject should be monitored closely during this period. The anxiolytic effect may be observed within a few days of commencing treatment.

The elderly are particularly liable to adverse effects with tricyclic antidepressants, especially agitation, confusion and postural hypotension.

Similarly to other tricyclic antidepressants, it has anticholinergic, antihistaminic and anti-a1 adrenergic effects which may cause common adverse effects. For a better control of these adverse effects, it is recommended to start with a low dose and increasing gradually until a therapeutic dose is achieved.

Prothiaden should be avoided in patients with a history of epilepsy and in patients with urinary retention. Use with caution in patients with cardiovascular disorders.

Tricyclic antidepressants potentiate the central nervous depressant action of alcohol. Anaesthetics given during tricyclic antidepressant therapy may increase the risk of arrhythmias and hypotension. If surgery is necessary, the anaesthetist should be informed that a patient is being so treated (see section 4.5). On stopping treatment, it is recommended that antidepressants should be withdrawn gradually, wherever possible. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Suicide / suicidal thoughts or clinical worsening

Depression is associated with an increased risk of suicidal thoughts, self harm and suicide (suicide-related events). This risk persists until significant remission occurs. As improvement may not occur during the first few weeks or more of treatment, patients should be closely monitored until such improvement occurs. It is general clinical experience that the risk of suicide may increase in the early stages of recovery.

Patients with a history of suicide-related events, or those exhibiting a significant degree of suicidal ideation prior to commencement of treatment are known to be at greater risk of suicidal thoughts or suicide attempts, and should receive careful monitoring during treatment. A meta-analysis of placebo-controlled clinical trials of antidepressant drugs in adult patients with psychiatric disorders showed an increased risk of suicidal behaviour with antidepressants compared to placebo in patients less than 25 years old.

Close supervision of patients and in particular those at high risk should accompany drug therapy especially in early treatment and following dose changes. Patients (and caregivers of patients) should be alerted about the need to monitor for any clinical worsening, suicidal behaviour or thoughts and unusual changes in behaviour and to seek medical advice immediately if these symptoms present.

Use in children and adolescents under 18 years of age

Prothiaden should not be used in the treatment of depression in children and adolescents under the age of 18 years. Studies in depression in this age group did not show a beneficial effect for tricyclic antidepressants. Studies with other classes of antidepressants have shown risk of suicidality, self-harm and hostility to be related to these compounds. This risk cannot be excluded with prothiaden. In addition, prothiaden is associated with a risk of cardiovascular adverse events in all age groups. Furthermore, long-term safety data in children and adolescents concerning growth, maturation and cognitive and behavioural development are not available (see also section 4.8 Undesirable effects and Section 4.9 Overdose).

Prothiaden should not be given concurrently with a monoamine oxidase inhibitor, nor within fourteen days of ceasing such treatment. The concomitant administration of Prothiaden and SSRIs should be avoided since increases in plasma tricyclic antidepressant levels have been reported following the co-administration of some SSRIs.

Prothiaden may alter the pharmacological effect of some concurrently administered drugs including CNS depressants such as alcohol and narcotic analgesics; the effect of these will be potentiated as will be the effects of adrenaline and noradrenaline (some local anaesthetics contain these sympathomimetics). Anaesthetics given during tricyclic antidepressant therapy may increase the risk of arrhythmias and hypotension.

Prothiaden has quinidine like actions on the heart. For this reason, the use of drugs that affect cardiac conduction or prolong the QT interval may increase the risk of arrhythmias when taken with tricyclic antidepressants.

The use of tricyclics with thyroid hormones may precipitate cardiac arrhythmias.

In general, the hypotensive effect of antihypertensives is enhanced by tricyclic antidepressants, but there may be antagonism of the effect of adrenergic neurone blockers and of clonidine. It is advisable to review all antihypertensive therapy during treatment with tricyclic antidepressants.

Treatment with Prothiaden should be avoided during pregnancy unless there are compelling reasons. There is inadequate evidence of the safety of the drug during human pregnancy.

There is evidence that dosulepin is secreted in breast milk but this is at levels which are unlikely to cause problems.

Initially, Prothiaden may impair alertness. Patients likely to drive or operate machinery should be warned of this possibility.

The following adverse effects, although not necessarily all reported with dosulepin, have occurred with other tricyclic antidepressants:

Atripine-like side effects including dry mouth, disturbance of accommodation, constipation, hesitancy of micturition and sedation are common early in treatment, but usually lessen.

Dizziness is also a common side effect of tricyclic antidepressants.

Uncommon adverse effects include drowsiness, sweating, postural hypotension, tremor skin rashes, tachycardia, confusion and hallucinations. Interference with sexual function may occur.

Potentially serious adverse effects are rare. These include depression of the bone marrow, agranulocytosis, hepatitis (including altered liver function), cholestatic jaundice, convulsions and inappropriate ADH secretion.

Psychotic manifestations, including mania and paranoid delusions, may be exacerbated during treatment with tricyclic antidepressants.

Cases of suicidal ideation and suicidal behaviours have been reported during dosulepin therapy or early after treatment discontinuation (see section 4.4).

Withdrawal symptoms may occur on abrupt cessation of tricyclic therapy and include insomnia, irritability and excessive perspiration. Similar symptoms in neonates whose mothers received tricyclic antidepressants during the third trimester have also been reported.

Cardiac arrhythmias and severe hypotension are likely to occur with high dosage or in deliberate overdosage. They may also occur in patients with pre-existing heart disease taking normal dosage.

Class effects

Epidemiological studies, mainly in patients 50 years of age and older, show an increased risk of bone fractures in patients receiving SSRIs and TCAs. The mechanism leading to the risk is unknown.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via HPRA Pharmacovigilance, Earlsfort Terrace, IRL – Dublin 2; Tel: +353 1 6764971; Fax: +353 1 6762517.

Not applicable.