In recent months, there has been concern raised internationally about the increased risk of suicidal ideation and self-harm behaviour in children and adolescents who are prescribed these drugs for the treatment of major depressive disorders (MDD). The PVAC has reviewed the reports from the UK Committee on Safety of Medicines (CSM), US Food and Drug Administration (FDA) advisory committees and the American College of Neuropsychopharmacology.

The antidepressants available in Singapore that are affected by this review include the following 9 drugs: bupropion, citalopram, escitalopram, fluoxetine, fluvoxamine, mirtazepine, paroxetine, sertraline and venlafaxine (See Table below for further details).

The PVAC notes that the available data to-date does not clearly establish an association between the use of these drugs and increased suicidal thoughts or actions in paediatric patients. Nevertheless, neither is it possible at this point to rule out an increased risk of these adverse events for any of these drugs until more data is available.

It would be worthwhile for healthcare professionals to note that none of these drugs is licensed in Singapore for treating major depressive disorders (MDD) in children and adolescents based on data submitted at point of marketing authorisation.

In view of the above recent safety concerns, HSA advises that the use of any SSRIs and related antidepressants in children and adolescents with MDD should be undertaken only within the context of comprehensive management of the patients, as outlined in the Clinical Practice Guidelines on Depression recently issued by MOH. Physicians should carefully monitor patients receiving antidepressants for possible worsening of depression or suicidality, especially at the beginning of therapy or when the dose either increases or decreases.

In addition, the choice of an SSRI for children and adolescents with MDD should be made only after taking into account the recent reports put up by the the UK and the US drug regulatory authorities as indicated in para 2. Please also note that the current local package inserts for paroxetine and venlafaxine recommend against their use in children and adolescents.

Children and adolescents who are currently being treated for MDD with any of these antidepressants should not have their medications ceased abruptly as there may be withdrawal symptoms associated with abrupt discontinuation.

HSA is working with the relevant pharmaceutical companies to reinforce the labelling on the package inserts of all the SSRIs and related antidepressants to reflect the need for stronger warnings for close monitoring for worsening depression and increase suicidality among children and adolescents with MDD prescribed with SSRIs and related antidepressants.

Table 1: List of registered oral SSRIs and related antidepressants in Singapore

No.	Antidepressant	Product Name	Available strengths
1	Bupropion	Wellbutrin SR tablet	150 mg
2	Citalopram	Cipram  tablet	20 mg
3	Escitalopram	Lexapro tablet	5 mg, 10 mg, 15 mg, 20 mg
4	Fluoxetine	APO-Fluoxetine capsule	10 mg, 20 mg
		Deprexin capsule	20 mg
		Fluoxetine capsule	20 mg
		Fluoxone Divule tablet	20 mg
		Fluxetil capsule	20 mg
		Fluxetin capsule	20 mg
		Foxtin-20 capsule	20 mg
		Magrilan capsule	20 mg
		PMS-Fluoxetine capsule	20 mg
		Proctin capsule	20 mg
		Prodep capsule	20 mg
		Provatine tablet	10 mg, 20 mg
		Prozac 20 capsule	20 mg
		Prozac Dispersible tablet	20 mg
		Zactin capsule	20 mg
5	Fluvoxamine	Faverin tablet	50 mg, 100 mg
		Fluvoxamine Maleate tablet	50 mg, 100 mg
6	Mirtazapine	Remeron tablet	15 mg, 30 mg, 45 mg
		Remeron Soltab	15 mg, 30 mg, 45 mg
7	Paroxetine	Seroxat tablet	20 mg, 30 mg
8	Sertraline	Zoloft tablet	50 mg, 100 mg
9	Venlafaxine	Efexor XR capsule	75 mg, 150 mg
		Efexor tablet	37.5 mg, 50 mg, 75 mg