New advice on prescribing anti-depressants

21 October 2004

New advice on prescribing anti-depressants

Medsafe has sent a letter to all prescribers informing them about new advice relating to the known risks and benefits associated with prescribing medications to treat depression in young people and in adults.

The Medicines Adverse Reactions Committee (MARC), an expert advisory committee to the Ministry of Health, has reviewed this issue and have made several recommendations that apply to all antidepressants including Selective Seretonin Reuptake Inhibitors (SSRI), Tricyclic Antidepressants (TCAs), and Monoamine Oxidase Inhibitors (MAOIs).

Ministry of Health spokesman, Dr Stewart Jessamine says "There is a need for new warnings to go on all antidepressant medicine datasheets to indicate possible increased suicide risk and the need to closely monitor patients with depression."

In addition to this, the MARC have advised that when treating children and adolescents with depression the risk of suicidal thoughts and behaviour with SSRIs generally outweigh the possible benefits from the medication. "However we need to make the point that there is no clinical evidence of increased completedsuicides in any age group using SSRIs," says Dr Jessamine. "The most important thing for people taking these medications is that they keep taking them as prescribed. You can discuss any concerns with your doctor at the next scheduled visit, or if you're very worried call to see your doctor sooner."

"There are some Tricyclic Antidepressants that are currently approved for use in treating depression in children and adolescents, but we will be requiring that the datasheets about this be updated. They will say these medicines are NOT recommended for use in patients under 18 years of age unless upon the advice of an appropriate specialist. This is because the risks of heart problems with tricyclics generally outweigh the benefits for children and adolescents."

Dr Jessamine says "In some instances, a clinician may decide that these medications are the most appropriate way to treat a child or adolescent with Major Depressive Disorder. If that is the case, then the prescriber must discuss the risks and benefits with the patient / parent and obtain informed consent."

For adults, the risk / benefit ratio with all antidepressants is still favourable. "Although there is some evidence that there is a possible increased risk of suicidal thoughts and behaviours in some adults taking SSRIs, the overall proven benefits outweighs the possible risks," says Dr Jessamine.

"All patients with Major Depressive Disorder should be regularly monitored for suicide risk regardless of whether they are taking anti-depressants or not. And it is especially important that specialist advice is sought before starting, stopping or changing any antidepressant treatment in children or adolescents."

Dr Jessamine says "Prescribers will always face dilemmas when treating severely depressed young people because options are limited and there are questions around the effectiveness and safety of the medicines available for treatment. The dilemma comes when weighing up the risk of NOT prescribing one of these medicines, that is why we are telling doctors to get advice from an appropriate specialist."

Background

The SSRI medicines available in New Zealand are:

· Citalopram (brand names: Cipramil, Celapram) · Escitalopram (brand name: Lexapro, Cipralex) · Fluoxetine (brand names: Fluox, Prozac, Apo-fluoxetine, Lovan, Plinzene, Flexetor, Fluohexal) · Fluvoxamine (brand name: Luvox) - not marketed · Paroxetine (brand name: Aropax) · Sertraline (brand name: Zoloft) · Venlafaxine (brand name: Efexor)

TCAs currently available in New Zealand are:

. Amitriptyline (brand name: Amitrip) . Clomipramine (brand name: Anafranil, Apo-clomipramine, Clopress) . Desipramine (brand name: Pertofran) . Doxepin (brand name: Anten) . Dothiepin (brand name: Dopress) . Imipramine (brand name: Tofranil) . Maprotiline (brand name: Ludiomil) . Mianserin (brand name: Tolvon) . Noritriptyline (brand name: Norpress) . Trimipramine (brand name: Tripress, Surmontil)

Other antidepressants available in New Zealand are: . Mirtazapine (brand name: Remeron) . Moclobemide (brand name: Aurorix, Apo-moclobemide) . Reboxetine (brand name: Edronax) . Tranylcypromine (brand name: Parnate)

In New Zealand, none of the SSRIs have ever been licensed for use in those aged less than 18 years (however, it is recognised that off-label use occurs in this age group). All NZ data sheets (information provided for medicine prescribers) for all SSRIs currently state that "Safety and effectiveness in children has not been established". All but fluoxetine and sertraline go further to state that "use is not recommended in children". Data sheets are available on the Medsafe web site www.medsafe.govt.nz.

In June 2003, the UK Committee on Safety of Medicines issued a letter to UK prescribers advising against the use of paroxetine as therapy for children and adolescents with depressive illness. This advice was based on new data from GlaxoSmithKline (GSK)-sponsored clinical trials of Aropax in paediatric patients. At this time, the New Zealand data sheet for paroxetine (Aropax) was updated to advise that clinical trials do not support the use of paroxetine in the treatment of children with major depressive disorder (MDD). In addition, GlaxoSmithKline issued a related Dear Doctor letter to New Zealand prescribers.

In June 2003, Medsafe and the Medicines Adverse Reactions Committee (MARC; an expert advisory committee to the Minister of Health) reviewed the 'Technical document summaries - Summary of clinical safety data' for paroxetine provided to Medsafe by GSK. The Committee agreed that the data were not of sufficient quality to justify any additional regulatory action (beyond that already taken by GSK) regarding the use of paroxetine at that time. The decision was made to keep a watching brief on this issue.

In August 2003, Wyeth updated the New Zealand data sheet for venlafaxine (Effexor) to advise against prescribing venlafaxine as therapy for children and adolescents with depressive illness. This was based on data from paediatric trials, which showed increased reports of suicide-related adverse events in paediatric patients receiving venlafaxine treatment for MDD. In addition, Wyeth issued a related Dear Doctor letter to New Zealand prescribers.

In December 2003, the UK Committee on Safety of Medicines (CSM) issued a letter to UK health professionals informing them that a CSM Expert Working Group had completed a review of the safety and efficacy of SSRIs in the treatment of paediatric MDD. On the basis of this review of the available clinical trial data, the CSM advised prescribers that paroxetine, citalopram, escitalopram, sertraline, and venlafaxine are contraindicated (meaning should not be used) in paediatric MDD. The balance of risks and benefits of fluoxetine in these patients was deemed to be favourable. A copy of this letter, which also provides general prescribing advice, can be found at http://www.mca.gov.uk/aboutagency/regframework/csm/csmhome.htm

In March 2004, the Medicines Adverse Reactions Committee decided there was not enough information to warrant changing the existing advice about the prescribing of SSRIs to people under the age of 18. There was a commitment to place a high priority on reviewing the safety of SSRIs as more data became available.

In September 2004, two FDA advisory committees discussed an analysis of paediatric suicidality information based on new data and concluded that there is some increased risk of suicidal thoughts and behaviours associated with all SSRIs studied. The MARC is in broad agreement with this conclusion but notes that there is no clinical trial evidence to associate SSRIs with risk of completed suicide in any age group.

In September 2004, the MARC recommended that datasheets for Tricyclic Antidepressants currently approved for use in treating MDD in children and adolescents be updated to say these medicines are not recommended for use in patients under 18 years of age unless upon the advice of an appropriate specialist (and contraindicated in children under 13 years of age). In addition, the MARC have recommended updates to all antidepressant medicine datasheets (including SSRIs, TCAs, and MAOIs) to provide advice on monitoring for clinical worsening and warn of possible increased suicide risk with all antidepressant treatments. An excerpt of the draft MARC minutes (22 September meeting) is available on the Medsafe web site: http://www.medsafe.govt.nz/Profs/adverse.htm

ENDS

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