Canada. "Dear Healthcare

Professional" letters have been issued by the manufacturers of seven selective serotonin reuptake inhibitors (SSRIs) and other newer antidepressants, in conjunction with Health Canada, highlighting important safety information regarding potential behavioural and emotional changes. A new Class warning has been incorporated into the labelling for mirtazapine (Organon's Remeron RD/ Remeron),(1) fluvoxamine (Solvay Pharma's Luvox),(2) venlafaxine (Wyeth Pharmaceutical's Effexor/ Effexor XR),(3) sertraline (Pfizer's Zoloft,(4) paroxetine (GlaxoSmithKline's Paxil),(5) fluoxetine (Eli Lilly's Prozac)(6) and citalopram (Lundbeck's Celexa).(7)

The Class warning highlights results of placebo-controlled clinical trials in paediatric patients, which suggest that, compared with placebo, use of SSRIs and other newer antidepressants may be associated with behavioural and emotional changes, including an increased risk of suicidal ideation and behaviour. However, due to small numbers and variability in placebo groups, the relative safety profiles of different agents cannot be reliably determined.

Additional data in both paediatric and adult patients include reports of severe agitation-type events including akathisia, agitation, disinhibition, emotional lability, hostility, aggression and depersonalisation, with events sometimes occurring within several weeks of treatment initiation. The warning advises close monitoring for suicidal ideation or other suicidal behaviour in all patients. In addition, it is advised that treatment with these agents, with the exception of fluoxetine, should not be discontinued abruptly due to the risk of discontinuation symptoms; discontinuation should instead be gradual. For fluoxetine, plasma levels of fluoxetine and norfluoxetine decrease gradually at the conclusion of therapy, making tapering unnecessary in most patients.(6)

References:

1. "Dear Healthcare Professional" letter from Organon Canada Ltd. Available on the Internet at www.hc-sc.gc.ca

2. "Dear Healthcare Professional" letter from Solvay Pharma, May 2004. Available on the Internet at www.hc-sc.gc.ca

3. "Dear Healthcare Professional" letter from Wyeth, 26 May 2004. Available on the Internet at www.hc-sc.gc.ca

4. "Dear Healthcare Professional" letter from Pfizer Canada Inc., 26 May 2004. Available on the Internet at www.hc-sc.gc.ca

5. "Dear Healthcare Professional" letter from GlaxoSmithKline Inc., May 2004. Available on the Internet at www.hc-sc.gc.ca

6. "Dear Healthcare Professional" letter from Eli Lilly Canada Inc., 18 May 2004. Available on the Internet at www.hc-sc.gc.ca

7. "Dear Healthcare Professional" letter from Lundbeck Canada Inc., 26 May 2004. Available on the Internet at www.hc-sc.gc.ca