Paroxetine (Paxil, Seroxat): increased risk of suicide in pediatric patients

Reason for posting: Mood and anxiety disorders are often managed with selective serotonin reuptake inhibitors (SSRIs) such as paroxetine because of their presumed efficacy and positive safety profile.1^,2^,3^,4 However, recent placebo-controlled trials have revealed concerns about paroxetine's efficacy and safety in the pediatric population. These concerns led the drug's manufacturer, GlaxoSmithKline, to issue “Dear Health Care Professional” letters in several countries, including the United States, the United Kingdom and Canada.5

The drug: Paroxetine is the ninth most commonly prescribed drug in Canada, with over 3 million prescriptions filled in 2002 (www.imshealthcanada.com/htmen/1_0_5.htm). It is a potent 5-HT receptor inhibitor and is partly metabolized by cytochrome P450 (2D6).6 It is indicated for the treatment of depression, obsessive–compulsive disorder, panic disorder, social phobia, generalized anxiety disorder and post-traumatic stress disorder in adults6 and is often used off-label in pediatric populations.5

The US Food and Drug Administration recently reviewed additional safety and efficacy data for the use of paroxetine in pediatric populations (www.fda.gov/bbs/topics/ANSWERS/2003/ANS01230.html). The pooled results of 3 unpublished trials involving pediatric patients with major depressive disorder failed to show paroxetine to be more efficacious than placebo.5 In addition, the pooled results showed that suicidal thoughts, suicide attempts and episodes of self-harm were more frequent among the paroxetine users (5.3% of 378 children) than among those in the placebo group (2.8% of 285 children).5 In a separate placebo-controlled trial involving children with social anxiety disorder, 2.4% of the 165 children given paroxetine had suicide-related adverse events as compared with none of 157 children given a placebo.5 The safety of the drug in the contexts of social anxiety disorder and obsessive–compulsive disorder in children and adolescents is currently being investigated further.

No completed suicides have been reported in GlaxoSmithKline's pediatric clinical trial program for children taking paroxetine, nor have any been reported in Canada. About 1% of the paroxetine-associated pediatric adverse events reported to Health Canada between 1993 and Apr. 30, 2003, were because of suicidal ideation.

What to do: Paroxetine is contraindicated for patients under the age of 18. Although patients with mood disorders often require careful supervision because of an inherent risk of suicide, any pediatric patient currently taking paroxetine should be screened for suicidal thoughts, suicide attempts or episodes of self-harm. Serious consideration should be given to changing therapies in all pediatric patients except those who have nearly completed successful courses. The drug should not be discontinued abruptly (this can lead to serious SSRI withdrawal symptoms);7 rather, a gradual tapering of the dose is recommended. The relative safety of other antidepressants and SSRIs in pediatric populations is unclear. The current warnings do not apply to adult users of paroxetine.

Eric Wooltorton CMAJ