All antidepressants may not be created equal when it comes to worsening of suicidal ideation during treatment, researchers found.
Men taking nortriptyline (Aventyl, Pamelor) were 2.4 times more likely to have an increase in suicidal thoughts than were those taking escitalopram (Lexapro), Nader Perroud, MD, of King's College London, and colleagues reported online in BMC Medicine.
Nortriptyline, a tricyclic antidepressant, was also associated with a 9.8-fold higher risk of new onset of suicidal ideation compared with the selective serotonin reuptake inhibitor (SSRI) in the prospective open-label trial.
The reason behind the difference may be that nortriptyline acts predominantly on the noradrenergic system, which, when overactive, is associated with anxiety and agitation.
Because "suicidal ideation is more common in agitated and irritable types of depression," the researchers said, "it is possible that nortriptyline may induce or worsen suicidal thoughts in some male subjects possibly through an induction of this more agitated type of depression."
Another possibility is that nortriptyline is less effective against mood symptoms, they noted.
All antidepressants now carry black box warnings of suicidality risk, particularly in children and young adults, and especially early in treatment, but whether this risk differs between agents or by gender has been debated.
Prior studies have looked only at emergence of suicidal thoughts in patients who reported none initially, which "highlights the relatively rare cases with de novo treatment-emergent suicidal ideation," Perroud's group said, but could be "'throwing the baby out with the bath water' through removing a large proportion of patients at risk."
So they analyzed findings from the Genome-Based Therapeutic Drugs for Depression (GENDEP) trial, "the largest comparative study of an SSRI and tricyclic antidepressant," to look at both issues.
The multicenter study included 811 adults with moderate to severe unipolar depression allocated to open-label, flexible dose escitalopram or nortriptyline for 12 weeks. Among them, 473 reported suicidal ideation at baseline.
Overall, suicidal ideation dropped significantly over time in both treatment groups (P less than 0.0001).
And although nortriptyline was associated with higher mean suicidal scores than escitalopram throughout treatment (P less than 0.0001), the difference disappeared after adjusting for baseline scores (P=0.449).
Increases in suicidal ideation - defined as 0.5 standard deviation or greater score increase - were seen at some point in 31.9% of patients.
Treatment group did not appear to have an impact on suicidal ideation changes during therapy in the overall cohort, but it did make a difference in men.
Among men, the overall rate of increase in suicidal thoughts was 35.29% with nortriptyline compared with 23.7% with escitalopram. Even after adjustment for depression severity at baseline and during the study, the effect remained significant. - 31521
Men taking nortriptyline (Aventyl, Pamelor) were 2.4 times more likely to have an increase in suicidal thoughts than were those taking escitalopram (Lexapro), Nader Perroud, MD, of King's College London, and colleagues reported online in BMC Medicine.
Nortriptyline, a tricyclic antidepressant, was also associated with a 9.8-fold higher risk of new onset of suicidal ideation compared with the selective serotonin reuptake inhibitor (SSRI) in the prospective open-label trial.
The reason behind the difference may be that nortriptyline acts predominantly on the noradrenergic system, which, when overactive, is associated with anxiety and agitation.
Because "suicidal ideation is more common in agitated and irritable types of depression," the researchers said, "it is possible that nortriptyline may induce or worsen suicidal thoughts in some male subjects possibly through an induction of this more agitated type of depression."
Another possibility is that nortriptyline is less effective against mood symptoms, they noted.
All antidepressants now carry black box warnings of suicidality risk, particularly in children and young adults, and especially early in treatment, but whether this risk differs between agents or by gender has been debated.
Prior studies have looked only at emergence of suicidal thoughts in patients who reported none initially, which "highlights the relatively rare cases with de novo treatment-emergent suicidal ideation," Perroud's group said, but could be "'throwing the baby out with the bath water' through removing a large proportion of patients at risk."
So they analyzed findings from the Genome-Based Therapeutic Drugs for Depression (GENDEP) trial, "the largest comparative study of an SSRI and tricyclic antidepressant," to look at both issues.
The multicenter study included 811 adults with moderate to severe unipolar depression allocated to open-label, flexible dose escitalopram or nortriptyline for 12 weeks. Among them, 473 reported suicidal ideation at baseline.
Overall, suicidal ideation dropped significantly over time in both treatment groups (P less than 0.0001).
And although nortriptyline was associated with higher mean suicidal scores than escitalopram throughout treatment (P less than 0.0001), the difference disappeared after adjusting for baseline scores (P=0.449).
Increases in suicidal ideation - defined as 0.5 standard deviation or greater score increase - were seen at some point in 31.9% of patients.
Treatment group did not appear to have an impact on suicidal ideation changes during therapy in the overall cohort, but it did make a difference in men.
Among men, the overall rate of increase in suicidal thoughts was 35.29% with nortriptyline compared with 23.7% with escitalopram. Even after adjustment for depression severity at baseline and during the study, the effect remained significant. - 31521
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