In a study of 811 people treating major depression over a 12-week period with the drugs nortriptyline (marketed as Aventyl and Pamelor) and competitor escitalopram (marketed as Lexapro and Cipralex), researchers found that men taking nortriptyline showed a dramatic increase in suicidal thoughts, compared to those taking the competing drug. The study was published this week in the open-access journal BMC Medicine.
Escitalopram is a selective serotonin reuptake inhibitor (SSRI), and works by limiting the amount of the neurotransmitter serotonin re-absorbed by particular nerve cells in the brain. Nortriptyline is a tricyclic antidepressant (TCA), that works similarly to SSRIs, but blocks the reuptake of three neurotransmitters—serotonin, norepinephrine, and to a lesser degree, dopamine—as opposed to “selectively” blocking just serotonin.
The research, led by psychiatrist Dr. Nader Perroud at King’s College London found that, while, across the study population suicidal thoughts generally decreased on both medications, among men taking nortriptyline there was a marked trend in emerging suicidal thoughts and increased suicidal thoughts. Specifically, men taking nortriptyline had 9.8 times higher incidence of experiencing suicidal thoughts for the first time, compared with those taking the competing drug; men who had already experienced some suicidal ideation had a 2.4 times higher occurrence of worsening thoughts of suicide, compared with those taking escitalopram. These correlations were stronger in men with more severe depression—and men with a history of suicide attempts or those who were retired or unemployed were at particularly high risk for increase in thoughts of suicide, the researchers found.
What’s more, while previous research has suggested that a surge in suicidal thoughts is generally limited to the first weeks of treatment with antidepressants, that was not the case in this research. Instead, emerging thoughts of suicide and worsening suicidal ideation “were relatively evenly distributed over the 12 weeks of follow up,” the researchers write. “This is of particular concern as it shows that there is little reason for either intensive monitoring over the first weeks, or for complacency later in the course of treatment, which could be an interpretation of current clinical guidelines,” they conclude.
Further research is needed to confirm these findings, the researchers say, and a placebo-controlled trial in particular would help to narrow the findings to specific effects of the medications. Yet, in the meantime, the researchers hope that the study at least raises awareness among prescribing doctors, and emphasizes the importance of ongoing monitoring of patients on new treatment regimens. The researchers put it more emphatically: “The monitoring of suicidal ideation should not be restricted to the early phases of treatment.”