Posted by Phillipa on November 2, 2009, at 19:34:39
To Me rather strange article on Nortriptaline vs escitalopram In suicidal new thoughts or old ones. Difficult to pinpoint real conclusion. Phillipa
From Medscape Medical News
More Suicidal Ideation With Nortriptyline vs Escitalopram Among Men, but Both Drugs Decrease Adverse Effects
Fran Lowry
Click here October 30, 2009 The tricyclic antidepressant nortriptyline and the selective serotonin reuptake inhibitor (SSRI) escitalopram both decrease suicidal ideation in men and women; however, in men, nortriptyline is associated with an almost 10-fold increase in suicidal thoughts at 5 weeks vs escitalopram.The finding, from a partially randomized, open-label study published online October 14 in BMC Medicine, suggests that men being treated with nortriptyline for depression be carefully monitored for the occurrence of suicidal ideation for at least 5 weeks and possibly longer.
"Reports of higher rates of suicide-related adverse events during treatment with...SSRIs and other antidepressants compared to placebo have prompted regulatory bodies in the US and Europe to issue warnings alerting clinicians to the risk of suicide during the first weeks of antidepressant treatment," write Nader Perroud, MD, from the Institute of Psychiatry, Kings College London, London, United Kingdom, and colleagues. "These warnings have had an impact on prescribing and may have paradoxically increased the risk of suicide in the population."
The aim of this study was to investigate the course and predictors of both new and worsening suicidal thoughts during treatment with tricyclic antidepressants or SSRIs.
The Genome-Based Therapeutic Drugs for Depression (GENDEP) trial, a large comparative study of an SSRI and a tricyclic antidepressant, was carried out in 811 adults of European ethnicity between the ages of 18 and 72 years with moderate to severe unipolar depression. They were randomly allocated to receive flexible-dose nortriptyline (50 - 150 mg/day) or escitalopram (10 - 30 mg/day) for 12 weeks. Patients with contraindications for one of the drugs were allocated nonrandomly to the other antidepressant.
Suicidal ideation was assessed with a composite score based on relevant items of the Hamilton Rating Scale for Depression, the Beck Depression Inventory, and the Montgomery-Asberg Depression Rating Scale.
Increases in this score were classified as treatment-emergent suicidal ideation (TESI) or treatment-worsening suicidal ideation (TWOSI), according to the absence or presence of suicidal ideation at study entry.
Nortriptyline Linked With Higher TESI, TWOSI
The investigators report that, overall, suicidal ideation markedly decreased during treatment with both drugs. However, nortriptyline was associated with a higher rate of both TESI and TWOSI in men.
Men who took nortriptyline were found to have a 9.8-fold increase in new suicidal thoughts (or TESI) and a 2.4-fold increase in worsening suicidal thoughts (or TWOSI) vs men who took escitalopram.
New suicidal thoughts peaked in the fifth week of treatment, whereas worsening suicidal thoughts were highest in the sixth week of treatment.
Predictors of TESI included depression severity during follow-up, younger age at onset of depression, higher number of previous depressive episodes, unemployment, and being married. Predictors of TWOSI included depression severity during follow-up, history of suicide attempts, and retirement status.
Study Limitations
The study authors write that their study has limitations. First, it was not placebo controlled and therefore was unable to distinguish the specific effects of either antidepressant from those of placebo or the natural fluctuations in the course of depression; it was also open label. Also, the results could not be generalizable to other forms of suicidal behaviors such as suicide attempts and suicide completion. Finally, the study did not take into account the influence of alcohol or substance use disorders, as these were exclusion criteria in GENDEP.
These limitations notwithstanding, the trial results "clearly indicate that TESI and TWOSI are associated with severe forms of depressive disorder and poor treatment response," the authors conclude. "Retired or unemployed men and those with a history of past suicide attempts are at particular risk of worsening in suicidal ideation and should be carefully monitored. The monitoring of suicidal ideation should not be restricted to the early phases of treatment."
Comments: Other Issues in the Study
Harry Croft, MD, medical director, San Antonio Psychiatric Research Center, San Antonio, Texas, told Medscape Psychiatry he thought that the fact that suicidal thinking decreased during the 12 weeks regardless of which drug patients were taking was significant.
However, he took issue with the method used to measure suicidal ideation. "In all of our depression trials now, the FDA requires that we use a scale to measure suicidality which is the Columbia Suicide Assessment Scale. But in this study, they used items from 3 different instruments for measuring depression to assess suicidal thoughts. That's one of the weaknesses of this study. Use of the Columbia scale would have told us more specifically whether thoughts were truly suicidal or not."
Dr. Croft also voiced concern that misleading reporting may give people the wrong message about the usefulness of antidepressants in general.
"I'm looking at a headline on a psychiatry Web site that reads 'popular antidepressant associated with a dramatic increase in suicidal thoughts amongst men.' That gives the wrong message. Nortriptyline might cause more suicidal thinking than the newer SSRI, it may be because of the way it works, its side effects, we don't really know why. But the good news is, we don't use the tricyclics very much any more. What I'm afraid of is that when the last person gets the message it will be, 'Did you know that antidepressants cause a ten fold increase in thinking about suicide?' That wasn't what this study was about at all."
Weighing in with his opinion, Ewald Horwath, MD, professor and interim chair of the Department of Psychiatry, University of Miami Miller School of Medicine, Miami, Florida, stressed that the main finding of the study is that treatment with either drug was associated with a very significant reduction in suicidal ideation with time. "I think it's important to remember that," he told Medscape Psychiatry.
The finding that the increase in suicidal ideation peaked at 5 weeks in this study differs from findings from some other studies, which have reported increases in suicidal thoughts to occur earlier in treatment, within the first week or two, he said.
Also, severity of depression was very strongly associated with a higher rate of increased suicidal ideation, Dr. Horwath pointed out.
"If you look at the overall effects of the antidepressants, most people would argue that we are treating a population of people who are depressed, and suicidal ideation is one of the symptoms of depression. People who are more severely depressed are more likely to develop suicidal ideation, so it's difficult to attribute cause to the drug. The one thing one could say from this study is that if a doctor is treating a male with nortriptyline, he or she should monitor a little bit more for suicidal ideation during the first couple months of treatment," he said.
That nortriptyline is used less often than the newer SSRIs also makes the significance of the study findings for clinical practice "fairly modest," Dr. Horwath added. "The older drugs like nortriptyline are still used but they have a lot more side effects, so they are usually reserved for people who haven't responded to an SSRI or who have more severe depression. But these are the people who need more close monitoring, anyway."
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thread:924185
URL: http://www.dr-bob.org/babble/20091029/msgs/924185.html