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Older antidepressant spurs more suicidal thinking in men than newer medication

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The largest clinical trial to date comparing an older, tricyclic antidepressant with a newer antidepressant of the selective serotonin reuptake inhibitor (SSRI) class has found that the emergence of suicidal thinking was almost 10 times more common in men taking the older drug than in those taking the newer medication.

The study also found that for men and women taking either medication, suicidal thinking was spread over the first six weeks of treatment, but peaked at roughly the fifth week before declining significantly after week six. Taking place at academic medical institutions across Europe, the trial, called Genome-Based Therapeutic Drugs for Depression--or GENDEP--gauged the responses to antidepressants of 811 persons ranging from 18 to 72 with depression.

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The results of the study, published in the British journal BMC Medicine, suggest that an older generation of antidepressant--still widely prescribed--is not without the risk of suicidal thoughts that is widely attributed to newer medications in the SSRI class. Indeed, for some populations, it may be far higher.

The study authors note that tricyclic antidepressants--in this case nortriptyline--can sometimes increase agitation and irritability--a feature of depression more commonly found in men in the first place. Exacerbating that agitation might make the tricyclic antidepressant nortriptyline a more powerful prompt to suicidal thoughts for some, they surmised.

The study also underscores an important lesson for patients starting on an antidepressant and the physicians who care for them: Earlier studies have suggested that suicidal thoughts were most frequent in the first couple of weeks of treatment or after a change in dose. But this European study suggests that suicidal thoughts continue--and indeed may escalate--into a patient’s fifth or sixth week on a new antidepressant, before falling off. Patients and their families and physicians should continue to be watchful for changes in thoughts or behavior well into a new therapy.

-- Melissa Healy

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