Paragraphs nine and ten read: "All of the antidepressant classes were associated with elevated risks of all-cause mortality, attempted suicide or self-harm, falls, fractures, and upper GI bleeding compared with no antidepressant use."

"SSRIs and other antidepressants also were associated with greater risks of stroke or transient ischemic attack and epilepsy or seizures, and SSRIs were associated with increased risks of MI and hyponatremia

http://www.medpagetoday.com/Geriatrics/Depression/27869

Antidepressant Risk for Seniors Varies by Class

By Todd Neale, Senior Staff Writer, MedPage Today
Published: August 03, 2011
Reviewed by Zalman S. Agus, MD; Emeritus Professor
University of Pennsylvania School of Medicine and
Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner
Tricyclics may be the safest choice for older patients who need an antidepressant, researchers found.

Compared with tricyclics, selective serotonin reuptake inhibitors (SSRIs) and "other" antidepressants conferred a higher risk of all-cause mortality, stroke or transient ischemic attack, falls, fractures, epilepsy or seizures, and hyponatremia (HRs 1.15 to 3.04), according to Carol Coupland, PhD, of the University of Nottingham in England, and colleagues.

At least part of the difference may be explained by the fact that clinicians can prescribe lower doses of tricyclics than of other antidepressants, the researchers reported online in BMJ. '

They noted, however, that even in an analysis stratified by dose, tricyclics tended to carry a lower risk of several negative outcomes in each category.

"If our findings are confirmed in other studies, this would have implications for the selection of antidepressant treatment in older people, who are already at higher risk of many of these adverse outcomes," they wrote.

Older people may be more likely to have adverse reactions to drug treatment because of a higher burden of comorbidities, age-related physiological changes, and the use of greater numbers of medications, according to Coupland and colleagues.

To explore the differences in severe adverse effects in older individuals following antidepressant use, the researchers examined data from 60,746 individuals 65 and older (mean age 75) treated for depression at one of 570 general practices in the U.K.

During an average follow-up of five years, 89% of the patients received at least one prescription for an antidepressant.

Of nearly 1.4 million antidepressant prescriptions, 54.7% were for SSRIs, 31.6% were for tricyclics, and 13.5% were for other antidepressants. The median duration of use was about one year.

All of the antidepressant classes were associated with elevated risks of all-cause mortality, attempted suicide or self-harm, falls, fractures, and upper GI bleeding compared with no antidepressant use.

SSRIs and other antidepressants also were associated with greater risks of stroke or transient ischemic attack and epilepsy or seizures, and SSRIs were associated with increased risks of MI and hyponatremia.

Compared with no antidepressant use, SSRIs conferred the highest risk of falls (HR 1.66) and hyponatremia (HR 1.52), and other antidepressants were associated with the highest risks of all-cause mortality, attempted suicide or self-harm, stroke or transient ischemic attack, fracture, and epilepsy or seizures (HRs 1.37 to 5.16).

Tricyclics were not associated with the highest hazard for any of the outcomes.

Eleven drugs -- five SSRIs, four tricyclics, and two other antidepressants -- accounted for 96% of all prescriptions, and there were significant differences between individual drugs in their relationships with seven adverse outcomes.

Trazodone, mirtazapine, and venlafaxine were associated with the highest risks of several of the outcomes.

"Although it is not necessary to seek a specialist opinion before starting treatment, clinicians, including those in primary care, need to be aware of the special circumstances surrounding the prescription of antidepressants to older people with depression (such as undetected cerebrovascular comorbidity, frequency and types of adverse events that can be life threatening)," according to Ian Hickie, MD, of the Brain and Mind Research Institute at the University of Sydney.

"Older people therefore require careful monitoring for adverse effects, with provision of information (to the patient and [caregiver]) about the risks of falls, confusion, agitation, and increased suicidal ideation," he wrote in an accompanying editorial.

"They should also be advised that adverse effects are most commonly encountered during the first few weeks of treatment. For this reason, patients should be monitored at least weekly during the first month of treatment and again when drugs are stopped," Hickie wrote.

Coupland and colleagues acknowledged some limitations of their analysis.

"As this is an observational study," they wrote, "it is susceptible to confounding by indication, channeling bias, and residual confounding, so differences in characteristics between patients prescribed different antidepressant drugs that could account for some of the associations between the drugs and the adverse outcomes may remain."

The project was funded by the NIHR Health Technology Assessment (HTA) Program.

All study authors had financial support from the NIHR Health Technology Assessment Program. The authors declared no financial relationships with any organizations that might have an interest in the submitted work in the previous three years. One of the study authors is director of QResearch, which is a not-for-profit venture between the University of Nottingham and Egton Medical Information Systems (a commercial supplier of general practice clinical computer systems), and director of ClinRisk Ltd. (a medical software company). One of the author study authors has received financial support for speaking at meetings sponsored by several pharmaceutical companies about the non-drug treatment of depression and bipolar disorder.

Hickie reported no support from any organization for his editorial. He is supported principally by a National Health and Medical Research Council (NHMRC) Australian Medical Research Fellowship. Research studies done by Hickie are mainly funded by NHMRC project and program grants. He has led or participated in other depression awareness projects for health professionals and the broader community, supported by governmental, community agency, and drug industry partners, including Wyeth, Eli Lily, Servier, Pfizer, and AstraZeneca. These programs have focused on the identification and active management of depression and anxiety, with a strong emphasis on promotion of both nonpharmacological and pharmacological interventions. Hickie has participated in a multicenter clinical trial of the effects of agomelatine on sleep architecture in depression. He was previously CEO and then clinical adviser of beyondblue, the Australian government-supported national depression initiative. He has participated in the development of guidelines for the treatment of depression, funded by the Australian government, and has served on advisory boards in relation to specific antidepressants, including nefazodone, duloxetine (Cymbalta), and desvenlafaxine (Pristiq).