Abstract
Objectives To investigate the association between antidepressant treatment and risk of several potential adverse outcomes in older people with depression and to examine risks by class of antidepressant, duration of use, and dose.
Design Cohort study of people aged 65 and over diagnosed as having depression.
Setting 570 general practices in the United Kingdom supplying data to the QResearch primary care database.
Participants 60,746 patients diagnosed as having a new episode of depression between the ages of 65 and 100 years from 1 January 1996 to 31 December 2007 and followed up until 31 December 2008.
Main outcome measures Hazard ratios associated with antidepressant use for all cause mortality, attempted suicide/self harm, myocardial infarction, stroke/transient ischaemic attack, falls, fractures, upper gastrointestinal bleeding, epilepsy/seizures, road traffic accidents, adverse drug reactions, and hyponatraemia, adjusted for a range of potential confounding variables. Hazard ratios were calculated for antidepressant class (tricyclic and related antidepressants, selective serotonin reuptake inhibitors, other antidepressants), dose, and duration of use and for commonly prescribed individual drugs.
Results 54 038 (89.0%) patients received at least one prescription for an antidepressant during follow-up. A total of 1,398,359 antidepressant prescriptions were issued: 764 659 (54.7%) for selective serotonin reuptake inhibitors, 442 192 (31.6%) for tricyclic antidepressants, 2203 (0.2%) for monoamine oxidase inhibitors, and 189 305 (13.5%) for the group of other antidepressants. The associations with the adverse outcomes differed significantly between the antidepressant classes for seven outcomes. Selective serotonin reuptake inhibitors were associated with the highest adjusted hazard ratios for falls (1.66, 95% confidence interval 1.58 to 1.73) and hyponatraemia (1.52, 1.33 to 1.75) compared with when antidepressants were not being used. The group of other antidepressants was associated with the highest adjusted hazard ratios for all cause mortality (1.66, 1.56 to 1.77), attempted suicide/self harm (5.16, 3.90 to 6.83), stroke/transient ischaemic attack (1.37, 1.22 to 1.55), fracture (1.64, 1.46 to 1.84), and epilepsy/seizures (2.24, 1.60 to 3.15), compared with when antidepressants were not being used. Tricyclic antidepressants did not have the highest hazard ratio for any of the outcomes. Significantly different associations also existed between the individual drugs for the same seven outcomes; trazodone (tricyclic antidepressant), mirtazapine, and venlafaxine (both in the group of other antidepressants) were associated with the highest rates for some of these outcomes. Absolute risks over 1 year for all cause mortality were 7.04% for patients while not taking antidepressants, 8.12% for those taking tricyclic antidepressants, 10.61% for selective serotonin reuptake inhibitors, and 11.43% for other antidepressants.
Conclusions Selective serotonin reuptake inhibitors and drugs in the group of other antidepressants were associated with an increased risk of several adverse outcomes compared with tricyclic antidepressants. Among individual drugs, trazodone, mirtazapine, and venlafaxine were associated with the highest risks for some outcomes. As this is an observational study, it is susceptible to confounding by indication, channelling 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. Further research is needed to confirm these findings, but the risks and benefits of different antidepressants should be carefully evaluated when these drugs are prescribed to older people.
In this study, antidepressants were classified as follows:
Selective serotonin reuptake inhibitors (SSRIs) include: Citalopram (Celexa), Fluoxetine (Prozac), Paroxetine (Paxil, Seroxat), Sertraline (Zoloft) and Escitalopram (Lexapro)
Tricyclic (TCA) antidepressants include: Amitriptyline, Dosulepin, Lofepramine, and Trazodone
“Other” antidepressants include: Venlafaxine (Effexor) and Mirtazapine (Remeron)
| EXCERPT OF RESULTS FROM TABLE 3, Hazard ratios for six adverse outcomes including “all cause mortality” and “attempted suicide/self harm” | |
| Antidepressant class | Calculated Hazard Ratio |
| All cause mortality | |
| Not taking antidepressants | 1.00 |
| Tricyclic antidepressants | 1.16 (1.10 to 1.22) |
| Selective serotonin reuptake inhibitors | 1.54 (1.48 to 1.59) |
| Other antidepressants | 1.66 (1.56 to 1.77) |
| Attempted suicide/self harm | |
| Not taking antidepressants | 1.00 |
| Tricyclic antidepressants | 1.70 (1.28 to 2.25) |
| Selective serotonin reuptake inhibitors | 2.16 (1.71 to 2.71) |
| Other antidepressants | 5.16 (3.90 to 6.83) |
Editor’s further note: From the New York Times article and from the BMJ study above, we know that up to 6 of 7 elderly patients are inappropriately diagnosed with depression. When they are diagnosed, they are almost always given antidepressants, usually SSRIs. These SSRIs increase their mortality overall, and increase their risk of suicidal thinking. Now read the article below, and think about what factor might be missing from the analysis:
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Murder-suicides in Elderly Rise
WebMD
By Christine Cosgrove
One Sunday morning, Charlie Woods returned home from church to find two police officers waiting at his door. First the officers asked if he had any health problems. Then they told him both his parents were dead. His father had killed his mother, firing six bullets through the bedroom door of their Tallahassee home. Then the 59-year-old man turned the gun on himself.
Since 1988, when Woods’ parents died, the homicide-suicide rate among couples 55 and older in Florida has increased about tenfold, according to Donna Cohen, a professor of psychiatry and behavioral sciences at the University of South Florida’s department of aging and mental health.
Though statistics for the entire nation are not available, Cohen believes the Florida numbers are representative of the rest of the country. She estimates that nearly 20 older Americans die each week in homicide-suicides.
These are not couples who, in the sunset of their years, romantically choose oblivion together. Cohen has found that the typical homicide-suicide case involves a depressed, controlling husband who shoots his ill wife. “These are acts of depression and desperation,” she says. “The wife does not want to die and is often shot in her sleep. If she was awake at the time, there are usually signs that she tried to defend herself.”
“There’s nothing loving about murdering another person,” adds Woods, whose 53-year-old mother was not ill and did not want to die.
It’s not clear why more and more elderly men — the murderers are almost all men — are depressed enough to kill themselves and their wives. One reason may be loneliness, says Patrick Arbore, Director of the Center for Elderly Suicide Prevention at the Goldman Institute on Aging. He points out that more and more seniors live isolated from their friends and families.
In one study of an area in Florida, Cohen found that two-thirds of the men who killed their wives and themselves had visited their doctors within three weeks before committing the deadly act. None, however, were being treated for depression.
But a doctor is unlikely to diagnose a condition like depression in a six-minute office visit, partly for lack of time and partly because older people tend to put up a good front in the doctor’s office.
“We can’t really pass the buck to the physician here. It’s important for adult children and members of the community to pay attention and to listen — to really listen — to what these older people are saying,” says Arbore. “Sometimes comments like ‘I’m going to kill myself’ are so provocative that we can’t believe it and let it go by.”
Changes in eating or sleeping, talk of feeling helpless or hopeless, loss of interest in activities, or giving things away are all signs of depression. In addition, Cohen says adult children should be aware that the following situations are risk factors for homicide-suicide:
- The couple has been married a long time and the husband has a dominant personality.
- The husband is a caregiver and the wife has Alzheimer’s disease or a similar disorder.
- One or both have multiple medical problems, and the health status of one is changing.
- A move to a nursing home or assisted living facility is pending or under discussion.
- The couple is becoming more socially isolated, withdrawing from family, friends, and social activities.
- The couple has been arguing or there is talk of divorce.
Cohen urges adult children to come right out and ask a parent if he has thought about suicide or homicide-suicide. “Don’t worry about giving them ideas,” says Cohen. If the answer is yes, ask them about their plans. The more detailed the plans are, the more likely they’ll be carried through, she says.
If you believe there is a risk for homicide-suicide in your family, call a suicide crisis center, a suicide hotline, a family physician, a psychiatric or medical emergency room, or a community mental health center. And if there is a gun in the house, remove it. Cohen notes that areas of the country where gun laws are stricter, such as the northeast, have much lower homicide-suicide rates than those where firearms are more easily available.
“People think about killing themselves or their partner for weeks, months, even years,” she says. “Be alert to signs of depression and get help quickly.”