Antidepressant Use and Adverse Outcomes in Older People
Antidepressant Use and Adverse Outcomes in Older People
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.
Depression is a common condition in older people, affecting around 10-15% of those living in the community. In the United Kingdom, depression is largely treated in primary care with antidepressant drugs. Antidepressants are one of the most commonly prescribed drug groups in primary care. Around 39 million prescriptions for antidepressants were issued in the community in England in 2009 across all ages, an increase of 35% over five years. Prescriptions increased most for the class of selective serotonin reuptake inhibitor antidepressants—a 47% increase over five years, compared with an 18% increase for the class of tricyclic and related antidepressants and a 37% increase for other antidepressants. A systematic review in older people found that tricyclic antidepressants and selective serotonin reuptake inhibitors were equivalent in terms of efficacy but that classic tricyclic antidepressants were associated with a higher discontinuation rate owing to side effects. The National Institute for Health and Clinical Excellence recommends that the choice of an antidepressant should be guided by consideration of side effects and the patient's preferences but that normally a selective serotonin reuptake inhibitor in generic form should be chosen.
Little is known about more serious adverse effects of antidepressants, particularly in older people, in whom adverse drug events may be more common in the treatment of depression compared with younger groups because of higher levels of comorbidity, age related physiological changes, and polypharmacy. The under-representation of older people in clinical trials of antidepressants and the fact that most such trials are short term make deriving reliable or precise estimates of the incidence of adverse events in this group difficult. This problem is further compounded when criteria for trials exclude older people with comorbid conditions. Although several observational studies have examined different adverse outcomes associated with use of antidepressants, few have been specific to an older population.
We therefore did a large cohort study of antidepressant use in older people to investigate the association between antidepressant treatment and risk of several potential adverse outcomes. We directly compared antidepressant class effects and examined dose and associations with use of commonly prescribed individual drugs. We aimed to derive a comprehensive and integrated picture of the relative safety and balance of risks for antidepressant drugs in older people diagnosed as having depression.
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.
Introduction
Depression is a common condition in older people, affecting around 10-15% of those living in the community. In the United Kingdom, depression is largely treated in primary care with antidepressant drugs. Antidepressants are one of the most commonly prescribed drug groups in primary care. Around 39 million prescriptions for antidepressants were issued in the community in England in 2009 across all ages, an increase of 35% over five years. Prescriptions increased most for the class of selective serotonin reuptake inhibitor antidepressants—a 47% increase over five years, compared with an 18% increase for the class of tricyclic and related antidepressants and a 37% increase for other antidepressants. A systematic review in older people found that tricyclic antidepressants and selective serotonin reuptake inhibitors were equivalent in terms of efficacy but that classic tricyclic antidepressants were associated with a higher discontinuation rate owing to side effects. The National Institute for Health and Clinical Excellence recommends that the choice of an antidepressant should be guided by consideration of side effects and the patient's preferences but that normally a selective serotonin reuptake inhibitor in generic form should be chosen.
Little is known about more serious adverse effects of antidepressants, particularly in older people, in whom adverse drug events may be more common in the treatment of depression compared with younger groups because of higher levels of comorbidity, age related physiological changes, and polypharmacy. The under-representation of older people in clinical trials of antidepressants and the fact that most such trials are short term make deriving reliable or precise estimates of the incidence of adverse events in this group difficult. This problem is further compounded when criteria for trials exclude older people with comorbid conditions. Although several observational studies have examined different adverse outcomes associated with use of antidepressants, few have been specific to an older population.
We therefore did a large cohort study of antidepressant use in older people to investigate the association between antidepressant treatment and risk of several potential adverse outcomes. We directly compared antidepressant class effects and examined dose and associations with use of commonly prescribed individual drugs. We aimed to derive a comprehensive and integrated picture of the relative safety and balance of risks for antidepressant drugs in older people diagnosed as having depression.
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