The NHS Health Technology Assessment programme has featured a cohort study evaluating the risks of antidepressant treatment in older people. The study objectives were as follows:

• to determine relative and absolute risks of predefined adverse events in older people with depression, comparing classes of antidepressant drugs [tricyclic and related antidepressants, selective serotonin reuptake inhibitors, monoamine oxidase inhibitors (MAOIs) and other antidepressants] and commonly prescribed individual drugs with non-use of antidepressant drugs;
• to directly compare the risk of adverse events for SSRIs with TCAs;
• to determine associations with dose and duration of antidepressant medication;
• to describe patterns of antidepressant use in older people with depression; and
• to estimate costs of antidepressant medication and primary care visits.

A total of 60,746 patients (aged between 65 and 100 years from 1 January 1996 to 31 December 2007 and followed up until 31 December 2008) from 570 general practices in the United Kingdom supplying data to the QResearch primary care database were included in the study.

The primary outcome measures were 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 also 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.

A total of 54,038 (89.0%) patients received at least one prescription for an antidepressant during follow-up. The following results were reported:

• 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.
• 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.
• The mean incremental cost (for all antidepressant prescriptions) ranged between £51.58 (amitriptyline) and £641.18 (venlafaxine) over the 5-year post-diagnosis period.

The researchers concluded that “this study has found that 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 the most commonly prescribed individual drugs, trazodone, mirtazapine, and venlafaxine were associated with the highest rates for some outcomes. As this is an observational study, it is susceptible to confounding by indication, channelling bias, and residual confounding. Other differences in characteristics may exist between patients prescribed different antidepressant drugs, which have not been adjusted for and which may account for some of the associations between the drugs and the adverse outcomes, thus further research is needed to confirm these findings”.

The British Medical Journal has featured this study, together with an editorial discussing the study.

The editorial concludes that “Older people require careful monitoring for adverse effects, with provision of information (to the patient and carer) about the risks of falls, confusion, agitation, and increased suicidal ideation. 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. Independently of the severity of depression or the prescription of drugs, all patients should be provided with appropriate psychological support and advice about behavioural interventions—particularly those aimed at increasing their daily activity and improving their sleeping patterns.”