Carol Coupland Paula Dhiman

Tony ArthurRichard Morriss

Julia Hippisley-CoxUniversity of Nottingham

Garry BartonUniversity of East Anglia

Antidepressant use and the risk of stroke in older

people

Depression in older people

Depression is a common condition in older people (around 15%)

It is associated with increased rates of morbidity and mortality

It is mainly treated in primary care, frequently with antidepressants

2

Adverse effects of antidepressants

Around 14 million prescriptions for antidepressants were issued to people aged 60+ in 2007, an increase of 10.1% compared with 2006 and 79.0% compared with 2000

Little is known about adverse effects of antidepressants in older people

Some studies have shown that antidepressants may increase risk of stroke

3

Study designCohort study carried out using QResearch primary care database.

Patients were included if:they had a recorded diagnosis of

depression the diagnosis was made at the age of 65 or

over the diagnosis was between 1/1/1996 to

31/12/2007they were no more than 100 years at

diagnosisthe diagnosis occurred at least 12 months

after registration with a study practice.

4

Exposures

Antidepressant prescriptions categorised as:Tricyclic and related antidepressants (TCAs)Selective Serotonin Reuptake Inhibitors

(SSRIs)Monoamine oxidase inhibitors (MAOIs) Other antidepressantsCombined treatment

Antidepressants also categorised by dose, duration and individual drugs.

5

AnalysisOutcome was diagnosis of stroke or transient ischaemic attack (TIA) during follow-up to 31/12/2008.Cox’s proportional hazards model used to calculate unadjusted and adjusted hazards ratios for antidepressant use (time varying)Adjusted for:

• age , sex, study year, previous diagnosis of depression, severity of depression (mild, moderate or severe), smoking status

• deprivation, based on Townsend deprivation score• comorbidities (ischaemic heart disease, diabetes,

hypertension, stroke, cancer, dementia, epilepsy, Parkinson’s disease, hypothyroidism, obsessive-compulsive disorder)

• use of other drugs (statins, NSAIDS, anti-psychotics, lithium, aspirin, antihypertensive drugs, anticonvulsants, hypnotics/anxiolytics).

6

ResultsThere were 60,464 patients in the study cohort54,038 (89.0%) received at least one prescription

for an antidepressant drug during follow-upThere were 1,398,359 prescriptions for

antidepressants 31.6% for TCAs, 54.7% for SSRIs, 0.2% for MAOIs,

and 13.5% for the class of other antidepressants. The median duration of treatment with

antidepressants during follow-up was 364 days (IQR 91, 1029).

7

Stroke/TIA outcome

During follow-up 5369 (9.9%) of patients had an incident stroke/TIA, during 265,410 person-years of follow-up

Crude incidence rate was 202 per 10,000 person-years (95% CI (197 to 208).

8

Hazard ratios for antidepressant class

*note: hazard ratios compared to periods of non-use of antidepressants

0.8

01.0

01.2

01.4

01.6

01.8

02.0

0adju

sted h

aza

rd r

atio

TCAs SSRIs Other combinedantidepressant class

Adjusted hazard ratios and 95 % CI for stroke

9

Hazard ratios for antidepressant dose

*note: hazard ratios compared to periods of non-use of antidepressants

0.8

01.0

01.2

01.4

01.6

01.8

02.0

0adju

sted h

aza

rd r

atio

antidepressant dose

Adjusted hazard ratios and 95 % CI for stroke

10

Hazard ratios for antidepressant timing

*note: hazard ratios compared to periods of non-use of antidepressants

0.0

0.5

1.0

1.5

2.0

2.5

3.0

adju

sted h

aza

rd r

atio

antidepressant timing

Adjusted hazard ratios and 95 % CI for stroke

11

Hazard ratios for individual drugs0.8

01.0

01.2

01.4

01.6

01.8

02.0

0adju

sted h

aza

rd r

atio

antidepressant drug

Adjusted hazard ratios and 95 % CI for stroke

*note: hazard ratios compared to periods of non-use of antidepressants12

Excess risks

For each 10,000 patients treated with: SSRIs - 38 additional people would have

a stroke in one year compared with no treatment

other antidepressants - 81 additional people would have a stroke in one year compared with no treatment

13

Summary of findings

Stroke risk is significantly increased for SSRIs and the class of other antidepressant drugs, compared with TCAs and periods of no use of antidepressants.

Little evidence of a dose response relationship.

Stroke rates were highest in the first 28 days of starting an SSRI antidepressant

Among individual antidepressant drugs the highest hazard ratios were for Venlafaxine Hydrochloride and Mirtazapine.

14

Strengths

Large study in a primary care settingAccounted for many confounding

variablesOne of few studies to investigate effects

of individual drugsDetailed information on antidepressants

prescribed

15

Limitations

Difficult to distinguish effects of antidepressant treatment from effects of depression itself

May be channelling bias - different drugs prescribed according to various patient characteristics

Residual confounding – some stroke risk factors may not be recorded in GP records

16

Conclusions

SSRIs and drugs in the class of other antidepressants may have increased risks of stroke compared with TCAs.

A careful evaluation of benefits and adverse outcomes is needed when prescribing antidepressants to older people which should include consideration of TCAs

17

AcknowledgementsThis project is funded by the NHS R&D

Programme Health Technology Assessment Programme (project number 06/42/01) and will be published in full in the Health Technology Assessment journal. See the HTA programme website for further project information.

We thank the contribution of practices and patients who provide data to QResearch

Department of Health DisclaimerThe views and opinions expressed are those of the research teamand do not necessarily reflect those of the Department of Health.

18