antidepressant use and the risk of stroke in older people
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Antidepressant use and the risk of stroke in older people. Carol Coupland Paula Dhiman Tony Arthur Richard Morriss Julia Hippisley-Cox University of Nottingham Garry Barton University of East Anglia. Depression in older people. - PowerPoint PPT PresentationTRANSCRIPT
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 peopleDepression 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
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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
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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.
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ExposuresAntidepressant 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.
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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).
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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).
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Stroke/TIA outcomeDuring 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).
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Hazard ratios for antidepressant class
*note: hazard ratios compared to periods of non-use of antidepressants
0.80
1.00
1.20
1.40
1.60
1.80
2.00
adju
sted
haz
ard
ratio
TCAs SSRIs Other combinedantidepressant class
Adjusted hazard ratios and 95 % CI for stroke
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Hazard ratios for antidepressant dose
*note: hazard ratios compared to periods of non-use of antidepressants
0.80
1.00
1.20
1.40
1.60
1.80
2.00
adju
sted
haz
ard
ratio
antidepressant dose
Adjusted hazard ratios and 95 % CI for stroke
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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
haz
ard
ratio
antidepressant timing
Adjusted hazard ratios and 95 % CI for stroke
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Hazard ratios for individual drugs0.
801.
001.
201.
401.
601.
802.
00ad
just
ed h
azar
d ra
tio
antidepressant drug
Adjusted hazard ratios and 95 % CI for stroke
*note: hazard ratios compared to periods of non-use of antidepressants12
Excess risksFor 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
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Summary of findingsStroke 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.
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StrengthsLarge study in a primary care settingAccounted for many confounding
variablesOne of few studies to investigate effects
of individual drugsDetailed information on antidepressants
prescribed
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LimitationsDifficult 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
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ConclusionsSSRIs 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
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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.
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