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Beta blockers and Depression: an unjust association

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38 yo WF with hx of major depression, PTSD. Started on Lopressor 25 mg bid by PCP for tachycardia ... To ED admitted to y for tx of depression. Prior TTE 1/02: ... – PowerPoint PPT presentation

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Title: Beta blockers and Depression: an unjust association


1
Beta blockers and Depression an unjust
association?
  • Vanessa R. Cole, MD
  • AIM presentation
  • March 27, 2002

2
Case presentation
  • Prior TTE 1/02 EF70, no valve regurgitation
  • BP109/53, HR 104
  • Tachycardic, no m/r/g
  • Lungs CTA B
  • Evaluation of indication for continued b-blocker
    therapy
  • 38 yo WF with hx of major depression, PTSD
  • Started on Lopressor 25 mg bid by PCP for
    tachycardia
  • Felt fatigued/lethargic
  • To ED ? admitted to y for tx of depression

3
Beta-blocker indications
  • Hypertension, arrythmias, angina, secondary
    prevention in CAD
  • Anxiety, migraine headaches
  • Hyperthyroidism
  • Glaucoma
  • Tremors

4
CNS effects of b-blockers
  • Bad dreams, sleep disturbances, fatigue,
    hallucinations, memory mood changes
  • Postulated to cross the blood-brain barrier and
    act on b-receptors in the brain
  • Lipophilic drugs implicated in greater degree of
    CNS effects, i.e. propanolol
  • Hydrophilic drugs should theoretically pose less
    risk of depression, i.e. atenolol nadolol

5
Criteria for diagnosis of depression, DSM IV
  • Depressed mood
  • Loss of interest or pleasure in activities
  • Significant weight loss or gain
  • Insomnia or hypersomnia
  • Psychomotor agitation or retardation
  • Feelings of worthlessness or guilt
  • Diminished ability to concentrate
  • Recurrent thoughts of death

6
Association established
  • Case reports in early 1980s - possible
    association between propanolol or ophthalmic
    timolol and depression
  • Complicated by use of b-blockers in patient
    population with chronic disease states
    predisposing to depression

7
Association established
  • Avorn et. al., 1986
  • Medicaid population, n 143,253
  • Cross-sectional study
  • TCA use compared among patients on 7
    antihypertensives, insulin, hypoglycemics
  • TCA use was significantly higher in pts on
    b-blockers
  • Prevalence rate ratio of 1.5 (95CI 1.4-1.7)

8
Association established
  • Thiessen et. al., 1990
  • Saskatchewan Prescription Drug Plan, n 3218
  • Retrospective cohort
  • Relative risk for use of antidepressant in
    b-blocker cohort was 2.6 (95 CI 2.3-3.0)
  • Relative risk for antidepressant use with
    propanolol was 4.8 (95 CI 4.1-5.5)
  • No significant increased risk with hydrophilic or
    other lipophilic b-blockers

9
Causal association?
  • Antidepressant dispensings not a valid proxy for
    depression
  • Antidepressant meds have multiple indications
  • Possible increased tendency for physicians to
    treat b-blocker side effects (fatigue, sedation)
    with antidepressants
  • Unclear time course

10
Controversy
  • Bright et. al., 1992
  • Case-control study of Medicaid population, n
    4302
  • Identified cases by prescription of
    antidepressant, depression dx, or ECT procedure
    code

11
Controversy
  • Odds ratio for use of b-blockers in
    antidepressant RX was 1.45 (1.23 - 1.70)
  • OR with depression diagnosis or ECT, 1.16 (0.90 -
    1.51)
  • Adjusting for benzodiazepine use, frequent RX or
    frequent outpt office visits ? null effect

12
Using clinical criteria
  • Gerstman et. al., 1996
  • Prospective cohort in Harvard Community Health
    Plan, n 3782
  • Examined occurrence of depression in new users of
    b-blockers other antihypertensives
  • Used DSM III criteria for major depression, with
    minor depression meeting lt 5 criteria
  • Adjusted RR for depression with b-blockers was
    0.8 (0.3-1.9), with propanolol was 0.8 (0.1-2.7)

13
Epidemiologic analysis
  • Hallas, 1996
  • 11,244 incident antidepressant users in Odense
    University Database
  • Prescription sequence symmetry analysis,
    application of logistic regression model
  • No clear causal association between b-blockers or
    propanolol antidepressant use
  • Number of persons starting antidepressants after
    b-blockers was similar to following opposite
    order

14
Conclusions
  • Beta-blockers are associated with side effects of
    fatigue, sedation, which may have significant
    impact on quality of life
  • Available evidence does not clearly causally link
    b-blockers with depression, as diagnosed by
    strict clinical criteria
  • Cross-sectional, case-control, retrospective
    studies provide suboptimal data
  • Several unresolved issues, which could be
    elucidated by future research

15
Does this patient need Lopressor?
  • No clear indication for use of b-blocker
  • No cardiac risk factors
  • Cardiac enzymes, TSH, FLP normal
  • Recommended non-invasive stress testing as an
    outpatient
  • If RX were indicated, unclear in patient with
    history of major depression

16
Future directions
  • Randomized controlled trials needed - could be
    incorporated into studies of b-blockers
    therapeutic endpoints
  • Analysis of subgroups patients with hx of MDD,
    serious conditions requiring b-blockers, those
    on b-blockers for less serious conditions (i.e.
    HTN)
  • Risk/benefit ratio
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