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Treatment for Geriatric Depression. All classes have proven efficacy in elderly patients Yet, some evidence exists that antidepressants are less helpful in those over 75 Likely due to the difficulty in general treating depression in the elderly Role of cerebral vascular disease a factor

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treatment for geriatric depression
Treatment for Geriatric Depression
  • All classes have proven efficacy in elderly patients
    • Yet, some evidence exists that antidepressants are less helpful in those over 75
      • Likely due to the difficulty in general treating depression in the elderly
        • Role of cerebral vascular disease a factor
      • 8 to 12 weeks in younger adults may stretch to 12-16 weeks in the elderly
      • More concern with adverse events
        • More possible medications to interact with
        • Slower metabolism, excretion
how to choose an antidepressant
How to Choose an Antidepressant
  • Approach to the patient
    • Fatigue, insomnia, poor appetite
    • Pain, HTN, heart disease, renal disease, liver disease, diabetes
    • Anxiety, psychosis, cognition
  • Approach to the drug
    • How metabolized
      • CYP450 system and drug interactions
slide3
Fatigue
    • ¾ of patients with depression report fatigue
      • Serotonin-mediated
        • countered by adrenergic, dopaminergic agents
      • Effexor (venlafaxine), Cymbalta (duloxetine), Zoloft (sertraline), Prozac (fluoxetine)
      • Augmentation agents
        • Ritalin (methylphenidate), Provigil (modafinil)
      • Cognitive behavioral therapy, exercise
    • Make sure it is depression
      • OSA common and looks like depression
      • Especially if fatigue is the last resistant symptom
slide4
Insomnia
    • Common symptom in depression
      • Serotonin 5HT2-mediated
        • If activated insomnia occurs
          • SSRIs, SNRIs
        • If blocked sleepiness occurs
          • Remeron (mirtazapine)
        • Other agents
          • Ambien (zolpidem) and Sonata (zaleplon)
          • Lunesta (eszopiclone)
          • Rozerem (ramelteon); M1, M2 receptor
      • Sleep journal, sleep hygiene, avoid naps
    • Make sure it is depression
      • Not a primary sleep disorder, medications, caffeine, exercise
slide5
Weight loss, poor appetite
    • Common symptom of depression
    • Many antidepressants cause weight gain
      • We often look drug-induced weight gain as serendipity rather than an adverse event
    • Remeron (mirtazapine)
      • Like sleep, this effect lost when dose is increased above 30mg/d; comes as a dissolvable tablet for dysphagia
    • Nortriptyline
      • Histaminergic properties
    • SSRIs
      • Paxil (paroxetine)-most robust weight gaining SSRI
      • Prozac (fluoxetine) and Zoloft (sertraline)-less robust
slide6
Pain
    • Antidepressants do posses anti-pain properties
      • Mainly neuropathic pain
        • Peripheral neuropathy (PN), e.g.
      • Tricyclic antidepressants very helpful in pain
        • Elavil (amitriptyline) used often as pain agent
          • Doses too low for effective treatment of mood
        • Pamelor (nortriptyline) safer as an antidepressant
      • SNRIs
        • Cymbalta (duloxetine) and Effexor (venlafaxine)
      • SSRIs
        • Too selective for serotonin; TCAs and SNRIs have the right balance of serotonergic and noradrenergic reuptake activity
      • Wellbutrin (bupropion)
        • One positive study with PN
slide7
Hypertension (HTN)
    • There is a strong correlation between HTN and depression
      • Goes both ways
    • Main thesis is based on a hyperactive sympathetic nervous system for both
      • Variable evidence for TCAs, MAOIs
      • SSRIs have few HTN effects
        • Prozac (fluoxetine)and Zoloft (sertraline) increase autonomic tone/improve orthostasis
      • Effexor (venlafaxine)
        • Dose-dependent HTN in 5%
        • Above 300mg/d it was 15%
          • However, no increased risk if you had previous HTN
          • 1/3 of patients experienced lower BP
slide8
Heart disease
    • Depression common in ischemic heart disease
      • Increases the risk of future events
      • 1/5 of those with an acute MI develop MDD
        • If you develop MDD after MI you have 5x the risk of a second MI in 6 mos.
    • SSRIs are preferred
      • SNRIs, Remeron, Wellbutrin all used
      • TCAs are too cardio-toxic
        • Orthostasis
        • Slowed conduction
        • Tachycardia
slide9
Renal disease
    • Depression worsens ARF, CRF, ESRD
    • Renal failure and dialysis increase risk of depression
  • Antidepressants
    • Prozac, Zoloft, Celexa, Lexapro all used
      • Paxil concentration increased in ESRD
    • Effexor, Cymbalta and Remeron
      • Clearance reduced, elimination prolonged
      • Not recommended, esp. if CC<30cc/min
    • Wellbutrin
      • Metabolites accumulate in ESRD, increase seizure risk
    • Tricyclics
      • Last resort antidepressant
slide10
Liver Disease
    • High prevalence of depression in cirrhosis, hepatitis
      • Interferon alpha carries a 33% risk of developing depression
    • All antidepressants are liver metabolized
      • All have cases of hepatotoxicity
        • Nefazodone carried risk of hepatic failure
      • SSRIs
        • Celexa and Lexapro commonly used
        • Gi bleeding noted in SSRIs
      • Avoid Effexor and Cymbalta
      • Remeron
        • Bone marrow suppression and agranulocytosis
      • Wellbutrin has been used
slide11
Diabetes
    • The prevalence of depression in diabetes is nearly 30%
      • Depression affects blood glucose regulation
    • Antidepressant treatment should not add to the burden
      • Tricyclics, Remeron, Paxil
        • Avoid as all are appetite enhancers
      • Lexapro and Celexa
        • Fairly weight neutral
        • Luvox, Prozac and Zoloft are in the middle
      • Effexor and Cymbalta
        • Appear safe
      • Wellbutrin
        • Very weight neutral
slide12
Anxiety
    • All antidepressants treat anxiety
    • SSRIs, SNRIs and Wellbutrin
      • Carry risk of increased anxiety and agitation
  • Psychosis
    • No particular agents noted to be clearly more helpful
      • Luvox may be able to manage both sets of symptoms
  • Cognition
    • No agent by itself
    • Relief of the mood problem causes improvement
drug interactions
Drug Interactions
  • CYP450 interactions
    • Buy a laminated card
      • Inhibition
        • Prozac (2C9, 2D6), Luvox (1A2, 2C19, 3A4) and Paxil (2D6)--strong inhibitors
        • Cymbalta, Zoloft, Wellbutrin--weak
        • Effexor, Lexapro, Celexa, Remeron--none
      • Inducers
        • none
  • Substrates
    • All major enzymes but 2C9
slide14
SSRIS
    • dextromethoraphan,tryptophan, MAOIs, TCAs, venlafaxine, mirtazapine
      • Serotonin syndrome
      • TCA toxicity
      • MAOI combinations are potentially lethal
    • warfarin (Coumadin)
      • Increased warfarin effects due to protein binding
      • Do not expect to see elevated warfarin concentration, except with fluvoxamine
slide15
Fluvoxamine (Luvox)
    • theophylline, clozapine, warfarin, carbamazepine, diltiazem, thioridazineVenlafaxine (Effexor)
    • Haloperidol
      • Increases haloperidol concentration
    • Indinavir
      • Decreases protease inhibitor concentration
slide16
Bupropion (Wellbutrin)
    • Desipramine (likely other 2D6 substrates)
      • Increases concentration of desipramine
      • Elevated concentrations due to metabolic inhibition, with possible toxicity
  • Fluoxetine (Prozac)
    • carbamazepine, phenytoin
      • Elevated anticonvulsant concentration
slide17
Venlafaxine (Effexor)
    • Haloperidol
      • Increases haloperidol concentration
    • Indinavir
      • Decreases protease inhibitor concentration
  • Bupropion (Wellbutrin)
    • Desipramine (likely other 2D6 substrates)
      • Increases concentration of desipramine
alternatetreatment
AlternateTreatment
  • ECT
    • Works rapidly for those who can’t wait
      • Psychotic depression, especially
    • Hospital venue
      • Anesthesia
      • 30-60 second seizure; 6-12 treatments
    • Maintenance treatment
    • Adverse effects minimal
      • Short-term memory loss; lasts less than 2 mos.
      • Mortality rate 0.01%