Transcript Geriatric Depression

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