Treatment for Geriatric Depression

1
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

2
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

3

• 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

4

• 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

5

• 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

6

• 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

7

• 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

8

• 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

9

• 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
• Wellbutrin
• Metabolites accumulate in ESRD, increase seizure
  risk
• Tricyclics
• Last resort antidepressant

10

• 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

11

• 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

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• 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

13
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

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• 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

15

• Fluvoxamine (Luvox)
• theophylline, clozapine, warfarin, carbamazepine,
  diltiazem, thioridazineVenlafaxine (Effexor)
• Haloperidol
• Increases haloperidol concentration
• Indinavir
• Decreases protease inhibitor concentration

16

• 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

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• Venlafaxine (Effexor)
• Haloperidol
• Increases haloperidol concentration
• Indinavir
• Decreases protease inhibitor concentration
• Bupropion (Wellbutrin)
• Desipramine (likely other 2D6 substrates)
• Increases concentration of desipramine

18
AlternateTreatment

• ECT
• Works rapidly for those who cant 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