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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 • 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 Approach Fatigue, insomnia, poor appetite Pain, HTN, heart disease, renal disease, liver disease, diabetes Anxiety, psychosis, cognition Approach to the patient to the drug How metabolized • CYP450 system and drug interactions 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 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 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 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 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 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 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 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 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 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 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 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 Fluvoxamine (Luvox) theophylline, clozapine, warfarin, carbamazepine, diltiazem, thioridazineVenlafaxine (Effexor) Haloperidol • Increases haloperidol concentration Indinavir • Decreases protease inhibitor concentration 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 Venlafaxine (Effexor) Haloperidol • Increases haloperidol concentration Indinavir • Decreases protease inhibitor concentration Bupropion (Wellbutrin) Desipramine (likely other 2D6 substrates) • Increases concentration of desipramine 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%