FUQUA CENTER FOR LATE-LIFE DEPRESSION PSYCHOPHARMACOLOGY UPDATE Eve H. Byrd, MSN, MPH, FNP.BC, Psych CNS Fuqua Center for Late-Life Depression Emory University Most Common Disorders in Older Adults FUQUA CENTER FOR LATE-LIFE DEPRESSION In order of prevalence: Anxiety Severe cognitive impairment Mood disorders Am Assoc of Geriatric Psychiatry, 2011 Growing number of older adults with Psychotic Disorders Epidemiology – Depressive Syndromes FUQUA CENTER FOR LATE-LIFE DEPRESSION Community dwelling older adults 1%-4% Major Depressive Disorder 35% depressive symptoms Long Term Care older adults 10- 15% depressive syndromes Blazer DG. Depression in late life: review and commentary. J Gerontol A Biol Sci Med Sci 2003; 58(3): 249–65. Hybels CF, Blazer DG. Epidemiology of late‐life mental disorders. Clin Geriatr Med 2003; 19(4): 663–96, v. Impact FUQUA CENTER FOR LATE-LIFE DEPRESSION Increased health care costs Increased service utilization 5.3 office visits for vs. 2.9/ per year without depression Less compliance with medical treatment Hospital readmissions Katon WJ, Lin E, Russo J, Unutzer J. Increased medical costs of a population‐based sample of depressed elderly patients. Arch Gen Psychiatry. 2003 Sep;60(9):897‐903; Alexopoulos GS. Depression in the elderly. Lancet 2005; 365(9475): 1961–70. Medical Evaluation FUQUA CENTER FOR LATE-LIFE DEPRESSION Medical History Psychosocial History (drug, etoh, marriages, work hx) Family Medical/ Psychiatric History Labs (CBC, Chem 7, B12 and Folate, TSH, vitamin D) CT scan (when there are concerns regarding memory or psychosis) Depressive Disorders DSM V Major Depressive Disorder FUQUA CENTER FOR LATE-LIFE DEPRESSION At least one of the two, (1) depressed mood or (2) loss of interest or pleasure 5+ symptoms, 2-week period, represent a change from previous functioning Major Depressive Disorder FUQUA CENTER FOR LATE-LIFE DEPRESSION Weight loss when not dieting or weight gain Insomnia or hypersomnia nearly Psychomotor agitation or retardation Fatigue or loss of energy Feelings of worthlessness or excessive or inappropriate guilt (which may be delusional) Diminished ability to think or concentrate, or indecisiveness Recurrent thoughts of death (not just fear of dying), recurrent suicidal ideation without a specific plan, or a suicide attempt or a specific plan for committing suicide. Others FUQUA CENTER FOR LATE-LIFE DEPRESSION Unspecified Depressive Disorder Substance/Medication- Induced Depressive Disorder Depressive Disorder Due to Another Medical Condition Geriatric Depression FUQUA CENTER FOR LATE-LIFE DEPRESSION Cognitive changes Somatic symptoms Fatigue Loss of interest Depression without sadness Kamara TS, Whyte EM, Mulsant BH et al. Does major depressive disorder with somatic delusions constitute a distinct subtype of major depressive disorder with psychotic features? J Affect Disord 2009; Gallo JJ, Rabins PV, Lyketsos LG, Tien AY, Anthony JC. Depression without sadness: functional outcomes of nondysphoric depression in later life. J Am Geriatr Soc. 1997;45:570-578; Sneed JR, Culang ME, Keilp JG, et al. Antidepressant medication and executive dysfunction: a deleterious interaction in late-life depression. Am J Geriatr Psychiatry 2010; 18:128–135. Depression and Dementia FUQUA CENTER FOR LATE-LIFE DEPRESSION Over 50% of patients with dementia have depressive symptoms 20% meet major depressive criteria Brown EL, Raue P, Halpert KD, Adams S, Titler MG. Detection of depression in older adults with dementia. J Gerontol Nurs 2009; 35(2): 11–15. Symptoms of Depression vs. Dementia FUQUA CENTER FOR LATE-LIFE DEPRESSION Depression: Impairment in attention Psychomotor slowing Slowed speed of information processing Impaired executive functioning Dementia: Global cognitive impairment Dementia vs. Depressive Disorder FUQUA CENTER FOR LATE-LIFE DEPRESSION Dementia Screening and/or neuropsychological test Depressed - show poor effort, results inconsistent over time Dementia - cover deficits with confabulations Treatment Mild Depression FUQUA CENTER FOR Expert Consensus Guidelines LATE-LIFE DEPRESSION Preferred Treatment Alternate Treatment Antidepressant Antidepressant alone medication and or psychotherapy psychotherapy alone SSRI, Venlafaxine XR Bupropion, Mirtazapine Adapted from Alexopolus et al (2001)A postgraduate medicine special report Severe Depression FUQUA CENTER FOR Expert Consensus Guidelines LATE-LIFE DEPRESSION Preferred Treatment Alternate Treatment Antidepressant Electroconvulsive medication and Therapy psychotherapy OR Tricyclic antidepressant antidepressants, medication alone Mirtazapine, SSRI, Bupropion Venlafaxine XR (SNRI) Adapted from Alexopolus et al, Pharmacotherapy FUQUA CENTER FOR LATE-LIFE DEPRESSION st 1 choice - Selective serotonin reuptake inhibitors (SSRIs) nd 2 choice - Serotonin-Norepinephrine reuptake inhibitors (SNRIs) Roose S, Schatzberg AF. The efficacy of antidepressants in the treatment of late‐life depression. J Clin Psychopharmacol 2005; 25:S1–7 Pharmacotherapy FUQUA CENTER FOR LATE-LIFE DEPRESSION Selective Serotonin Reuptake Inhibitors Fluoxetine (Prozac) Sertraline (Zoloft) Paroxetine (Paxil) Citalopram (Celexa) Escitalopram (Lexapro) Fluvoxamine (Luvox) SSRIs Side Effects FUQUA CENTER FOR LATE-LIFE DEPRESSION Headache GI side effects Hyponatremia Excessive activation Sleep disturbance Tremor Sexual dysfunction QT prolongation (Citalopram 20mg or less) Pharmacokinetics FUQUA CENTER FOR LATE-LIFE DEPRESSION Inhibition of CP450 Strongest - Fluoxetine (Prozac), flovoxamine, nefazodone Caution SSRIs and WARFARIN Inhibition of P450 cytochromes FUQUA CENTER FOR LATE-LIFE DEPRESSION Drug Name CYP1A2 CYP2C9 CYP2C19 CYP2D6 CYP3A4 CYP2B6 Citalopram+00+00 Escitalopram000+00 Fluoxetine + ++ +/++ +++ + + Fluvoxamine +++ ++ +++ + + + Paroxetine + + + +++ + +++ Sertraline+++/+++++ Pharmacotherapy FUQUA CENTER FOR LATE-LIFE DEPRESSION Serotonin and Norepinephrine Reuptake Inhibitors Venlafaxine (Effexor, Effexor XR) Duloxetine (Cymbalta) Desvenlafaxine (Pristiq) Milnacipran (Ixel, Savella) Levomilnacipran (Fetzima) Tofenacin (Elamol, Tofacine) SNRI Side Effects FUQUA CENTER FOR LATE-LIFE DEPRESSION Most common: loss of appetite, weight loss, and sleep disturbance. Possible: drowsiness, dizziness, fatigue, headache, increase in suicidal thoughts, nausea/vomiting, sexual dysfunction (less than in SSRIs), and urinary retention. SNRI Side Effects FUQUA CENTER FOR LATE-LIFE DEPRESSION Increased Norepinephrine: anxiety, mildly elevated pulse, and elevated blood pressure – usually dose related Cymbalta – Monitor liver function tests and creatinine Serotonin and Psychiatric Symptoms FUQUA CENTER FOR LATE-LIFE DEPRESSION Mood Anxiety: OCD, GAD, PTSD, Social Phobia & Panic Disorder Impulsivity Aggression Eating Disorders: Bulimia, Anorexia Pharmacotherapy FUQUA CENTER FOR LATE-LIFE DEPRESSION Others Mirtazapine (Remeron) – Noradrenergic and specific serotonergic Bupropion (Wellbutrin) (SR/XL) – Norepinephrine Reuptake Inhibitor and non-competitive antagonist of multiple neuronal n ACH receptors Mirtazapine (Remeron) FUQUA CENTER FOR LATE-LIFE DEPRESSION Helpful when do not tolerate SSRIs Sedating at low dosage Stimulates appetite Minimal warfarin interaction Could exacerbate REM sleep behavior in PD Neutropenia, agranulocytosis Onofrj M, Luciano AL, Thomas A, Iacono D, D’Andreamatteo G. Mirtazapine induces REM sleep behavior disorder (RBD) in parkinsonism. Neurology 2003;60:113–5. Bupropion FUQUA CENTER FOR LATE-LIFE DEPRESSION CYP2D6 inhibitor ↑ paroxetine, sertraline, fluoxetine, diazepam ↑ bupropion blood levels CYP2B6 inducers, such as carbamazepine, clotrimazole, rifampicin, ritonavir, St John's Wort, phenobarbital, phenytoin and others ↓ bupropion Bupropion lowers the threshold for epileptic seizures Bupropion FUQUA CENTER FOR LATE-LIFE DEPRESSION No sexual dysfunction Smoking cessation Activating (will cause sleep disturbance if given late in day) Asthenia Alopecia Pharmacotherapy FUQUA CENTER FOR Older Medications LATE-LIFE DEPRESSION Tricyclics MAOIs Nortriptyline (Pamelor) Isocarboxazid (Marplan) Amitriptyline (Elavil) Phenalzine (Nardil) Desipramine (Norpramin) Tranylcypromine (Parnate) Imipramine (Tofranil) Selegiline (EMSAME) Doxepin (Adapin, patch Sinequan) etc Clomipramine (Anafranil) etc Dosing guidelines FUQUA CENTER FOR LATE-LIFE DEPRESSION Muslant, et al (2001) Pharmacologic treatment of depression in older adults: PROSPECT algorithm. International Jrnl of Geriatric Psychiatry, 16, 582-589 Depression with Psychosis FUQUA CENTER FOR LATE-LIFE DEPRESSION Depression with psychotic symptoms is common among elderly patients. Somatic delusions, nihilism, persecution and jealousy are common psychotic features. Treatment should include the association of antidepressants and antipsychotics to improve treatment efficacy. Meyers BS, Flint AJ, Rothschild AJ, et al. A double-blind randomized controlled trial of olanzapine plus sertraline vs olanzapine plus placebo for psychotic depression: the study of pharmacotherapy of psychotic depression (STOP-PD). Arch Gen Psychiatry 2009; 66:838–847. Adjunctive treatments FUQUA CENTER FOR LATE-LIFE DEPRESSION Atypical antipsychotics Others Aripiprazole (Abilify) Buspirone (Buspar) Lurasidone (Latuda) Lithium (Eskalith, Olanzapine (Zyprexa) Lithobid) Quetiapine (Seroquel) Thyroid hormone Risperdidone (Risperdal) Ziprasidone (Geodon) Electroconvulsive Therapy (ECT) FUQUA CENTER FOR LATE-LIFE DEPRESSION 80% response