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 rate
When do not respond to medications, psychotic, not eating or drinking or actively suicidal
Manly DT, Oakley SP Jr, Bloch RM. Electroconvulsive therapy in old‐old patients Am J Geriatr Psychiatry. 2000 Summer;8(3):232‐6. Non-pharmacological treatments FUQUA CENTER FOR LATE-LIFE DEPRESSION
Cognitive Behavioral Therapy
Interpersonal Therapy
Problem Solving Therapy
Behavioral Activation
Reynolds CF 3rd, Dew MA, Martire LM, et al. Treating depression to remission in older adults: a controlled evaluation of combined escitalopram with interpersonal psychotherapy versus escitalopram with depression care management. Int J Geriatr Psychiatry 2010; 25:1134–1141. ReCap/ Recommendations FUQUA CENTER FOR LATE-LIFE DEPRESSION
Use SSRI’s/ SNRI’s in the elderly Will also treat Anxiety May need comparable doses as younger patients 10‐ 12 weeks to get full effect Psychotherapy is important! Anxiety Disorders Generalized Anxiety Disorder (GAD) FUQUA CENTER FOR LATE-LIFE DEPRESSION
Excessive anxiety and worry (apprehensive expectation) regarding a number of issues
The individual finds it difficult to control the worry Generalized Anxiety Disorder FUQUA CENTER FOR LATE-LIFE DEPRESSION
The anxiety and worry are associated with three (or more) of the following six symptoms: Restlessness or feeling keyed up or on edge. Being easily fatigued. Difficulty concentrating or mind going blank. Irritability. Muscle tension. Sleep disturbance (difficulty falling or staying asleep, or restless, unsatisfying sleep). FUQUA CENTER FOR Prevalence of Anxiety Disorders LATE-LIFE DEPRESSION
Community dwelling older adults Disorders 1 - 15 % Symptoms 15 – 52%
Primary care patients 14 – 20%
Bryant et al, Jrnl of Affective Disorders, 2008; Kroenke, Spitzer, Williams, Monahan, Lowe, Annals of Internal Med, 2007 Nonpharmacological Treatment FUQUA CENTER FOR LATE-LIFE DEPRESSION
Cognitive Behavioral Therapy
Relaxation training
No systematic studies in older adults.
Wetherell JL et al. Augmenting antidepressant medication with modular CBT for geriatric generalized anxiety disorder: a pilot study. Int J Geriatr Psychiatry. 2010 Pharmacotherapy FUQUA CENTER FOR LATE-LIFE DEPRESSION
Antidepressants
Benzodiazepines
Buspirone
Beta-blockers
Antihistaminic
Neuroleptics Antidepressants FUQUA CENTER FOR LATE-LIFE DEPRESSION
SSRI’s Sertraline (Zoloft) Escitaolpram (Lexapro)
Mirtazapine (Remeron) Helpful with nauseated, losing weight and trouble sleeping Benzodiazapines FUQUA CENTER FOR LATE-LIFE DEPRESSION
Indicated in Panic Attacks Short term use while maximizing treatment with SSRIs Buspirone (Buspar) FUQUA CENTER FOR LATE-LIFE DEPRESSION
High affinity for serotonin 1A receptors enhancing brain dopaminergic and noradrenergic activity. Clinical trials found it effective for GAD but not for panic disorder Others FUQUA CENTER FOR LATE-LIFE DEPRESSION
Usually not used in Older Adults
Beta Blockers
Antihistamines Evidence-Based Clinical Treatment Models for
Older Adults with Depression FUQUA CENTER FOR LATE-LIFE DEPRESSION
Key Components: Screening , patient education, close monitoring, therapy offered (Cognitive Behavioral Therapy or Problem Solving Therapy) IMPACT Unutzer et al, Med Care 2001: 39 (8):785-99 PROSPECT Bruce et al, JAMA 2004: 291(9), 1081-1091