FUQUA CENTER FOR LATE-LIFE

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 or ) 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  or hypersomnia nearly  or retardation  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 without a specific plan, or a 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. medication and executive dysfunction: a deleterious interaction in late-life depression. Am J Geriatr Psychiatry 2010; 18:128–135. Depression and 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  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 alone

 SSRI, Venlafaxine XR  ,

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  , 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, 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