Laura Amodeo SCDU Psiconcologia AO San Giovanni Battista di Torino

1. Sympthoms in the elderly: Anxiety and depression Laura Amodeo SCDU Psiconcologia AO San Giovanni Battista di Torino Roma 19 october 2012

2. Depression Anxiety • Fear • Apprehension • Restlessness • Gastrointestinaldisorders • Appetite or weightchange • Pervasive worry • Persistenmuscletension • Decreasedconcentration • Sleepdisorders • Depressed mood • Anhedonia • Guilt or feelings of worthlessness • Suicidalideation • Hyperarousal • Agoraphobia • Anancasm

3. Environmentalstress DEPRESSION IN ELDERLY Socio-economic background : loss of self-efficacy, lack of responsibility, loneliness, economicdistress Structuralalterations (leukoencephalopathy, ventricularextension, corticalatrophy) Changes in CNS Cognitive Disorders Neurochemicalchanges Hyperactivity HPA axis, lowercatecholamineconcentrations, decreased response to endogenous and exogenous catecholamines Depressogeniceffects of medications Corticosteroids, Chemotherapyagents, Hormonal agents, Cardiovascularmedications, etc Organicdisease

4. affective Depressed mood Anhedonia Loss of interest Dysphoria Irritability Attention deficit Decision-makingskills Anxiety Hopelessness motor cognitive Symptomatic cluster Slowedmovement Restlessness Memory disturbances somatic Fatigue Headache Cronicpain Loss of appetite and weight Sleepdisorders Loss of libido

5. DDM Disthimia MIND Categoricalmodel Dimensional model Subthreshold depression

6. Higher levels of healthcare utilization Over threshold anxiety Belowthresholddepression Over thresholddepression Belowthresholdanxiety Fink et al, 2009; Barsky et al, 2001

7. Higherrisk for suicide in the elderly Higher risk for suicide in the cancer patients Suicide risk in depressed geriatric cancer patients Related to cancer: Uncontrolledpain Progressionof the disease Poorprognosis Fatigue Side effects Related to mental status : Suicidalthoughts Depression Hopelessness Impulsive behavior, loss of control Related to patients: Previous suicide attempt Bereavement/feelings of loss Poor social support Male Massie and Popkin,1998 Torta e Mussa, 1999

8. What is the Best Antidepressant for the Elderly? • Therapeutic efficacy well documented • Tolerability and safety • Lowest potential for drug interactions • Easy handling • Safe in overdose

9. 1950 1960 1970 Fenelzine Agomelatine Imipramine Maprotiline Mifepristone Isocarbossazide Clomipramine Amoxapine 5HT4agonists Mianserine Tranilcipromine Nortriptline Trazodone Amitriptiline Desipramine 2010….. 1980 1990 2000 Fluoxetine Nefazodone Escitalopram Sertraline Mirtazapine Duloxetine Paroxetine Venlafaxine Fluvoxamine Tianeptine Citalopram Reboxetine Bupropione Milnacipran Moclobemide

10. Current disease Compliance Symptomatic cluster Psychopharmacology Multiple Choice DIAGNOSIS PATIENT CHARACTERISTICS • Cancer clusters • Hierarchical patterns in psychiatric symptoms • Polypharmacotherapy • Othersymptomatic cluster (pain)

12. Elderly patients < Oxidative metabolism = conjugation Late and prolonged appearance of active metabolites Disturbances in the hepatic function Age-related changes in pharmacokinetics and pharmacodynamics Changes in the volume of distribution Decreased renal clearance Liposoluble drugs: higher distribution Hydrosoluble drugs: higher concentration Higher blood concentration of drugs <plasma protein binding Higher concentration of free drugs < Muscle tissue > Adipose tissue

13. Tolerability Effectiveness Dose-flexibility Efficacy Efficacy Safety Safety Effectiveness Effectiveness Elderly TAILORED THERAPY

14. Results   Thirty consecutive cancer patients (F = 21; M = 9) meeting DSM-IV TR criteria for mood disorders (MD) were enrolled in the study and randomly assigned to slow or standard paroxetine titration. Both treatment groups showed a significant mood improvement (change in MADRS total score) from baseline to end point (arm A—F(2,18) = 33.68 p < 0.001; arm B—F(2,12) = 6.97 p < 0.005). A significantly higher rate of patients in arm A compared with arm B showed no side effects after 2 weeks (40% vs. 6.7%, respectively). A multinomial logistic regression confirmed such differences between arms (chi square = 20.89 p = 0.004). The self-evaluating scale (SIDE) confirmed this difference: 60% of subjects in arm B perceived side effects compared to only 11.1% of patients in arm A. Conclusions   The results of this study suggest that slow paroxetine up-titration is better tolerated and at least as effective as the standard paroxetine up-titration in cancer patients with depression.

15. SOMATIC CLUSTER PSYCHOLOGICAL CLUSTER Neurovegetative responses eg: sweting, tachycardia, hypertension, hyperpnea, GI disorders Neuromuscular responses eg: hypervascularization, hypertonia, muscle tension ANXIETY Emotional alarm hyperarousal, hypervigilance, feelings of anxiety or fear Cognitive evaluation perception of danger, elaboration of the reaction (Fight-or-Flight response)

16. BDZsin oncology and palliative care Anxiolytic Sedative-Hypnotic Amnesia Muscle-relaxant Anticonvulsant lorazepam lormetazepam midazolam midazolam diazepam caveat Asthenia Paradoxeffect Cognitive impairment clonazepam

17. Parenteral use of BDZs

18. Haloperidol Serenase/Haldol butirrophenones Tipicalantipsychotic Fluphenazine Moditen D. tioxantenes Zuclopentixol Clopixol Chlorpromazine Largactil phenotiazine Promazine Talofen dibenzo-x-azepine Clotiapine Entumin Tiapride Sulpiride benzamides

19. M1 5-HT2A H1 5-HT2A 5-HT1A α1 MARTA Clozapine Olanzapine Quetiapine α1 SDA Risperidone Ziprasidone α2 5-HT2C D2 5-HT3 D2 D3 5-HT6 5-HT7 5-HT2A 5-HT1A Partialdopaminergicagonist Aripiprazole D2 D3

20. Thankyou!! Laura Amodeo SCDU Psiconcologia AO San Giovanni Battista di Torino Roma 19 october 2012