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

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Depressed mood Depressed mood Anhedonia Anhedonia Guilt or feelings of worthlessnessGuilt or feelings of worthlessness Suicidal ideationSuicidal ideation Depressed mood Depressed mood Anhedonia Anhedonia Guilt or feelings of worthlessnessGuilt or feelings of worthlessness Suicidal ideationSuicidal ideation Hyperarousal Hyperarousal Agoraphobia Agoraphobia Anancasm Anancasm Hyperarousal Hyperarousal Agoraphobia Agoraphobia Anancasm Anancasm Fear Fear Apprehension Apprehension Restlessness Restlessness Gastrointestinal disorders Gastrointestinal disorders Appetite or weight changeAppetite or weight change Pervasive worry Pervasive worry Persisten muscle tensionPersisten muscle tension Decreased concentrationDecreased concentration Sleep disordersSleep disorders Fear Fear Apprehension Apprehension Restlessness Restlessness Gastrointestinal disorders Gastrointestinal disorders Appetite or weight changeAppetite or weight change Pervasive worry Pervasive worry Persisten muscle tensionPersisten muscle tension Decreased concentrationDecreased concentration Sleep disordersSleep disorders DepressionDepressionAnxietyAnxiety

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Environmental stress Socio-economic background : loss of self- efficacy, lack of responsibility, loneliness, economic distress Changes in CNS Structural alterations (leukoencephalopathy, ventricular extension, cortical atrophy) Hyperactivity HPA axis, lower catecholamine concentrations, decreased response to endogenous and exogenous catecholamines Neurochemical changes Depressogenic effects of medications Organic disease Corticosteroids, Chemotherapy agents, Hormonal agents, Cardiovascular medications, etc DEPRESSION IN ELDERLY Cognitive Disorders

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Symptomatic cluster affectiveaffective motormotorcognitivecognitive somaticsomatic Depressed mood Anxiety Hopelessness Slowed movement Restlessness Loss of appetite and weight Sleep disorders Loss of libido Anhedonia Loss of interest Attention deficit Decision-making skills Memory disturbances Fatigue Headache Cronic pain Dysphoria Irritability

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Dimensional model Subthresholddepression DDM Disthimia MIND Categorical model

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Over threshold anxiety Over threshold anxiety Below threshold depression Higher levels of healthcare utilization Over threshold depression Below threshold anxiety Fink et al, 2009; Barsky et al, 2001

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Massie and Popkin,1998 Torta e Mussa, 1999 Massie and Popkin,1998 Torta e Mussa, 1999 Suicide risk in depressed geriatric cancer patients Higher risk for suicide in the elderly Higher risk for suicide in the cancer patients Related to cancer: Uncontrolled pain Progression of the disease Poor prognosis Fatigue Side effects Related to cancer: Uncontrolled pain Progression of the disease Poor prognosis Fatigue Side effects Related to patients: Previous suicide attempt Bereavement/feelings of loss Poor social support Male Related to patients: Previous suicide attempt Bereavement/feelings of loss Poor social support Male Related to mental status : Suicidal thoughts DepressionHopelessness Impulsive behavior, loss of control Related to mental status : Suicidal thoughts DepressionHopelessness Impulsive behavior, loss of control

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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

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Fenelzine Isocarbossazide Tranilcipromine1950 1980 Fluoxetine Sertraline Paroxetine Fluvoxamine Citalopram Bupropione Imipramine Clomipramine Nortriptline Amitriptiline Desipramine 1960 Escitalopram Duloxetine 2000 Tianeptine2010..1990 Nefazodone Mirtazapine Venlafaxine 1970 Maprotiline Amoxapine Mianserine Trazodone Reboxetine Moclobemide Milnacipran Agomelatine Mifepristone 5HT 4 agonists

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PATIENT CHARACTERISTICS DIAGNOSIS Current disease Compliance Symptomatic cluster Psychopharmacology Multiple Choice Psychopharmacology Multiple Choice -Cancer clusters -Hierarchical patterns in psychiatric symptoms -Polypharmacotherapy -Other symptomatic cluster (pain)

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

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

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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 AF(2,18) = 33.68 p < 0.001; arm BF(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.

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

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BDZs in oncology and palliative care Anxiolytic Sedative-Hypnotic Amnesia Muscle-relaxant Anticonvulsant lorazepam lormetazepammidazolam midazolam diazepam clonazepam caveat Asthenia Paradox effect Cognitive impairment

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Parenteral use of BDZs DIAZEPAMLORAZEPAMDELORAZEPAM half-life longmedium-shortmedium-long duration of action shortprotractedprotracted absorption +++++ rapidity +++++++ metabolism longmediumlong active metabolites yesnoyes use of i.m. noyesyes

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Tipical antipsychotic butirrophenonesbutirrophenones dibenzo-x-azepinedibenzo-x-azepine phenotiazinephenotiazine benzamidesbenzamides Haloperidol Serenase/Haldol Zuclopentixol Clopixol Promazine Talofen Chlorpromazine Largactil Clotiapine Entumin tioxantenestioxantenes Tiapride Sulpiride Fluphenazine Moditen D.

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1 2 5-HT6 5-HT7 5-HT3 5-HT2C 5-HT1A M1M1 H1H1 5-HT2A D2 D3 MARTA Clozapine Olanzapine Quetiapine D2 5-HT2A SDA Risperidone Ziprasidone 1 D2 D3 5-HT2A 5-HT1A Partial dopaminergic agonist Aripiprazole

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Laura Amodeo SCDU Psiconcologia AO San Giovanni Battista di Torino Thank you!! Roma 19 october 2012 Roma