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Transcript of 1 Pharmacotherapy of Depression and Anxiety Vickie Corbett Ripley, PharmD, BCPP Clinical Pharmacist...
1
Pharmacotherapy of Depression and Anxiety
Vickie Corbett Ripley, PharmD, BCPP
Clinical Pharmacist Practitioner
Coastal Plain Hosptial
Rocky Mount, NC
2
Pharmacotherapy for Major Depression
Etiology and Pathophysiology Diagnosis and clinical presentation Antidepressant efficacy
and side effects Treating major depression Special Populations Other treatment options Drug interactions
3
Limbic System Dysfunction
4
Spectrum of Psychiatric Disorders
ANXIETY
AFFECTIVE
PSYCHOSES
Panic disorderGADOCDAgoraphobia
Major DepressionBipolar DisorderDysthymia
SchizophreniaSchizoaffective
5
Anxiolytics
Norepinephrine
Anti-Psychotics
Dopamine
Anti-Depressants
Serotonin
Neurotransmitters and Psychiatric Pharmacotherapy
GABA, others
6
Phases of MDD Treatment
Severity
Time
7
Recurrence After Recovery from Major Depression
n = 555 Unipolar Depressives (1985-1994)
The NIMH Collaborative Depression Study, 1977-1992
15
33
4654
60 6167 70 73 74 75
0
25
50
75
100
0.5 1 2 3 4 5 6 7 8 9 10
Cumulative Probability of Recurrence, %
Time to Recurrence, years
8
Diagnosis of mental illnessDiagnosis of mental illness
DSM IV (Diagnostic and Statistical Manual of Mental Disorders – 4th edition)– Lists criteria necessary to meet diagnosis
– Useful for standardizing diagnoses
To meet most diagnoses generally must– Interfere with social or occupational functioning
– Must be interpreted in context of culture
DSM IV (Diagnostic and Statistical Manual of Mental Disorders – 4th edition)– Lists criteria necessary to meet diagnosis
– Useful for standardizing diagnoses
To meet most diagnoses generally must– Interfere with social or occupational functioning
– Must be interpreted in context of culture
9
Multiaxial AssessmentsMultiaxial Assessments
Axis I – Clinical Disorders Axis II – Personality disorders and
mental retardation Axis III – General medical conditions Axis IV – Psychosocial and
Environmental problems Axis V – Global assessment of
functioning (GAF)
Axis I – Clinical Disorders Axis II – Personality disorders and
mental retardation Axis III – General medical conditions Axis IV – Psychosocial and
Environmental problems Axis V – Global assessment of
functioning (GAF)
10
Axis I disordersAxis I disorders
Mood disorders– Major depressive disorder
– Bipolar disorder
Anxiety disorders– Generalized anxiety disorders
– Panic disorder
– Social phobia
– Obsessive Compulsive Disorder
Psychotic disorders - schizophrenia
Mood disorders– Major depressive disorder
– Bipolar disorder
Anxiety disorders– Generalized anxiety disorders
– Panic disorder
– Social phobia
– Obsessive Compulsive Disorder
Psychotic disorders - schizophrenia
11
DSM IV Classification of Major Depressive Episode
Depressed mood and/or loss of Interest present during a two week period
Plus at least FOUR of the following symptoms:– Weight change
– Sleep disturbance
– Psychomotor agitation or retardation
– Loss of energy
– Feelings of worthlessness/guilt
– Loss of ability to concentrate
– Suicidal ideations
12
Psychiatric Patient Presentation
Chief Complaint History of Present Illness Past Medical History Family and Social Histories Medications Allegies Review of Systems
Physical Examination Mental Status Exam
– Appearance, behavior, and speech
– Mood and Affect
– Sensorium
– Intelligence
– Thought process
Labs
13
Symptoms of Depression and Serotonin Function
Depressed or elated Mood Appetite changes Sleep changes Decreased libido Increased pain sensitivity Circadian rhythm disturbances Body temperature changes
14
Physical and Social Functioning in Depression and Chronic Illness
None Hyper-tension
Diabetes Arthritis AnginaOnly
CAD Depres-sion
0
10
20
30
40
50
60
70
80
90
100
Perc
ent o
f Per
fect
Fun
ctio
ning
None Hyper-tension
Diabetes Arthritis AnginaOnly
CAD Depres-sion
Physical Function Social Function
Wells, et al. J Amer Med Assoc 1989; 262:914-919
15
Symptoms of Depression (Sig: E caps)
S Sleep
I Interest
G: Guilt
E Energy
C Concentration
A Appetite
P Psychomotor retardation
S Suicidality
16
Treatment choices
Psychotherapy Light Exercise Diet Medication Medication and Psychotherapy Electroconvulsive therapy (ECT)
17
Psychotherapies
Interpersonal therapy Cognitive therapy Behavior therapy Group therapy
18
Psychotherapy
Less severe Less chronic Nonpsychotic Previous positive response Medical contraindication to medication
19
Algorithm for Treatment of Uncomplicated Major Depression
1st line: Favorite SSRI or TCA – Failed trial: switch to alternative
– Partial response - increase dose, switch or augment
– Fully remits (maintain at least 4 to 6 months or longer)
2nd line: Switch or Augment– Switch to other favorite - TCA or SSRI
– Augment with Li or TCA plus the SSRI (consult with psychiatrist)
3rd line: Failed or Partial response to 2nd line– Consult with psychiatrist
– Switch (nefazodone, mirtazepine, bupropion, venlafaxine)
– Augment with Li or TCA plus the SSRI
Adapted from Kando JC et al: in Pharmacotherapy, 4th ed, Dipiro, eds., 1999, p 1156
20
Target Symptoms and Therapeutic Response Rates
Week One:– anxiety
– insomnia
– decreased appetite
Weeks two and three:– increase in energy
– increase suicide risk
– increase in libido
Up to 4 to 8 Weeks:– Improvement in
dysphoria or sadness
– improvement in pessimism
– improvement in anhedonia
21
Treatment strategies if no response Confirm compliance Maximize dose Change drug Combine antidepressants Augmentation therapy
22
Augmentation medications
Lithium AED’s Stimulants Thyroid Estrogen Sleep aids Pain meds
23
Melancholic Depression
Clinical Presentation–Subtype of severe depression–Nearly complete absence of capacity for pleasure–Diurnal mood swings (worse in the morning)–Excessive guilt and weight loss
Unclear if SSRI’s as effective as TCA’s in treatment
Some data indicate that mirtazapine and venlafaxine more effective than SSRI’s
24
Atypical Depression
Clinical Presentation–Weight gain or increased appetite–Hypersomnia–Heavy feeling in arms or legs (leaden
paralysis)–Interpersonal rejection sensitivity
MAOI’s greater efficacy than TCA’s
Efficacy of SSRI’s relative to MAOI’s unclear
25
MDD with psychotic features
Clinical Presentation:–Delusions or hallucinations present
during depressive episodes
Usually need an antidepressant and an antipsychotic
26
Differentiation Between Depression and Dementia
Area Depression Dementia Depression history (self/family) Present Absent Depression symptoms precede
cognitive deficit Present Absent Duration of Symptoms Weeks Months-Years Cognitive Deficit Complains Silent Concern Cognitive Function Test
Performance deficits Inconsistent Consistent Response to MSE questions "I don't Know" Attempts to
answer Effort on Testing Little Tries hard
Baker FM. J National Med Assoc 1991; 83:340-344
27
AnxiolyticsBenzodiazepines Anti-
PsychoticsPhenothiazinesButyrophenonesAtypicals
Anti-Depressants TricyclicsMAO InhibitorsSSRIsMood Stabilizers
Psychiatric Pharmacotherapy
28
Serotonin receptors
5-HT 2– agitation
– akathisia
– anxiety
– panic attacks
– insomnia
– sexual dysfunction
29
Serotonin receptors
5-HT 3– nausea
– gastrointestinal distress
– diarrhea
– headache
30
Dopamine receptors
Stimulation can lead to – agitation
– aggravation of psychosis
31
Norepinephrine receptors
Stimulation can lead to– activation
– hypertension
– panic
32
Alpha 1 adrenergic receptors
Blockade can lead to– dizziness
– orthostatic hyotension
– reflex tachycardia
33
Histamine receptors (H1)
Blockade can lead to– sedation
– weight gain
34
Muscarinic cholinergic receptors Blockade can lead to
– blurred vision
– dry mouth
– sinus tachycardia
– constipation
– urinary retention
– memory impairment
35
Medications
TCA MAOI SSRI SNRI (venlafaxine) NDRI (buproprion) NaSSA (mirtazipine) SARI (nefazadone)
36
SSRI and New AntidepressantsMetabolism
Drug T½, h ActiveMetab
MetabT½
Time toSS, days
Non-Linear
Fluoxetine 45-137 Yes 200-250 20-45 Yes
Sertraline 26 Yes 62-104 5-15 DMSert
Paroxetine 21 --- No 4-10 Yes
Fluvoxamine 15 --- No 3-4 Yes
Venlafaxine 4-6 Yes 9-11 3 No
Nefazodone 2-4 Yes 18 3-4 Yes
Mirtazapine 20-40 --- No 5-10 No
Citalopram 35 Yes 49 7-17 No
37
Antidepressant Side Effects Drug Sedation Anticholinergic Orthostatic Amitriptyline ++++ +++ ++++ Doxepin ++++ +++ +++ Nortriptyline +++ +++ ++ Desipramine ++ ++ +++ Trazodone +++ - +++ Bupropion - + - Fluoxetine -/+ - - Sertraline -/+ - - Paroxetine ++ + - Venlafaxine +/++ + + Nefazodone ++ + + Mirtazapine ++++ ++ +
Adapted from: MJ Dewan et al J Geriatr Psychiat Neurol 1992; 40-44
38
Single mechanism drugs
Mostly noreinephrine– desirpramine
– buproprion
Mostly serotonin– SSRI’s
– nefazadone
39
Serotonin reuptake Inhibition Norepinephrine reuptake inhibition Anticholinergic effects Alpha1 blockade Histamine blockade
Tricyclic Antidepressants
40
Tricyclic Antidepressants
Useful in the treatment of a number of conditions–Depression
–Migraine prophylaxis
–Neuropathic pain
–Obsessive compulsive disorder (Clomipramine)
–Enuresis
–Panic disorder
–Sleep disorders
–Attention deficit / hyperactivity disorder
41
Tricyclic Antidepressants
Clomipramine (Anafranil) 25-250mg Amitriptyline (Elavil) 50-300mg Doxepin (Sinequan) 25-300mg Imipramine (Tofranil) 30-300mg Desipramine (Norpramin) 25-300mg
42
Tricyclic Antidepressant
Secondary amine– Desipramine (Norpramine)
– Nortriptyline (Pamelor)
– Protriptyline (Vivactil)
Tertiary amine– Amitriptyline (Elavil)
– Clomipramine (Anafranil)
– Imipramine (Tofranil)
– Doxepine (Sinequan)
– Trimipramine (Surmontil)
Greater NE relative to 5HT activity
Greater anticholinergic effects
Greater NE relative to 5HT activity
Greater anticholinergic effects
43
With most TCA’s start with 50 mg and increase by 25 to 50 mg every 3 days (lower for nortriptyline or protriptyline)
Secondary amine– Desipramine -- 100 to 300 mg– Nortriptyline -- 50 to 150 mg– Protriptyline -- 15 to 60 mg
Tertiary amine– Amitriptyline -- 100 to 300 mg– Clomipramine -- 100 to 250 mg– Imipramine -- 100 to 300 mg– Doxepin -- 100 to 300– Trimipramine 100 to 300
Secondary amine– Desipramine -- 100 to 300 mg– Nortriptyline -- 50 to 150 mg– Protriptyline -- 15 to 60 mg
Tertiary amine– Amitriptyline -- 100 to 300 mg– Clomipramine -- 100 to 250 mg– Imipramine -- 100 to 300 mg– Doxepin -- 100 to 300– Trimipramine 100 to 300
Tricyclic Antidepressant
44
TCA plasma concentrations
Nortriptyline - Curvilinear conc/response profile– 50 to 150 ng/ml
Desipramine– 125 to 300 ng/ml
Imipramine– 200 – 300 ng/ml
Not routinely performed but can be useful in certain situations
Should be obtained at steady state (at least 1 week after initiating or dose change)
45
TCA Adverse Events
Anticholinergic effects Antihistaminic effects Alpha1 adrenergic blockade Sexual dysfunction Cardiac conduction delays
– Can result in arrhythmias in overdose Decreased seizure threshold Toxic in overdose
– Do not use in acutely suicidal patients
46
Preferred uses of TCA’s
Depression with– Pain
– Fibromyalgia
– Migraine
– insomnia
47
Least preferred uses of TCA’s
Patients in whom anticholinergic effects would be problematic
Overweight patients Suicidal patients Cardiac patients Patients with dementia
48
Selective Sertotonin Reuptake Inhibitors (SSRI’s)
Fluoxetine (Prozac) Paroxetine (Paxil) Sertraline (Zoloft) Fluvoxamine (Luvox) Citalopram (Celexa) Escitalopram (Lexapro)
49
Uses of SSRI’s
Depression Social phobia Panic disorder Obsessive compulsive disorder Bulimia Nervosa Post Traumatic Stress Disorder Pre Menstrual Dysphoric Disorder (Sarafem)
50
SSRI Dosing
Dosing– Fluoxetine -- 20 to 60 mg– Paroxetine -- 20 to 50 mg – Sertraline -- 50 to 200 mg– Fluvoxamine -- 100 to 300 mg– Citalopram -- 20 to 60 mg– Escitalopram – 10 to 40 mg
Relatively safe in overdose Relatively safe in patients with cardiovascular
disease
51
SSRI Adverse Effects
Gastrointestinal– Nausea, vomiting, diarrhea
Sexual dysfunction Headache insomnia Fatigue Agitation Akathesia and dystonic reactions
– 5HT can reduce DA levels
52
Differences between SSRI’s
Most likely to cause sedation– Paroxetine, fluvoxamine
Paroxetine– Mild anticholinergic effects
Fluoxetine– Higher rates of anxiety and nervousness
Sertraline– More diarrhea
53
When to use SSRI
First line monotherapy Depression Anxiety (start with low doses) OCD Panic
54
Least preferred use of SSRI
Patients with sexual dysfunction Patients with secondary refractoriness Patients with nocturnal myoclonus Patients with consistent agitation Patients with consistent insomnia
55
SSRI Withdrawal Syndromes
More likely to occur with short t1/2 agents (paroxetine warning)
May affect up to 1/3 of patients and more likely to be reported with short half-life agents
May be due to sudden decrease in available synaptic 5HT in face of down-regulated receptors
Onset in 24 to 72 hours and last up to 7-14 days Symptoms: dizziness, nausea, lethargy, headache,
flu-like symptoms, parasthesia (electrical “shock-like” sensations)
56
Discontinuation syndrome
Worse with short acting drugs Taper dose Flu-like symptoms Anxiety GI distress Mood, appetite, sleep changes
57
Serotonin Syndrome
Symptoms–Altered mental status – confusion, agitation
–Autonomic dysfunction – diaphoresis, tachycardia, BP changes, fever
–Neuromusucular abnormalities – clonus
Allow 2 weeks between MAOI and other antidepressant administration–5 weeks for fluoxetine
58
Serotonin Syndrome
Occurs when several serotonergic drugs combined
Often involves MAOI’s as one of the drugs
Other serotonergic drugs implicated»SSRI’s»TCA’s»Serotonin releasing agents (i.e. MDMA or
“ecstasy”)»Dextromethorphan, meperidine, others
59
Potent 5HT2 receptor antagonist Relatively weak 5HT reuptake inhibition Alpha1 receptor blockade Metabolism:
– OH-Nefazodone = 1.5 - 4 hours
– triazole-dione = 18 hours
– mCPP = 4-8 hours
Usual Dosage: 300 - 600 mg/day in 2 divided doses Preserves sleep architecture Potent CYP3A4 inhibitor
Nefazodone (Serzone, Bristol-Myers Squibb)
60
Therapeutic uses of nefazadone depression in association with
– anxiety, agitation, sleep disturbances
Prior SSRI induced sexual dysfunction Inability to tolerate SSRI’s Tolerance to SSRI’s
61
Lest preferred use of nefazadone Patients with hypersomnia Non-compliance with BID dosing Retarded depression Patients with difficulty with dose titration
62
Dual-Action Drugs
Norepinephrine and serotonin
– clomipramine
– venlafaxine
– mirtizapine
63
NaSSA
Noradrenergic and specific serotonergic antidepressant
– mirtazipine (Remeron) 15-90mg
64
Mirtazapine (Remeron®, Organon) Initial Dosing:
– Start with 15mg qd (hs) (supplied as 15 and 30 mg tablets)– Average effective dose is 20-25mg qd– Maximum dose=45mg qd
Half life – Women have longer half-life than men 37 vs 26 hours– Half-life allows for qd dosing
Dosage adjustments:– Any dosage should be made after one to two weeks– Adjust dose for hepatic disease– Slow titration in the elderly
65
Mirtazapine (Remeron, Organon)
Receptors: -5HT2 and 5HT3 antagonist, histamine 1, minimal activity on alpha 1, muscarinic, and dopamine
Common Side Effects: Somnolence, dry mouth, weight gain Cautions: Can precipitate mania, hepatotoxicity (dose adjust in
hepatic disease) Drug Interactions: additive cognitive and motor CNS
depression, Metabolized by CYP2D6, 1A2, 3A4,Wait 14 days after stopping MAOI
Dosing: Start with Start with 15mg qd, usually 20-25 mg qd, maximum dose = 45mg qd
66
Therapeutic uses of mirtazapine Depression with anxiety or agitation Depression with insomnia Problems with SSRI’s Weight loss Severe depression Loss of response to SSRI’s
67
Least preferred uses of mirtazapine Hypersomnia Motor retardation Cognitive slowing overweight
68
SNRI
Serotonin/norepinephrine reuptake inhibitor
– venlafaxine (Effexor) 75-375mg
69
Serotonin reuptake inhibition Norepinephrine reuptake inhibition Dopamine reuptake inhibition
Usual dose: 75 to 225 mg
Dose
Venlafaxine (Effexor, Wyeth-Ayerst)
70
Therapeutic uses of venlafaxine At low doses, use as an SSRI At high doses has dual action Patients with hypersomnia Patients with GAD Patients with weight gain
71
Least preferred use of venlafaxine Agitated patients Patients with sexual dysfunction Patients with insomnia Patients with labile HTN
72
Venlafaxine Adverse Effects
Nausea, constipation Headache Dizziness Nervousness Somnolence Dry mouth Sexual dysfunction Increased blood pressure (monitor closely)
73
NDRI
Norepinephrine/dopamine reuptake inhibitor
– buproprion (Wellbutrin) 200-450mg
74
Therapeutic uses of buproprion Patients with retarded depression patients with hypersomnia Non-responders to SSRI’s Non-tolerators of SSRI’s Patients concerned about sexual dysfunction Patients concerned about weight gain Patient with cognitive slowing
75
Least preferred use of buproprion Patients with seizure disorders Patients who are seizure prone Patients with head injury Patients non-compliant with multiple daily doses Patients with agitation Patients with insomnia
76
Comparative Safety and Tolerability Summary
Nausea
–Common with all
–Dose related, dissipates with use Diarrhea- higher incidence with Sertraline Dry Mouth- VEN, NEF > PAR, SER > FLU, FVX Anorexia- More likely with Fluoxitine, Venlafaxine Anxiety/nervousness- More common with Fluoxitine Sexual Dysfunction- all SSRIs, Ven > Nefazodone
CL DeVane Human Psychopharmacology 1995; 10:S185-S193,
77
Monoamine Oxidase Inhibitors (MAOI’s)
Used in patients with atypical MDD/ anxiety Phenelzine (Nardil) Tranylcypromine (Parnate) Hypertensive crisis can occur when combined with
high tyramine foods or sympathomimetics– Aged cheeses, sour cream, wines, beer, canned or processed meats,
fermented foods, coffee, chocolate
– Amphetamines, ephedrine, other decongestants
Doses: Phenelzine – 15 to 90 mg
Tranylcypromine – 20 to 60 mg
78
MAOI adverse effects
All agents– Sexual dysfunction
– Mild anticholinergic effects
More likely with phenelzine– Orthostatic hypotension
– Sedation
More likely with tranylcypromine– Insomnia
79
Drugs Metabolized by Human Liver Cytochromes P450s
Superfamily
Families
Subfamilies
Memberswith narrowtherapeuticindex
TheophyllineImipramine
(S)-WarfarinPhenytoinCarbamazepineTolbutamide
ImipramineDesipramineAmitriptylineNortriptylineThioridazine
TerfenadineCyclosporineTriazolamImipramineCarbamazepine
1
A
2
C
1A2 2C9/19
P-450
D
2D6
3
A
3A4
D. Rodrigues Pharmacogenetics Conf, May 1996
80
Inhibition of Cytochromes P450 Drug 1A2 2C 2D6 3A4
Fluoxetine (Prozac)
0 ++ ++++/++++ ++/+++
Sertraline (Zoloft)
0 ++/++ +/++ ++/++
Paroxetine (Paxil)
0 0 +++ 0
Fluvoxamine (Luvox)
++++ ++ 0 +++
Venlafaxine (Effexor)
0 0 0/+ ?
Nefazodone (Serzone)
0 0 0 ++++
Mirtazapine (Remeron)
0 0 0 0
Citalopram (Celexa)
0/? 0/? 0/+ 0
81
1A2substrates/inhibitors Antispychotics TCA’s Fluoroquinolones theophylline
82
Drug interactions
1A2
– Fluvoxamine ++++
83
2D6substrates/inhibitors Antiarrhythmics Antipsychotics Beta blockers Opiates TCA’s
84
Drug interactions
2D6
– Fluoxetine ++++
– Sertraline +
– Paroxetine ++++
– Venlafaxine +?
85
2Csubstrates/inducers/inhibitors Barbiturates NSAIDS Warfarin Antifungals TCSA’a
86
Drug interactions
2C
– Sertraline ++
– Fluoxetine ++
– Fluvoxamine ++
87
3A4 substrates/inducers/inhibitors Antiarrhythmics Antifungal Antihistamines Antipsychotics Barbiturates Benzodizepines Calcium channel blockers Grapefruit juice TCA’s
88
Drug interactions
3A4
– Sertraline +
– Fluoxetine ++
– Fluvoxamine +++
– Nefazadone ++++
89
Drug Interactions - Herbal Remedies
St. John’s Wort (Hypericum perforatum)– Drugs that interact with MAOIs
Ginko (Ginko biloba)– Anticoagulants (2 cases), or ASA
Kava (Piper methysticum)– Benzodiazepines (1 alprazolam case), alcohol
Ginseng (Siberian ginseng)– potentiates MAOIs, stimulants (caffeine) and haloperidol
Yohimbine (Pausinystalia yohimbine) a2 antagonist – TCA, MAOIs, antimuscarinic agents potentiate yohimbine
Wong AHC et al Archives Gen Psychiatry 1998; 55(11) 1033-1044
Wong AHC et al Archives Gen Psychiatry 1998; 55(11) 1033-1044
90
St. John’s Wort Reduces the AUC of the HIV-1 PI Indinavir
Open-label, Eight healthy volunteers (6M/2F) 29-50 yo
Indinavir 800 mg orally(q8h x4) Blood samples 0-8 hours (AUCss) Before and after SJW 300 mg tid x 14 d
(Hypericum Buyers Club) AE’s: taste changes (50%), nausea (25%),
circumoral paresthesias (25%) associated with indinavir. Reduced intensity and duration with SJW.
Increased resistance and Tx failure? 0
25
50
75
100
AUC Cp 8h Cpmax
Per
cent
Dec
reas
ePiscetelli SC Burstein AH, Alfaro RM, The Lancet, 2000; 355(9203) 12 FebPiscetelli SC Burstein AH, Alfaro RM, The Lancet, 2000; 355(9203) 12 FebPiscetelli SC Burstein AH, Alfaro RM, The Lancet, 2000; 355(9203) 12 FebPiscetelli SC Burstein AH, Alfaro RM, The Lancet, 2000; 355(9203) 12 Feb
91
Basic algorithm
Monotherapy
– Allow time for drug to work (4-6 weeks)
– Symptoms will resolve gradually
– Maximize dose
92
Selection of Antidepressant
Presenting symptoms Previous response Family history Neurotransmitter profile Co-morbid conditions Human data
Side effect profile Potential drug interactions Patient age Compliance Cost
93
Monitoring Antidepressant Therapy Monitor antidepressant regimen
– Is the dosage appropriate?– Response favorable and adequate?– Side effects present?
Review new chart entries– New orders?– New Diagnoses?– Changes in life events?
Review progress notes– Physician, nursing, social service, psychiatric service
Continue therapy– 9-12 months if first episode. If multiple: chronic maintenance
S.M. Feldman ASCP November 1995
94
Clinical Management of Treatment Emergent Adverse Effects
Continuation of current pharmacotherapy Dose Reduction Trial period of discontinuing medication Antidepressant substitution Adjunctive therapy (cases reported)
95
Combining other medications
Add augmentation therapy Consider drug interactions Monitor other medications - OTC’s and herbals - beta blockers - steroids
96
Combining medications
Use two drugs with different mechanisms SSRI plus
– venlafaxine
– mirtazipine
– buproprion
– nefazadone
– Or combinations of non SSRI’s
97
Depression Co-MorbidityDepression Co-Morbidity
20%Diabetes mellitus20%Myocardial infarction
30% to 50%Parkinson's disease11% to 30%Epilepsy
35% to >50%Chronic pain15%Chronic medical illness
20% to 50%Stroke25% to 38%Terminal solid tumors
Depression Prevalence Medical Illness
98
Concurrent medical disorders
Asthma - avoid MAOI Cardiac disease - avoid TCA Dementia - avoid TCA and other anticholinergic
drugs Seizures - avoid buproprion and TCA Glaucoma - avoid TCA HTN - watch orthostasis
99
Antidepressant Selection in the Cardiac Patient
Avoid concomitant Type IA antiarrhythmics (TCA with quinidine or procainamide)
BUP, SSRIs, VFX, SRZ appear to be low risk for arrhythmias and orthostatic hypotension
Venlafaxine is associated with increases in BP MAOIs, Trazodone, maprotiline, amoxapine,
SSRIs, and venlafaxine have not been well studied in CHF
APA Practice Guidelines, Am J Psychiatry
100
Comorbid MDD and Cardiac Disease
Tricyclic antidepressants complicate and/or are contraindicated in specific cardiac conditions– Hx ventricular arrhythmia
– subclinical sinus node dysfunction
– conduction defects (including asymptomatic)
– prolonged QT intervals
– recent history of myocardial infarction
Consider using bupropion, fluoxetine, sertraline, paroxetine, nefazodone, citalopram or ECT
APA Practice Guidelines, Am J Psychiatry
101
Comorbid MDD and Cardiac Disease
MAO inhibitors may induce orthostatic hypotension and lead to drug-drug interactions
Monitor patient for emergence of cardiac symptoms, ECG changes, or orthostatic BP decrements
Major depression is a major risk factor for increased cardiac morbidity and mortality.
APA Practice Guidelines, Am J Psychiatry
102
Depression and Coronary Artery Disease
Januzzi et al. Archives of Internal Med 2000;160(13):1913-21.
103
Case of JC
30 year old, married female, 4 children Feelings of helpless, hopeless, worthless, guilt Started with birth of last child 6 months ago Sleepy and tired all the time, no energy East too much Decreased libido No interest in much FH + depression No other medical problems
104
Case of BH
54 year old married female, 2 children grown 30 year hx MDD Multiple medications have been tried Medical Dx – fibromyalgia, IBS, chronic sinusitis Meds – Remeron. Lortab, Bently, Allegra D,
various OTC and herbals Previous Ads – Prozac, Paxil, AMI, Effexor,
Zoloft, Serzone, Celexa, “everything else” c/o weight gain, still depressed
105
MDD Presentation in Late Life
Often lacks family history of depression Highest Suicide risk of all age groups
– twice the risk in elderly white males– less in elderly black males– same in females
Often associated with medical illness– Stroke (50% develop clinically significant depression)
– Parkinson’s disease (40 to 90% have associated depression)
Typically seen by primary care physicians and may need referrals to mental health specialist for certain aspects of treatment
106
Diagnosis and Treatment of Depression in Late Life
Recognition may be more difficult in late life– “normal aging” and overshadowed by physical illness
Similar social and demographic risk factors: – female sex, single (esp. widowed), stressful life events, lack of
supportive social network
Treatment with sufficient:– doses (plasma concentrations) of antidepressants
– length of treatment (e.g. at least 6 to 12 weeks in the elderly) to maximize likelihood of recovery
– maintenance treatment for 6 to 12 or more months
NIH Consensus Development Conference
107
MDD Symptomatology in Late Life
Symptoms: irritability, agitation, somatic delusions
Somatic complaints: pain syndromes (general, headache, chest, GI), cardiac (palpitations, tightness), abdominal (constipation)
Loss of interest or pleasure may appear as apathy
108
Symptomatology in Late Life (cont’d)
Difficulty in concentration may appear as inattentiveness
Disorientation, memory loss, distractibility as “dementia”
– 10% of “senile or pseudo dementia” is actually depression (now called “dementia syndrome of depression”)
– depression can coexist with dementia
Heterogeneity of geriatric depression (early Vs late onset)
– early onset has more recurrences, more (+) family history
109
Response to Effective Treatment of Depression in Late Life
Majority should expect partial or complete remission of depressive symptoms
Amelioration of pain and suffering associate with physical illness
Enhancement of general mental, physical and social functioning
Minimization of cognitive disability
NIH Consensus Development Conference
110
MDD Presentation in the Elderly
“R.M., a 71-year-old male, is brought for psychiatric evaluation by his daughter, C.M., with whom he has been living for the past 3 years. C.M. reports that R.M. had been in good health until 3 months ago when he was noted to keep to himself and began showing little interest in his usual activities. She reports that he used to be a happy, very outgoing personality He has lost weight over the past 4 months, has been noted to be irritable, anxious, and has trouble falling asleep. He also frequently becomes agitated over insignificant things. He has appeared on occasion to be confused and slow in understanding concepts. ....”
LK Laird and WH Benefield, Jr. Applied Therapuetics, 1996, pp 76/15-18
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MDD Presentation in the ElderlyCont’d
“...His recent physical examination is normal except for benign prostatic hypertrophy (BPH). Laboratory examinations are WLN except for a subnormal serum creatinine. He currently is on no medication except for a daily stool softener and a bulk laxative.
Mental Status Examination reveals a thin, nervous, sad-appearing man. His responses to questions are slow. Affect is sad. He shows no signs of delusions or hallucinations. He shows mild impairments in his ability to think through problems and mathematical exercises. He denies suicidal ideation but feels hopeless at the present time.”
LK Laird and WH Benefield, Jr. Applied Therapuetics, 1996, pp 76/15-18
112
MDD Presentation in the Elderly
“How does a depressive episode in late life, such as that in R.M., differ from a depressive episode earlier in life?”
“What is R.M.’s differential diagnosis?” “Should R.M. be placed on antidepressant therapy?” What factors would influence drug selection?
LK Laird and WH Benefield, Jr. Applied Therapuetics, 1996, pp 76/15-18
113
The Case of R.M., Cont’d
How does the pharmacokinetic profile of the SSRI’s affect your choice?
What are the significant drug interacts that should be considered with R.M.’s pharmacotherapy if treatment for other common disorders were added?
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For a first episode of depression patients should be on medication for at least 12 months
115
For a second episode of depression, the patient should be on medication for 2 to 3 years
116
For a third episode of depression, most patients stay on medication for life
117
When deciding to take a patient off an antidepressant, the patient’s medical and psychosocial situations must be considered
118
Patient education
Do not perpetuate the stigma of psychiatric illness
Treat the patient with the same empathy, respect and concern you would treat a patient with a medical disorder
Explain depression as a medical disorder Do not be afraid to discuss the signs and
symptoms of depression
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Patient education
Encourage compliance with medication Help patients understand the medications and
common side effects Help patients understand there is no magic
bullet, but most people are successfully treated
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Questions
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