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Depression & Alzheimer's
Depression & Alzheimer's
NAPLEX
p. 109
Antidepressants
Types of depression
• Major depressive disorder, single episode
• Major depressive disorder, recurrent
• Dysthymic disorder
• Dysthymic disorder, not otherwise specified
• Secondary mood disorder due to nonpsychiatric medical condition
Biochemical basis of endogenous depression – reduced / imbalance of NE / 5-HT in CNS
Drug selection/adequate therapeutic trial
Antidepressant Selection FactorsAntidepressant Selection Factors
Patient factors Age, comorbid conditions, medication profile,
preference, previous successes and failures of specific agents
Other factors Cost, convenience, adverse-effect profile,
safety Typical response rate: 4 to 6 weeks Adequate trail is 6 month on effective dose
Patient factors Age, comorbid conditions, medication profile,
preference, previous successes and failures of specific agents
Other factors Cost, convenience, adverse-effect profile,
safety Typical response rate: 4 to 6 weeks Adequate trail is 6 month on effective dose
Antidepressants (cont’d)
Common Adverse Effects by Receptor Subtype
H-1 receptor blockade:
Sedation, drowsiness, weight gain
Acetylcholine blockade:
dry mouth, blurred vision, tachycardia, constipation, urinary retention, memory impairment
Norepinephrine blockade:
Tremors, jitteriness, tachycardia, diaphoresis, HTN, erectile dysfunction
5-HT blockade:
sexual dysfunction, N/V/D, anorexia, anxiety, asthenia, insomnia, EPS
Antidepressants (cont’d)
Common Adverse Effects by Receptor Subtype
5-HT2 blockade:
sexual dysfunction, hypotension
Alpha-1 blockade:
orthostasis, drowsiness
Alpha-2 blockade:
priapism
Withdrawal syndrome:
Flu-like syndromes, dizziness, adverse GI effects, paresthesias, mood, appetite, and sleep changes
Antidepressants (cont’d)
Agent Dosing Kinetics and Pharmacology Side Effects
Tertiary - TCAs
Amitriptyline(Elavil)
Initial Dosing: 25 - 50 mg HSMaintenance: 150-200mg / dayChronic pain: 25 -100mg / dayMax: 300 mg/day
98% PBt1/2: 24 hoursMetabolized via 1A2 and 2D6active metabolite: nortriptylineBL: >100 ng/ml (amit+nort)
Common Side Effects:Orthostatic HypotensionAntihistaminergicAnticholinergicAntiadrenergicPhotosensitivitySexual DysfunctionSIADHSwitching (depression to mania)
Imipramine(Tofranil)
Initial Dosing: 25 - 50 mg HS(lower for panic)Maintenance: 150-200mg / dayMax: 300 mg/day
98% PBt1/2: 24 hoursMetabolized via 1A2 and 2D6active metabolite: imipramineBL: >200 ng/ml (imip+ desip)
Doxepin(Sinequan)
Initial Dosing: 25 - 50 mg HSMaintenance: 150-200mg / dayMax: 300 mg/day
98% PBt1/2: 24 hoursactive metaboliteMetabolized via 1A2 and 2D6
Clomipramine(Anafranil)
Initial Dosing: 25 - 50 mg HS(lower for panic)Maintenance: 150-200mg / dayHigher for OCD * only TCA effective
for OCDMax: 250 mg/day (incr. Risk of
seizures)
98% PBt1/2: 36 hoursactive metabolite: n-desmethyl
clomipramine (t1/2: 52 hours)Metabolized via 1A2, 2D6Clomip: 5HTNDClomip: NE
Secondary TCAs
Nortriptyline(Pamelor)
Initial dose: 25 - 50 mgMaintenance: 100-125mg / dayMax: 150mg/day
98% PBt1/2: 24 hoursMetabolized via 2D6BL: 50-150 ng/mlTwice as potent as other TCAs
side effects same as above but less severe
Nortriptyline: least orthostaticDesipramine: least
anticholinergic and least weight gain
Desipramine(Norpramin)
Initial dose: 25 - 50 mg HSMaintenance: 150-200mg/dayMax: 300 mg/day
98% PBt1/2: 24 hoursmetabolized via 2D6BL: >100 ng/ml
Medication Dosing Guidelines Kinetic Parameters / Pharmacology
Side Effects
Nefazodone(Serzone)
Di: 25mg BIDDm: 300-500mgMax: 600mg/d
Inhib: 3A4Act. Metab: m-CPPt1/2: 12 hrs - inhibition of own metabolism
allows for Q Day dosing (Cpss reached am day 5)
Hepatotoxicity – Discontinued!
Same serotonin receptor stimulation profile with some mild inhibition of norepinephrine reuptake blockade, blocks 5HT2, therefore: see less anxiety, insomnia, and akathisia
Sedation may occurLittle to no sexual dysfunction. No priapism.Photosensitivity and SwitchingHepatotoxicity - Discontinued
Venlafaxine(Effexor)
Di:25mg BIDDm: 225-350mgMax:375mg/dSA allows for once daily
dosing.
40-50%PBNo InhibitionAct. Metab:O-D-venlafaxinet1/2: 12 hrs (Cpss am day 4)MOA: Low dose sertonergic, Moderate doses
adds noradrenergic, at high doses dopaminergic activity added
Stimulates all serotonin receptorsNoradrenergic stimulation, DA side effects possible
but uncommon, Photosensitivity and Switching can occur
Dose dependent hypertension (>375mg/day) very patient variable
Mirtazapine(Remeron)
Di: 15mgDm: 30-45Max: 60mg
t1/2: 24hrs (Cpss am day 5)no inhibition
Not associated with GI side effects of SSRIsSedation and weight gain most common, at higher
doses may be more stimulatingPhotosensitivity and Switching can occurLittle to no sexual dysfunction
Bupropion(Wellbutrin)
Di: 75mg BIDDm:150mg BID SRMax:450mg/dMax one time
dose=150mg reg rel.
Not for panicSR does NOT allow for
once a day dosing
Active and Inactive metabolitest1/2: 12hrs (Cpss am of day4)MOA: Increases levels of norepinephrine and
dopamine
Overstimulation, headache, insomnia, nausea, agitation
High doses may cause psychotic symptomsLittle to no sexual dysfunctionPhotosensitivity and Switching (less?)Contraindicated in seizure disorder.
Medication Dosing Guidelines Kinetics and Pharmacology Side Effects
Fluoxetine(Prozac)
Inital dose: 10 - 20 mg a day (2.5 mg for panic)
For depression and panic: 10 - 20 mg
For OCD: higher maintenance doses required
94% PBT1/2: 1-3 days (parent)active metabolite: norfluoxetine (t1/2: 7-10 days)Inhibits 2D6 and 3A4PG use considered safe, especially 2nd and 3rd
trimesters
Side effects: Non-selective activation of serotonin receptors by increased serotonin.
Receptor Stimulation5HT1A Antidepressant
Anti-obsessional Antipanic / antisocial
phobia, Anti-bulimia5HT1D Antimigrane5HT2 Anxiety, Akathisia,
Agitation, Insomnia, Panic attacks, Sexual Dysfunction
Blockade at the receptor antagonizes these actions
5HT3 Nausea, GI distress, Diarrhea, Headache
Blockade at this receptor antagonizes these actions
Most stimulating: Prozac > Zoloft > Celexa > Paxil > Luvox
Most diarrhea: Zolft > Paxil > Prozac > Celexa > Luvox
All cause photosensitivity and switching (from depression to mania), Hyponatremia
Fluvoxamine(Luvox)
Initial dose: 25mg BID(smaller for panic)Maintenance for
depression: 200mg
for OCD higher
77% PBT1/2: 12 hoursNo active metabolitesInhibits 1A2, 2C, 3A4, 2D6
Sertraline(Zoloft)
Initial dose: 50mg HS(smaller for panic)Maintenance for
depression: 150mg
for OCD higher
95% PBactive metabolite (N-desmethylsertraline)T1/2: 24 hoursInhibits: 2D6 (mild)PG use - initial reports indicate safety
Paroxetine(Paxil)
Initial dose: 10 - 20 mg a day (smaller for panic)
Maintenance for depression: 40mg
for OCD higher
95% PBT1/2: 24 hoursNo active metabolitePG use - initial reports indicate safety
Citalopram(Celexa)Escitalopram(Lexapro)- L isomer,
Initial dose: 10- 20 mg a day (smaller for panic)
Maintenance for depression: 40mg
for OCD higher
80% PBT1/2: 24 hoursMetabolites less active than parent compoundSlight Inhibition of 1A2, 2D6, 2C19Substrate for 3A4 (parent) and 2C19 (metab)PG: Category C, use not recommended at this time
due to lack of information
Trazodone(Deseryl)
Initial dose: 25 mg a day Primary use: SLEEPMaintenance forsleep: 50 - 150mg HS(150mg MAX)Depression: 400mg/d
93% PBActive metabolite (m-CPP)T1/2: 12 hoursProserotonergic - not an SSRI
High alpha-adrenergic blockade results in high incidence of orthostatic hypotension
Very SedatingPriapism - rare, urologic emergency
Antidepressants (cont’d)
Monoamine Oxidase (MAO) Inhibitors
- effective in refractory depression
Isocarboxazid (Marplan)
Phenelzine sulfate (Nardil)
Tranylcypromine sulfate (Parnate)
Antidepressants (cont’d)
Substances to be avoided when using MAO inhibitors
Food with Tyramine Content
• Aged cheeses
• Sauerkraut
• Smoked aged, or pickled meat or fish
• Yeast extracts
• Fava beans
• Beer, red wine
• Avocados
• Meat extracts
Antidepressants (cont’d)
Substances to be avoided when using MAO inhibitors (cont’d)
Medications
• Phenylpropanolamine
• Pseudoephedrine
• Meperidine (Demerol)
• Methyldopa (Aldomet)
• Morphine
• Reserpine
Alzheimer's DrugsAlzheimer's Drugs
NAPLEX
p. 118
Drugs for Alzheimer’s Disease
Cholinesterase inhibitors: all enhance cholinergic activity• Donepezil (Aricept)• Galantamine (Razadyne) (Reminyl – D/C))• Rivastigmine (Exelon)
- Exelon patch approved 7-2007
Glutamate antagonists• Memantine (Namenda)
Miscellaneous agents• Vitamin E• Selegiline (Eldepryl)
Cholinesterase Inhibitors DosingCholinesterase Inhibitors Dosing
Drug Starting dose
Time before Increasing dose
Increase dose by
Max dose
Donepezil (Aricept)
5mg QHS 6 weeks 5mg QHS 10mg QHS
Rivastigmine (Exelon)
1.5mg BID 2 weeks 1.5mg BID
6mg BID
Galantamine (Razadyne)
4mg BID 4 weeks 4mg BID Recommen-ded range of 16-24 mg a day.
• Dose dependent side effects require titration• Start low and take in steps to avoid side effects
Drugs for Alzheimer’s Disease
Adverse Effects
Cholinesterase inhibitors:• Hepatotoxicity• Cholinergic effects (N/D, anorexia, salivation)• Bradycardia• Headache
Glutamate antagonists• Hypertension• Tachycardia• Insomnia
A prescription is presented for galatamine (Razadyne). The patient is most likely being treated for:
A) Alzheimer'sB) Nocturnal enuresisC) Manic-depressive illnessD) ADHDE) Insomnia
A prescription is presented for galatamine (Razadyne). The patient is most likely being treated for:
A) Alzheimer'sB) Nocturnal enuresisC) Manic-depressive illnessD) ADHDE) Insomnia
A prescription is presented for galatamine (Reminyl). The patient is most likely being treated for:
A) Alzheimer'sB) Nocturnal enuresisC) Manic-depressive illnessD) ADHDE) Insomnia
A prescription is presented for galatamine (Reminyl). The patient is most likely being treated for:
A) Alzheimer'sB) Nocturnal enuresisC) Manic-depressive illnessD) ADHDE) Insomnia
Orthostatic hypotension is characterized by which of the following symptoms?
A. Peripheral vasoconstriction
B. Increased urination
C. Urinary retention
D. Dizziness
E. Dry mouth
Orthostatic hypotension is characterized by which of the following symptoms?
A. Peripheral vasoconstriction
B. Increased urination
C. Urinary retention
D. Dizziness
E. Dry mouth
Orthostatic hypotension is characterized by which of the following symptoms?
A. Peripheral vasoconstriction
B. Increased urination
C. Urinary retention
D. Dizziness
E. Dry mouth
Orthostatic hypotension is characterized by which of the following symptoms?
A. Peripheral vasoconstriction
B. Increased urination
C. Urinary retention
D. Dizziness
E. Dry mouth
Which SSRI(s) is not required to be tapered when discontinued?
I Fluoxetine (Prozac)II Paroxetine (Paxil)III Sertaline (Zoloft)
A) I onlyB) III onlyC) I & II onlyD) II & III onlyE) I, II, III
Which SSRI(s) is not required to be tapered when discontinued?
I Fluoxetine (Prozac)II Paroxetine (Paxil)III Sertaline (Zoloft)
A) I onlyB) III onlyC) I & II onlyD) II & III onlyE) I, II, III
Which SSRI(s) is not required to be tapered when discontinued?
I Fluoxetine (Prozac)II Paroxetine (Paxil)III Sertaline (Zoloft)
A) I onlyB) III onlyC) I & II onlyD) II & III onlyE) I, II, III
Which SSRI(s) is not required to be tapered when discontinued?
I Fluoxetine (Prozac)II Paroxetine (Paxil)III Sertaline (Zoloft)
A) I onlyB) III onlyC) I & II onlyD) II & III onlyE) I, II, III
How long is an adequate continuation of an antidepressant before considering a different agent?I. 4 weeksII. 2 monthsIII. 6 months
A) I onlyB) III onlyC) I & II onlyD) II & III onlyE) I, II, III
How long is an adequate continuation of an antidepressant before considering a different agent?I. 4 weeksII. 2 monthsIII. 6 months
A) I onlyB) III onlyC) I & II onlyD) II & III onlyE) I, II, III
How long is an adequate continuation of an antidepressant before considering a different agent?I. 4 weeksII. 2 monthsIII. 6 months
A) I onlyB) III onlyC) I & II onlyD) II & III onlyE) I, II, III
How long is an adequate continuation of an antidepressant before considering a different agent?I. 4 weeksII. 2 monthsIII. 6 months
A) I onlyB) III onlyC) I & II onlyD) II & III onlyE) I, II, III
What is considered an optimal augmentation approach to someone not responding to SSRI therapy?I Add Lithium 600mg BIDII Add Cytomel 25mcg/dayIII Add Bupropion 150mg/day
A) I onlyB) III onlyC) I & II onlyD) II & III onlyE) I, II, III
What is considered an optimal augmentation approach to someone not responding to SSRI therapy?I Add Lithium 600mg BIDII Add Cytomel 25mcg/dayIII Add Bupropion 150mg/day
A) I onlyB) III onlyC) I & II onlyD) II & III onlyE) I, II, III
What is considered an optimal augmentation approach to someone not responding to SSRI therapy?I Add Lithium 600mg BIDII Add Cytomel 25mcg/dayIII Add Bupropion 150mg/day
A) I onlyB) III onlyC) I & II onlyD) II & III onlyE) I, II, III
What is considered an optimal augmentation approach to someone not responding to SSRI therapy?I Add Lithium 600mg BIDII Add Cytomel 25mcg/dayIII Add Bupropion 150mg/day
A) I onlyB) III onlyC) I & II onlyD) II & III onlyE) I, II, III
Good Luck!Good Luck!
You will all do great!You will all do great!