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NAPLEX
Depression &
Alzheimer's
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 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
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
Amitriptyline
(Elavil)
Initial Dosing: 25 - 50 mg HS
Maintenance: 150-200mg / day
Chronic pain: 25 -100mg / day
Max: 300 mg/day
98% PB
t1/2: 24 hours
Metabolized via 1A2 and 2D6
active metabolite: nortriptyline
BL: >100 ng/ml (amit+nort)
Imipramine
(Tofranil)
Initial Dosing: 25 - 50 mg HS
(lower for panic)
Maintenance: 150-200mg / day
Max: 300 mg/day
98% PB
t1/2: 24 hours
Metabolized via 1A2 and 2D6
active metabolite: imipramine
BL: >200 ng/ml (imip+ desip)
Common Side Effects:
Orthostatic Hypotension
Antihistaminergic
Anticholinergic
Antiadrenergic
Photosensitivity
Sexual Dysfunction
SIADH
Switching (depression to mania)
Doxepin
(Sinequan)
Initial Dosing: 25 - 50 mg HS
Maintenance: 150-200mg / day
Max: 300 mg/day
98% PB
t1/2: 24 hours
active metabolite
Metabolized via 1A2 and 2D6
Clomipramine
(Anafranil)
Initial Dosing: 25 - 50 mg HS
(lower for panic)
Maintenance: 150-200mg / day
Higher for OCD * only TCA effective
for OCD
Max: 250 mg/day (incr. Risk of
seizures)
98% PB
t1/2: 36 hours
active metabolite: n-desmethyl
clomipramine (t1/2: 52 hours)
Metabolized via 1A2, 2D6
Clomip: 5HT
NDClomip: NE
Nortriptyline
(Pamelor)
Initial dose: 25 - 50 mg
Maintenance: 100-125mg / day
Max: 150mg/day
98% PB
t1/2: 24 hours
Metabolized via 2D6
BL: 50-150 ng/ml
Twice as potent as other TCAs
Desipramine
(Norpramin)
Initial dose: 25 - 50 mg HS
Maintenance: 150-200mg/day
Max: 300 mg/day
98% PB
t1/2: 24 hours
metabolized via 2D6
BL: >100 ng/ml
Tertiary - TCAs
Secondary TCAs
side effects same as above but
less severe
Nortriptyline: least orthostatic
Desipramine: least
anticholinergic and least weight
gain
Medication
Dosing Guidelines
Kinetic Parameters /
Pharmacology
Side Effects
Nefazodone
(Serzone)
Di: 25mg BID
Dm: 300-500mg
Max: 600mg/d
Inhib: 3A4
Act. Metab: m-CPP
t1/2: 12 hrs - inhibition of own metabolism
allows for Q Day dosing
(Cpss reached am day 5)
Same serotonin receptor stimulation profile with
some mild inhibition of norepinephrine
reuptake blockade, blocks 5HT2, therefore: see
less anxiety, insomnia, and akathisia
Sedation may occur
Little to no sexual dysfunction. No priapism.
Photosensitivity and Switching
Hepatotoxicity - Discontinued
Hepatotoxicity – Discontinued!
Venlafaxine
(Effexor)
Di:25mg BID
Dm: 225-350mg
Max:375mg/d
SA allows for once daily
dosing.
40-50%PB
No Inhibition
Act. Metab:O-D-venlafaxine
t1/2: 12 hrs (Cpss am day 4)
MOA: Low dose sertonergic, Moderate doses
adds noradrenergic, at high doses
dopaminergic activity added
Stimulates all serotonin receptors
Noradrenergic stimulation, DA side effects possible
but uncommon, Photosensitivity and
Switching can occur
Dose dependent hypertension (>375mg/day) very
patient variable
Mirtazapine
(Remeron)
Di: 15mg
Dm: 30-45
Max: 60mg
t1/2: 24hrs (Cpss am day 5)
no inhibition
Not associated with GI side effects of SSRIs
Sedation and weight gain most common, at higher
doses may be more stimulating
Photosensitivity and Switching can occur
Little to no sexual dysfunction
Bupropion
(Wellbutrin)
Di: 75mg BID
Dm:150mg BID SR
Max:450mg/d
Max one time
dose=150mg reg
rel.
Not for panic
SR does NOT allow for
once a day dosing
Active and Inactive metabolites
t1/2: 12hrs (Cpss am of day4)
MOA: Increases levels of norepinephrine and
dopamine
Overstimulation, headache, insomnia, nausea,
agitation
High doses may cause psychotic symptoms
Little to no sexual dysfunction
Photosensitivity 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% PB
T1/2: 1-3 days (parent)
active metabolite: norfluoxetine
(t1/2: 7-10 days)
Inhibits 2D6 and 3A4
PG use considered safe, especially 2nd and 3rd
trimesters
Fluvoxamine
(Luvox)
Initial dose: 25mg BID
(smaller for panic)
Maintenance for
depression:
200mg
for OCD higher
77% PB
T1/2: 12 hours
No active metabolites
Inhibits 1A2, 2C, 3A4, 2D6
Sertraline
(Zoloft)
Initial dose: 50mg HS
(smaller for panic)
Maintenance for
depression:
150mg
for OCD higher
95% PB
active metabolite (N-desmethylsertraline)
T1/2: 24 hours
Inhibits: 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% PB
T1/2: 24 hours
No active metabolite
PG use - initial reports indicate safety
Side effects: Non-selective activation of
serotonin receptors by increased
serotonin.
Receptor Stimulation
5HT1A
Antidepressant
Anti-obsessional
Antipanic / antisocial
phobia, Anti-bulimia
5HT1D
Antimigrane
5HT2
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
Citalopram
(Celexa)
Escitalopram
(Lexapro)
- L isomer,
Initial dose: 10- 20 mg a
day (smaller for
panic)
Maintenance for
depression: 40mg
for OCD higher
80% PB
T1/2: 24 hours
Metabolites less active than parent compound
Slight Inhibition of 1A2, 2D6, 2C19
Substrate 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: SLEEP
Maintenance for
sleep: 50 - 150mg HS
(150mg MAX)
Depression: 400mg/d
93% PB
Active metabolite (m-CPP)
T1/2: 12 hours
Proserotonergic - not an SSRI
High alpha-adrenergic blockade results in
high incidence of orthostatic
hypotension
Very Sedating
Priapism - 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
NAPLEX
Alzheimer's Drugs
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 Dosing
• Dose dependent side effects require titration
• Start low and take in steps to avoid side effects
Drug
Starting
dose
Time before
Increasing
dose
6 weeks
Increase
dose by
Max dose
Donepezil
(Aricept)
5mg QHS
5mg QHS
10mg QHS
Rivastigmine 1.5mg BID
(Exelon)
2 weeks
1.5mg BID
6mg BID
Galantamine 4mg BID
(Razadyne)
4 weeks
4mg BID
Recommended range of
16-24 mg a
day.
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)
B)
C)
D)
E)
Alzheimer's
Nocturnal enuresis
Manic-depressive illness
ADHD
Insomnia
A prescription is presented for galatamine
(Reminyl). The patient is most likely being
treated for:
A)
B)
C)
D)
E)
Alzheimer's
Nocturnal enuresis
Manic-depressive illness
ADHD
Insomnia
Orthostatic hypotension is characterized by
which of the following symptoms?
A.
B.
C.
D.
E.
Peripheral vasoconstriction
Increased urination
Urinary retention
Dizziness
Dry mouth
Orthostatic hypotension is characterized by
which of the following symptoms?
A.
B.
C.
D.
E.
Peripheral vasoconstriction
Increased urination
Urinary retention
Dizziness
Dry mouth
Which SSRI(s) is not required to be tapered when
discontinued?
I Fluoxetine (Prozac)
II Paroxetine (Paxil)
III Sertaline (Zoloft)
A)
I only
B)
III only
C)
I & II only
D)
II & III only
E)
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 only
B)
III only
C)
I & II only
D)
II & III only
E)
I, II, III
A)
B)
C)
D)
E)
How long is an adequate continuation of an
antidepressant before considering a different agent?
I.
4 weeks
II.
2 months
III.
6 months
I only
III only
I & II only
II & III only
I, II, III
A)
B)
C)
D)
E)
How long is an adequate continuation of an
antidepressant before considering a different agent?
I.
4 weeks
II.
2 months
III.
6 months
I only
III only
I & II only
II & III only
I, II, III

A)
B)
C)
D)
E)
What is considered an optimal augmentation
approach to someone not responding to SSRI
therapy?
I
Add Lithium 600mg BID
II
Add Cytomel 25mcg/day
III
Add Bupropion 150mg/day
I only
III only
I & II only
II & III only
I, II, III

A)
B)
C)
D)
E)
What is considered an optimal augmentation
approach to someone not responding to SSRI
therapy?
I
Add Lithium 600mg BID
II
Add Cytomel 25mcg/day
III
Add Bupropion 150mg/day
I only
III only
I & II only
II & III only
I, II, III
Good Luck!
You will all do great!