Transcript Mid-Ohio Psychological Services, Inc. Staff Training on

Mid-Ohio Psychological
Services, Inc.
Staff Training:
Psychopharmacology
Daniel DiSalvo, CNP
February 8, 2008
Outline
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
Welcome, Introduction & Lunch
Content
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Pharmacodynamics/kinetics & Basic Principles
Antidepressants
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MAOIs, TCAs
SSRIs
SNRIs
Other
Mood Stabilizers
Antipsychotics
Discussion
Question & Answer
Conclusion
Psychopharmacology

The study of the effects of drugs on
affect, mood, cognition and behavior
and the use of drugs to treat disorders
of the central nervous system where it
is the expressed intent to alter mood,
thought or behavior.
The Concept of
Chemical Imbalance
NT
in deficit
in excess
acetylcholine
dopamine
memory impairment/delirium
aggression/depression
dementia/depression
psychosis/anxiety/
confusion/aggression
serotonin
depression/impulsivity/anxiety
anxiety
norepinephrine depression/anxiety/dementia
anxiety/aggression
GABA
anxiety/impulsivity
cognitive/motor slowing
glutamate
cognitive slowing/dementia seizures/neuronal degeneration
The Basis of Psychopharmacology
Correcting the chemical imbalance – either
increasing or decreasing activity of that NT.
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1.
2.
3.
4.
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1.
2.
For disorders associated with
hypofunctioning:
Stimulate NT release
Use chemical (drug) that mimics NT
Block metabolic inactivation of NT
Block reuptake
For disorders associated with
hyperfunctioning:
Inhibit or reduce NT release
Block target receptors
Antidepressants
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>8 different pharmacological MOAs
>2 dozen ADs
Most block monoamine reuptake
Some block alpha-2 receptors
Others might work on the enzyme MAO
Some have direct actions on only one
monoamine NT system, while others work on
multiple monoamine NT systems
The immediate pharmacological actions of all
ADs eventually have the effect of boosting
the levels of monoamine NTs
Why Does It Take So Long?
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Down Regulation: no matter what their initial
actions on receptors and enzymes, ADs eventually
cause a desensitization of key NT receptors in a time
course consistent with the delayed onset of AD action
of these drugs.
Delayed actions of ADs may not only explain the
delay in onset of therapeutic action of ADs; they may
also explain why some patients fail to respond to
ADs, as…
It is possible that in such patients the initial
pharmacological actions are not translated into the
required delayed pharmacologic and genetic actions.
Function
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Pharmacokinetics: How the body acts on the drug.
Pharmacodynamics: How the drug acts on the body,
especially the brain.
Drug is absorbed and delivered through the gut wall
to the liver to be biotransformed so that it can be
excreted.
CYP450: enzyme in the gut wall or liver converts the
drug substrate into a biotransformed product in the
bloodstream.
After the passing through the gut wall and liver, the
drug will exist partly as unchanged drug and partly as
biotransformed drug.
CYP450 Systems
1A2
2D6
2C9
2C19
3A4
Substrates of
this enzyme:
clomipramine
imipramine
5-10% of
Caucasians are
poor
metabolizers
20% of
Japanese and
Chinese persons
Inhibitors:
bupropion,
fluphenazine,
sertraline
Some BDZs are
substrates
Biggie for ADs
Several SSRIs
are inhibitors
(paroxetine,
fluoxetine –
most)
fluvoxamine
inhibits
3-5% of
Caucasians
Inducers:
carbamazepine,
ethanol,
phenytoin,
St. Johns’ wort
Some ADs are
inhibitors
(nefazodone)
Mood stabilizers
Classical ADs: MAOIs & TCAs
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MAOIs – the very first! 1950s, 1960s
Anti-TB drug
Great for panic and social phobia
Used to stop ‘em…dead!
Subtypes: A (depression – 5-HT, NE),
B (anti-neurodegenerative Parkinson’s)
Hypertensive crisis
MAOI Diet
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Cheese pizza, sour cream, yogurt, and all cheeses except cream
and cottage
Beef and chicken livers, unrefrigerated fermented sausage,
summer sausage, bologna, salami, pepperoni, tofu, pickled
fish/herring, lox caviar, dried salted herring/other smoked fish
Broad bean pods, fava beans, Italian green beans, snow pea
pods, sauerkraut, avocados
Chocolate cake, cookies, ice cream, pudding, chocolate candy
Chianti, sherry, red, burgundy, ale, beer, vermouth, Reisling,
liqueurs
Salad dressings with cheese or MSG
Brewer’s yeast/yeast extract (e.g., some soups, sauces, gravies),
MSG, meat tenderizers , soy sauce.
MAOI Medication Interactions
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Sympathomimetics
General anesthetics
Local or spinal anesthetics w/ epi (e.g., Novocaine)
OTC cough, cold and sinus w/ sympathos (e.g.,
Actifed, Sudafed, Contact, Dristan, Afrin, NyQuil,
Dimetapp, Triaminic, etc.)
Demerol and other narcotics containing codeine,
morphine, hydrocodone (e.g., Percocet, Percodan)
Cocaine
Macrolantin
Other ADs
Drug
Form
MAOIs-A
Generic
Daily
Dose
Max
Price
(qd
dose)
Marplan 10mg
tab
No
30mg
60mg
$2.45
Nardil
15mg
tab
No
60mg
90mg
$2.64
Parnate 10mg
tab
No
40mg
60mg
$3.94
MAOIs-B & RIMAs

Selegiline – parkinsonism…
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Emsam (selegiline): greater affinity for B,
but works on both at AD doses
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6/9/12mg transdermal/qd – no restrictions at 6
RIMAs not available in US
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Manerix – few dietary restrictions
Pharmacological Actions MAOIs
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Readily absorbed through GI
Peak plasma in 2hr.
T ½ is 2-3hr.
Irreversibly inactivate MAOs – i dose
can last for 2w.
Therapeutic Indications –
MAOIs
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Depression, esp. that associated with mood
reactivity, extreme sensitivity to interpersonal
loss or rejection, prominent anergia,
hyperphagia, hypersomnia (atypical features)
Also great for panic, PTSD, AN, BN, SP and
pain syndromes.
Refractory
Panic (high)
OCD (none)
GAD (moderate)
BDD (moderate)
Precautions &
Adverse Reactions – MAOIs

Orthostasis, insomnia, weight gain, edema, sexual
dysfunction

(divide dose, increase fluids/salt, support stockings, take in a.m., add
sleep agent, or…switch)
HTN crisis w/o tyramine (Parnate) – avoid
Taper and wait for >2w w/ a switch
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Paresthesias, myoclonus, muscle pains
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Pyridoxine 50-150mg/d
Less cardiotoxic, epileptogenic compared to TCAs
Caution, though, w/ renal, CV and hyperthyroidism
May alter dosage of a hypoglycemic agent
Associated w/ induction of mania in pts. in depressed phase of
BPAD I and triggering psychotic decompensation in scz
Contraindicated in pregnancy/nursing
Precautions &
Adverse Reactions – MAOIs

OD: agitation  coma w/
hyperthermia, HTN, tachypnea,
tachycardia, dilated pupils and
hyperreflexia, involuntary movements
(face, jaw)
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Asymptomatic 1-6hrs.
acidify urine, dialyze
Multi-drug (esp. 5-HT) – increase effects
Precautions &
Adverse Reactions – MAOIs
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Labs:
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DM meds (hypoglycemia)
minimal, false elevation of TFTs
Periodic LFTs
TCAs
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Wide range: MDD, Panic, GAD, PTSD, OCD, EDs,
Pain Syndrome
Yet, very toxic and we have alternatives
Significant FPE
Peak plasma 2-8hrs
T ½ 10-70hrs
2D6: (Is) quinidine, cimetidine, fluoxetine, sertraline,
paroxetine, phenothiazines, carbamazepine, some
antiarrhymics (propafenone, flecainide)
Block reuptake of NE, 5-HT
Competitive antagonists of muscarinic acetylcholine,
H1, alpha-1, -2
Use if cannot tolerate anxiety/GI upset (SSRIs)
TCAs –
Approved / Off-Label Uses
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MDD: induce mania in susceptible pts. (compared to
bupropion, SSRIs)
Panic: imipramine, yet anxiogenic, so start low, go slow
GAD: doxepin, imipramine
OCD: clomipramine (2-4w…4-5m) and depressed pts. w/
marked obsessive features
EDs: imipramine, desipramine, clomipramine
Pain: any
Enuresis: imipramine
Peptic ulcer: doxepin
Others: narcolepsy, nightmare d/o, PTSD, sometimes for
ADHD, sleepwalking, separation anxiety, sleep terrors,
premature ejaculation, movement d/os
Precautions & Adverse
Reactions – TCAs
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Anticholinergic, sedation, orthostasis, seizure,
conduction abnormalities, weight gain
Can induce mania (over SSRIs, bupropion)
May exacerbate psychotic d/os
Confusion, delirium
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Tachycardia, flattened T waves, prolonged QTc
intervals, depressed ST segments
Don’t use w/ cardiac pts., unless other agents
have failed (monitor)
Sore throat in initial stages – monitor
Transient increase in LFTs vs. hepatitis
Drug Interactions – TCAs
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MAOIs
Antihypertensives
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Esimil, Ismelin (block reuptake)
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propranolol, clonidine (also block)
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Aldomet + TCA = agitation
DA blockers
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perphenazine = doubling of plasma [ ] of both products (add to anticholinergic SE
profile, too)
Sympathomimetics
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Serious CV effects
CNS depressants
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Opioids, EtOH, anxiolytics, hypnotics, OTC cold remedies
Oral contraceptives
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BCPs may decrease TCA plasma [ ] through the induction of hepatic enzymes
Diamox, ASA, cimetidine, thiazide diuretics, fluoxetine, sodium bicarbonate = increase,
while ascorbic acid, ammonium chloride, barbiturates, cigarette smoking,
carbamazepine, chloral hydrate, lithium decrease levels
TCA Labs
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Can get levels, though
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Should be clinically driven
TCA Dosages / Clinical Guidelines
DRUG
TABLET (mg)
CAPSULES
PARENTERAL
(mg/mL)
imipramine
10, 25, 50
75, 100, 125, 150
12.5
desipramine
10, 25, 50, 75,
100, 150
25, 50
trimipramine
amitriptyline
25, 50, 100
10, 25, 50, 75,
100, 150
nortriptyline
protriptyline
5, 10
amoxapine
25, 50, 100, 150
doxepin
maprotiline
clomipramine
SOLUTION
(mg/mL)
10
10, 25, 50, 75
10/5
10, 25, 50, 75,
100, 150
10
25, 50, 75
25, 50, 75
Clinical Guidelines of TCAs
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Prior to tx: PE, CBC w/ diff, lytes, LFTs, EKG (esp. women >40,
men >30)
Contraindicated in pts. w/ a QTc >450msc
Consider using newer agents 1st, esp. if pt. has an interfering
medical dx
In kids, elderly – avoid, but if need to use, EKG should be
monitored frequently
Those w/ chronic pain might be sensitive to initial dosing, but
may benefit later
Taper to avoid cholinergic rebound syndrome
Dosing & Levels – TCAs
Drug
Usual Adult Dosage Range
(mg/d)
Therapeutic Plasma [ ]
(mcg/mL)
Tofranil
150-300
150-300
Norpramin
150-300
150-300
Surmontil
150-300
?
Elavil
150-300
100-250
Pamelor
50-150
50-150
Vivactil
15-60
75-250
Asendin
150-400
?
Sinequan
150-300
100-250
Ludiomil
150-230
150-300
Anafranil
130-250
?
TCAs & OD
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Serious, can easily be fatal
NRF, <1w quantity for those at risk
amoxapine – most fatal
OD Sx:
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agitation, delirium, convulsions,
hyperreflexia, bowel/bladder paralysis,
dysregulation of BP, T and
mydriasis…coma, respiratory depression
cardiac arrhythmias may not be
correctable, and are at risk for up to 4d s/p
OD d/t long T ½
SSRIS
(the ones we know and love)
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fluoxetine – 1987
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Rapidly eclipsed the MAOIs/TCAs
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Don’t necessarily work better, but are safer and have
a less (different) SE profile
Subtle differences between compounds: T 1/2 ,
potency for reuptake inhibition and affinity for some
other receptors
Overall, less effects on adrenergic, histaminergic and
cholinergic
Pharmacologic Actions – SSRIs
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Selectively block the reuptake of 5-HT presynaptically
Slightly different pharmacokinetic profiles, as each drug is
structurally different from the others
Many are highly protein bound
Varying T ½ - 24hr to several days
 fluoxetine (active metabolite) = 7-15d
 citalopram = 1.5d
 sertraline / paroxetine = 1d
All are well absorbed and not generally affected by food
administration except for sertraline (level may be increased w/
food)
No correlation between T ½ and time to onset
All eliminated in urine as active metabolites
citalopram / escitalopram – more selective for 5-HT receptor
blockade
Indications For / Off-Label Use
of SSRIs
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MDD – acute, single, recurrent, prevention, etc.
DD, PD
OCD (may need more, take longer)
GAD, SP, PTSD
AN, BN (APA recommends use for persistent depression after pt.’s gained wt.)
BDD
PMDD
Children
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Repetitive-type abnormalities, e.g., autism, ADHD (as adjunct), MR/DD,
chronic enuresis
Other complex behavioral d/os
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Obesity (high dose fluoxetine)
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Binge eating (sertraline)
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Substance abuse
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Decrease aggressive behaviors – impulsivity / uncontrolled anger in all ages
Migraine / cluster HAs
Diabetic neuropathy, facial pain, fibrositis, arthritis, RLS
Pharmacokinetic Profiles –
SSRIs
Drug
Time to
T½
Peak Plasma
[]
T½
metabolite
Time to
PlasmaSteady State Protein
(days)
Binding (%)
fluoxetine
6-8h
4-6d
4-16d
28-35
95
fluvoxamine
3-8h
15h
--
5-7
80
paroxetine
5-6h
21h
--
5-10
95
sertraline
4.5-8.5h
26h
62-104h
5-7
95
escitalopram
3-5h
30h
50-60h
10
90
citalopram
4h
35h
3h
7
80
Basics – SSRIs
Drug
Generic/Supply
Dose/Day
Price Index ($
cost of dose/d)
Prozac
Y/Soln, Tabs, Delayed Cap
60mg
1.10
Zoloft
Y/Soln, Tabs
100mg
3.02 (brand)
Paxil
Y/Soln, Tabs
40mg
2.97
Luvox
Y/Tabs
200mg
5.25
Lexapro
N/Soln, Tabs
20
2.65
Celexa
Y/Soln, Tabs
40
2.65
Precautions & Adverse
Reactions – SSRIs
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¾ of pts. experience no SEs
¼ have SEs in first 2w, usually subside
10-15% are unable to tolerate
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Sexual dysfunction: 50-80%, might not go away…
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GI: sertraline, fluvoxamine, citalopram
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Decrease dose; switch (bupropion, nefazodone); add
(bupropion)
N, V, D, anorexia, dyspepsia – transient?
Weight gain: initially lose, but 1/3 will gain
(>20lbs.); paroxetine (d/t anticholinergic SE)
HAs: 18-20% (fluoxetine – most); alternately,
SSRIs are wonderful for tension HAs/migraines
Precautions & Adverse
Reactions – SSRIs
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CNS
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Anxiety: fluoxetine (most), but then tx it
Insomnia/sedation: ¼ have insomnia (fluoxetine – take in
a.m.); sertraline = fluvoxamine; citalopram/paroxetine –
sedation
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Tx w/ trazodone, BDZ, other off-labels
Nightmares: small amount of pts. (resolves)
Seizures: 0.1 - 0.2% of all pts. txd w/ SSRIs (comparable to
other ADs/placebo)
EPS:
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Tremor 5-10%
TD (exceptionally rare)
Pts. w/ well-controlled Parkinson’s – acute worsening of their motor
symptoms
Bruxism (buspirone)
Most common w/ fluoxetine
Precautions & Adverse
Reactions – SSRIs
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Anticholinergic:
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paroxetine (mild)
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Can decrease plt. function = bruisability
paroxetine, fluoxetine (reversible neutropenia – rare, usually if concurrent
w/ clozapine)
Electrolyte / Glucose:
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Dry mouth (up to 20%)
Dose-dependent
Hematologic:
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opposite of S.L.U.D.
Hypoglycemia (rare – DM pts. need to be careful)
Hyponatremia/ADH release (also rare) – if diuresing/H2O deprived
Endocrine / Allergic:
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Decrease prolactin/galactorrhea (breast changes may take several months
to correct)
Various rash types – 4% (d/c)
Precautions & Adverse
Reactions – SSRIs
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5-HT Syndrome:

SSRI + MAOI or SSRI + L-tryptophan or SSRI + lithium = can raise 5-HT
concentrations to toxic levels, causing cascade of:
 D
 Restlessness
 Extreme agitation
 Hyperreflexia
 Autonomic instability
 Myoclonus
 Seizures
 Hyperthermia
 Uncontrollable shivering, rigidity
 Delirium
 Coma
 Status epilepticus
 CV collapse
 Death
Precautions & Adverse
Reactions – SSRIs
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5-HT Syndrome Tx:
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D/C offender
Supportive care
Nitro
Cyproheptadine
Methysergide
Cooling blankets
Chlorpromazine
Dantrolene
Benzodiazpines
Anticonvulsants
Mechanical vents
Paralyzing agents
Precautions & Adverse
Reactions – SSRIs
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SSRI W/D:
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Abrupt discontinuation, esp. w/ a shorter T
½ (paroxetine, fluvoxamine)
After 6w; ends by 3w
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dizziness, weakness, N, HA, rebound
depression, anxiety, insomnia, poor
concentration, UR Sx, paresthesias, migrainelike Sx
Tx: don’t abruptly stop; use fluoxetine
SSRIs & Labs
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None
SNRIs
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“3rd Generation” ADs
5-HT, NE – equal affinity
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duloxetine, venlafaxine, mirtazapine
Differences among the three:
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mirtazapine – antagonist of central presynaptic alpha2adrenergic receptors; potent antagonist of H1
venlafaxine – a little faster onset w/ rapid dose
increase; great for severe MDD w/ melancholy; 1st
non-bdz drug (other than buspirone) to be approved
for GAD
duloxetine – compared w/ venlafaxine, it has a greater
effect on 5-HT reuptake in vitro; approved for diabetic
neuropathic pain
Other ADs
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bupropion (DA, NE) – late 80’s
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trazodone
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structurally related to nefazodone, structurally unrelated to SSRIs, TCAs,
MAOIs
active metabolite is mCPP (5-HT2c agonist), is especially sedating (off-label
use), blocking H1
priapism (1:6000; surgical intervention in 33%)
nefazodone
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augmentation, SEs, off-label, etc.
be careful w/ OD and EDs – sz d/o
mixed 5-HT antagonist/reuptake inhibitor
great for anxiety
less sedation, hypotension than TCAs, trazodone
atomoxetine (NOT approved for depression) – NRI; could use off-label
Special Considerations in the
Selection of an AD
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Gender:
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women have less gastric acid / slower emptying =
slower GI absorption
volume distribution = more adiposity than lean
muscle
H2O retention associated w/ menses = affects
volume distribution, too
PO contraceptives can alter hepatic metabolism
(TCAs)
Special Considerations in the
Selection of an AD

Ethnicity:
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AAs slow metabolizers compared to Europeans d/t
metabolic enzyme expression
AAs have higher plasma levels per dose of AD
(demonstrated most w/ TCAs)
Asians are slower to metabolize nortriptyline than
other groups
Minorities were less likely than nonminorities
to be offered AD treatment, independent of
dx (study of CMHCs’ prescribing practices in
Westchester County, NY)
Special Considerations in the
Selection of an AD

Age:
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Remember: start low, go slow
Comorbidities:
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Elderly? Steady-state [ ] are minimally affected by
age (except paroxetine)
Renal – dose adjustment (except fluoxetine,
sertraline)
Liver – can increase levels of TCAs (monitor); give
lower doses of SSRIs; don’t use nefazodone
Pregnant Women and Nursing Mothers:
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
Risks vs. benefits
Generally safe, but be careful of w/d for neonate
Mood Stabilizers
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Agents that are geared at affecting one
phase of illness w/o worsening any
other phase(s)
3 families:
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lithium
anticonvulsants
atypicals
Lithium
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1970
Used the longest, quite frequently and is excellent for
mania, maintenance – all phases
Yet non-response rate can be as high as 40%
Narrow TI
Structurally simple = Li+
MOA: unclear if NTs are involved, like they are in
depression tx; occurs intracellularly w/ secondmessenger systems
A monocovalent cation – a direct competitior of Mg+
@ regulatory enzyme, IMPase = reduces intracellular
Ca+/protein kinase C activation
Lithium
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lithium carbonate, Lithobid, Eskalith CR =
immediate and extended (better tolerated,
convenience)
Peak plasma 1-4h
T ½ 18-36h
Rapid, complete absorption
Low protein binding
No first-pass effect
95% drug excretion by kidneys
Can remit mania in many cases, but clinically
an antiepileptic or atypical is also used
Lithium – Labs / PreTreatment Testing
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CBC
Lytes
KFTs
TFTs
EKG
Pregnancy

Check level q3-6mos, as well as associated
labs/EKG

Normal range: 0.5-1.5mEq/L
Lithium

150mg, 300mg, 600mg cap


$15.54, $17.77, $42.30 (#100)
Eskalith CR 450mg cap

$81.97 (#180)
Adverse Effects – Lithium
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Narrow TI
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Prolonged exposure to >2.0mEq/L: CNS
impairment, renal collapse, coma, permanent
brain injury, death
Tox s/s: tremor, confusion, ataxia, N, V, D,
tinnitus, blurred vision, HA, dizziness.
Common SEs: N, V, D, tremor, polydipsia,
polyuria, weight gain, hypothyroidism
(reversible), fatigue
Drug Interactions – Lithium
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Increase levels
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ACE Is
Alprazolam
Antipsychotics
Fluoxetine
Ibuprofen
Indomethacin
Naprosyn
NSAIDs
Some antibiotics
Aldactone
Thiazide diuretics
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Decrease levels
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Caffeine
Carbonic anhydrase
Is
Dilor
Laxatives
Osmotic diuretics
Atenolol
Theophylline
Lithium & Pregnancy
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No!…?
1st trimester = Ebstein’s anomaly (1:2000)
However, discuss the risk and benefit
Be very clear in initial interview about risks,
as a female pt. might be well into her 1st
trimester…
Retrospective studies have shown to use
aggressive pharmacotherapy in the
immediate PPP (90% of bipolar I females are
at risk for relapse in first 2mos of PP)
Depakote / Depakene
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Acts at Na channels, at steps in GABA metabolism,
and on the activity of histone deacetylase
-Kote “coats”
Available in IR, ER
Rapid absorption, reaching peak plasma in 2-4h
Bioavailability unaffected by food, though
absorption may be delayed
Rapid distribution and high (90%) plasma protein
binding
T ½ 9-16h
Depakote / Depakene
Uses / Indications
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Bipolar I d/o
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Acute, maintenance, prophylaxis
 SCZ (off-label)
 IED, kleptomania, other behavioral
dyscontrol syndromes
 Physical aggression, restlessness, agitation
 Also off-label for anxiety d/os such as panic,
PTSD, OCD, BN
 MDD
 EtOH, sedative/hypnotic w/d; cocaine detox
 Borderline PD
Depakote / Depakene – PreTreatment / Labs
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CBC w/ diff., LFTs, check levels and
associated labs q3-6mos
Level: 50-100mcg/mL, but be clinicallydriven
Check for bleeding and bruisability
Depakote / Depakene
Preparations
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Depakene: 250mg caps, #100, $207.01
Depakote: 125mg tab, #180, $110.29;
also available in 250mg and 500mg
tabs, and in ER (which does not affect
timing of lab, but affects timing of
dose)
Depakote / Depakene
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Common SEs:
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Alopecia
GI upset
Sedation
Tremor
Weight gain
Rare SEs:
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Acute pancreatitis
Anemia
Ataxia
Bone marrow suppression
Breast enlargement
Dermatitis
Diplopia, dizziness
Edema
Hepatotoxicity
Irregular menses
Leukopenia
Nystagmus
Parotid gland swelling
Stevens-Johnson syndrome
Thrombocytopenia
Depakote / Depakene
Drug Interactions
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2D6 metabolism
Can increase phenobarb, phenytoin, TCAs,
Retrovir, diazepam
Can decrease lamotrigine, carbamazepine
DVP levels can be increased by ASA, highly
protein-bound drugs
DVP levels can be decreased by
carbamazepine, Rifampin, mefloquine
Depakote / Depakene &
Pregnancy / Nursing
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Do not give to pregnant or nursing pts.
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Associated w/ neural tube defects (e.g.,
spina bifida) in 1-2% of all women during
1st trimester
This risk can be reduced if FA (1-4mg/d) is
taken 90d prior to and throughout
gestation
Antipsychotics
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Rapidly expanding!
Atypicals over conventionals, w/ birth of
clozapine
Newer agents have less EPS, TD, cognitive
impairment, and improvement in negative Sx
Nonconventionals are used for other d/os, not
just psychosis
Atypicals:
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Clozaril, Zyprexa, Seroquel, Risperdal, Geodon,
Abilify
Pharmacology – Atypicals
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All have affinity for DA, but vary in potency
5-HT2a > D2 (different SE profile compared to conventionals)
 Attracted to alpha1/2-adrenergic, muscarinic acetylcholine,
H1 as well
Antagonize DA, 5-HT2a
Rapidly absorbed from GI tract w/ extensive FPM
Highly lipophilic – cross BBB
Primarily metabolized by 2D6, 1A2, 3A4 & 2C19
Average T ½ is 20-24h, except for aripiprazole: 95h
Parenteral form: olanzapine, aripiprazole, ziprasidone as IR and
risperidone as decanoate
Indications for Use –
Antipsychotics
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SCZ, Schizoaffective d/o
Acute manic/mixed episodes – bipolar
MDD w/ psychosis
Delusional d/o
Delirium
Dementia
MR
Developmental d/o (e.g., autism)
Huntington’s
Tourette’s
Substance-induced psychotic d/o (stimulants, PCP,
levodopa, steroids)
Preparations / Dosage –
Antipsychotic
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Risperdal
(mg tabs 0.25, 0.5, 1, 2, 3, 4; soln; M-tabs;
RisConsta):
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2-8mg/d
Geodon (mg caps 20, 40, 60, 80; soln): 80-200mg/d
Clozaril (mg tabs 25, 100): 25-600mg/d
Zyprexa (mg tabs 2.5, 5, 7.5, 10, 15, 20; Zydis; soln): 530mg/d
Seroquel (mg tabs 25, 50, 100, 200, 300, 400): 150800mg/d
Abilify (mg tabs 5, 10, 15, 20, 30; soln): 10-30mg/d
Drug Selection & Initiation of
Treatment – Antipsychotics
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Tests: height, weight, waist circum., BMI;
interview about personal and family h/o
diabetes or lipid dysregulation
Obtain FBS, lipid panel
Is this psychotic episode consistent w/ SCZ?
Have affective syndromes such as mania and depression with psychotic features
been ruled out?
Is this the patient’s first episode?
Previous AP exposure – efficacy and tolerability profiles?
H/O EPS or TD?
H/O NMS?
What Sx are current predominant: + or -?
H/O noncompliance/depot exposure?
If AP trials have failed, were the doses/duration of tx adequate?
Etc.
Side Effect Profile of SGAs
aripiprazole
clozapine
risperidone
olanzapine
quetiapine
ziprasidone
EPS
+
0
++
+
0
+
TD
+
0
++
+
0
+
NMS
?
+
+
+
?
+
Prolactin
0-+
0
+++
0-+
0
0-+
QTc
0
0
+
0
+
++
Hypotension
+
+++
+
++
++
+
Anticholinergic
0
+++
0
++
+
0
Hepatic
+
+++
+
++
+
+
Agranulocytosis
0
++
0
0
0
0
Sedation
+
+++
+
++
+++
+
Seizure
0-+
+++
0
0-+
0-+
0-+
Side Effect Profile of SGAs
Weight Gain
Tiers
Clozaril
Zyprexa
Seroquel
Geodon
Risperdal
Abilify
Monitor
for
Metabolic
Syndrome!
Case Study
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32yo MWF who’s escorted to the clinic by her BF. Pt.’s been c/o,
and partner corroborates, that she’s been feeling quite sad
lately, cannot get out of bed, has been w/ regular crying spells,
is sleepless, has felt hopeless and believes she’d be better off
dead. She adds that she has no health insurance and is 13w
pregnant. You observe that she is nearly morbidly obese. She
is not sure, but she’s been so sad that she thinks she’s been
hearing her name being called and hears occasional,
indecipherable whispers. She’s w/ severe GI discomfort,
associated w/ her pregnancy, as well as sedation, probably
within the context of both pregnancy and mood. The BF’s
asking for a medication to help the pt., and the pt. is very
willing to try a product.
What thoughts come to mind as far as a product for this pt.?
Discussion
Divide into small groups to
process this case.
Questions, Comments,
Concerns?
Thank you for your time, interest and
participation.
Daniel DiSalvo
614-519-4880