Psychopharmacology

What you need to know to survive the

LMCC and Internship
Khalid Bazaid, MD, FRCPC
Assistant Professor
Child & Adolescent Psychiatrist
Childrens Hospital of Eastern Ontario

April 2015
Based on the 2014 lecture by Dr. Lisa McMurray

Objectives
To review:
indications for
mechanism of action
side effects (remember not everyone gets
these)
monitoring parameters

for the major classes of psychotropic

medications
To practice applying this knowledge

MCC Objectives for the Qualifying Examination

(with my updates for DSM-5)

Initiate pharmacologic treatment of

ADHD
Agitation in Delirium
Dementia/Major Neurocognitive Disorder
Major Depressive Disorder
Manic Episode
Anxiety Disorders
Obsessive-Compulsive Disorder (formerly an anxiety
disorder)
Substance withdrawal
Substance Use disorders (e.g. nicotine replacement)

MCC Objectives for the Qualifying Examination

Judicious use of pharmacotherapy in

personality disorders
Attention to risk of abuse, overdose

Recognize Medication-Induced Movement

disorders
e.g. dystonia due to antipsychotics

Which of the following is NOT a

common side effect of SSRIs?

a.
b.
c.
d.
e.

Nausea
Headache
Rigidity
Anxiety
Sleep disruption

Which of the following receptors does

Mirtazepine/Remeron NOT block?

a.
b.
c.
d.
e.

Histamine
5HT1
5HT2
5HT3
Alpha 2

At which dose level does Venlafaxine/Effexor XR

typically begin to have a noradrenergic effect?

a.
b.
c.
d.

75mg
150mg
225mg
300mg

Which is not an indication for the

use of Benzodiazepines?

a.
b.
c.
d.
e.

Catatonia
Long term hypnotic
Mania
Alcohol withdrawal
Anxiety

How are the novel hypnotics (e.g. Zopiclone,

Zolpidem) different from Benzodiazepines?

a. Do not cause falls

b. Do not lead to tolerance
c. Used as long term hypnotics
d. More selective for the alpha one subtype
of GABA-A receptor

Which of these is the most prominent side

effect of atypical antipsychotics?

a.
b.
c.
d.

Rigidity
Dystonia
Dyskinesia
Akathisia

Which of the following is an example of a

low potency typical antipsychotic?

a.
b.
c.
e.
f.

Haloperidol (Haldol)
Pimozide (Orap)
Olanzapine (Zyprexa)
Clomipramine (Anafranil)
Chlorpromazine (Thorazine)

Which class of cognitive enhancers is indicated

in mild to moderate Alzheimers Disease?
a. Cholinesterase inhibitor
b. NMDA receptor antagonist

Which mood stabilizer can reduce the risk

of suicide in Bipolar Disorder?

a.
b.
c.
d.

Valproic Acid/Epival
Lamotrigine/Lamictal
Lithium
Carbamazepine/Tegretol

What is the most common excitatory

neurotransmitter in the brain?

a.
b.
c.
d.
e.

Serotonin
Glutamate
Norepinephrine
GABA
Dopamine

Antidepressants: Indications

MDD
Premenstrual Dysphoric Disorder
GAD
Social phobia
PTSD
OCD
Panic Disorder
Pain disorders (DSM-5 Somatic Symptom Disorder with
predominant pain)
(insomnia)

SSRI: Mechanism of Action

In depression, the serotonin neuron has a relative deficiency of

serotonin and the autoreceptors and postsynaptic receptors are
increased in number & sensitivity
When the reuptake pump is blocked, the level of serotonin increases in
the somatodendritic area, sending a message to the nucleus to decrease
production of autoreceptors
This leads to disinhibition of the serotonin neuron, releasing more
serotonin at the axon terminal
Increased levels of serotonin in the synapse leads to changes in the
post synaptic neuron gene products such as down regulation
(decreased number and sensitivity) of postsynaptic receptors and
increased production of BDNF

SSRI: Side Effect Profile

Headache
Anxiety and Agitation (mood and psychomotor circuits)
Nausea (weight/appetite circuit and GI receptors)
Diarrhea (peripheral GI 5HT3 & 5HT4 receptors)
Sexual dysfunction (spinal projections) and Sleep disruption or
Somnolence (sleep circuit)

SSRI: Rare but Dangerous Side Effects

UGI bleeding (platelet dysfunction), esp. in combo with
NSAIDs or other blood-thinning agents
SIADH
Osteoporosis and fractures in the elderly
Serotonin syndrome

SSRI discontinuation syndrome

Incidence: 20% after 6 weeks of use

Flu-like symptoms
Insomnia
Nausea
Imbalance
Sensory disturbances
Hyperarousal (agitation/anxiety)

Prevent with slow taper

Norepinephrine & Dopamine Reuptake

Inhibitor:Mechanism of Action
(Bupropion/Wellbutrin)
Blockade of norepinephrine and dopamine reuptake
pumps, leads to similar cascade as with SSRIs

NDRI: Side Effect Profile

Seizures (not with extended release formulations & following correct

dosing; contraindicated with Bulimia or electrolyte disturbances)
Headache, Hypertension (SNS activation)
Agitation (mood and psychomotor circuits) and Anticholinergic*
(relative decrease in parasympathetic tone)
Rash
Emesis, decreased appetite and weight loss (SNS activation)
Sleep disruption, Shaking and Sweating (sleep and psychomotor
circuits and SNS activation)
* (red as a beet, dry as a bone, blind as a bat, mad as a hatter, hot as a
hare; bowel & bladder lose their tone & the heart goes off alone)

Serotonin & Noradrenergic reuptake

Inhibitors: Mechanism of Action
(Venlafaxine/Effexor, Desvenlafaxine/Pristiq, Duloxetine/Cymbalta)

Blockade of serotonin reuptake at lower dose range

Blockade of serotonin and norepinephrine reuptake in mid
dose range
Blockade of serotonin, norepinephrine and dopamine
reuptake at very high dosages

SNRI: Side Effect Profile

As with SSRIs in lower to mid dose range
As with NDRI in mid to high dose range

SNRI: Rare but Dangerous Side Effects

As with SSRIs

NaSSA: Mechanism of Action

Blocks Alpha 2 autoreceptors on norepinephrine neurons &

heteroreceptors on Serotonin neurons, causing more NE & 5HT to be
released
NE neurons from the locus coeruleus innervate midbrain raphe 5HT
neurons. Therefore, increased NE causes a further increase in 5HT
release
Blocks 5HT2 receptors, having an anxiolytic effect & blocking sleep
& sexual side effects
Blocks 5HT3, blocking GI side effects from peripheral receptors &
from brainstem chemoreceptor trigger zone
Blocks H1 histamine receptors, causing sedation & weight gain

NaSSA: Side Effect Profile

Weight gain (H1 blockade)

Anticholinergic (relative decrease in parasympathetic tone)
very weak effect
Drowsiness (H1 blockade)
Equilibrium

NaSSA: Rare but Dangerous Side Effects

Neutropenia

Serotonin syndrome

Hepatotoxicity

SIADH

QT prolongation (Health Canada, 28 March 2014, post-marketing)

SARI: Mechanism of Action

Serotonin 2A antagonists/reuptake inhibitors (Trazodone/Desyrel)

Primarily blocks 5HT2A, reducing sexual dysfunction & sleep

disruption & increasing effect of 5HT1A stimulation (5HT2A &
5HT1A oppose one anothers actions in several ways)

Weak 5HT reuptake inhibitor, increasing 5HT stimulation of 5HT1A

(therapeutic effects)

H1 blockade causes sedation

Alpha One blockade leads to orthostatic hypotension

SARI: Side Effect Profile

Orthostatic hypotension
Sedation

SARI: Rare but Dangerous Side Effects

Serotonin syndrome
Priapism

TCA: Mechanism of Action

Tricyclic antidepressants:
3 amines (eg amitriptyline, imipramine, doxepine)
2 amines (eg nortriptyline, desipramine)

Originally developed as treatment for schizophrenia (similar 3-ringed

chemical structure); found ineffective for psychosis but helpful for
depression.
Therapeutic effects and side effects from blocking Serotonin,
Norepinephrine & Dopamine Reuptake
Some also have 5HT2 blocking ability (blocks sex & sleep side
effects)
Side effects from blocking H1 histamine receptors, muscarinic
receptors, alpha one adrenergic receptors
Overdose can lead to seizures and arrhythmias due to blockade of ion
channels

TCA: Side Effect Profile

Antihistamine weight gain & sedation
Anticholinergic (remember toxidrome from NDRI)
Anti-alpha adrenergic dizziness, orthostatic
hypotension

TCA: Rare but Dangerous Side Effects

Torsades de Pointes (due to blockade of fast sodium channels)

EKG rule out bradycardia and prolonged QTc

Lytes rule out electrolyte imbalance

Make sure not on type 1 or 3 antiarrythmic drugs

SIADH
Serotonin Syndrome

MAOI: Mechanism of Action

Monoamine oxidase inhibitors:
the classics (phenylzine/nardil, tranylcypromine/parnate)
Reversible inhibitor: (moclobemide/mannerix)

HISTORY:
The first clinically effective antidepressants
Originally, an anti-tuberculosis drug, found to decrease
comorbid depression

Irreversibly bind MAO (2 wks) & destroy its function, therefore

decrease monoamine breakdown, increasing 5HT, NE & DA

MAOI: Side Effect Profile

Side effects related to increase in serotonin norepinephrine
& dopamine (see SSRIs & NDRIs)
Orthostatic hypotension

MAOI: Rare but Dangerous Side Effects

Hyperthermia i.e.Serotonin Syndrome
even more susceptible than with other serotonergic antidepressants;
need to avoid anything that has serotonergic effects such as
antidepressants and opioids)
When you see an MAOI, get a pharmacy consult, the patient should
consult their pharmacist about any over - the counter medications
Hypertensive crisis
Consult the dietician Re: MAOI diet
Patients need to avoid all foods with tyramine (aged foods such as
aged cheeses and wines or tap beer) and any medications with
noradrenergic effects (cold remedies, stimulants etc)
Hepatotoxicity
Blood dyscrasias

Serotonin Syndrome: HARMED

Hyperthermia
Agitation/Autonomic instability
Rigidity/Reflexes increased
MyoClonus/tremors
Encephalopathy
Diaphoresis

Hypertensive Crisis
Norepinephrine (NE) is the amine most closely linked with
control of blood pressure
MAO normally inactivates norepinephrine (NE)
Tyramine, an amine present in aged foods, causes release of
norepinephrine (NE)
In the presence of MAOI, this increased NE cannot be
broken down, resulting in a hypertensive crisis

Starting Antidepressants: General Guidelines

Start with a reuptake inhibitor or mirtazapine (not a TCA or MAOI)

Start at lowest possible dose (half of this with anxiety and in the
elderly and medically frail)
Increase by this increment about every five half lives (or about once a
week) until one of the following endpoints:
Intolerable side effects
Full response
Maximum dose
Continue to monitor for therapeutic effects, side effects and safety
How you use them is more important than which one you choose

Choice of Initial Antidepressant in Adults

There is comparable efficacy between and within classes of medication,
therefore, initial selection is based on:
Symptom profile
Side effect profile in relation to the individual patient
Patient preference
Cost
History of previous response of the patient or family members
Comorbid psychiatric or medical illnesses
Potential drug-drug interaction

The BEST antidepressant is the one that a patient will actually

take acutely and for the long hauland one that you know well

Treatment choices in children

Concerns were raised about the safety of
antidepressants (Paroxetine and Venlafaxine) in
children and youth in 2004
Further metaanalyses and epidemiologic studies now
confirm that antidepressants in children and youth are
safe with close (weekly) monitoring.
Problems with Venlafaxine and Paroxetine may have
been related to poor adherence and discontinuation
symptoms

Choice of Initial Treatment in children/youth

Mild to moderate depression:
Start with psychotherapy or non-medication interventions as
first line
Second line is to add medication; best evidence is for
Fluoxetine; other SSRIs could be considered next
Moderate to severe depression:
First line is to consider medication but depending on
patient/family preference, may also start with psychotherapy or
monitoring
Note that the clinical presentation in children and youth can
change quickly; they may appear severely depressed one week
then by the next week be in a new relationship and everything is
better

Course of Recovery From

Depression
Response

2-3 weeks:

3-4 weeks:

6-8 weeks:

Improved
sleep,
appetite,
vegetative
shifts

objective
improvement
energy
suicidal
ideation may

subjective
improvement

Goals of antidepressant therapy

REMISSION of symptoms and maintaining that level of
improvement in order to prevent relapse and recurrence
Rate of relapse is significantly less for patients who achieve full
remission of symptoms
Patients who have been ill longer tend to be more treatment
resistant; there is also evidence of hippocampal atrophy with
prolonged illness, leading to the concept of disease progression
and the hope that this can be modified by treating all mood
episodes to the point of remission

Stimulants: Indications

ADHD
Narcolepsy
(treatment resistant depression)
(apathy in elderly)

Stimulants: Mechanism of action

(1)
Increases dopamine and NE actions by blocking
their reuptake and facilitating their release
Improves the efficiency of information processing
in the frontal subcortical circuits, relieving
frontally mediated symptoms of inattention,
hyperactivity and impulsivity.

Stimulants: Mechanism of action

(2)
Action in DL prefrontal cortex improves attention,
concentration, executive function and wakefulness
Action in cortical and subcortical motor areas may
improve hyperactivity
Action in the orbital frontal cortex may improve
impulsivity
Action in medial prefrontal cortex may improve
depression, fatigue and sleepiness

Stimulants:
Common Side Effects
Headaches and Heart concerns (palpitations,
tachycardia and hypertension)
Insomnia, Irritibility and Increased stimulation
Dizziness
Exacerbation of tics, tremor
Stomach: anorexia, nausea, abdo pain, weight
loss, possibly slowing of normal growth in
children

Stimulants:
Rare Side Effects

Psychosis
Leukopenia
Anemia
Seizures

Stimulants:
Ongoing Monitoring
Blood pressure at baseline and with dose
increases
In children, ongoing monitoring of height
and weight

ECT: Indications

Common
MDE
Mania
Mixed state
Catatonia
Schizophenia with
prominent affective
symptoms
Schizoaffective disorder

Uncommon
Delirium
NMS
Parkinsons Disease

ECT: Indications (cont.)

Indications for First Line Use:

Need for rapid improvement (suicide, malnutrition, catatonia,
severe psychosis or agitation)
When other treatments are more risky (elderly)
Patient preference
Psychotic depression (gold standard 80-90% response)

ECT: Mechanism of Action

Neurotransmitter theory
Enhances DA, 5HT & NE neurotransmissiom
Neuroendocrine theory
Increased release of neurohormones including prolactin, TSH,
ACTH & endorphins
Neurogenesis theory
Increased neuroplasticity
Release of BDNF
Anticonvulsant theory
Increase in seizure threshold during course of ECT; CSF of animals
receiving ECS is anticonvulsant when given IV to recipient animals

ECT: Side Effect Profile

Common
Headache
Muscle ache
Nausea
Memory impairment
Delirium
Amnesia (anterograde & retrograde)
Few longterm deficits

ECT: Side Effect Profile

Rare:
Mortality 1/10 000 per course of ECT (6-12 treatments)
Cardiovascular
initial vagal stimulation
Bradycardia / asystole / ectopic activity
sympathetic stimulation during tonic clonic phase of seizure
Increased HR & increased BP
Sometimes parasympathetic rebound with second phase of bradycardia
Prolonged apnea
Pseudocholinesterase deficiency
Prolonged seizure
Treat with IV benzo

ECT: Relative Contraindications

(weigh pros & cons)

Space occupying cerebral lesions

Increased ICP
Recent MI
Recent CVA
Aneurysm
Retinal detachment
Pheochomocytoma

Mood Stabilizers: Indications

A heterogeneous group of medications
Used to treat diverse conditions, including

Bipolar Disorder
Migraine or cluster headaches
Chronic aggression or impulsivity
Seizure disorders
Pain conditions (TGN, migraine)
Lithium reduces suicidal risk in Bipolars and
augments antidepressants in MDD

What is a mood stabilizer?

These medications can be thought of as
treating one or more of the following
phases:
Acute bipolar depression
Acute bipolar mania
Maintenance

Choice of Treatment in BD
(Bipolar Disorder)

First line for acute mania:

First line for acute bipolar depression:

Lithium,
Valproic Acid
atypical antipsychotics (olanzapine, risperidone, quetiapine, ziprasidone, aripiprazole
lurasidone)
taper and discontinue antidepressants

Lithium
lamotrigine
quetiapine
Lurasidone (July 2013)
do not use antidepressant monotherapy

First line for maintenance therapy:

Lithium
Valproic acid
Lamotrigine
Atypical antipsychotics quetiapine, risperidone LAI and Olanzapine

Goals of treatment in BPAD

Treat to complete remission
It has been theorized that under-treated discrete
depressive and manic episodes may progress to
mixed and dysphoric episodes, rapid cycling and
treatment resistance
The hope is that recognition and full treatment of
mood episodes may prevent progression to more
difficult mood states

Lithium: Mechanism of Action

MOA is unclear
Thought to be involved in:
Modulating second messenger systems (ie G protein-coupled receptors,
through which most hormones and neurotransmitters mediate their
effects) which leads to:

Increasing GABA activity

Reducing glutamate activity
Stabilizing catecholamine receptors
Blocking the effects of some hormones (eg. ADH and TSH) on end organs

Works in acute bipolar mania, depression and maintenance

phases
Decreases suicide, deliberate self harm and death from all
causes in patients with mood disorders

Lithium: Side Effect Profile

Lethargy
Insipidis (diabetes insipidis)
Tremor/Teratogen (increased risk Ebsteins anomaly (0.1%
vs 0.005%) in first trimester)
Hypothyroid
Increased weight
Vomiting, nausea, GI
Miscellaneous: EKG changes (T wave flattening or
inversion, sick sinus syndrome), acne, hair loss,
hypercalcemia

Lithium: Toxicity
Narrow therapeutic index!!!
Anything that affects water and electrolyte imbalance can
contribute to Lithium toxicity (CAUTION with flu, dehydation,
meds)
Levels are increased by NSAIDS, diuretics, ACE inhibitors,
tetracycline, anticonvulsants
Levels are decreased by caffeine and salt

Lithium: Toxicity

There is delayed distribution and elimination in the brain relative to serum

therefore early signs are peripheral and later signs are central unless high
level is chronic, in which case peripheral and central symptoms will occur
simultaneously

Peripheral symptoms: nausea, vomitting, cramping, diarrhea

Central symptoms: tremulousness, hyperreflexia, ataxia, mental status

changes, coma, seizures

Can lead to irreversible neurotoxicity including cognitive impairment,

peripheral neuropathy and cerebellar dysfunction
Hospitalize for levels >2.0 or based on clinical symptoms

Lithium: Initial Work-up

Lytes, BUN, Cr (renally excreted)

Calcium
TSH (5% hypothyroidism)
EKG with rhythm strip (contraindicated with sick sinus
syndrome)
B-hcg
Metabolic baseline including baseline weight and BMI;
consider checking for diabetes/pre-diabetes and
hypercholesterolemia in those who are overweight (BMI
25-30) or obese (BMI>30)

Lithium: Ongoing Monitoring

Lithium level every five days until steady state is reached
then at 3-6 months, with signs of dehydration or toxicity
or with change in medications or salt intake
Repeat kidney functions, TSH and EKG every 6-12
months, Calcium
Monitor weight and BMI during treatment and re-check
for diabetes/pre-diabetes and hypercholesterolemia if >5%
weight gain

Lithium : Rx

Adult
Acute mania about 1800mg/day (bid-tid dosing)
Acute mania level 1.0 1.5
Maintenance usually about 900-1200 mg/d; give at hs for renal
protection
Maintenance level 0.6-1.0

Geriatric
Dosing 150 600 mg/d (bid dosing)
Level 0.4 0.8
For maintenance, give at hs for renal protection

Valproic Acid: treatment effects

Treats bipolar mania
First line for bipolar depression in
combination with lithium or
SSRI/bupropion
Second line monotherapy for bipolar
depression
Indicated for maintenance phase

Valproic Acid: Acute Side Effect Profile

STUN

Sedation (31%)
Tremor (10-29%)
Unsteadiness (dizziness)
Nausea (20%) /GI

Valproic Acid:
longer term side effects

On the surface:
Acne , hair loss

Under the surface:

weight gain, edema

Systemic:
thrombocytopenia
liver dysfunction +/- elevated ammonia levels
reproductive changes incl menstrual irregularities (up to 45%),
PCOS, teratogenicity (5-15%)

Avoid use in women of childbearing age

Valproic Acid: Initial Work-up & Ongoing

Monitoring
Initial
CBC + LFTs
Epival level every 3-4 days until steady state reached
Metabolic baseline including baseline weight and BMI; consider
checking for diabetes/pre-diabetes and hypercholesterolemia in those
who are overweight (BMI 25-30) or obese (BMI>30)
Ongoing
Repeat tests monthly x 6 months then Q6mos or if symptoms develop
Monitor weight and BMI during treatment and re-check for
diabetes/pre-diabetes and hypercholesterolemia if >5% weight gain

Valproic Acid: Rx
Reference only
Starting dose:
250 qhs (geriatrics)
250 bid-tid (adults)
15-30 mg/kg/day in bid dosing for acute mania in
adults
Levels: 350 800 umol/l

Lamotrigine: Treatment effects

Treats bipolar depression (modest effect)
First line maintenance treatment

Lamotrigine: Side Effect Profile

Rash 0.3% adults / 1% in children. With slow titration

risk was
reduced to 0.01% comparable to other
anticonvulsants. Can develop into Stevens-Johnson
Syndrome (increased risk with Valproate)
Activation (3-8%), Ataxia
Spaced out (cognitive slowing), Sedation, Sleep
disturbances
H/A, Hypersensitivity reactions

Lamotrigene: Rx
Start with 25 mg/d
Double the dose every 2 weeks
Usual maintenance dose is 200 mg in 2 divided doses
(reached by week six)

Atypical Antipsychotics:
Olanzapine and Quetiapine
All atypical antipsychotics are indicated to
treat bipolar mania
Quetiapine is first line monotherapy for
bipolar depression; so is Lurasidone
Olanzapine, Quetiapine, Aripiprazole, and
Risperidone LAI are first line maintenance
treatments

Anxiolytics: Indications
eg. Benzodiazepines (lorazapam)
Short term hypnotic (But decrease REM,
Stages 3 & 4 sleep)
Anxiolytic
Acute mania
Alcohol withdrawal
Catatonia

Anxiolytics:
Mechanism of action
Affinity of GABA-A receptor for GABA
(a positive allosteric modulator)
GABA-A receptors with alpha one subunits
most important for sleep
GABA-A receptors with alpha two or three
subunits are most important for anxiety (but
all available at this time are non-selective
and therefore also sedating)

Anxiolytics: Side effects

Memory decline
Addiction(dependency &withdrawal)
Ataxia/Falls
Drowsiness/dizziness/disinhibition

Anxiolytics:Contraindications
With COPD or sleep apnea
Avoid in the elderly; with long term use
taper by 25 % q-monthly after treating the
underlying anxiety disorder with an SSRI as
indicated

Novel hypnotics
(e.g. Zopiclone/Imovane)
Indications: short term hypnotic agents
Mechanism of action:
Some are selective for the alpha 1 subtype of
GABA-A receptor (sedating effects) and not
the alpha 2 (anxiolytic, muscle relaxant and
alcohol potentiating) or alpha 5 (linked to
memory)
Side Effects:
Similar to benzodiazepines

Antipsychotics: Indications

Psychotic illness
Delirium
Mood disorder with psychosis
Severe agitation or aggression

Typical Antipsychotics:
Mechanism of action
D2 blockade
Produces antipsychotic effect in the mesolimbic pathway
Causes worsening of negative and cognitive symptoms in the
mesocortical pathway, where a dopamine deficit is thought to
cause these symptoms
Causes
EPS
(dystonia,
dyskinesia,
akathesia,
parkinsonism)in the nigrostriatal pathway
Causes increased prolactin in the tuberoinfundibular pathway
(gynecomastia, galactorrhea and sexual dysfunction)

Typical Antipsychotics: Side effects

High potency
EPS
Haldol
Loxapine
Perphenazine
Chlorpromazine

QT prolongation with pimozide, CPZ

Low potency
Antihistamine
AntiAlphaAdrenergic
Anticholinergic

Atypical Antipsychotics:
Indications
Same as typicals
Agitation/aggression in dementia NOT
responding
to
adequate
nonpharmacological interventions
Bipolar Disorder
Augmentation in MDD

Features of
Atypical Antipsychotics
Block both D2 and 5HT2A
Cause less EPS than typical antipsychotics
Improve positive symptoms as well as
typical antipsychotics

Atypical Antipsychotics:
Mechanism of action
5HT2A, when stimulated, normally stops
dopamine release; when this is blocked, it
causes dopamine release
The different dopamine pathways have
varying amounts of D2 and 5HT2A
receptors

Atypical Antipsychotics:
Mechanism of action cont
In pathways with more 5HT2A receptors to block, SDAs lead
to dopamine release(i.e. the mesocortical pathway, reducing
negative and cognitive symptoms)
In pathways with more D2 receptors to block, SDAs cause
dopamine blockade (i.e.the mesolimbic pathway, with
antipsychotic effects)
In pathways where receptor numbers are relatively equal,
there is no change in the amount of dopamine (i.e. in the
tuberoinfundibular pathway, preventing increased prolactin)
In the nigrostriatal pathway, there are just enough 5HT2
receptors to bring the D2 blockade down below 80%, the
critical number to prevent EPS.

Atypical Antipsychotics:
Side Effects
Less effects on:
EPS, negative symptoms and cognition
A

different set of concerns:

Weight gain (get baseline weight)
Akathisia
Sedation
Hyperglycemia/Hyperlipidemia(baseline fasting
lipids and glucose)
Dizziness (orthostatic hypotension; check BP)
In dementia increase mortality and risk of
cardiovascular events
Risk of agranulocytosis and seizure (dose
dependent) with Clozapine

Atypical Antipsychotics:
Monitoring
Baseline personal and family history of vascular
risk factors
Obtain baseline weight and calculate BMI; BMI
monthly for three months and then 3x per year
Baseline waist circumference at the umbilicus, BP,
fasting glucose and lipid profile; repeat at 3
months and then annually

Neuroleptic Malignant
Syndrome
Antipsychotic use (+) fever (+) rigidity (+) 2
others of:

Fever
Encephalopathy (neuro s/s or change in mental status)
Vital signs unstable
Elevated CPK/ WBC
Rigidity

Cognitive Enhancers
Cholinergic Agents
Donepezil/Aricept
- Rivastigmine/Exelon
- Galantamine/Reminyl
-

NMDA Antagonist
- Memantine/Ebixa

Cognitive Enhancers:
Indications
AChEI: early to moderate Alzheimers
severe Alzheimers
Some evidence for:
Lewy Body Dementia
Galantamine in Mixed Dementia
Donepezil in Vascular Dementia

Memantine: Moderate to severe AD

Cholinesterase Inhibitors: Effects

Abilities
Behaviour
Cognition
Decrease in caregiver time
Entry into Nursing Home

Cholinesterase Inhibitors
Mechanism of Action
Inhibits centrally-acting
acetylcholinesterase, making more
acetylcholine available
This compensates in part for degenerating
cholinergic neurons that regulate memory

AChEI: Common Side Effects

Muscle Cramps
Insomnia/
incontinence
Nausea
Diarrhea

Diarrhea
Urination
Miosis/muscle weakness
Bronchorrhea
Bradycardia
Emesis
Lacrimation
Salivation/sweating

Cholinesterase Inhibitors:
use caution or consultation with:
History of seizures
History of bradycardia, sinus node
dysfunction or other serious conduction
abnormality
History of PUD or other risk factors for GI
bleeding
History of COPD or asthma

Memantine: Effects
Socialization
Household tasks
ADL
Persecutory ideation
Excessive activity (agitation)

Memantine:
Mechanism of action
A dysfunction of glutamatergic neurotransmission,
manifested as neuronal excitotoxicity, is hypothesized to be
involved in the etiology of Alzheimers disease
Memantine binds the NMDA receptor with a higher affinity
than Mg2+ (which are normally there), inhibiting a
prolonged influx of Ca2+ (thereby preventing excitotoxicity)
The receptor can still be activated by the relatively high
concentrations of glutamate released following
depolarization of the presynaptic neuron

Memantine: Common Side Effects

Confusion
Headache
Equilibrium (dizziness)
Constipation
Kidney function
(But in large studies had a similar rate of
treatment emergent side effects as placebo)

Cognitive enhancers:
monitoring
Response may be seen 1 month, typically 3
months
Realistic expectation is to maintain

PRACTICE CASES

CDMQ 1
A 25 year old man (who was previously a PhD candidate at McGill but
has been unemployed and not seeking work for the last two years) is
brought in to the emergency by police.
Police were called as he had been breaking into the homes of strangers
saying that he was looking for Amour. They were concerned by his
disorganized speech and brought him into hospital for assessment.
When seen in the emergency, he is not concerned about being in hospital.
He says that he has been possessed by the goddess of love, Amour,
and is looking for others like himself. When introduced to the
assessing psychiatrist, he tells her that he heard her say the number 17
which alerted him to the fact that there is a special connection between
his circumstance and the television show House.

Which of the following is the

most likely diagnosis?
A. Major depressive disorder
B. Schizophrenia
C. Delirium
D. ADHD
E. Dissociative identity disorder

Which of the following medications would be most

appropriate to discuss starting with the patient?

A. Olanzapine/Zyprexa 5 mg at bedtime
B. Haldoperidol/Haldol 10 mg twice daily
C. Chlorpromazine/Thorazine 100 mg at
bedtime
D. Risperidone/Risperdal Consta 50 mg IM
q2wks
E. Quetiapine/Seroquel XR 900 mg at bedtime

Which of the following side effects

would you counsel the patient about?
A. Headaches, agitation, nausea, diarrhea
B. Tremor, increased blood pressure, increased
sweating
C. Insomnia, decreased appetite, elevated blood
pressure, tics
D. Weight gain, akathisia, sedation, increased lipids
and sugars
E. Sedation, increased thirst, tremor, hypothyroidism,
nausea, hair loss

CDMQ 2
A 30 year old woman presents to your family
medicine clinic after several visits to the local
emergency department for episodes of racing heart,
shortness of breath, nausea and a sense that she was
dying. Cardiograms and bloodwork (CBC, TSH)
were normal. As a result of these episodes, she has
become reluctant to leave the house as she is afraid
this will happen when she is driving or when in a
situation where she will not be able to access help.

Which of the following is the

most accurate diagnosis?
A. Hyperthyroidism
B. Generalized anxiety disorder
C. Panic disorder without agoraphobia
D. Panic disorder with agoraphobia
E. Major depressive disorder

In the emergency, this lady received some lorazepam/ativan

which she found quite helpful. She would like a prescription
for this medication. How would you respond to this request?
A. Describe to her that although benzodiazepines can help
reduce anxiety symptoms acutely that they are not in fact first
line treatment. They can best be used as an adjunct to the
first line SSRI while waiting for these to become effective
B. Give her a prescription for ativan 0.5 mg bid for one month
and follow up at that time to reassess
C. Reinforce with her that benzodiazepines are the best way of
dealing with panic attacks and give her a prescription of
ativan 1 mg bid prn to be used as soon as she experiences
symptoms so that she never needs to experience the trauma of
a full blown panic attack again.

You give her a prescription for escitalopram 10 mg daily and

lorazepam 0.5 mg bid for one week at which point you will
follow up with her. Which of the following side effects
should you discuss with her in regards to the lorazepam?
A. This medication can cause drowsiness and
incoordination. Longer term use will lead to dependence.
B. The most common side effects are weight gain and
sedation
C. The most common side effects are drowsiness and
orthostatic hypotension
D. The most common side effects are restlessness, nausea,
diarrhea and sexual dysfunction
E. This medication can rarely cause a serious rash and must
be adjusted upwards slowly

CDMQ 3
A forty five year old woman with a history of multiple previous
psychiatric hospitalizations is brought in to hospital by police
They were called by her mother who says she has been calling at all hours
of the day and night, very upset and talking really quickly. She has been
borrowing large sums of money which her mother later found out she used
to gamble, which is out of character for her. Tonight she showed up at her
mothers home and was yelling in the street that her father was a menace
to society and she would save everyone by killing him.
In the emergency room, she is irritible, crying and cannot sit still. She is
speaking so quickly that it is difficult to follow what she is saying. She
describes her mood as depressed. She admits she has not been eating
well in a few weeks and feels so worthless that she has been thinking
about killing herself.

Which of the following is the most accurate

description of her current episode?
A. Major depressive episode
B. Bipolar affective disorder, current episode
depressed
C. Bipolar affective disorder, current episode
manic
D. Bipolar affective disorder, current episode
mixed
E. Borderline personality disorder

You decide to start a mood stabilizer; she tells you that she
has had a bad reaction with one of these medications in the
past where she had to pee a lot and her sodium level was
really high. Which of the following most likely caused this?

A. Lamotrigine/Lamictal
B. Valproic acid/Epival
C. Quetiapine/Seroquel
D. Risperidone/Risperdal
E. Lithium

You decide to start Quetiapine as well as standard admission

prn medication, given her significant agitation and recent
threats of violence. You are called by nursing staff in the
middle of the night to inform you that the patient is acutely
distressed, with her head arched back and her tongue
protruding. What is the best treatment for this condition?

A. Haloperidol/Haldol 10 mg IM STAT
B. Lorazepam/Ativan 2 mg IM STAT
C. Propranolol 20 mg PO tid
D. Benztropine/Cogentin 2 mg PO bid
E. Benztropine/Cogentin 2 mg IM STAT

CDMQ 4
A 70 y.o. man reluctantly attends your family medicine clinic
with his daughter. She is concerned as he has not been getting
out for the last few months and has lost a lot of weight, about 20
lbs. She continues to invite him to spend time with her and her
family but he has recently been declining, preferring to stay
home and do nothing. He seems tired and sad all of the time.
When you see him, you note that he moves and speaks more
slowly than he did in the past .
When you ask him if he feels that he may be ill, he responds
that he knows that he is being punished for having shoplifted
once when he was a teenager and that he deserves to feel this
way.

Which of the following would be the

best treatment for this condition?
A. Start Citalopram/Celexa 20 mg daily
B. Start Seroquel XR/Quetiapine 100 mg qhs
C. Start both A&B simultaneously
D. ECT/electroconvulsive therapy
E. Start Donepezil/Aricept 5 mg qhs

You continue to follow up with this patient after he is in

complete remission from his depression. Which of the
following conditions will he be at increased risk for in follow
up given his late presentation with depression?

A. Delirium
B. Schizophrenia
C. Dementia
D. Panic disorder
E. Borderline personality disorder

Over the next few years, he gradually begins to complain of

memory deficits, shows evidence of word finding problems
and now requires assistance with grocery shopping and
paying his bills. His MMSE score has dropped from 30 to 23
during this time period. Which of the following treatments
would be most appropriate?

A. Start Citalopram/Celexa 20 mg daily

B. Start Seroquel XR/Quetiapine 100 mg qhs
C. Start both A&B simultaneously
D. ECT/electroconvulsive therapy
E. Start Donepezil/Aricept 5 mg qhs

THANK YOU!
GOOD LUCK