Psychopharmacolo gy What you should know to survive the LMCC and Internship Dr. Kate Huntington [email protected] March 2012
Jan 23, 2016
PsychopharmacologyWhat you should know to survive the
LMCC and Internship
Dr. Kate Huntington
March 2012
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
Which of the following is not a common side effect of SSRI’s?
• a. Nausea
• b. Headache
• c. Rigidity
• d. Anxiety
• e. Sleep disruption
Which of the following receptors does Mirtazepine/Remeron not block?
• a. Histamine
• b. 5HT1
• c. 5HT2
• d. 5HT3
• e. Alpha 2
At which dose level does Venlafaxine/Effexor XR typically
begin to have a noradrenergic effect?
• a. 75mg
• b. 150mg
• c. 225mg
• d. 300mg
Which is not an indication for the use of Benzodiazepines?
• a. Catatonia
• b. Long term hypnotic
• c. Mania
• d. Alcohol withdrawal
• e. Anxiety
How are the novel hypnotics 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. Rigidity
• b. Dystonia
• c. Dyskinesia
• d. Akathisia
Which of the following is an example of a low potency typical
antipsychotic?
• a. Haloperidol/Haldol
• b. Pimozide/Orap
• c. Olanzapine/Zyprexa
• e. Clomipramine/Anafranil
• f. Chlorpromazine/Thorazine
Which class of cognitive enhancers is indicated in mild to moderate
Alzheimer’s Disease?
• a. Cholinesterase inhibitor
• b. NMDA receptor antagonist
Which mood stabilizer can reduce the risk of suicide in Bipolar
Disorder?
• a. Valproic Acid/Epival
• b. Lamotrigene/Lamictal
• c. Lithium
• d. Carbamazepine/Tegretol
What is the most common excitatory neurotransmitter in the brain?
• a. Serotonin
• b. Glutamate
• c. Norepinephrine
• d. GABA
• e. Dopamine
SSRI’s: Indications
• MDD• Premenstrual Dysphoric Disorder• GAD• Social phobia• PTSD• OCD• Panic Disorder
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 NSAID’s or other blood-thinning agents
• SIADH
• Osteoporosis and fractures in the elderly
• Serotonin syndrome
• SSRI discontinuation syndrome (slow taper)• Flu-like symptoms• Insomnia• Nausea• Imbalance• Sensory disturbances• Hyperarousal (agitation/anxiety)
Norepinephrine & Dopamine Reuptake Inhibitor:Mechanism of Action
(Bupropion/Wellbutrin)
• Blockade of norepinephrine and dopamine reuptake pumps, leads to similar cascade as with SSRI’s
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)
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 SSRI’s in lower to mid dose range
• As with NDRI in mid to high dose range
SNRI: Rare but Dangerous Side Effects
• As with SSRI’s
NaSSA: Mechanism of Action
• Blocks Alpha 2 autoreceptors on norepinephrine neurons & heteroreceptors on Serotonin neurons, causing more NE & 5HT to be released (puts the brakes on the brakes)
• 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: constipation, urinary retention, dry mouth, blurred vision, drowsiness, sinus tachycardia, confusion/delirium, fever (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)
• Drowsiness (H1 blockade)
• Equilibrium
NaSSA: Rare but Dangerous Side Effects
• Neutropenia
• Serotonin syndrome
• Hepatotoxicity
• SIADH
SARI: Mechanism of ActionSerotonin 2A antagonists/reuptake inhibitors (Trazodone/Desyrel)
• Primarily blocks 5HT2A, reducing sexual dysfunction & sleep disruption & increasing effect of 5HT1A stimulation (5HT2A & 5HT1A oppose one another’s 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
TCA: Mechanism of ActionTricyclic antidepressants:
3° amines (eg amitriptyline, imipramine, doxepine) 2° amines (eg nortriptyline, desipramine)
HISTORY: 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 & sodium channels in the heart & brain
TCA: Side Effect Profile
• Antihistamine – weight gain & sedation
• Anticholinergic – (remember toxidrome from NaSSA and 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 ActionMonoamine 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 SSRI’s & NDRI’s)
• 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• Teratogenicity• Blood dyscrasias
Serotonin Syndrome: HARMED
• Hyperthermia
• Agitation/Autonomic instability
• Rigidity/Reflexes increased
• MyoClonus/tremors
• Encephalopathy
• Diaphoresis
For reference only
Hypertensive Crisis
• Norepinephrine is the amine most closely linked with control of blood pressure
• MAO normally inactivates norepinepherine
• Tyramine, an amine present in aged foods, causes release of norepinepherine
• 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 mirtazepine (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
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 haul
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 SSRI’s 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 Course of Recovery From DepressionDepression
Response
2-3 weeks:
Improved sleep,
appetite, vegetative
shifts
3-4 weeks:
objective improvement
energysuicidal
ideation may
6-8 weeks:
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)
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 supplementary or prefrontal motor cortex 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
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
• Parkinson’s 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 – 95% 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)
• No longterm deficits
ECT: Side Effect Profile
• Rare:• Mortality 2 / 1 000 000• 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
• Bipolar Affective Disorder (BPAD)
• Migraine or cluster headaches
• Chronic aggression or impulsivity
• Lithium reduces suicidal risk in BPAD and augments antidepressants in MDD and OCD
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 BPAD (Bipolar Affective Disorder)
• First line for acute mania: • Lithium, • Valproic Acid • atypical antipsychotics (olanzapine, risperidone, quetiapine, ziprasidone,
aripiprazole) • taper and discontinue antidepressants
• First line for acute bipolar depression: • Lithium• lamotrigine • quetiapine
• 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
• Again, the goal is to treat to complete remission of all mood symptoms
• 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• Tremor/Teratogen (increased risk Ebstein’s anomaly
(0.1% vs 0.005%) in first trimester)• Hypothyroid• Increased weight• Vomitting, nausea, GI• Miscellaneous: EKG changes (T wave flattening or
inversion), acne, hair loss
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, thiazide diuretics, ACEI, 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)
• TSH (5% hypothyroidism)
• EKG with rhythm strip (contraindicated with sick sinus syndrome)
• B-hcg
• Metabolic baseline including baseline weight , BMI, waist circumference , BP, fasting glucose and lipid profile
• Personal and family history of obesity, dyslipidemia, hypertension and cardiovascular disease
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
• BMI monthly for three months and then q4mths
• Waist circumference at the umbilicus, BP, fasting glucose and lipid profile repeat at 3 months and then annually
Lithium : Rx
• Adult
• Dosing 600 – 1500 mg/d (bid dosing)
• Level 0.5 – 1.2
• Geriatric
• Dosing 150 – 600 mg/d (bid dosing)
• Level 0.4 – 0.8
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 ProfileSTUN
• Sedation (31%)
• Tremor (10-29%)
• Unsteadiness (dizziness)
• Nausea (20%) /GI
Valproic Acid:longer term side effect
monitoring• On the surface:
– Acne , hair loss
• Under the surface: – weight gain, edema
• Systemic: – blood dyscrasias (esp plt dysfn) – liver dysfunction +/- elevated ammonia levels– reproductive changes incl menstrual irregularities (up to
45%), PCOS, teratogenicity (5-15%)
Valproic Acid: Initial Work-up & Ongoing Monitoring
Initial• CBC + LFT’s• Epival level every 3-4 days until steady state reached• Metabolic baseline including baseline weight and calculate BMI• Baseline personal and family history of obesity, dyslipidemia,
hypertension and cardiovascular disease• Baseline waist circumference at the umbilicus, BP, fasting glucose and
lipid profile
Ongoing• Repeat tests monthly x 6 months then Q6mos or if symptoms develop• BMI monthly for three months and then q4mths• Waist circumference at the umbilicus, BP, fasting glucose and lipid profile
repeat at 3 months and then annually
Valproic Acid: RxReference only
• Starting dose:
• 250 qhs (geriatrics)
• 250 bid-tid (adults)
• Levels: 350 – 800 umol/l
Lamotrigine: Treatment effects
• Treats bipolar depression
• First line maintenance treatment
Lamotrigene: Side Effect Profile
• Rash – 0.3% adults / 1% in children. With slow titration risk was reduced to 0.01% comparable to other anticonvulsants.
• 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
Atypical Antipsychotics:Olanzapine and Quetiapine
• All atypical antipsychotics are indicated to treat bipolar mania
• Quetiapine is first line monotherapy for bipolar depression
• Both olanzapine and quetiapine are first line maintenance treatments
Anxiolytics: Indicationseg. 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 one 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: Reported to be less tolerance, dependence and
withdrawal on discontinuation than BZD
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 effectsTypical Antipsychotics: Side effects
High potencyHigh potencyEPSEPS
Haldol
Chlorpromazine
Loxapine
Perphenazine
QT prolongation with pimozide, CPZ
Low potencyLow potencyAntihistamineAntihistamineAntiAlpha-AntiAlpha-AdrenergicAdrenergicAnticholinergicAnticholinergic
Atypical Antipsychotics: Indications
• Same as typicals
• Agitation/aggression in dementia NOT responding to adequate non-pharmacological interventions
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, SDA’s lead to dopamine release(i.e. the mesocortical pathway, reducing negative and cognitive symptoms)
• In pathways with more D2 receptors to block, SDA’s 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:Atypical Antipsychotics:Side EffectsSide 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 EnhancersCognitive Enhancers
Cholinergic Agents- Donepezil/Aricept
- Rivastigmine/Exelon
- Galantamine/Reminyl
NMDA Antagonist- Memantine/Ebixa
Cognitive Enhancers: Cognitive Enhancers: IndicationsIndications
AChEI: early to moderate AD
Lewy Body Dementia
Galantamine in Mixed Dementia
Donepezil in Vascular Dementia
Memantine: Moderate to severe AD
Cholinesterase Inhibitors: Indications
• AAbilities
• BBehaviour
• CCognition
• DDecrease in caregiver time
• EEntry into Nursing Home
Cholinesterase InhibitorsMechanism 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: Indications
SocializationHousehold tasksADLPersecutory ideationExcessive activity (agitation)
Memantine: Mechanism of action
• A dysfunction of glutamatergic neurotransmission, manifested as neuronal excitotoxicity, is hypothesized to be involved in the etiology of Alzheimer’s 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: Cognitive enhancers: monitoringmonitoring
• 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, akathesia, 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 mother’s 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. Lamotrigene/Lamictal
B. Valproic acid/Epival
C. Quetiapine/Seroquel
D. Risperidone/Risperdal
E. Lithium
You decide to start Seroquel as well as standard admission prn’s 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 and
seems to be having a great deal of difficulty breathing. 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
PRE-TEST REVIEW
Which of the following is not a common side effect of SSRI’s?
• a. Nausea
• b. Headache
• c. Rigidity
• d. Anxiety
• e. Sleep disruption
Which of the following receptors does Mirtazepine not block?
• a. Histamine
• b. 5HT1
• c. 5HT2
• d. 5HT3
• e. Alpha 2
At which dose level does Venlafaxine typically begin to have
a noradrenergic effect?
• a. 75mg
• b. 150mg
• c. 225mg
• d. 300mg
Which is not an indication for the use of Benzodiazepines?
• a. Catatonia
• b. Long term hypnotic
• c. Mania
• d. Alcohol withdrawal
• e. Anxiety
•
How are the novel hypnotics 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. Rigidity
• b. Dystonia
• c. Dyskinesia
• d. Akathisia
Which of the following is an example of a low potency typical
antipsychotic?
• a. Haldol/Haloperidol
• b. Pimozide/Orap
• c. Olanzapine/Zyprexa
• e. Clomipramine/Anafranil
• f. Chlorpromazine/Thorazine
Which class of cognitive enhancers is indicated in mild to moderate
Alzheimer’s Disease?
• a. Cholinesterase inhibitor
• b. NMDA receptor antagonist
Which mood stabilizer can reduce the risk of suicide in Bipolar
Disorder?
• a. Valproic Acid/Epival
• b. Lamotrigene/Lamictal
• c. Lithium
• d. Carbamazepine/Tegretol
What is the most common excitatory neurotransmitter in the brain?
• a. Serotonin
• b. Glutamate
• c. Norepinephrine
• d. GABA
• e. Dopamine
THANK YOU!GOOD LUCK