PSYCH: depression, anxiety related disorder, schizophrenia, bipolar,

Question 1

side effects with antidepressant subside within — weeks

Answer 1

2 weeks

Question 2

patient is responding to treatment but is bothered by side effects, what do you recommend?

Answer 2

switch between the same class of agents within 3-8 weeks ( side effects subside within 2 weeks)

Question 3

CANMAT 1st line agent for depression

Answer 3

SSRI: sertraline, fluoxetine, paroxetine, citalopram, escitalopram
SNRI: venlafaxine, duloxetine,
bupropion
Mirtazapine

Question 4

2nd line therapy for depression

Answer 4

moclobemide
quetiapine
trazodone
tricyclic antidepressants

Question 5

acronyms for SSRI side effects

Answer 5

HANDS 
H= headache 
A= anxiety 
N: nausea 
D: diarrhea and other 
S: sexual dysfunction and sleep dysfunction

Question 6

optimal response time for antidepressant

Answer 6

8 weeks

Question 7

network analysis found the following antidepressant to be superior in efficacy

Answer 7

escitalopram, sertraline, venlafaxine, mirtazapine

Question 8

sertraline: unique side effects

Answer 8

Unique: tends to have more diarrhea and male sexual dysfunction

Question 9

antidepressant that has least sexual dysfunction

Answer 9

mirtazapine, bupropion, moclobemide

Question 10

antidepressant with Low weight gain potential

Answer 10

bupropion, SNRI ( less than SSRI- paroxetine have the most weight gain

Question 11

antidepressant that lower seizure threshold

Answer 11

bupropion, TCAs

Question 12

antidepressant that have high potential of withdrawal symptoms and lowest

Answer 12

high: venlafaxine, paroxetine
lowest: fluoxetine (long t/2 life) and bupropion ( no withdrawal)

Question 13

SSRI drug interactions

Answer 13

NSAIDs: bleeding risk
serotonergic agent increases serotonin syndrome
Fluoxetine and paroxetine= potent 2D6 inhibitor ( metoprolol, desipramine) avoid or use with caution
fluvoxamine= potent 1A2 inhibitor

Question 14

SSRI: relevant PK - absorption and metabolism

Answer 14

absorption: with or without food. sertraline increases bioavailability with food
metabolism: Only fluoxetine, citalopram, sertraline form active metabolites. potential concerning in liver dysfunction

Question 15

drug of choice for pregnancy and breast feeding

Answer 15

pregnancy: sertraline, escitalopram, citalopram
alternative: desvenlafaxine, duloxetine, fluoxetine, fluvoxamine, mirtazapine, TCAs (except clomipramine and doxepin) and venlafaxine
avoid: paroxetine

Breast: sertraline, escitalopram or citalopram

alternative: paroxetine and nortriptyline.
avoid: fluoxetine due to long t1/2 and high levels in breast milk

Question 16

venlafaxine unique side effects

Answer 16

unique: dose-related hypertension occurs rarely, particularly at doses ≥225 mg/day.

Question 17

bupropion contraindications

Answer 17

contraindicated in anorexia or bulimia nervosa and seizure disorders, Abrupt discontinuation of alcohol or sedatives

Question 18

mirtazapine MOA, adverse effects and interactions

Answer 18

Serotonin and alpha adrenegic antidepressant (can last until morning even if taken at supper), & weight gain due to increased appetite
Significantly less sexual dysfunction versus other ADs
DI: alcohol/CNS depressants intensifies mirtazapine effect on mental and motor skills, MAOI, QT prolongation drugs

Question 19

TCA and it’s unique side effects

Answer 19

tertiary amines: Amitriptyline,
clomipramine ( the most serotonergic TCA, highest seizure risk,) is still favoured in the treatment of OCD r), imipramine, trimipramine, doxepin
Secondary: nortriptyline, desipramine ( lowest anticholinergic side effects)
Secondary are better and tertiary amines
side effects: sedation, anticholinergic effects, especially Cardiovascular toxicity (avoid TCAs in patient with history of overdose) , QT prolongation,

Question 20

MAOIs and significant drug interaction

Answer 20

reversible: Moclobemide
irreversible: phenelzine and tranylcypromine
significant DI: tyramine ( hypertensive crisis)

Question 21

Switching antidepressant recommended washout period

Answer 21

antidepressant–> antidepressant( no washout, crossover technique)
antidepressant—> MAOI ( stop antidepressant 2 weeks prior to initiation of MAOIs, 5 weeks for fluoxetine due to long t/12)

Question 22

duration of therapy for depression

Answer 22

1st and 2nd episodes: 6-9 {minimum 9 months}
3rd episodes: atleast 2 years
other indication for minimum of 2 years
( older age, psychotic features, suicidality, frequent episodes, residual symptoms, difficult to treat episodes, comorbid psychiatric or medical condition)- reduced relapse by 70%

Question 23

discontinuation syndrome side effects and how long it should last?

Answer 23

F = flu-like symptoms fatigue, lethargy, malaise, muscle aches
I = Insomnia
N = Nausea
I = Imbalance
S = Sensory disturbances paresthesias, electric-shock sensations
H = Hyperarousal anxiety, agitation
**withdrawal last for 2 weeks
fluoxetine= lowest incidence of withdrawal, bupropion= no withdrawal
When discontinuing antidepressants, taper slowly over 4–6 weeks. This is particularly important for paroxetine and venlafaxine.

Question 24

how to manage treatment resistant depression: switch or augment with?

Answer 24

Antidepressants can be switched either within a medication class or to a different class. 
augment with aripiprazole, olanzapine, quetiapine and risperidone, brexpiprazole, lithium and bupropion

Question 25

Non pharm treatment for anxiety related disorder

Answer 25

avoid caffeine, alcohol, stimulants exposure based techniques in specific phobia, stress management, sleep hygiene, aerobic exercises several times a week, **CBT (1ST line)

Question 26

pharmacotherapy for anxiety related disorder ( 1st, 2nd line) PD, SAD , GAD OCD, PTSD

Answer 26

PD: 1st: SSRI , SNRI ( venlafaxine for all except OCD), 2nd: TCA( imipramine and clomipramine) and mirtazapine and BZD SAD: 1st line: SSRI and SNRI ( venlafaxine) and pregabalin 2nd: BZD, gabapentin, MAOI ( phenelzine) GAD : 1st line: SSRI, SNIRI (both v/d), pregabalin, 2nd: BZD, Quetiapine XR, bupropion, buspirone, hydroxyzine, TCA (imipramine) OCD: 1st: SSRI 2nd: mirtazapine, venlafaxine PTSD: SSRI, SNRI ( venlafaxine) 2nd: mirtazpine, TCA ( phenelzine) ** avoid BZD**

Question 27

DOC for pregnancy and breastfeeding for anxiety related disorder

Answer 27

pregnancy: CBT, SSRI,SNRI and BZD. Avoid paroxetine Breastfeeding: paroxetine or sertraline avoid BZD

Question 28

role of BZD in anxiety

Answer 28

Benzodiazepines used for a limited period of time, e.g., up to 6–8 weeks, may also be effective in providing rapid relief from anxiety or panic attacks when needed, or to help reduce anxiety and agitation related to initiation of SSRIs and SNRIs.

Question 29

role of propranolol in anxiety

Answer 29

used in SAD for specific task related anxiety ( fear of public speaking or stage fright- take lose dose propranolol 30 mins prior)

Question 30

role of buspirone

Answer 30

2nd in GAD, slower onset compared to BZD , less sedating, low addiction tendencies, minimal withdrawal symptoms compared to BZD

Question 31

role of prazosin

Answer 31

Prazosin is an alpha1-adrenergic antagonist that reduces sympathetic outflow in the brain. It is often used in clinical practice for the treatment of PTSD-associated nightmares,

Question 32

SNRI side effects

Answer 32

venlafaxine, desvenlafaxine, duloxetine headache, insomnia, sweating, nausea, dry mouth and sexual dysfunctions HANDS

Question 33

Bupropion: MOA, AE and and CI

Answer 33

MOA: NE and dopamine reuptake inhibitor (NDRI) AE: anxiety, agitation, seizure, no sexual dysfunction (due to not inhibiting serotonin) BID doing separately at least 8 hurst's CI: seizure disorder, anorexia/bulimia nervosa, electrolyte disturbances

Question 34

trazodone MOA, side effects,

Answer 34

MOA: serotonin antagonist and reuptake inhibitor (SARI) AE: drowsiness, sedation, orthostasis, headache, fatigue **pripasim**

Question 35

TCA: MOA, side effects, interactions

Answer 35

MOA: serotonin-NE reuptake inhibitors Side effects: anticholinergic (urinary retention, dry mouth, constipation), worsening of heart arrhythmias, heart block, QT prolongation, weight gain Interactions: Avoid ACH drugs, CNS depressants, MAOI ( fatal), **highly toxic in overdose due to cardiac toxicity**

Question 36

MAOIs side effects and significant a/e

Answer 36

Moclomide is reversible and phenelzine and tranylcypromine and irreversible side effects: insomnia, palpitation, tachycardia, orthostatic, hypotension and sexual dysfunction

Question 37

4 keys dopaminergic tracts involved in schizophrenia

Answer 37

Tract 2 and 3 are implicated in schizophrenia 1- nigrostriatal- dopamine receptor blockade--> EPS 2- mesolimbic---> increased dopamine --> positive symptoms 3- mesocortical --> decreased dopamine--> negative symptoms 4. tuberoinfundibular--> dopamine blockage---> increased prolactin

Question 38

do both FGA and SGA have similar efficacy?

Answer 38

All FGAs and SGAs, with the exception of clozapine, have similar efficacy in treating the positive (psychotic) SGA They are thought to improve or at the least not worsen cognitive and negative symptoms.

Question 39

list the medication that belongs to FGA and its adverse effects

Answer 39

**note** FGA typically blocks Dopamine receptor and SGA blocks both Dopamine and 5HT2A Low-potency agents (e.g., chlorpromazine, methotrimeprazine), less dopamine blockage and more other receptor blockage including H1 ( sedation, weight gain, increased appetite,) M1 receptor ( anticholinergic effects) and alpha 1 ( orthostatic hypotension) high-potency agents (e.g., fluphenazine, haloperidol), more dopamine blockage, have greater rates of extrapyramidal side effects (EPS) (e.g., parkinsonism, tardive movement disorders such as tardive dyskinesia), neuroleptic malignant syndrome (NMS) and elevated prolactin levels note: Zuclopenthixol Acetate (Clopixol Acuphase) – “not a LAIA or a shot acting IM AP” Not intended for long-term use. Duration should not exceed 2 weeks. Max cumulative dosage should not exceed 400mg and number of injections should not exceed 4.

Question 40

list SGA and TGA medication and its adverse effects

Answer 40

second gen: asenapine, , clozapine, lurasidone, olanzapine, paliperidone, quetiapine, risperidone, ziprasidone AE: high risk of weight gain: THE PINE ( clozapine, olanzapine, quetiapine) high risk of ACH >30% ( clozapine and quetiapine) - dry mouth, constipation, urinary retention high EPS: THE DONE ( risperidone and paliperidone) high Hyperprolactinemia : THE DONE risperidone and paliperidone) third gen: (aripiprazole, brexpiprazole) unique MOA: partial antagonist of Dopamine and serotonin receptor ( LOW risk of weight gain, EPS, ACH) AE: ari has high risk of Akathisia. other ae includes anxiety, insomnia, tremor, compulsive behaviour

Question 41

treatment for EPS symptoms including acute dystonia Akathisia Tardive dyskinesia

Answer 41

acute dystonia (Severe muscle spasm – may involve tongue: BDL drugs: Benztropine Diphenhydramine and Lorazepam akathisia (Inner restlessness, cannot sit still, excessive motor activity): if dose reduction is not effective, beta-blockers (e.g., propranolol 10–120 mg/day) are treatment of choice with monitoring for hypotension. Lorazepam and mirtazapine also provide symptom relief. Anticholinergics are ineffective. Tardive dyskinesia (Involuntary movement of face, jaw, tongue, lips, eyes, limbs, trunk, neck) : no evidence-based treatment—prevention is key use SGA

Question 42

Why do anticholinergic agents (benztropine, diphenhydramine) treat AP-induced EPS

Answer 42

Dopamine and acetylcholine have a reciprocal relationship with each other in the nigrostriatal pathway. Therefore, AP with high anticholinergic effects are less likely to cause EPSE (e.g. clozapine!)

Question 43

treatment for treatment resistance schizophrenia?

Answer 43

clozapine

Question 44

Clozapine serious AE and monitoring parameters

Answer 44

MYOCARDITIS ( Risk of myocarditis (0.06-3.88%, highest risk in first month). • Mortality rate 10-23% • Troponin and CRP weekly x 4 weeks when clozapine is started AGRANULOCYTOSIS Risk of agranulocytosis (incidence 1-2%, 88% of cases during first 6 months) • Dose independent. Pharmacists must verify: 1) patient is enrolled with clozapine program 2) patients’ hematological status before dispensing clozapine. Dispense quantity limited to freq. of bloodwork Constipation: Severe constipation occurs in ~15% of patients on clozapine • Severe constipation can lead to adynamic ileus • Mortality rate 7.3% • Very important to ask patients about bowel function and ensure they have adequate bowel medication (e.g. sennosides, PEG 3350) SEIZURES: Risk: 1% at <300 mg/day; 2.7% at 300-600 mg/day; 4.4% at >600 mg/day.41 SLOW titration,  dose (~50%), +/- antiepileptic e.g. VPA, lamotrigine, caution: EtOH, lithium, haloperidol, TBI

Question 45

know clozapine AGRANULOCYTOSIS monitoring and management for GREEN, YELLOW AND RED results

Answer 45

GREEN ( WBC >3.5) --> monitor q weekly x 6 months, (26weeks) q2wk x 6months, then q4wk if stable Yellow: (WBC 2-3.4) --> continue clozapine but monitor for flu like symptoms--> monitor twice weekly RED: (WBC <2 ) --> STOP STAT D/C indefinitely --> Repeat in 24 hours, then at least weekly x 4 weeks and prn.

Question 46

if patient missed clozapine dose?

Answer 46

Missed doses: If no clozapine for ≥48h, must restart titration from beginning

Question 47

role of long acting injectable antipsychotics (LAIs)? | know which agent is q4wk, q12wk and q2wk

Answer 47

Long-acting injectable antipsychotics (LAIs), such as aripiprazole, paliperidone palmitate or risperidone, should be offered as an option in all phases of illness, including the first episode, after first establishing tolerability with oral formulations Q4Wk: 3rd gen ARIPiprazole (Abilify), 2nd gen Paliperidone palmitate INVEGA SUSTENNA, 1st gen Haloperidol HALDOL Q12WK: 2nd gen Paliperidone palmitate INVEGA TRINZA Use after stable for ≥4months on INVEGA SUSTENNA Q2WK: 2nd RisperiDONE RISPERDAL CONSTA, 1st gen Flupent(h)ixol FLUANXOL and Zuclopenthixol CLOPIXOL

Question 48

distinguish the difference between BIPOLAR I AND BIPOLAR II? difference between MANIAC VS HYPOMANIAC?

Answer 48

Bipolar I: Manic episodes +/- depressive episodes Bipolar II: hypomanic + major depressive episodes + no history of manic episodes hypomania is similar to mania but episode is not severe enough to cause marked social impairment, no psychotic features and lasting at least 4 days consecutive days and present most of each days

Question 49

first line for: acute mania acute depression maintenance

Answer 49

acute mania: Li, divalproex, atypical antipsychotic ( risperidone and quetiapine) acute depression: Li, divalproex, lamotrigine, quetiapine, lurasidone maintenance: li, divalproex, lamotrigine atypical

Question 50

what class of meds should be avoid in bipolar?

Answer 50

antidepressant Carries risk of switching (rapid change from depression to mania ie: RAPID CYCLIC: Risk highest with TCAs & venlafaxine (>10%, avoid), followed by SSRIs (<5%) and low risk with bupropion antidepressant+ mood stabilizer: avoid--> not better than mood stabilizer alone

Question 51

what is the role of lamotrigine in bipolar?

Answer 51

role: acute depressive episode and maintenance . mono therapy of lamotrigine is not recommended in presence of mania

Question 52

role of lithium in bipolar, therapeutic range, when to expect efficacy and side effects / monitoring

Answer 52

role: acute mania, maintenance and mild depression therapeutic levels: acute mania: 0.8-1.2 mmol/L note: higher dose in mania and reduce for maitenance maintenance: 0.6-1.0 mmol/L ``` side effects: Weight gain, GI upset, polyuria, polydipsia, fine tremor, ↑ WBC, hypothyroidism, ↑ potassium & calcium ``` monitor: Monitor thyroid (causes hypo or hyperthoyrodism HYPO more common though) and renal function at least every 6 months.

Question 53

what increases or decreases lithium level?

Answer 53

↑lithium level: ACEIs, ARBs, CBZ, diuretics, fluoxetine, metronidazole, NSAIDs (not low-dose ASA), sodium depletion, spironolactone. ↓lithium level: caffeine, metamucil, NaCl, theophylline, topiramate. Maintain a consistent salt (Na + ) diet and adequate fluid intake!

Question 54

how long does mood stabilizer take to see effect?

Answer 54

2-4 weeks | max: 6-8weeks

Question 55

role of divaloproex/ valproic acid, side effects and monitoring? difference between divaloproex/ valproic

Answer 55

first in acute mania/ depressive episodes, and maintenance side effects: GI upset, CNS slowing (sedation and somnolence) alopecia, weight gain, - Rare: thrombocytopenia, decreased WBC, hepatotoxicity ``` **Same as divalproex above except that valproic acid generally has more GI side effects -Divalproex and valproic acid are not interchangeable medications (need to check serum levels if patient is changed between agents – especially if on treatment for seizures) ```

Question 56

what is one significant consideration when wanting to use valproic acid?

Answer 56

: avoid valproate in females of child-bearing potential as often ↑ risk of congenital and cognitive defects

Question 57

lamotrigine side effects and significant drug interaction?

Answer 57

``` ae: Nausea, chest pain, peripheral edema, somnolence, dysmenorrhea, dyspepsia, nystagmus -Rare: Risk of SJS if titrated too quickly, aseptic meningitis, neutropenia, leukopenia, pancytopenia, aplastic anemia ``` *weight neutral** drug interactions: ↑level: valproate (& ↑risk of rash) **reduce lamotrigine by 50%), sertraline. ↓level: OCs, CBZ, phenytoin,

Question 58

what should be do first before starting CBZ?

Answer 58

rash (check HLA-B*1502 before starting treatment),

Question 59

CBZ side effects and drug interaction?

Answer 59

ae: GI upset (take with food) , CNS slowing ( somnolence and dizziness), rash, decreased WBC rare: aplastic anemia, LFTs, hyponatremia, SLE Many. Strong 3A4 inducer  ↓levels of: antipsychs, benzos, bupropion, 3A4 substrate. ↑CBZ level: clarithro/erythromycin, diltiazem, , fluoxetine, fluvoxamine, lamotrigine, verapamil, valproate. ↓CBZ level: phenytoin, phenobarb, St. John's Wort, theophylline.

Question 60

bipolar DOC in pregnancy and lactation

Answer 60

pregnancy: lamotrigine most agents have teratogenic risk, the risk increases if patient is on multiple medications (aim for monotherapy), decrease serum concentration, try to avoid in 1st semester but must balance risk to mother/fetus of uncontrolled bipolar vs. risk of medications

Question 61

management for patient who is experiencing tremor on lithium?

Answer 61

decreased dose reduce caffeine or the addition of a beta-blocker such as propranolol or atenolol.

Question 62

what is an important counselling point for patient on Ziprasidone and Lurasidone ?

Answer 62

take with food, minimum 500 calories

Question 63

complication of lithium

Answer 63

``` diabetes insipidus, hypothyroidism and arrhtymias Leukocytosis Insipidus Tremor/teratogenic Hypothroydism ```

Question 64

when should you check the trough lithium plasma levels in healthy adult patient?

Answer 64

t1/2 is 24 hours check trough after 5 half lives so 120 hours, only if toxicity signs and symptoms appear sooner, you can measure trough earlier than 5 half lives

Question 64

when should you check the trough lithium plasma levels in healthy adult patient?

Answer 64

t1/2 is 24 hours check trough after 5 half lives so 120 hours, only if toxicity signs and symptoms appear sooner, you can measure trough earlier than 5 half lives

Question 65

usual dose of haloperidol for schizeperian

Answer 65

2mg IM NOT 10mg IM

Question 65

usual dose of haloperidol for schizophrenia

Answer 65

2mg IM NOT 10mg IM

Question 66

what is the MOA of tardive dykinesia?

Answer 66

Supersensitivity of the dopamine receptors as a result of chronic D2 blockade.

Question 67

What is the rate of response expected to a trial of an antipsychotic?

Answer 67

60%

Question 68

Risperidone is a second-generation antipsychotic but it is believed that it begins to display receptor blockade similar to the FGAs at doses greater than _________

Answer 68

6mg

Question 69

The propensity of SGAs to cause weight gain can be ordered as:

Answer 69

Clozapine > Olanzapine > Quetiapine > Risperidone.

Question 70

Despite adequate treatment for schizophrenia, what percentage of patients will continue to experience chronic or severe symptoms?

Answer 70

25%

Question 71

If a patient is switched to clozapine for treatment-resistance, an adequate trial would be considered to be

Answer 71

6 months

Question 72

Which of the following antipsychotics has partial agonist activity at D2 and 5HT1A and potent antagonism activity at 5HT2A receptors?:

Answer 72

aripiprazole

Question 73

Which of the following antipsychotics has partial agonist activity at D2 and 5HT1A and potent antagonism activity at 5HT2A receptors?:

Answer 73

ziprasidone

Question 74

What are the symptoms of activation syndrome often seen with ziprasidone

Answer 74

Ziprasidone-induced activation syndrome consists of anxiety, agitation, restlessness, and insomnia. Also included: increased energy and hypomania.

Question 75

Smoking can affect the metabolism of which antipsychotics?:

Answer 75

clozapine; Smokers may require higher doses of clozapine than non-smokers, leading to increased side effects and adverse effects.

Question 76

which antipsychotics have the highest rate of weight gain

Answer 76

Among second generation antipsychotics, clozapine and olanzapine are associated with the greatest weight gain followed by quetiapine, risperidone, paliperidone and aripiprazole (3rd gen).

Question 77

what happen when CBZ is taken with aripriprazole

Answer 77

Carbamazepine (or other strong inducers of CYP2D6 or CYP3A4 can decrease aripiprazole levels significantly.

Question 78

Patients taking clozapine should have a WBC count how often?

Answer 78

Weekly for the first 26 weeks of therapy.

Question 79

hyperprolactinermia is common in which antipyschotic?

Answer 79

Hyperprolactinemia is a common side effect of all first generation antipsychotics, risperidone and paliperidone. No differences in prolactin levels have been found with quetiapine.

Question 80

Which of the following antipsychotic drugs is least likely to cause weight gain?

Answer 80

Ziprasidone

Question 81

Which is a gateway or cardinal symptom that characterizes the manic phase of bipolar disorder?

Answer 81

Elevated mood

Question 82

Antidepressant that causes significant priapism

Answer 82

Trazodone

Question 83

Which antidepressant is the most anorexic

Answer 83

Fluoxetine