Summary Recall (Schizophrenia, Depression, Bipolar) Flashcards
What are some key clinical features of Schizophrenia? (DSM-5 Criteria)
What exclusions must be made?
Thought Disorder: 2 Sx for 1 month
1. Positive Sx (Hallucination, Delusion, Disorganized thoughts, Grossly disorganized or catatonic behavior)
2. Negative Sx (Affective flattening, Avolition)
Social and Occupational Dysfunction:
1. Work
2. Interpersonal relations
3. Self-care
Total Duration: 6 months
Exclusions:
1. Schizoaffective / Mood Disorders
2. Substance Use
3. Medical Disorders
Pharmacological Management Efficacy, ADR, Algorithm for Schizophrenia
Efficacy:
1. Positive Sx (D2) - FGA and SGA
2. Negative Sx (5HT2A) - SGA
ADRs:
1. EPSE (Muscles) - FGA > SGA
2. Metabolic - SGAs
3. Sedation and Weight gain (SGA -pines)
Algorithm:
1. Antipsychotic
2. Antipsychotic
3. Clozapine
4. Combination FGA + FGA/SGA OR
Clozapine + Add-ons
What is the adequate trial duration for antipsychotics in Schizophrenia?
2-6 weeks (3 months for clozapine)
What adjunctive treatment for schizophrenia?
Benzodiazepines for agitation
Antidepressant for depression
What is considered treatment resistant schizophrenia?
Failed response to at least 2 adequate trials of antipsychotics of which one is an atypical SGA
Monitoring parameters for Clozapine
Baseline and Period FBC (Agranulocytosis)
Schizophrenia
Acute Stabilization Phase: Goals and Choice of Therapy, and Monitoring
- Reduce agitation, aggression, hostility, improve sleep
- Cooperative = PO Antipsychotics +/- Benzodiazepines
- Uncooperative = IM Fast-acting antipsychotics / Benzodiazepines
- Monitor for EPSE (Dystonia, Pseudo-parkinsonian ADRs)
- Monitor Vitals
Schizophrenia
Acute Phase Treatment Dosing
1. Cooperative
PO Lorazepam 1-2 mg
OR
PO Antipsychotics:
Risperidone 1-2 mg
Olanzapine 5-10 mg
Quetiapine 50-100 mg
Haloperidol 2-5 mg with pre-treatment ECG
Schizophrenia
Acute Phase Treatment Dosing
2. Uncooperative:
IM Lorazepam 1-2 mg
OR
IM Antipsychotics
Olanzapine 5-10 mg
Aripiprazole 9.75 mg (Less hypotensive)
Haloperidol 2-5 mg with pre-treatment ECG
Promethazine 25-50 mg
How to manage EPSE for antipsychotics?
- Dystonia, tremors/rigidity:
– Anticholinergics, or
– SWITCH to lower-potency antipsychotics (e.g. Quetiapine, Sulpiride) - Akathisia
– Clonazepam and/or Propranolol (beware of bradycardia/hypotension), or
– SWITCH to SGA or lower-potency antipsychotic - Tardive Dyskinesia (irreversible if detected late in advanced stages)
– Discontinue any anticholinergics
– SWITCH to low potency SGA
– Treat with Valbenazine
How to manage metabolic side effects for antipsychotics?
- Keep current antipsychotic to prevent relapse but treat the emergent DM/dyslipidemia with lifestyle and meds (e.g. Metformin; Statins)
OR
- SWITCH to Aripiprazole, Brexpiprazole, Cariprazine, Lurasidone, Haloperidol
What is the clinical presentation of Major Depressive Disorder? In SAD CAGES
What exclusions?
Interest loss (Must have)
Sleep (More or Less)
Appetite Loss
Depressed Mood (Must have)
Concentration decline
Activity Retardation
Guilt
Energy decline
Suicidality
At least 5 out of 9 with either interest loss or depressed mood during a 2-week period.
Exclusions:
1. Drug-induced
2. Medical Conditions
3. Bipolar Disorder (Identify mania)
Pharmacological Management of MDD is necessary in…
Moderate-severe depression according to the Patient Health Questionnaire-9 (PHQ-9 score > 10)
Phases of Pharmacological Treatment of MDD? What is the adequate trial period?
- Acute Phase = 4-8 week adequate trial
- Physical Sx reduced in 1-2 weeks
- Mood Sx reduced in 4-8 weeks - Continuation Phase = 4-9 months after acute phase for 1st episode uncomplicated MDD
Total duration: 6-12 months
What is considered treatment-resistant depression and what are the options?
2 or more adequate trials fail (Insufficient response = Less than 50% improvement)
Options:
1. ECT (GA)
2. Symbyax Capsule (Olanzapine + Fluoxetine)
How do we avoid antidepressant discontinuation syndrome?
Gradual tapering by halving tablet of lowest strength every 1-2 weeks if patient is on regular dosing for > 6-8 weeks
Exceptions: Fluoxetine and Bupropion
What antidepressants are suitable for pregnancy, lactation, renal impaired, hepatic impaired, post-MI depression and elderly patients?
Pregnancy = Nortriptyline (TCA)
Lactation = Sertraline (SSRI) or Mirtazapine (NaSSA)
Renal impaired = Vortioxetine
Hepatically impaired = Avoid agomelatine
Post-MI depression = Sertraline
Elderly = Avoid TCAs (Anticholinergic, hypotensive, CNS)
What are 4 important Pharmacodynamic drug interactions with antidepressants?
Serotonergic agents & Serotonin Syndrome
- Triptans, MAOi, Opioids, Linezolid, Ritonavir
Bleeding Risks → Mitigate with adding of PPIs
- SSRIs + NSAIDs/Warfarin/Steroids
CNS Depressants = Alcohol
Anticholinergic agents
What are important pharmacokinetic drug interactions and CYP enzymes involved with antidepressants? Which antidepressants have less CYP interactions?
CYP1A2, 2C19, 2D6, 3A4
Potent CYP Inhibitors:
Fluvoxamine (1A2, 2C19)
Fluoxetine, Paroxetine, Bupropion (2D6)
Fewer CYP interactions:
Mirtazapine
Escitalopram
SNRIs
Vortioxetine
What are the FINISH symptoms of antidepressant discontinuation syndrome?
Sx (FINISH) within 36-72h
Flu-like
Insomnia
Nausea
Imbalance
Sensory disturbance
Hyperarousal
What are common side effects to look out for in serotonergic antidepressants, venlafaxine, mirtazapine, bupropion, TCAs?
- All serotonergic agents (SSRI, SNRI, SMS,TCA): GI side effects, sexual dysfunction
- Venlafaxine can cause/worsen hypertension
- Mirtazapine can cause sedation & weight gain (may be beneficial for insomnia and poor appetite); may reverse sexual side effects of serotonergic agents
- Bupropion has no serotonergic effects (hence minimal sexual side effects) but not suitable for h/o seizures, psychosis or eating disorders
- TCAs: poor tolerability – sedation, anticholinergic, orthostatic hypotension, arrhythmias, seizures, fatal on overdose)
- Suicidality association in patients ≤ 24 years old – need to counsel patients & carers.
What are the therapeutic and adverse effects of antipsychotics on receptors of D2, 5HT1A, 5HT2A, 5HT2C, H1, Alpha 1, M1, IKr?
D2: Improve (+) Sx, EPSE, Hyperprolactinemia
5HT2A: Improve (-) Sx
5HT2C: Weight gain
H1: Sedation
Alpha 1: Orthostasis
M1: Anticholinergic effect (Dry mouth, blur vision, constipation)
IKr: QTc prolongation
