Managing + Monitoring antipsychotic-induced SEs Flashcards
EPSE - Dystonia
- Description
- Risk
- Management
Dystonia: muscle spasm, onset within minutes (IM/IV) or hours (PO)
Risks:
- High potency antipsychotics (e.g., haloperidol)
- Neuroleptic-naive patients
- Young males
Management: to relieve muscle side effects
- IM anticholinergics PRN (benztropine 2mg, diphenhydramine) to relax the muscle - however, may cause/worsen constipation
EPSE - Pseudo-parkinsonism
- Description
- Risk
- Management
Pseudo-parkinsonism: tremors, rigidity, bradykinesia, salivation, bradyphrenia; onset days to weeks
Risks:
- Elderly females
- Previous neurological damage (head injury, stroke)
Management: to relieve muscle side effects
- Reduce antipsychotic dose
- Switch to lower potency antipsychotic
- Switch to SGA (e.g., Quetiapine)
- Anticholinergics PRN (e.g., Benzhexol/Trihexyphenidyl, oral/IM Benztropine 2mg) - however, may cause/worsen constipation
EPSE - Akathisia
- Description
- Risk
- Management
Akathisia: restlessness; onset hours to weeks
Risks: High-potency antipsychotics > Risperidone > Olanzapine > Quetiapine/Clozapine
(IC9) Note that akathisia correlates directly with duration on medication
Management:
- Reduce antipsychotic dose
- Switch to lower potency antipsychotic
- Switch to SGA (e.g., Quetiapine)
- Clonazepam (low dose) PRN
- Propranolol (NSBB) - caution: bradycardia, hypotension
- NOT helpful: anticholinergics
EPSE - Tardive dyskinesia
- Description
- Risk
- Management
Tardive dyskinesia: involuntary orofacial movements (face, lip, tongue), also writhing of the limbs (hand movements, pelvic thrusting); late-onset 3-6m (‘tardive’)
Risks: FGA > SGA, worsen with anticholinergic drugs
Management:
- DISCONTINUE any anticholinergics
- Reduce antipsychotic dose
- Switch to lower potency antipsychotic
- Switch to SGA (e.g., Clozapine possibly effective)
- Valbenazine 40-80mg/day - a reversible inhibitor of vesicular monoamine transporter 2 (VMAT2)
- Clonazepam PRN
Which EPSE are reversible with discontinuation of the drug, and which are not? (IC9)
Reversible: dystonia, pseudo-parkinsonism
Irreversible: tardive dyskinesia (Irreversible if detected late in advanced stages), akathisia
Hyperprolactinemia
- Description
- Risk
- Management
Hyperprolactinemia: can cause galactorrhea, amenorrhea, decreased libido, gynaecomastia
Risk: FGAs, Paliperidone > Risperidone > other SGAs
Management:
- Reduce FGA dose
- Switch to Aripiprazole
- Dopamine agonist (e.g., amantadine - used in PD, bromocriptine)
Metabolic
- Description
- Risk
- Management
Metabolic: weight gain, emergent diabetes, increase lipids
Risks:
- High: Clozapine, Olanzapine (CO)
- Mod: Chlorpromazine, Quetiapine, Risperidone (QRC)
- Low: Aripiprazole, Brexpiprazole, Cariprazine, Lurasidone, Ziprasidone, Haloperidol (ABC, LZH)
Management:
- Lifestyle modification: diet, exercise
- Treat diabetes: e.g., metformin
- Treat hyperlipidemia: e.g., statins
- Switch to a low risk agent
Cardiovascular - orthostatic hypotension
- Description
- Risk
- Management
- Risks: Chlorpromazine > Risperidone, Paliperidone, Quetiapine > Olanzapine, Ziprasidone, Aripiprazole, Sulpiride
Management:
- Get up slowly from sitting or lying position
- Switch to lower risk agent
Cardiovascular - QTc prolongation
- Description
- Risk
- Management
Risks:
- High doses
- IV Haloperidol
Management:
- Switch to lower risk agent (e.g., Quetiapine, Risperidone, Olanzapine)
Cardiovascular - VTE/PE
- Description
- Risk
- Management
Risks: low potency FGA
Management:
- prevent, monitor, treat emergent DVT
CNS - sedation
- Description
- Risk
- Management
Risks: Chlorpromazine, Clozapine > Quetiapine > Olanzapine > Risperidone, Paliperidone, Ziprasidone, Aripiprazole
Management:
- switch to lower risk agent
- administer in early evening for sedation to wear off by morning
- may consolidate once nightly dosing where appropriate
CNS - seizure
- Description
- Risk
- Management
Risks: Clozapine, Chlorpromazine > other SGAs
*Recall Clozapine, Chlorpromazine, and Quetiapine cannot consolidate as once daily dosing
Management:
- Switch to high-potency agents (e.g., Haloperidol)
CNS - Neuroleptic malignant syndrome (NMS) A&E
- Description
Neuroleptic malignant syndrome (NMS) aka Malignant hyperthermia
- Muscle rigidity (leadpipe rigidity)
- High fever
- Autonomic dysfunction (incr PR, labile high BP, diaphoresis/sweating)
- Altered consciousness
- Incr CK (due to muscle breakdown, can cause rhabdomyolysis)
- May cause kidney to shut down
CNS - Neuroleptic malignant syndrome (NMS) A&E
- Risk
- What are 3 causes of NMS
Risks:
- high-potency antipsychotics (e.g., haloperidol)
Three triggers of NMS:
- Succinylcholine (muscle relaxant)
- Initiation of an antipsychotic - dopamine receptor antagonist (onset: hours to 3 days, within 30 days)
- Sudden discontinuation of Levodopa
Mechanism related to sudden dopamine blockade
CNS - Neuroleptic malignant syndrome (NMS) A&E
- Management
Management:
- IV Dantrolene - 50mg TDS (diluted in WFI only)
- Oral dopamine agonist (e.g., amantadine, bromocriptine)
- Supportive measures
- Switch to SGA
Hematological A&E
- Description
- Risk
- Management
Dcr WBC, agranulocytosis: dcr absolute neutrophil count
Risk: Clozapine (monitor FBC)
Management:
- Discontinue clozapine if severe: WBC <3x10^9/L or ANC <1.5x10^9/L
Monitoring parameter for side effects
- Weight gain
- Obesity
- DM
- HLD
- Hyperprolactinemia
- BP
- EPSE
- Agranulocytosis
- QTc prolongation
General requirements:
Every visit: EPSE, fall risk, mental state exam, aggression, suicidality, vitals - BP, PR, temperature
at 12w/3m, then annually: FBG, HbA1c, lipid, BMI, waist circumference
at 6m, then annually: prolactin
Annually: cardio ECG
Drug-specific requirements:
- Agranulocytosis (Clozapine) - WBC, ANC (weekly for first 18w, then monthly)
- QTc prolongation (Ziprasidone) - ECG, repeat if there are risks/symptoms of QTc prolongation
Special populations
- Pregnancy
Watch for gestational diabetes, esp for Clozapine, Olanzapine
Special populations
- Breastfeeding
Suitable in breastfeeding: Olanzapine, Quetiapine
*Pt on Clozapine should continue on the drug and stop breastfeeding
Special populations
- Renal impairment
Oral Aripiprazole preferred
AVOID sulpiride, amisulpride (mainly renally excreted)
Special populations
- Hepatic impairment
Sulpiride, Amisulpride preferred as they are mainly renally excreted
Special populations
- Elderly
Avoid drugs with high propensity for a1-adrenergic blockade (orthostatic hypotension) or anticholinergic side effects (constipation, urinary retention, delirium)
Avoid long t1/2 drugs
Start low go slow
Simplify the regime
Precaution: FGAs and SGAs may increase mortality, CVD events, and stroke in dementia patients
Interactions with antipsychotics:
- Drugs with CNS depressant effects
Additive CNS effects
- E.g., BZD, Clozapine
- With alcohol, opioids, other psychotropics
Interactions with antipsychotics:
- Drugs with antimuscarinic, antihistaminic, a1-adrenergic blockade, or dopamine blockade
Additive adverse effects
Interactions with antipsychotics:
- Dopamine-augmenting agents (e.g., Levodopa, amantadine, bromocriptine)
Mutual antagonism with antipsychotics (negate effect of each other)
Interactions with antipsychotics:
- Antihypertensives, Trazodone
Increase hypotensive effects (esp with a1 adrenergic antagonists - orthostatic hypotension)
Interactions with antipsychotics:
- Lithium
Neurotoxicity
Interactions with antipsychotics:
- CYP1A2 inducers - Rifampicin, Phenobarbitone, Phenytoin, Cigarette smoking
Decreases phenothiazines, haloperidol, clozapine, olanzapine, ziprasidone
*If pt quits smoking, may need to decrease dose
Interactions with antipsychotics:
- CYP1A2 inhibitor: Fluvoxamine, Quinolone, Macrolide, Isoniazid, Ketoconazole
Increases phenothiazines, haloperidol, clozapine, olanzapine, ziprasidone
Inetarctions with antipsychotics:
CYP1A2 substrates: CCHOZ
CYP2D6 substrates: PROB AH
CYP3A4 substrates: RABZQ
CYP1A2 substrates:
- Phenothiazines
- Clozapine
- Haloperidol
- Olanzapine
- Ziprasidone
CYP2D6 substrates:
- Phenothiazines
- Risperidone
- Haloperidol
- Aripiprazole / Brexpiprazole
- Olanzapine
CYP3A4 substrates:
- Risperidone
- Aripiprazole / Brexpiprazole
- Ziprasidone
- Quetiapine
Interactions with antipsychotics:
Carbamazepine
Agranulocytosis with Clozapine
Evaluation of therapeutic outcomes
- Monitor for effectiveness of therapy
- Mental status exam
- Psychiatric rating scales
- Monitor for adverse effects
- Metabolic parameters: FBG, HbA1c, lipids, BW, BP
- EPSE: dystonia, pseudo-parkinsonism, akathisia, tardive dyskinesia
- Pt self-assessment
Timecourse of treatment response
- Early improvements
- Late improvements
Early improvements
- 1st week: dcr agitation, aggression, hostility
- 2-4 weeks: dcr paranoia, hallucinations, bizarre behaviors, improved organization in thinking
Late improvements
- 6-12 weeks: dcr delusions, negative symptoms may improve
- 3-6 months: improvement in cognitive symptoms with SGAs
