22.1 Pharmacotherapy: Antipsychotics Flashcards
“antipsychotics” used to be called what? (1)
“neuroleptics”
Describe: Overall mechanism of action of antipsychotic (1)
block, to varying degrees, DA activity in target brain pathways
Antipsychotic described for what? (2)
- primarily indicated for psychotic symptoms in: schizophrenia and related disorders, manic episodes, depressive episodes, substance use, medical conditions (i.e. neoplasm)
- other uses: treatment-resistant MDD, severe GAD, complex PTSD, severe OCD, borderline PD, behavioural symptoms of dementia, delirium, Tourette Syndrome, substance abuse in dual diagnosis, Huntington’s disease, ASD, impulse control disorders
- adjunctive management of agitation, aggression, severe anxiety, severe sleep difficulties when sedative-hypnotics are contraindicated
Describe onset: Antipsychotic (2)
- rapid calming effect and decrease in agitation;
- thought disorder responds in 1-4 wk
Name reasons to combine antipsychotics (1)
- no reason to combine two or more antipsychotics
Name effectiveness of antipsychotics (3)
- all antipsychotics are equally effective, except for clozapine (considered to be most effective in treatment-refractory psychosis)
- atypical antipsychotics (second generation) are as effective as typical (first generation) antipsychotics but are thought to have better adverse effect profiles; main difference is lower risk of EPS and TD
- choose a drug to which the patient has responded to in the past or that was used successfully in a family member
Describe duration antipsychotics (2)
- if no response in 4-6 wk, switch drugs
- duration: minimum 6 mo and usually for life in most patients with primary psychotic disorders; variable for other indications
Name Dopamine Pathways Affected by Antipsychotics (4)
- Mesolimbic
- Mesocortical
- Nigrostriatal
- Tuberoinfundibular
Describe effects and associated pathology of this dopamine pathway affected by antipsychotic: Mesolimbic (2)
- Effects: Emotion orginiation, reward
- Associated Pathology: HIGH dopamine causes positive symptoms of schizophrenia (delusions, hallucinations)
Describe effects and associated pathology of this dopamine pathway affected by antipsychotic: Mesocortical (2)
- Effect: Cognition, executive function
- Associated Pathology: LOW dopamine causes negative symptoms of schizophrenia
Describe effects and associated pathology of this dopamine pathway affected by antipsychotic: Nigrostriatal (2)
- Effects: Movement
- Associated pathology: LOW dopamine causes EPS
Describe effects and associated pathology of this dopamine pathway affected by antipsychotic: Tuberofundibular (2)
- Effect: Prolactin hormone release
- Associated pathology: LOW dopamine causes hyperprolactinemia
Describe: Long-Acting Preparations of antipsychotics (6)
- antipsychotics formulated in oil for IM injection
- received on an outpatient basis
- indications: individuals with schizophrenia or other chronic psychosis who relapse because of non- adherence
- should have been exposed to oral form prior to first injection
- dosing: start at low dosages, then titrate every 2-4 wk to maximize safety and minimize side effects
- side effects: risk of EPS, parkinsonism, increased risk of NMS
Describe: Canadian Guidelines for the Treatment of Acute Psychosis in the Emergency Setting (4)
- haloperidol 5 mg IM ± lorazepam 2 mg IM
- loxapine PO 25 mg ± lorazepam 2 mg IM
- olanzapine 2.5-10 mg (PO, IM, quick dissolve)
- risperidone 2 mg (M-tab, liquid)
Compare Typical (First Generation) vs. Atypical (Second Generation) Antipsychotics: Mechanism
- Typical: Block postsynaptic dopamine receptors
- Atypical:
- Block postsynaptic dopamine receptors (D2)
- Block serotonin receptors (5-HT2) on presenaptic dopaminergic terminals, triggering DA release and reversing DA blockade in some pathways
Compare Typical (First Generation) vs. Atypical (Second Generation) Antipsychotics: Pros
- Typical:
- Inexpensive
- Plenty of injectable forms are available
- Atypical:
- Fewer EPS
- Low risk of tardive syndroms
- Mood stabilizing effects
Compare Typical (First Generation) vs. Atypical (Second Generation) Antipsychotics: Cons
- Typical:
- More EPS
- Tardive syndromes long-term
- Not mood stabilizing
- Atypical:
- Expensive
- Few injectable forms available
- Metabolic side effects (weight gain, hyperglycemia, lipid abnormalities, metabolic syndromes)
- Exacerbation (or new onset) of obsessive behaviour
Name: Commonly Used Atypical Antipsychotics (5)
- Risperidone (Risperdal®)
- Olanzapine (Zyprexa®, Zydis®)
- Quetiapine (Seroquel®)
- Clozapine (Clozaril®)
- Ariprazole (Abilify®)
Name advantages: Risperidone (Risperdal®) (2)
- Lower incidence of EPS than typical antipsychotics at lower doses (<8 mg)
- Associated with less weight gain compared to clozapine and olanzapine
Name disadvantages relative to other SGAs: Risperidone (Risperdal®) (7)
- Highest risk of EPS/TD among SGAs- avoid if high risk for EPS or existing movement disorder or elderly
- Elevated prolactin
- Sexual dysfunction
- Galactorrhea
- Gynecomastia
- Menstrual disturbance
- Infertility
Name formulations: Risperidone (Risperdal®) (2)
- Quick dissolve (M-tabs)
- Long- acting (Consta®)
Name advantages: Olanzapine (Zyprexa, Zydis) (3)
- Better overall efficacy compared to haloperidol
- Well tolerated
- Low incidence of EPS and TD
Name disadvantages relative to other SGAs: Olanzapine (Zyprexa, Zydis) (2)
- Weight gain and metabolic effects - avoid in DM
- Sedating - avoid if high risk for falls or fracture
Name formulations: Olanzapine (Zyprexa, Zydis) (2)
- Quick dissolve formulation (Zydis®) used commonly in ER setting for better compliance
- IM form available
Name advantages: Quetiapine (Seroquel) (2)
- Associated with less weight gain compared to clozapine and olanzapine
- Mood stabilizing
Name disadvantages relative to other SGAs: Quetiapine (Seroquel) (2)
- Sedating/ortho hypotension - avoid if high risk for falls or fracture
- QT prolongation in high doses - caution if cardiac risk
Name advantages: Clozapine (Clozaril®) (3)
- Most effective for treatment-resistant schizophrenia
- Does not worsen tardive symptoms; may treat them
- Approximately 50% of patients benefit, especially paranoid patients and those with onset after 20 yr
Name disadvantages relative to other SGAs: Clozapine (Clozaril®) (6)
- Weight gain and metabolic effects - avoid in DM
- Sedating/ortho hypotension - avoid if high risk for falls or fracture
- Potentially severe constipation - avoid if risk of fecal impaction or bowel perforation
- Cardiomyopathy – caution if existing heart disease
- Seizures – caution if seizure disorder
- Agranulocytosis (1%) – avoid in existing leukopenia/ neutropenia
Name considerations: Clozapine (Clozaril®) (2)
- Weekly blood counts for 6 mo, then q2wk
- Do not use with other drugs that may cause bone marrow suppression due to risk of agranulocytosis
Name advantages: Aripiprazole (Abilify®) (3)
- Less weight gain and risk of metabolic syndrome compared to olanzapine
- a lower incidence of EPS compared to haloperidol
- mood stabilizing
Name disadvantages relative to other SGAs: Aripiprazole (Abilify®) (2)
- Insomnia
- akathisia
Classify commonly used atypical antipsychotics according to risk of weight gain (Risperidone, Clozapine, Quetiapine, Olanzapine)
Risk of weight gain: Clozapine > Olanzapine > Quetiapine > Risperidone
Describe: Neuroleptic Malignant Syndrome (3)
- psychiatric emergency
- due to strong DA blockade; increased incidence with high potency and depot antipsychotics
- risk factors
- medication factors: sudden increase in dosage, starting a new drug
- patient factors: medical illness, dehydration, exhaustion, poor nutrition, external heat load, male, young adults
- mortality: 5%
Describe clinical features: Neuroleptic Malignant Syndrome (5)
- tetrad:
- mental status changes (usually occur first)
- fever
- rigidity
- autonomic instability
- develops over 24-72 h
Describe labs: Neuroleptic Malignant Syndrome (3)
- ⬆️ creatine phosphokinase
- leukocytosis
- myoglobinuria
Describe tx: Neuroleptic Malignant Syndrome (6)
- supportive
- discontinue antipsychotic drug
- hydration
- cooling blankets
- dantrolene (hydrantoin derivative, used as a muscle relaxant)
- bromocriptine (DA agonist)
Name extrapyramidal sx of antipsychotics (4)
- Dystonia
- Akathisia
- Pseudoparkinsonism
- Dyskinesia
Describe this extrapyramidal sx in antipsychotics: Dystonia
- Acute or Tardive
- High Risk Groups
- Presentation
- Onset
- Acute or Tardive: Both
- High Risk Groups: Acute: Young asian and black males
- Presentation: Sustained abnormal posture; torsions, twisting, contraction of muscle groups; muscle spasms (i.e. oculogyric crisis, laryngospasm, torticollis)
- Onset:
- Acute: within 5d
- Tardive: >90d
Describe this extrapyramidal sx in antipsychotics: Dystonia
- Treatment (2)
Acute:
- benztropine
- diphenhydramine
Describe this extrapyramidal sx in antipsychotics: Akathisia
- Acute or Tardive
- High Risk Groups
- Presentation
- Onset
- Acute or Tardive: Both
- High Risk Groups: Older females
- Presentation:
- Motor restlessness; crawling sensation in legs relieved by walking
- very distressing, increased risk of suicide and poor adherence
- Onset:
- Acute: within 10d
- Tardive: >90d
Describe this extrapyramidal sx in antipsychotics: Akathisia
- Treatment (4)
- Acute:
- lorazepam
- propranolol
- diphenhydramine
- reduce dose or change antipsychotic to lower potency
Describe this extrapyramidal sx in antipsychotics: Pseudoparkinsonism
- Acute or Tardive
- High Risk Groups
- Presentation
- Onset
- Acute or Tardive: Acute
- High Risk Groups: Older females
- Presentation:
- Tremor; rigidity (cogwheeling); akinesia; postural instability (decreased/absent arm- swing, stooped posture, shuffling gait, difficulty pivoting)
- Onset: Acute: within 30 d
Describe this extrapyramidal sx in antipsychotics: Pseudoparkinsonism
- Treatment (2)
Acute:
- benztropine
- reduce dosage or change antipsychotic to low potency atypical antipsychotic
Describe this extrapyramidal sx in antipsychotics: Dyskinesia
- Acute or Tardive
- High Risk Groups
- Presentation
- Onset
- Acute or Tardive: Tardive
- High Risk Groups: Older patients
- Presentation:
- Purposeless, constant movements, involving facial and mouth musculature
- less commonly – the limbs; rarely, the diaphragm (“hiccups”)
- Onset: Tardive: >90d
Describe this extrapyramidal sx in antipsychotics: Dyskinesia
- Treatment
- no good treatment
- may try clozapine
- discontinue drug or reduce dosage
Describe use of anticholinergic agents with antipsythotics (3)
- types
- benztropine (Cogentin®) 2 mg PO, IM, or IV OD (1-6 mg)
- diphenhydramine (Benadryl®) 25-50 mg PO/IM qid
- do not routinely prescribe with antipsychotics
- give anticholinergic agents only if at high risk for acute EPS or if acute EPS develops
- do not give these for tardive syndromes because they worsen the condition
