antipsychotic MOA
block dopamine activity in target brain pathways
neuroleptic
old name for antipsychotic
antipsychotics indicated for
psychotic symptoms!
- schizophrenia & related
- manic or depressive episodes
- substance use
- medical condition (eg neoplasm)
non-psychosis uses of antipsychotics - conditions
- treatment-resistant MDD
- severe GAD
- complex PTSD
- severe OCD
- borderline PD
- behavioural Sx of dementia
- delirium
- tic disorder
- substance abuse in dual Dx
- Huntington’s disease
- pervasive developmental disorders
- impulse control disorders
non-psychosis uses of antipsychotics - symptoms
adjunctive for:
- agitation
- aggression
- severe anxiety
- sleep difficulties when sedative-hypnotics are contraindicated
onset of antipsychotics
- immediate decrease in agitation, calming effect
- 1-4w for thought disorder response
choosing an antipsychotic
- no reason to combine
- all comparably effective (except: clozapine most effective in treatment-refractory psychosis)
- 2nd gen antipsychotics as effective as 1st gen, but different a/e profile: mainly lower risk of EPS and TD
- choose a drug pt or family member has responded to 1st
when to switch antipsychotics
if no response in 4-6w, switch drugs
Emergency Treatment of Acute Psychosis - drugs & dosing
- haloperidol 5mg IM ± lorazepam 2mg IM
- loxapine 25mg ± lorazepam 2mg IM
- olanzapine 2.5-10 mg PO/IM/quick dissolve
- risperidone 2mg (M-tab, liquid)
Dopamine pathways affected by antipsychotics
Mesolimbic, mesocortical, nigrostriatal, tuberoinfundibular
Mesolimbic pathway
dopamine pathway; involved in emotion origination, reward; high dopamine causes delusions, hallucinations (+ sx of schizophrenia)
Mesocortical pathway
Dopamine pathway; involved in cognition, executive function; low dopamine causes negative Sx of schizophrenia
Nigrostriatal pathway
Dopamine pathway; involved in movement; low dopamine causes EPS (think Parkinson)
Tuberoinfundibular
Dopamine pathway; involved in prolactin hormone release; low dopamine causes hyperprolactinemia (–> gynecomastia, galactorrhea)
1st Gen Antipsychotics: MOA, Pros, Cons
MOA: Block postsynaptic D2 receptors
Pros: Inexpensive, many injectables available
Cons: EPS, tardive syndromes, not mood stabilizing
2nd Gen Antipsychotics: MOA, Pros, Cons
MOA:
- block postsynaptic D2 receptors
- Block serotonin (5-HT2) receptors on presynaptic dopaminergic terminals –> dopamine release; also –> reverses dopamine blockade in some pathways
Pros: Fewer EPS, low risk of tardive syndromes, mood stabilizing effects
Cons: Expensive. Few injectables. Metabolic side effects. Exacerbation (or onset) of obsessive behaviour.
Risperidone pros/cons
Pros: Lower EPS compared to 1st gen; less wt gain than clozapine, olanzepine
Cons: Highest risk of EPS/TD among 2nd Gen - avoid if high risk for movement disorder or elderly. Elevated prolactin - sexual dysfunction, galactorrhea, gynecomastia, menstrual disturbance, infertility
Olanzepine pros/cons
Pros: Better overall efficacy compared to haloperidol. Well tolerated. Low incidence of EPS & TD.
Cons: Wt gain & metabolic effects - avoid in DM. Sedating - avoid if high risk for falls or #.
Quetiapine pros/cons
Pros: Less wt gain than clozapine & olanzepine. Mood stabilizing.
Cons: Sedating. Orthostatic hypotension - avoid is high risk for falls or #. QT prolongation in high doses.
Clozapine pros/cons
Pros: Most effective for treatment-resistant schizophrenia. Does not worsen tardive Sx, & may treat them.
Cons: Wt gain, metabolic effects - avoid in DM. Sedating, orthostatic hypotension - risk fo falls & #. Potential severe constipation. Cardiomyopathy. Sz. Agranulocytosis!!! (1% - avoid if exisiting leukopenia/neutropenia, & get blood counts q1w for 6mo then q2w
Aripiprazole pros/cons
Pros: Less wt gain & metabolic syndrome than olanzapine. Less EPS than haloperidol
Cons: Insomnia
Commonly used 2nd gen antipsychotics
Risperidone Olanzapine Quetiapine Clozapine Aripiprazole
Anticholinergic effects
Red as a Beet, Hot as a Hare, Dry as a Bone, Blind as a Bat, Mad as a Hatter … … …
or, Anticholinergic: dry mouth, urinary retention, constipation, blurred vision, confusional states
How frequently are antipsychotics discontinued?
One trial with daily dosing recorded discontinuation rates from 64% to 82% w/in 6mo. So … a lot.
