Graded A+
Treatment-Resistant Schizophrenia defined as... - A lack of significant improvement in
symptoms despite treatment with at least two antipsychotics from two different
antipsychotic
classes at the recommended dosage for a period of at least 2-8 weeks
The Joint Commission has established three situations in which the use of more than
one antipsychotic at the time of discharge from a psychiatric inpatient setting is justified
- 1. Three or more failed trials of antipsychotic monotherapy
2. Cross-titration of antipsychotic medications
3. Augmentation of clozapine (as 4th line in treatment resistance)
Treatment of catatonia - 1. Benzodiazepines are first-line treatment
2. Electroconvulsive therapy (ECT) can be considered for benzodiazepine failure or
when rapid resolution of symptoms is needed
AP effect on Mesocortical pathway - Worsening negative symptoms
AP effect on Mesolimbic pathway - Relief of positive symptoms
AP effect on Nigrostriatal pathway - Development of Extrapyramidal symptoms
AP effect on Tuberoinfundibular pathway - Increase in prolactin release
How much D2 receptor occupancy is required for clinical benefits? - 65%
How much D2 receptor occupancy leads to movement adverse effects? - 78-80%
When do withdrawal symptoms usually begin after abrupt discontinuation of
antipsychotics? - Withdrawal symptoms usually begin 2-3 days after abrupt
discontinuance and may last up to 14 days (average incidence: 38%)
What is preferred: High vs Low potency FGA in pregnancy? - High potency FGAs are
recommended over the use of low potency FGAs to minimize adverse effects
(anticholinergic, hypotensive, antihistaminergic)
Depot formulations should be avoided to limit long-term exposure to the fetus
Fluphenazine decanoate - Conventional dosing method - i. Time to reach steady state is
4-6 weeks
ii. A significant amount of the depot injection being released early or "dose dumping"
may be responsible for the high peak in plasma concentration that occurs within the first
day of the injection
, iii. Because of individual patient pharmacokinetic variability, an oral overlap period of 1-
2 weeks may be needed
Haloperidol decanoate - Conventional dosing method - i. Time to reach steady state is
2-4 months
ii. Oral overlap is often necessary and may result in an increase in adverse effects such
as EPS
*Loading dose method*
i. The initial dose should be reduced in the second month to avoid accumulation as
steady state is approached
ii. Oral overlap is not required
List of FGAs - Fluphenazine
Haloperidol
Loxapine
Perphenazine
Pimozide
Chlorpromazine
Thioridazine
Thiothixene
Trifluoperazine
9 total
FGA onset of acute for acute symptoms of agitation, aggression, and increased motor
activity - Onset of action occurs *within a few days* for acute symptoms;
FGA onset of acute for psychotic symptoms, including hallucinations, delusions, and
disorganized thinking - may begin to respond to drug therapy *within 2 weeks*
How long does it take for symptoms of psychosis to respond fully to a specific drug and
dose - up to 4-6 weeks
**persons with poor response to antipsychotic medication in the first weeks of treatment
for schizophrenia may benefit from a switch to a different antipsychotic medication**
Onset of...
1. Dystonic Reaction
2. Pseudoparkinsonism
3. Akathisia
4. Tardive Dyskinesia (TD) - 1. Dystonic Reaction - within 1-4 days
2. Pseudoparkinsonism - several days to weeks
3. Akathisia - within 2-3 weeks of initiation (90% within 2.5 months)
4. Tardive Dyskinesia (TD) - months to years after initiation
Treatment options for...