Clozapine - 1 Flashcards
when was clozapine first made?
1950’s
the europian journey of clozapine?
Introduced in 1970’s
withdrawn despite affecitveness in 1976
Reintroduced in 1990 with mandatory blood monitoringg
cause of withdrawal of clozpaine in europe in 1976?
some death due to agranulocytosis
Indication for clozpane in schizo?
treatment-resistant schizophrenia
how is treatment-resistant schizophrenia (TRS) defined?
Ongoing symptoms and functional impairments despite two adequate trials of different antipsychotics with proper adherence.
% of TRS?
20-33%
% of TRS responding to clozapine?
a whopping 60%
what are those who don’t respond to even clozapine called?
Ultra Resistant ( no response to trial of 2 antipsychotic and clozapine)
% of schizophrenia that will be ultra Resistant?
12-20%
how long should you wait after clozapine administration to monitor blood level?
12 hours ideally
how many days should patients be on clozapine before monitoring is performed and why?
7 days
to achieve a steady state
what is average clozapine dose in the UK
450 mg / day
- - -
in what range of clozapine dose is response seen?
150-900 mg / day
what threshold most studies have suggested for clozapine?
0.34-0.42 mg/l
(can be as high as .5 mg/l)
is there an established threshold for clozapine?
No!!!!
what does a threshould above 0.5 mg/l mean?
-should be treated with caution
-there is a risk of @@@Seizure@@@
what patients might need lower dose?
non-smokers
elderly
females
patients on SSRs (enzyme inhibitors)
can inflammations affect clozapine level?
Yes, it increased.
what does Maudsley 14th edition say if the clozapine plasma level is < 0.35?
if poor response, increase.
if good response, maintain.
what does Maudsley 14th edition say if the clozapine plasma level is 0.35-0.5?
if good response, maintain
If poor, increase to >0.5 mg/l and consider prophylactic anticonvulsants
what does Maudsley 14th edition say if the clozapine plasma level is 0.5-1 mg/l?
*if there is a poor response, consider prophylactic anticonvulsant and consider augmentation.
if that is poorly tolerated, reduce the dose if augmentation worked.
*If good response and well tolerated, just consider prophylactic anticonvulsant and maintain the dose.
*If good response and poorly tolerated, consider prophylactic, reduce the dose ( if there is no history of poor response in low doses)
so when clozapine is between 0.5 to 1 mg/l, additing what agent must be considered?
prophylactic anticonulsant
what does Maudsley 14th edition say if the clozapine plasma level is > 1mg/l?
*if poor response, attempt augmentation and add anticonvulsant, then reduce the dose ( to >1 mg/l)…Consider abandoning clozapine
*If there is a good response but poorly tolerated, add anticonvulsant and slowly reduce the dose
*If there is good response and well tolerated, add anticonvulsant and monitor closely…only attempt dose reduction if toleration declined
when should clozapine abandoning be considered?
if blood level is above 1 mg/l and there is poor response to current dose and reduction.
