Download Module 3 – Case Study 2: Initiating Depot Antipsychotics

Module 3 – Case Study 3: Treatment Resistant Schizophrenia
Calvin's Pharmaceutical Care Plan
Calvin is a 28-year-old who identifies himself as Maori and European. He has been admitted to
an acute psychiatric unit after a serious self-harm attempt.
History at presentation: Calvin has a long history of schizophrenia, which has required 4
admissions since his first presentation 7 years ago. This is his third suicide attempt to “cleanse
the world of evil”, as he feels that by hurting himself the devil looses power. His medication
history revealed the following:
 Risperidone 6 mg daily - resulted in EPSE
 Olanzapine 25 mg/day - questionable response (readmitted after 6 months, unknown
adherence).
 Combination of depot flupenthixol with oral risperidone (up to 4 mg BD) - non-adherence
(unclear of the reason, possibly side effects - high risperidone dose), but most likely due to
lack of response – his community care worker has been administering “prn” haloperidol).
Possible diagnosis: Treatment refractory schizophrenia. The most common definition of
treatment resistant schizophrenia denotes patients who despite at least two adequate trials of
classical neuroleptic drugs, have persistent moderate to severe, positive symptoms, or
disorganized, or negative symptoms of schizophrenia, together with poor social and work function
over a prolonged period of time. Approximately 30% of schizophrenic patients meet these
criteria. This criteria certainly applies to Calvin. His DSM-IV multi-axial diagnosis for this
admission is summarized below:
Axis I – Treatment resistant schizophrenia
Axis II – Two serious self-harm attempts in the past
Axis III – Possible alcohol abuse
Axis IV – Not working for the past 4 months
Axis V – Global Assessment of Functioning (GAF) score is unavailable, but likely <50 (he is at
50% his normal level of functioning)
Management:
1. The most immediate management goal for Calvin is to minimize the risk of another self-harm
episode as a result of insufficient response to current pharmacological treatment for his psychotic
symptomatology. This can be achieved by the use of a medication known to be effective in
treatment resistant schizophrenia, such as clozapine. Calvin meets the criteria for the use of
clozapine as it is indicated in clients who have failed 2 attempts with other antipsychotics or who
have experienced extrapyramidal side effects as a result of previous antipsychotic management.
In addition, clozapine has been shown to be effective in managing people with schizophrenia
whose behaviour includes recurrent suicide attempts. Clozapine has been found to reduce the
lifetime risk of suicide from 10 -15% in schizophrenics to levels reported in the general public. It
is estimated that approximately 60-70%of treatment resistant schizophrenics will respond to
clozapine.
Workup for commencing clozapine includes: ECG (arrythmias), X-ray (myocarditis), fasting blood
glucose, lipid profile, weight (metabolic syndrome), and full blood count (agranulocytosis).
Agranulocytosis is defined as a granulocyte count of <400 mm 3, while granulocytopenia: <1500
mm3. Incidence: 0.5 to 2%, this risk has been significantly reduced as a result of a strict blood
monitoring that is required when prescribed clozapine. White blood cell (WBC) and differential
blood counts must be performed within 10 days prior to starting clozapine treatment to ensure
that only patients with normal leukocyte and absolute neutrophil counts (ANC) (WBC ≥ 3500/mm 3
= 3.5 x 109/L, and ANC ≥ 2000/mm 3 = 2. 0 x 109/L) should receive clozapine. After the start of
clozapine treatment, the WBC count and ANC must be monitored weekly for 18 weeks, and
thereafter at least every four weeks throughout treatment, and for 4 weeks after complete
discontinuation. For more information, review the Medsafe datasheet for clozapine available
from: http://www.medsafe.govt.nz/profs/Datasheet/c/Clozariltab.htm. At each consultation, the
patient should be reminded to contact the treating physician immediately if any kind of infection,
fever, sore throat or other flu-like symptoms develop. A differential blood count must be
performed immediately if any symptoms or signs of an infection occur.
It is also recommended to have an alternative pharmacological treatment plan for Calvin. People
with treatment resistant schizophrenia are often unwilling to commence clozapine, for two
reasons. Firstly, the monitoring of clozapine, especially for the first 18 weeks involves weekly
blood tests, and frequent monitoring of vital signs. This is a lot of contact with medical staff, and
patients who have been under-treated or who have not had a good response to other medications
are often reluctant to agree to this level of monitoring. They may be extremely paranoid, believe
there is no hope or point, or be needle phobic. Secondly, the understanding of treatment
resistant schizophrenia for some people may mean that they are at the “end” of the line of
treatment wise, they may be reluctant to start because if it doesn’t work, they believe there is
nothing left to try.
2. Maximize the antipsychotic effects while minimizing the potential risks associated with the
temporary use of various antipsychotics (clozapine, risperidone, and flupenthixol depot) during
the switch over period. Consequently, the best switching strategy is to keep Calvin on a reduced
dosage of risperidone (to provide some antipsychotic effect, specially against negative
symptoms) while waiting for the therapeutic effects of clozapine once optimal dosing is reached
(this may take up to 6 weeks). Although the depot antipsychotic has been discontinued, the depot
formulation of flupenthixol will continue to provide dopamine blockade for up to 5 x its half-life
(approximately 17 days after multiple dosing for flupenthixol decanoate), increasing the risk for
side effects (specially EPSE) during the switch over period.
Monitoring Plan: As previously mentioned, during the switching period, Calvin will be at an
increased risk for EPSE (rare with clozapine, but should be monitored initially), plus the common
side effects usually associated with clozapine initiation of therapy, such as anticholinergic side
effects (constipation) and sedation. Hypersalivation with clozapine is a common side effect, it
usually appears once higher doses have been reached. It is of unknown mechanism, but very
difficult for patients to cope with. Numerous pharmacological and non-pharmacological strategies
for this have been proposed (including the use of clonidine, atropine drops, and the application of
towels on the patient’s pillow to absorb the saliva secreted during sleep). During the first months
of treatment, Calvin’s haematological profile needs careful monitoring for any laboratory signs of
agranulocytosis (FBC weekly for the first 18 weeks, then monthly – as explained above) as well
as close observation for any clinical symptoms.
Monitoring for medication efficacy is as important as monitoring for side effects. Calvin’s initial
psychotic presentation has shown a marked improvement. Positive symptoms have decreased
(not responding to voices during the night, his ideas regarding the devil are troubling him less, he
is more settled and less agitated), and a decline in his negative symptoms is also evident
(improved sleep pattern, eating meals with fellow patients, appears happier). His potential for
compliance is also evident as he states that he is happy with his new tablets. At a dose of
450mg/day, reached at 4 weeks of clozapine treatment initiation, Calvin appears to be responding
to clozapine when the drug is likely to be achieving its therapeutic window. Another way of
monitoring this would be measuring clozapine blood levels. This option however, may not be
readily available in all treatment centers. Consensus is lacking on the optimal clozapine plasma
level needed to achieve a therapeutic response. For some patients, it may be 200 to 350 ng/mL,
which usually corresponds to 200 to 400 mg/d.