Graylands Hospital

DRUG BULLETIN
Pharmacy Department Brockway Road Mount Claremont WA 6010
Telephone (08) 9347 6400 Email DrugInformation.Graylands@health.wa.gov.au Fax (08) 9384 4586

Antipsychotic Monitoring
Graylands Hospital Drug Bulletin 2006 Vol. 14 No. 3 October ISSN 1323-1251

Introduction
Evidence supporting what constitutes best practice in Table 1 lists suggested baseline monitoring for
the monitoring of antipsychotics is lacking. patients starting on an antipsychotic drug and
Monitoring patients receiving antipsychotics can be suggested ongoing monitoring. More frequent
seen as having two overall goals; firstly, to identify monitoring may be indicated in certain situations;
treatable pathology in a high-risk population and these are discussed under the relevant monitoring
secondly, to link and track antipsychotic-induced parameter heading.
adverse effects. Antipsychotics have been associated
with causing a variety of cardiovascular, metabolic, Medical History
hepatic, haematologic and endocrine diseases. Certain antipsychotics are contraindicated or must be
used with caution in patients with other
Physical health monitoring is the responsibility of the comorbidities5. Judicious selection of an
patient, case manager, GP and psychiatrist. Mental antipsychotic is particularly important in patients
health services should ensure that a monitoring with a history of:
protocol is incorporated into the treatment plan of
every patient. All monitoring protocols must include Severe cardiac, renal or hepatic disease
a workable, effective call-up system and a process to Conditions that are risk factors for arrhythmia
audit compliance. eg bradycardia, electrolyte imbalance

Table 1: Key Monitoring Recommendations1,2,3,4

Baseline and Early Treatment Monitoring Ongoing Monitoring

Baseline At 1-2 Monthly At 3 3-monthly 6-monthly 12-monthly

weeks For 6 months
months
Medical history X
Weight (BMI) X X X
BSL X X X
Fasting lipid profile X X X# X
ECG X X* X*
FBP X X
U+E X X*
LFT X X
BP and pulse X X
Key:
BMI= Body mass index (kg/m2) ECG= Electrocardiograph U+E= Urea and electrolytes
BSL= Blood sugar level (measure FBP= Full blood picture LFT= Liver function test
fasting venous glucose level) BP= Blood pressure
* Suggested monitoring dependent on risk factors
# For high-risk drugs for the first year, then annually
There is additional, specific monitoring for clozapine; refer to the clozapine monitoring section
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 Parkinson’s disease Aside from the recommended regular monitoring, BSL
Diabetes should be measured at any time if weight loss,
Closed angle glaucoma, increased intraocular polydipsia, polyuria or unexplained tiredness
pressure, GI obstruction, prostatism, urinary occurs10. The following table outlines the diagnostic
retention, myasthenia gravis criteria for diabetes.
Epilepsy
Bone marrow disorders or history of blood Blood Glucose Level10
dyscrasias Diabetes ≥7.0mmol/L (fasting) or
Prolactin-dependent tumours ≥11.1mmol/L (random)
Respiratory failure Must occur on two occasions, or once
Phaeochromocytoma with diabetic symptoms
Current pregnancy or lactation
Impaired 5.5 –7.0 mmol/L (fasting) or
glucose 5.5 –11.0 mmol/L (random)
Aside from a patient’s medical history, a medication
tolerance (Diagnosis of diabetes if BSL ≥ 11.1
history including any drug allergies or adverse drug
mmol/L at 2 hours following oral
reactions should also be elicited.
glucose tolerance test)

Body Mass Index

Most antipsychotics can cause weight gain, although If diabetes is diagnosed, once daily antidiabetic
the greatest mean weight gain has been associated medication should be used where possible, so that
with clozapine and olanzapine6. Of the atypical treatment can be more easily supervised11.
antipsychotics, amisulpride and aripiprazole are Metformin is considered the preferred first-line
considered the lowest risk of causing weight gain2,7. antidiabetic agent11. HbA1c should be measured
BMI should be monitored monthly for the first six every 3–6 months to monitor glycaemic control. Ideal
months or at every visit on an outpatient basis1,3. glycaemic control is represented by an HbA1c < 7%1.
Patients should be encouraged to maintain a BMI
between 18.5-25kg/m2. Antipsychotic treatment Electrocardiograph
should be reviewed if BMI>30kg/m2 or if there is >5% QTc prolongation and resultant arrhythmia including
weight gain over baseline8. Prevention of weight torsades de pointes has been associated with a
gain should be the primary objective by encouraging number of antipsychotics. A baseline ECG is
behavioural modification of diet and physical recommended for all patients at the commencement
activity. of antipsychotic therapy1. If the baseline QTc interval
is >450ms, thioridazine should not be prescribed5;
Lipid Profile other antipsychotics should be used with caution.
Antipsychotics considered a high-risk of causing
hyperlipidaemia include clozapine, quetiapine, The ECG should be repeated 1-2 weeks after starting
olanzapine and the phenothiazines2. The National treatment and at 6-monthly intervals for patients
Heart Foundation recommends the following target with risk factors for arrhythmia, patients receiving
lipid levels: high-dose or high-risk antipsychotics or patients
receiving multiple medications known to prolong the
Target Lipid Levels9 QTc interval1. Antipsychotics generally accepted as
LDL-cholesterol < 2.5 mmol/L having a higher risk of causing torsades de pointes
(<2.0mmol/L for high-risk patients) include: chlorpromazine, droperidol, haloperidol,
Total cholesterol <4.0 mmol/L pimozide and thioridazine12 (see www.qtdrugs.org for
HDL-cholesterol > 1.0 mmol/L a complete list).
Triglycerides <1.5 mmol/L
Additional ECG monitoring is also recommended
when there are dose changes for high-risk drugs, or if
Please note that these recommendations may differ
patients experience signs of arrhythmia including
from PBS criteria for eligibility for lipid lowering
shortness of breath, dizziness, loss of consciousness
medications. Before lipid-lowering medications are
or palpitations1.
commenced, secondary causes of dyslipidaemia and
modifiable cardiovascular risk factors should be
If the QTc interval is prolonged to greater than
managed9.
500ms, the causative drug should be stopped, and
the patient referred to a cardiologist1. Antipsychotic
Blood Glucose Level therapy should be reviewed if the QTc interval
There is an increased risk of developing diabetes with becomes prolonged by greater than 60ms over
certain antipsychotics, particularly olanzapine, baseline or if there is abnormal T-wave morphology1.
clozapine and the phenothiazines. Although there is Switching to a lower-risk antipsychotic should also be
a correlation between diabetes and drug-induced considered if the QTc interval is greater than 440ms
weight gain, diabetes can occur independently. (men) or greater than 470ms (women) 2.

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Full Blood Picture careful monitoring of serum sodium is recommended.
Haematological abnormalities are frequently Refer to specialist medical care if Na<125mmol/L2.
encountered with antipsychotic therapy; however,
most of these are of little clinical significance. In a Liver Function Test
small minority of patients, potentially life- A baseline LFT is required to determine any hepatic
threatening haematologic abnormalities including impairment. Although LFTs are a poor marker of
neutropenia and agranulocytosis occur. Aside from hepatic metabolising capacity, if elevated, a lower
regular monitoring, the FBP should also be monitored starting dose of highly protein-bound, hepatically
if a patient develops clinical signs of infection such metabolised antipsychotics should be considered2. If
as fever, sore throat or flu-like symptoms. If the a patient has severe hepatic disease, avoid
neutrophil count is <1.5 X 109/L, treatment should be hepatotoxic drugs such as clozapine and
stopped and haematologist advice sought1. phenothiazines and monitor LFTs weekly, at least
initially2. If LFTs deteriorate after a new drug is
introduced, consider switching to another drug.
Urea and Electrolytes Antipsychotics often cause asymptomatic increases in
Baseline U+E monitoring is required to assess renal aminotransferase levels. Rarely, antipsychotics can
function and to make any necessary dose cause hepatotoxicity or hepatocellular cholestasis. A
adjustments. Electrolyte abnormalities, particularly LFT is indicated if a patient develops jaundice,
hypokalaemia, hypomagnesaemia and hypocalcaemia pruritus, dark urine, pale stools, nausea or loss of
can increase the risk of QTc prolongation and appetite.
arrhythmia; these should be corrected before
antipsychotic therapy is commenced2. Antipsychotics
have been associated with hyponatraemia caused by Blood Pressure
drug-induced syndrome of inappropriate antidiuretic Monitor both recumbent and standing blood pressure
hormone. U+Es should be monitored if a patient and pulse at baseline and during dose titration for
develops signs of hyponatraemia including confusion, antipsychotics with alpha1-adrenergic blocking
nausea, headache and lethargy. If mild activity including clozapine, risperidone, quetiapine,
hyponatraemia is detected, fluid restriction with chlorpromazine and thioridazine.

Additional Monitoring
Prolactin Thyroid Function Test
A prolactin level is indicated if a patient reports Changes in thyroid function may occur in patients
signs and symptoms of hyperprolactinaemia such as taking quetiapine. A baseline thyroid function test
sexual dysfunction, galactorrhoea, amenorrhoea or and follow up at one month may be advisable for
gynaecomastia. If prolactin-related adverse patients at risk of hypothyroidism1.
reactions are intolerable, consider reducing the dose
of medication or switching to a prolactin-sparing Clozapine Monitoring
antipsychotic3. For clozapine, monitoring of FBP is required weekly
for the first 18 weeks of therapy and then monthly
Creatine Kinase thereafter. Stop clozapine if neutrophils <1.5 X
Monitor creatine kinase (CK) as well as FBP (for 109/L; total leukocyte count <3.0 X 109/L; or if
leukocytosis) if a patient presents with fever, eosinophils >3.0 X 109/L13.
rigidity and diaphoresis to rule out neuroleptic
malignant syndrome. Raised CK (>1000IU/L) may The manufacturers of clozapine recommend
indicate possible neuroleptic malignant syndrome2. monitoring baseline markers of myocardial damage
using troponin I or T assay and serum creatinine as
well as an ECG. The baseline cardiac enzymes and
Electroencephalograph ECG should be repeated on days 7 and 14 of
Most antipsychotics produce a dose related treatment to detect any early signs of acute
reduction in seizure threshold. Monitor EEG if myocarditis. Stop clozapine if ECG shows significant
myoclonus or seizures occur. If EEG changes occur, changes13.
consider switching to a drug with a low
proconvulsive effect or adding an anticonvulsant. After 6 months of treatment, it is advised that
patients undergo echocardiography to test for the
Eye Examination development of chronic cardiac adverse effects as
Phenothiazines may induce cataracts or pigmentary well as to provide a baseline reading against which
retinopathy, which is dependent on both the dose future events may be measured13.
and duration of treatment. Ocular examinations
More frequent haematological and cardiac
should be performed annually or if changes in vision
monitoring may be indicated in certain cases; refer
are reported3.
to the manufacturer published clozapine protocol.
Graylands Hospital Drug Bulletin 2006 Vol 14 No.3
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 Therapeutic Drug Monitoring (TDM) of Psychotropics

Table 2: Interpretation of Sample Results2,5,14,15,16

Drug Target Sampling Time to Comments
Therapeutic Time Steady
Range State
Clozapine 350-600 µg/L Trough 2-3 days Plasma levels generally lower in males, younger
patients and smokers.
Lithium 0.5-1.2 mmol/L 12 hours 5 days Aim for the upper end in acute mania and lower end in
post –dose maintenance therapy.
Valproate 50-100 mg/L Trough 2-3 days Clinical value in bipolar disorder is controversial;
dosing should be guided by clinical response and
tolerability
Carbamazepine 6-12 mg/L Trough 2 weeks Time to steady state depends on its auto-induction.
Lamotrigine 1-14 mg/L Trough 5 days Recommended for compliance monitoring only
Olanzapine 20-80 µg/L 12 hours 1 week Dosing should be guided by response and tolerability
post –dose and TDM reserved for compliance monitoring and lack
Risperidone + 20-60 µg/L Trough 1 day of response at maximum dosage.
9-0H risperidone
Quetiapine 70-170 µg/L Trough 2 days
Amisulpride 100-400 µg/L Trough 2-3 days

TDM monitoring. Canadian journal of Psychiatry. 2005;50(9):555-562.

5
eMims Online. Donahoo E, editor: Health Communication Network; 2006
6
TDM is a valuable tool when used appropriately for Allison D, Mentore J, Heo M, Chandler L, Cappelleri J, Infante M, et al.
Antipsychotic-induced weight gain: a comprehensive research synthesis.
optimising drug therapy in clinical psychiatry. Table American Journal of Psychiatry 1999;156:1686-1696.
2 outlines practical issues of TDM for a number of 7
Taylor D, McAskill R. Atypical antipsychotics and weight gain — a
systematic review. Acta Psychiatrica Scandinavica. 2000;101:6 41.
psychotropic drugs. 8
Consensus development conference on antipsychotic drugs and obesity
and diabetes. Diabetes Care. 2004;27(2):596-601.
9
National Heart Foundation of Australia and the Cardiac Society of
Sampling Australia and New Zealand. Position statement on lipid management- 2005.
[homepage on the internet] 2005. Available from:
Before sampling, steady state plasma concentrations www.heartfoundation.com.au/downloads/Lipids_HLCPosStatementFINAL_2
should be reached in order to prevent 005.pdf.
10
misinterpretation of drug concentrations. In Lambert T, Chapman L (on behalf of the Consensus Working Group).
Diabetes, psychotic disorders and antipsychotic therapy: a consensus
practice, sampling for most psychotropic drugs is statement. MJA 2004; 181(10):544-548.
carried out one week after chronic daily dosing 11
Proietto J. Diabetes and antipsychotic drugs. Australian Prescriber.
2004;27(5):118-119.
either 12 hours post-dose or immediately before the 12
ArizonaCert Center for education and Research on Therapeutics. Drugs
next dose depending on the drug14. In both cases, that prolong the qt Interval and/or induce torsades de pointes ventricular
arrhythmia. Arizona: The university of Arizona [homepage on the internet]
samples taken more than 1-2 hours before or after c2006 [updated June 15 2006]. Available from http://www.qtdrugs.org/.
the scheduled time are likely to lead to falsely low 13
Clopine ConnectTM Protocol. Parkville, Victoria: Mayne Pharma Pty Ltd;
or high readings15. 2006 Available from www.clopineconnect.com.au.
14
Micromedex® Healthcare Series [intranet database]. Version 5.1.
Greenwood Village, Colo: Thomson Micromedex.
Interpretation of Results
15
Baumann P, Hlemke C, Ulrich S, Eckermann G, Gaertner I, Kuss H et al.
The AGNP-TDM expert group consensus guidelines: therapeutic drug
If the drug concentration is within therapeutic monitoring in psychiatry. Pharmacopsychiatry. 2004;37:243-265.
16
PathWest Laboratory Medicine WA. Laboratory Reference Ranges.
range, modification of dosage is recommended only November 2003. Available from http://www.pathwest.com.au/.
when justified by clinical reasons such as adverse
effects or lack of clinical response. When plasma
concentrations are unusually low, a repeat level is Acknowledgement:
recommended; this may help to determine irregular
Antipsychotic Monitoring was written by Karolinka Golebiewski
compliance, or presence of environmental or genetic
factors leading to rapid metabolism of the particular and Therapeutic Drug Monitoring was written by Jung Kim.
drug14,15. This bulletin was reviewed by members of the Pharmacy
References:
1
Western Australian Psychotropic Drugs Committee. Antipsychotic drug Department and Dr Nathan Gibson.
guidelines. Version 3. Western Australian Psychotropic Drugs Committee;
2006 Available from www.watag.org.au.
2
Taylor D, Paton C, Kerwin R. The Maudsley 2005-2006 prescribing
guidelines. 8th ed. London: Taylor and Francis; 2005. Comments are welcome at the email address:
3
Marder S, Essock S, Miller A, Buchanan R, Casey D, Davis J et al. Physical
health monitoring of patients with schizophrenia. American Journal of DrugInformation.Graylands@health.wa.gov.au
Psychiatry. 2004;161(8):1334-1348.
4
Poulin M, Cortese L, Williams R, Wine N, McIntyre R. Atypical
antipsychotics in psychiatric practice: practical implications for clinical

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