Graylands Hospital DRUG BULLETIN Pharmacy Department Brockway Road Mount Claremont WA 6010 Telephone (08) 9347 6400 Email [email protected] 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 Graylands Hospital Drug Bulletin 2006 Vol 14 No.3 - 1 - 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 medication should be used where possible, so that the greatest mean weight gain has been associated 11 with clozapine and olanzapine6. Of the atypical treatment can be more easily supervised . Metformin is considered the preferred first-line antipsychotics, amisulpride and aripiprazole are 11 considered the lowest risk of causing weight gain2,7. antidiabetic agent . HbA1c should be measured every 3–6 months to monitor glycaemic control. Ideal BMI should be monitored monthly for the first six 1 months or at every visit on an outpatient basis1,3. glycaemic control is represented by an HbA1c < 7% . Patients should be encouraged to maintain a BMI between 18.5-25kg/m2. Antipsychotic treatment Electrocardiograph 2 should be reviewed if BMI>30kg/m 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 1 activity. of antipsychotic therapy . 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 1 Target Lipid Levels9 QTc interval . Antipsychotics generally accepted as LDL-cholesterol < 2.5 mmol/L having a higher risk of causing torsades de pointes include: chlorpromazine, droperidol, haloperidol, (<2.0mmol/L for high-risk patients) 12 Total cholesterol <4.0 mmol/L pimozide and thioridazine (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 9 If the QT interval is prolonged to greater than managed . c 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. Graylands Hospital Drug Bulletin 2006 Vol 14 No.3 - 2 - careful monitoring of serum sodium is recommended. Full Blood Picture 2 Haematological abnormalities are frequently Refer to specialist medical care if Na<125mmol/L . 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 9 neutrophil count is <1.5 X 10 /L, treatment should be hepatotoxic drugs such as clozapine and 1 stopped and haematologist advice sought . phenothiazines and monitor LFTs weekly, at least 2 initially . 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.