Monitoring Parameters for Atypical Antipsychotics - A Review of

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					                   Monitoring Parameters for Atypical Antipsychotics

                                        – A Review of the Evidence


1. Introduction

    Patients with schizophrenia receive poor care for their physical health in general and
    treating psychiatrists must play a major role in the patient’s psychological and general
    medical health
    It has been shown that novel antipsychotics, (clozapine, olanzapine, risperidone and
    quetiapine1), are associated with weight gain, elevated glucose and elevated
    triglycerides which compound the risk for coronary artery disease2.
    Early patient education including advising on healthy diet, exercise and smoking
    cessation3, and intervention may prevent weight gain, development of diabetes
    mellitus and non-adherence.
    Psychiatrists and mental health workers are often the only medical professionals who
    interact with many individuals with schizophrenia4. This document has reviewed all the
    evidence currently available to aid prescribers and other healthcare professionals in
    monitoring for potential medical morbidities associated with atypical antipsychotic
    drugs including amisulpride to assure patient safety.

2. Monitoring Recommendations

The following recommendations are not exhaustive and should be tailored to the
individual patient on regular treatment doses of atypical antipsychotics according to
clinical need at the discretion of the prescriber.

    2.1 Weight and BMI
        Weight gain is one of the reasons of treatment non-adherence with antipsychotics2.
         2.1.2 Baseline weight 5, 6, monthly weights4 and BMI should be measured for all
         patients prescribed atypical antipsychotics.
         2.1.2 Nutritional intervention for obese individuals (BMI ≥30), or those experiencing
         significant weight gain (≥7%) should be provided during treatment4.
         Body Mass Index (BMI) can be calculated by dividing weight, (in kg), by height, (in
         meters), squared.
                                                   BMI = Weight (kg)
                                                         Height (m)2

    2.2 Lipids
        Clozapine and olanzapine are associated with the most significant increase in
        triglyceride levels2. A full lipid panel with fractionation of cholesterol should be
        performed annually as part of routine health monitoring for inpatients and
        outpatients4. A baseline 5, 6 and then three monthly fasting total triglycerides and
        cholesterol should be considered during the first year of atypical antipsychotic


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Jyoti Gupta. Mental health Pharmacist, Chelsea & Westminster Hospital.     June 2003.
         therapy4. This frequency may be decreased depending on the results obtained
         and the agent used4.


    2.3 Glucose
        2.3.1 Clozapine and olanzapine are associated with the greatest increase in
           glucose levels2. There are only a few reports describing an association
           between diabetes mellitus and quetiapine, risperidone or amisulpiride though
           this may reflect the lower prescribing rate of quetiapine and amisulpiride 1, 7.

              In most instances, hyperglycaemia, (due to olanzapine or clozapine), is not
              dose dependent, occurs between 10 days to 18 months after initiation of
              treatment, and is reversible on cessation6. At least 30-36.6% of patients who
              started taking clozapine and were followed up for five years were subsequently
              diagnosed and treated for diabetes7, 8.
              Screening for family and personal history of diabetes should be considered for
              all patients with schizophrenia, particularly those with high risk factors4 such as
              older age1, greater adiposity 1, ethnicity 6, family history, hypertension,
              dyslipidaemia, polycystic ovary syndrome and neuropsychiatric illnesses 1.
              Education about the symptoms of diabetes, (fatigue, thirst, polyuria, weight
              loss, blurred vision), should be preformed for those who will be started on
              higher risk agents (clozapine and olanzapine) or possess risk factors4.
         2.3.2 A baseline1, 4, 5, 6 and three monthly fasting glucose during the first year of
            therapy for patients with schizophrenia should be obtained in those receiving
            atypical antipyschotics1, 4. This may be reduced to six monthly1, 4, 5, 6 if no changes
            in fasting glucose are noted and if the individual lacks other risk factors4.

         2.3.3 All patients on any antipsychotic should receive annual fasting glucose1.

         2.3.4 Monthly examination for the first three months and glucose tolerance testing
            may be indicated in those who are at high risk for the development of diabetes,
            then three monthly for the first year followed by six monthly thereafter 4, 7.
            Glycosylated haemoglobin values reflect changes in glycaemic control over a
            period of 120 days and thus will lag several months behind abnormalities in
            fasting4. It is best used as a tool for those with established impairments in
            glucose control, but not as a routine method of screening for diabetes4.
         2.3.5 If diabetes mellitus develops, switching to another antipsychotic agent
            should be considered, though this may not be appropriate in treatment resistant
            patients with schizophrenia who respond to clozapine7. Seek advice from
            pharmacy.

    2.4 Liver Function Tests (LFT’s)
        All patients should have baseline LFT’s performed and thereafter three to six
        monthly9, 10 Patients who complain of gastrointestinal complaints, fever and chills,
        malaise, fatigue and muscle aches should be investigated11. Dose reduction may
        be required in those with hepatic insuffiency, (check individual drug SPC)

    2.5 ECG’s
        Cardiovascular mortality in psychiatric patients is high11. Several psychotropic
        drugs are associated with lengthening of the QT interval, (QTc), on the
        electrocardiogram which is a predictor of arrhythmia. Caution may be needed in

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Jyoti Gupta. Mental health Pharmacist, Chelsea & Westminster Hospital.         June 2003.
         the combination of antipsychotics and other psychotropics since QT dispersion
         may increase the risk of arrhythmia. Caution may also be needed in the
         combination of antipsychotics and drugs known to have pharmacokinetic and
         pharmacodynamic interactions as there could be an increased risk of
         cardiovascular side effects.
         It is advisable to perform an ECG prior administration of clozapine20, quetiapine and
         amisulpride then repeated once maintenance dose has been reached 9. Those
         prescribed high dose antipsychotics, (defined as ≥1g chlorpromazine or greater
         than maximum BNF dose), should have annual ECG’s.
         Table 1 indicates risk of increased QTc interval.

    2.6 Urea and Electrolytes (U&Es)
        Hypokalaemia is often seen in those with bulimia and anorexia and is linked to QTc
        lengthening as well as other electrocardiographic abnormalities which may
        increase the risk of arrhythmia. Dose reductions may be required in those with
        renal insuffiency, (check individual drug SPC).


    2.7 Full Blood Count (FBC)
        2.7.1 All antipsychotics have been associated with haematological disorders such
           as neutropenia and thrombocytopenia at varying incidences. A full blood count
           prior treatment and then three to six monthly thereafter should be initiated for all
           patients on antipsychotics 9,12 especially those on high doses.

         2.7.2 When using clozapine the SPC requirements for blood monitoring must be
            strictly adhered to in order to fulfil the licensing requirements - currently under
            the Clozaril Patient Monitoring Service (CPMS).

    2.8 Thyroid Function Tests (TFTs)
       Quetiapine treatment has been associated with small dose related13 decreases in
       thyroid hormone levels within two to four weeks of initiation 14. In nearly all cases,
       cessation of quetiapine treatment has reversed this process irrespective of
       duration of treatment14. Patients with compromised thyroid function, (e.g. previous
       radioactive iodine therapy, existing hypothyroidism), should have baseline and six
       monthly TFTs such that significant changes can be identified and treated 13.


    2.9 Prolactin
          Antipsychotics can cause hyperprolactinaemia, please refer to trust policy.


    2.10 Blood Pressure and Pulse
    Risperidone, olanzapine, clozapine and quetiapine all act on alpha-1 receptors and
    thus can potentially cause orthostatic hypotension. Amisulpride can also cause
    orthostatic hypotension though the risk is lower compared to other atypical
    antipsychotics.




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Jyoti Gupta. Mental health Pharmacist, Chelsea & Westminster Hospital.      June 2003.
3. On Admission

    If a patient is admitted under the care of the trust, the following tests and observations
    should all be performed within five days of admission, and documented in the notes.
    In the event of a patient refusing such tests, they should be performed as soon as
    consent is given.


         FBC                         Weight & BMI
         LFT                         Random Glucose, (fasting if possible).
         U&E                         Lipids (triglycerides and cholesterol)
         Bp                          Pulse




4. On Discharge

    All baseline tests, including those that are within range and other relevant information
    must be sent to the GP such that patient receives continuous monitoring whilst
    receiving atypical antipsychotic treatment.




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Jyoti Gupta. Mental health Pharmacist, Chelsea & Westminster Hospital.        June 2003.
  5. Summary

         Clozapine                      Olanzapine              Risperidone        Quetiapine         Amisulpride
Weight & Baseline5,6                    Baseline6 then          Baseline6 then     Baseline6 then     Baseline
BMI      then monthly4                  monthly4                monthly4           monthly4           weight9 then
                                                                                                      as necessary9
Lipids         Baseline5,6              Baseline5,6             Baseline5,6        Baseline5,6        Baseline then
               then three               then three              then three         then three         as necessary
               monthly in first         monthly in first        monthly in first   monthly in first
               year and                 year and                year and           year and
               reduce if                reduce if               reduce if          reduce if
               appropriate4             appropriate4            appropriate4       appropriate4
Blood          Baseline1,4,5,6          Baseline1,4,5,6         Baseline1,4,5,6    Baseline1,4,5,6    Baseline then
Glucose        Monthly for              Monthly for             Monthly for        Monthly for        as necessary
               high risk                high risk               high risk          high risk
               patients4                patients4               patients4          patients4
               Three                    Three                   Three              Three
               monthly1,4               monthly1,4              monthly1,4         monthly1,4
                for first year,          for first year,         for first year,    for first year,
               then six                 then six                then six           then six
               monthly1,4,5,6           monthly1,4,5,6          monthly1,4,5,6     monthly1,4,5,6
               May wish to              May wish to             May wish to        May wish to
               measure                  measure                 measure            measure
               HbA1c                    HbA1c                   HbA1c              HbA1c
               as guide, (see           as guide, (see          as guide, (see     as guide, (see
               section 2.3.4)           section 2.3.4)          section 2.3.4)     section 2.3.4)
LFT’s          Baseline9                Baseline9               Baseline9          Baseline9          Baseline9 then
               then three to            then monthly            then three to      then monthly       as necessary
               six monthly9,10          for three               six monthly9       for three
                                        months9                                    months9
ECG            Baseline9,20             Baseline                Baseline           Baseline           Baseline
               Repeat at                                                           Repeat at          Repeat at
               maintenance                                                         maintenance        maintenance
               dose9                                                               dose               dose
U & E’s        Baseline9 then           Baseline9 then          Baseline9 then     Baseline9 then     Baseline9 then
               six monthly9             six monthly9            six monthly9       six monthly9       six monthly9
FBC            Baseline9,20             Baseline9               Baseline9          Baseline9          Baseline9 then
               then as per              then three to           then three to      then three to      six monthly9
               SPC                      six monthly12           six monthly9       six monthly9
TFT’s                                                                              Baseline9,13
                                                                                    then
                                                                                   six monthly in
                                                                                   those with
                                                                                   compromised
                                                                                   thyroid
                                                                                   function13
Prolactin Refer to Trust                Refer to Trust          Refer to Trust     Refer to Trust     Refer to Trust
          Policy                        Policy                  Policy             Policy             Policy
Bp and    On initiation                 On initiation           On initiation      On initiation      On initiation in
Pulse     and during                    and during              and during         and during         the elderly21
          treatment as                  titration in the        titration18        titration14
          per SPC20                     elderly19


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  Jyoti Gupta. Mental health Pharmacist, Chelsea & Westminster Hospital.                      June 2003.
Table 1 Psychotropic Drugs that Prolong QT interval and /or Induce Torsades de
Pointes22
Psychotropic Drugs with Risk of Torsades de Pointes
Chlorpromazine
Haloperidol
Pimozide
Thioridazine
Psychotropic Drugs with Possible Risk of Torsades de Pointes
Chloral Hydrate
Lithium
Quetiapine
Risperidone
Venlafaxine
Ziprasidone
Psychotropic Drugs to be Avoided by Congenital Long QT Patients
Chloral Hydrate
Chlorpromazine
Haloperidol
Lithium
Pimozide
Quetiapine
Risperidone
Sibutramine
Thioridazine
Venlafaxine
Ziprasidone
Psychotropic Drugs Unlikely to Cause Torsades de Pointes
Amitriptyline
Doxepin
Fluoxetine
Galantamine
Imipramine
Nortriptyline
Paroxetine
Sertraline
Trimipramine




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        2. Donna A. Wirshing, M.D.; Jennifer A. Boyd, Pharm.D; Laura R. Meng,
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            Wirshing, M.D. The Effect of Novel Antipsychotics on Glucose and Lipid
            Levels. J Clin Psychiatry 2002 63:10 856-865




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