Section 3.1.2.1

Atypical Major Tranquilizers

CLOZAPINE

General Description

Clozapine (Clozaril) is an alternative drug for the treatment of psychotic disorders, particularly schizophrenia and schizoaffective disorder. It is a dibenzodiazepine, not to be confused with benzodiazepines; it is rarely associated with extrapyramidal adverse effects; and it is not suspected to cause tardive dyskinesia. Its major disadvantage is the 1-2% incidence of agranulocytosis.

Indications for Medication

The major indication for clozapine is the treatment of psychotic patients, usually affected by schizophrenia or schizoaffective disorder, who have not responded to traditional antipsychotic drugs, who have been unable to tolerate the adverse effects of the traditional antipsychotic drugs, or who have developed tardive dyskinesia.

Clozapine has shown to be as effective as standard antipsychotic drugs in both the short-term and long-term management of psychosis. Clozapine may be more effective than traditional antipsychotic drugs in reducing negative symptoms of schizophrenia.

Approximately 30-40% of patients who have not responded to standard antipsychotic treatment, do respond to clozapine treatment. These patients may not demonstrate a dramatic decrease in positive symptoms, but display improved functioning with increased socialization.

Clinical Guidelines

A schizophrenic or schizoaffective disorder patient who has unsuccessfully been treated with two or three different antipsychotic drugs from different classes in sufficient dose levels (1000mg of chlorpromazine equivalents), is probably a good candidate for treatment with clozapine.

There are a number of contraindications to clozapine. These contraindications include a history of a myeloproliferative disorder, a history of CNS depression or comatose states, previous clozapine-induced severe leukopenia, granulocytopenia and/or agranulocytosis, and laboratory abnormalities like an initial WBC of less than 4000/mm3 or an initial granulocyte count below 1500/mm3.

Other contraindications to clozapine include a debilitated physical state, a history of significant physical illness other than a GI or URI upset in the prior month, a history of hypersensitivity to a clozapine-related drug such as amoxapine or loxitane, and a continued use of an antiarrhythymic agent. Simultaneous use of other drugs will have a potential to suppress bone marrow functions, such as carbamazepine, propylthiouracil, sulfonamide or captopril.

Clozapine should be used with caution in patients with a history of seizure disorder, prostatic enlargement, narrow angle glaucoma, laboratory or clinical evidence of significant renal, hepatic or cardiopulmonary disease, a Jewish background, especially Ashkenazi Jew, and a history of neuroleptic malignant syndrome (NMS).

Clozapine should also be used with caution for patients with concomitant use of atropine-like drugs, antihypertensives, highly protein bound drugs (e.g., warfarin, valproic acid, phenytoin, digoxin), CNS depressants, or epinephrine (for acute asthma, anaphylaxis, and hypotension).

Clozapine should be started at a low dose and gradually titrated to a therapeutic level over several weeks-month. The initial dose is usually 25mg once or twice daily; and the dosage is usually increased at a rate of 25mg a day, every 2-3 days until a dose of 300mg is obtained.

The usual effective dose range of clozapine is around 400-500mg a day, although dose levels above 600mg may be necessary. Literature articles report clozapine efficacy with blood levels above 350ug/ml and recommend drug trials of 3-6 months to fully assess efficacy.

The gradual titration of clozapine to an effective range reduces the development of hypotension, syncope and sedation. These initial adverse effects usually decrease as the patient becomes tolerant to the medication.

If clozapine proves to be ineffective, the medication should be tapered gradually. Fast dose reductions can cause an anticholinergic rebound with symptoms of diaphoresis, flushing, diarrhea, and hyperactivity. In addition, these patients may become increasingly psychotic, agitated and disruptive.

Adverse Effects

The feature of clozapine that distinguishes it from standard antipsychotics is the absence of extrapyramidal adverse effects. Clozapine does not cause acute dystonia and it is associated with low incidence of parkinsonism, including the so-called rabbit syndrome and acute akinesia. Clozapine may also be associated with a much lower incidence of tardive dyskinesia.

The two most serious adverse effects associated with clozapine are agranulocytosis and seizures. Agranulocytosis is defined as a decrease in the number of white blood cells, with a specific decrease in the number of polymorphonuclear leukocytes and a relative lymphopenia. Agranulocytosis occurs in 1-2% of patients treated with clozapine, compared to 0.04-0.5% of patients treated with standard antipsychotics.

Clozapine is associated with the development of seizures. Approximately 5% of patients taking more than 600mg a day, 3-4% taking 300-600mg a day and 1-2% taking less than 300mg a day, have clozapine-associated seizures.

If seizures develop in a patient, clozapine should be temporarily stopped. Phenobarbital or valproic acid treatment can be initiated to reduce the seizure risk. Clozapine can be restarted at approximately 50% of its previous dose then raised slowly to its prior level. Carbamazepine should not be used for this seizure control because of its association with an increased risk of agranulocytosis.

The most common adverse effects associated with clozapine treatment include sedation, tachycardia, constipation, dizziness, hypotension, hyperthermia and sialorrhea. Weight gain, fainting spells, myoclonus, periodic catalepsy, gastro-intestinal upset and anticholinergic side effects have also been reported.

Clozapine use in pregnancy has not been studied so it should not be prescribed in pregnant women. Clozapine may pass into breast milk so it should not be taken by nursing mothers.

Drug-Drug Interactions

Clozapine should not be used with any other drug that is also associated with the development of agranulocytosis or bone marrow suppression. Such drugs include carbamazepine, propylthiouracil, sulfonamides and captopril.

Central nervous system (CNS) depressants, alcohol or tricyclic antidepressants co-administered with clozapine may increase the risk of seizures, confusion, and movement disorders including neuroleptic malignant syndrome.

Concomitant use of clozapine and benzodiazepines may be associated with a higher percentage of reported cases of orthostasis and syncope.

An adverse interaction may occur when clozapine and cimetidine are combined.

Fluoxetine may increase levels of clozapine and its metabolites to twice the normal levels.

Clozapine Therapy Guidelines Based on WBC and Granulocyte Count

WCB Count (mm3)

Granulocyte Count (mm3)

Guidelines

<3500 or history of myelo-proliferative disorder, or previous clozapine-induced agranulocytosis or granulo-cytopenia

 

Do not initiate treatment.

<3500 or >3500 with a substantial drop from baseline following initiation of treatment

 

Repeat WBC and differential counts. Symptoms of infection, lethargy, weakness, fever, sore throat.

<3000

<1500

Interrupt therapy, monitor for flu-like symptoms or other symptoms of infection, may resume therapy if no signs of infection develop. WBC count >3000 and granulocyte count >1500. However, continue twice weekly WBC and differential counts until WBC returns to 3500.

<2000

<1000

Consider bone marrow aspiration to ascertain granuloporetic status. If granulopoiesis is deficient, consider protective isolation. If infection develops, perform cultures and institute antibiotics. Do not rechallenge with clozapine since agranulocytosis may develop with a shorter latency.

Clozapine Adverse Reactions (n= 842)

Adverse Reaction (%)

Adverse Reaction (%)

CNS

Drowsiness/sedation 39

Dizziness/vertigo 19

Headache 7

Tremor 6

Syncope 6

Disturbed sleep/nightmares 4

Restlessness 4

Hypokinesia/akinesia 4

Agitation 4

Seizures (convulsions) 3

Rigidity 3

Akathisia 3

Confusion 3

Fatigue 2

Insomnia 2

Hyperkinesia 1

Weakness 1

Lethargy 1

Ataxia 1

Slurred speech 1

Depression 1

Epileptiform movements/

Myoclonic jerks 1

Anxiety 1

Cardiovascular

Tachycardia 25

Hypotension 9

Hypertension 4

Chest pain/angina 1

ECG change/cardiac abnorm 1

GI

Constipation 14

Nausea 5

Abdominal discomfort/

Heartburn 4

Nausea/vomiting 3

Diarrhea 2

Liver test abnormality 1

Anorexia 1


GU

Urinary abnormality 2

Incontinence 1

Abnormal ejaculation 1

Urinary urgency/frequency 1

Urinary retention 1

Respiratory

Throat discomfort 1

Dyspnea, shortness of breath 1

Nasal congestion 1

Autonomic Nervous System

Salivation 31

Sweating 6

Dry mouth 6

Visual disturbances 5

Hemic/Lymphatic

Leukopenia/decreased

WBC/neutropenia 3

Agranulocytosis 1

Eosinophilia 1

Musculoskeletal

Muscle weakness 1

Pain (back, neck, legs) 1

Muscle spasm 1

Muscle pain, ache 1

Miscellaneous

Fever 5

Weight gain 4

Rash 2

Tongue numb/sore 1

Policy & Procedure Excerpts from July 1996 P & P on
use of clozapine in HCA BH

METHOD

Patient Selection Criteria:

Patients considered for clozapine treatment must meet the following criteria:

1. A diagnosis of Schizophrenia or Schizoaffective Disorder, according to the current Diagnostic and Statistical Manual of Mental Disorders.

2. Between the ages of 16 and 75 years.

3. Written consent - If the patient is on voluntary status, a signed consent by the patient or parent/guardian is necessary. If patient is on a temporary or full conservatorship, a signed consent by the conservator as well as the patient or parent/guardian is necessary. Most important is the patient's willingness to consent to blood tests.

4. Documentation by the treating physician in the patient's medical record of the Treatment Authorization Request (TAR) for authorizing County prescription payment for non-Cal OPTIMA patients.

5. Clinical documentation in the patient's medical record of at least one of the following:

a. Treatment Resistance - Schizophrenic or Schizoaffective Disorder patients for whom there is documented evidence of poor response to at least two neuroleptics (from different classes) given for a minimum of four to six weeks in doses equivalent (for an adult) to six hundred milligrams of chlorpromazine that were discontinued due to the inadequacy of symptom response or severe Tardive Dyskinesia.

b. Intractable Extrapyramidal Side Effects - Schizophrenic or Schizoaffective Disorder patients who cannot be adequately treated with traditional antipsychotic medications due to the intolerable acute/severe extrapyramidal symptoms (with at least two neuroleptics) which are unresponsive to standard anti-Parkinson treatment.

c. Tardive Dyskinesia - Schizophrenic or Schizoaffective Disorder patients who require antipsychotic medication, but suffer from severe Tardive Dyskinesia (as measured on the AIMS scale), which is disabling to the degree that it interferes with the clients ability to participate in basic activities of daily living.

Other Considerations for Client Selection:

1. Family or significant support should be available. The patient should have a possibility of a permanent residence and not a history of transient life style.

2. Several acute hospitalizations or a prolonged hospitalization within the past several years, during which psychotropic medications have been prescribed, without the patient stabilizing adequately to be maintained in a community setting.

3. The patient's willingness to comply with lab work and/or other treatment programs and/or a history of similar compliance with other treatment modalities. The prompt reporting of any symptoms of infection, such as lethargy, weakness, fever, sore throat, malaise, mucous membrane ulceration or flu-like symptoms will be important.

4. A recorded physical examination within the last six months.

5. If a flushing out period is utilized prior to initiating clozapine treatment, the patient's history of violence to self and others when not on medication should be fully assessed to determine the efficacy of placing the individual on a new medication.

Contraindications for Use:

1. History of a myeloproliferative disorder;

2. Severe CNS depression or comatose states;

3. Previous Clozapine-induced severe leukopenia, granulocytopenia and/or agranulocytosis;

4. An initial WBC of less than 3500/mm3;

5. An initial granulocyte count below 1500/mm3;

6. A history of noncompliance with frequent mandatory lab work;

7. A debilitated physical state;

8. An age of 16 years or younger;

9. A history of significant physical illness other than a URI or GI upset in the prior month;

10. A history of hypersensitivity to a clozapine-related drug such as amoxapine or loxitane;

11. Pregnancy or lactating females;

12. Continued use of an antiarrhythymic agent; and/or,

13. Simultaneous use of other drugs having a well-known potential to suppress bone marrow functions such as carbamazepine, propylthiouracil, sulfonamide or captopril.

14. No prior standard antipsychotic treatment.

Cautions in Clozapine Usage:

Clozapine should be used with caution and pre-treatment specialty consultation in the following situations:

1. History of seizure disorder

2. Prostatic enlargement

3. Narrow angle glaucoma

4. Laboratory or clinical evidence of significant renal, hepatic or cardiopulmonary disease

5. A Jewish background, especially Ashkenazi Jew

6. A history of neuroleptic malignant syndrome (NMS), although no cases of NMS on clozapine alone have been reported

7. Concomitant use of atropine-like drugs, antihypertensives, high protein bound drugs (e.g., warfarin, valproic acid, phenytoin, digoxin), CNS depressants, or epinephrine (for acute asthma, anaphylaxis, and hypotension)

8. History of alcoholism or drug abuse

9. A risk of pregnancy or a pregnancy in progress

10. A need for the continued use of a medication that may cause bone marrow suppression such as sulfonamides, captopril, and phenytoin

11. A need for a continued use of any heterocyclic or MAOI-type antidepressant.

Documentation:

The following documents must be obtained and placed in the selected patient's chart prior to initiation treatment and entry into the clozapine Treatment System:

1. A County release of information form signed by the patient or their conservator, as appropriate, for the clozapine Patient Management System. Information required includes the patient's social security number, date of birth and pertinent laboratory findings.

2. Orange County major tranquilizer (clozapine) consent form signed by patient and conservator if patient is a conservatee.

3. Signed and completed Orange County form for Treatment Authorization Request For County Prescription Payment for non-Cal OPTIMA patients. The Adult Community Quality Improvement Psychiatrist will authorize payment if patient selection criteria and justification criteria are fully met.

4. The original form of the Treatment Authorization Request (TAR) For Prescription Payment for non-Cal OPTIMA patients will be returned to clinic physician.

5. A copy of the Treatment Authorization Request (TAR) For Prescription Payment for non-Cal OPTIMA patients will be maintained by the Adult Community Quality Improvement Psychiatrist or the Deputy Director for Children and Youth Services.

6. Clozapine Treatment Systems Form B which is the patient registration and the letter of confirmation from Clozapine National Registry. The confirmation letter is sent to the prescribing psychiatrist as soon as the information on form B is called into the National Registry.

INPATIENT CLOZAPINE TREATMENT SYSTEM

Upon completion of all appropriate documentation for patient selection, pre-treatment baseline data will be gathered, such as required medical examinations, laboratory findings and behavioral assessment or observations of the patient's status. Required patient information for entry into the Clozapine Treatment System (see below), standing order prescription, and laboratory reports should be relayed to the pharmacist.

The pharmacist should complete either pharmaceutical company's Clozapine National Registry information. For non-Cal OPTIMA inpatients, there is no need for a County Treatment Authorization Request (TAR) For County Prescription Payment - as the County will not assume prescription payment responsibility until the clozapine patients are treated in the County outpatient clinics. However, prior to transfer to an outpatient mental health clinic, the inpatient psychiatrist should send a County TAR to the Adult Community Quality Improvement Psychiatrist to assure outpatient payment for the clozapine can occur when the week of discharge medications is finished.

Titration of clozapine will begin on a slowly increasing schedule, with regular vital signs, weekly blood counts and monthly behavioral assessments documented in the patient's chart. The behavioral assessments must demonstrate significant improvement for the patient to be placed on maintenance clozapine. An adequate trial of clozapine may take six months.

Inpatient Clozapine Treatment Systems Procedures:

1. IPS facilities will qualify as facilities with off-site pharmacies.

2. Once the patient selection process is complete, the physician orders the initial laboratory tests for the patient; the laboratory performs these tests; and the laboratory reports the results to the physician. These laboratory results should include CBC with differential count, test for pregnancy, serum creatinine, full liver panel, complete urinalysis, electrolytes, total protein and albumin. In addition, an EKG should be performed within the past year; and complete vital signs should be taken for several days before starting.

3. Physician completes the Patient Safety Assurance form (B), and sends it to clozapine National Registry for "re-challenge check". If clozapine use is approved, WBC is above 3500, and authorization code number is given via clozapine National Registry, the physician sends first prescription, completed clozapine National Registry WBC Count Report Form (D), and completed Patient Safety Assurance Form (C), to the pharmacy.

4. Pharmacist verifies existence of authorization code number and fills first prescription.

5. Physician writes standing order for weekly or bi-weekly blood counts, and titration schedule prescription for the initial medication trial. Complete vital signs are required during the first three weeks of clozapine treatment as clinically indicated. Full liver function panel should be ordered every six months.

6. In order to continue dispensing weekly supplies to the patient, the pharmacist must continue to send WBC and dosage information weekly to the Clozaril National Registry. WBC reports must be submitted to the Clozaril National Registry within 7 days of collection.

7. Weekly supplies of clozapine are dispensed by the pharmacist pursuant to the physician's order, and only after receiving results of the corresponding weekly WBC count. If the WBC is over 3500, the pharmacist fills the 7-day prescription. If the WBC is between 2000 and 3500, the pharmacist checks with the physician about filling the prescription. If the WBC count is below 2000, the pharmacist must not dispense the next week's supply.

8. If laboratory WBC results are below 3500 at any point, a second WBC should be ordered by the physician and performed immediately. If the repeat results are still below 3500, physician should re-evaluate the patient for clozapine. Therapy should be interrupted when the WBC is below 3000. If the WBC results are between 3500 and 3000, therapy may be continued and WBC with differentials are required twice weekly. If WBC rises to normal, therapy can be continued. If the WBC results are between 3000 and 2000 or granulocyte counts are between 1500 and 1000, therapy will be interrupted and frequent WBC with differential is recommended. If WBC counts ever fall below 2000 or granulocyte counts below 1000, the following should be done:

A. Therapy must be discontinued and frequent WBC with differentials done until count rises to normal.

B. The pharmacist will be notified to discontinue dispensing medication immediately.

C. Form D with WBC information is to be sent to the Clozaapine National Registry.

D. Consultation with a hematologist or internist is recommended along with consideration for reverse isolation and bone marrow evaluation procedures. Any opportunistic infections should be aggressively treated.

9. If the physician discontinues therapy, four more weekly blood tests are required, with WBC information (Form D) sent to Clozaril National Registry. Copies of this form, which also specifies the patient's Clozapine status, will be placed in the patient's chart.

OUTPATIENT CLOZAPINE TREATMENT SYSTEM

All mental health outpatient clinics will be designated as "Clozapine Clinics." Each clinic will have a designated primary and secondary physician who will be responsible for seeing Clozapine patients and responsible for their medical treatment. Each clinic will also have a designated primary and secondary case manager. These case managers will be registered nurses (RNs) and will provide nursing support and services for the Clozapine physicians and patients.

For those patients who will be starting clozapine on an outpatient basis, the psychiatrist will complete appropriate documentation for patient selection and pre-treatment baseline data, including medical history, laboratory findings, and behavioral assessment or observations of the patient's status. Required patient information for entry into the Clozapine Treatment System (see below), standing order prescription, and laboratory reports will be relayed to the pharmacist.

For those patients who have already been started on clozapine and who have been referred to the County clinic from another setting and/or facility, the treating physician will re-evaluate the appropriateness of clozapine, order blood drawn after that initial assessment, and prescribe a weekly supply of clozapine. In addition, these clozapine patients will also be evaluated by their case manager (RN) [and therapist, if appropriate] at this time.

For non-Cal OPTIMA patients, the physician will complete and submit the initial or renewal County Treatment Authorization Request (TAR) to the Adult Community Services Quality Improvement Psychiatrist or the Deputy Director for Children and Youth Services - for authorizing County Prescription Payment for the non-Cal OPTIMA patients.

Titration of medication on an outpatient basis will begin on a slowly increasing schedule, with regular vital signs, weekly blood counts, and frequent behavioral assessments documented in the patient's chart. The initial outpatient psychiatrist visits may be weekly or several types per week under the Rehabilitation Model. An initial prescription for 175 mg will allow titration and adjustment during the first month.

Once the clozapine is stabilized, the behavioral assessments must demonstrate significant improvement for the patient to be placed on maintenance clozapine. An adequate trial of clozapine may take six months. The patient's clinical response must be fully documented at the six (6) month period with clear justification for continued clozapine. That justification must include reduction of psychotic symptoms and behavioral improvement.

For stabilized patients on clozapine, the outpatient psychiatrist visits will be once per month or more frequently as required. The weekly or bi-weekly lab results will be received by the next day and will be reviewed by the clinic physician. Any patients who need re-tests will be notified immediately to have their blood redrawn no later than the following day, and if necessary to discontinue clozapine use. In the event the patient is unable to get their blood re-drawn at the clinic in a timely enough manner to satisfy the physician, home blood draws will be available through a contract laboratory.

A. Outpatient Clozapine Treatment Systems Procedures For Initiating Clozapine:

1. Identified Community Mental Health Services clinic will qualify with off-site pharmacy. This is either the contract pharmacy that provides delivery of clozapine to clinic on a weekly basis, or another clozapine designated pharmacy that is registered with each prescribing psychiatrist using form B from the clozapine registry.

2. Once the patient selection process is complete, the psychiatrist orders the initial laboratory tests for the patient; the laboratory performs these tests; and the laboratory reports the results to the psychiatrist. These laboratory results should include CBC with differential count, test for pregnancy, serum creatinine, full liver panel, complete urinalysis, electrolytes, total protein and albumin. In addition, an EKG should be performed within the past year; and complete vital signs should be taken on several days before starting clozapine.

3. Psychiatrist completes the Patient Safety Assurance form (B), and calls the Clozapine National Registry. The Registry will issue a rechallenge number which is entered on form B. After receiving that number, the patient may begin receiving clozapine prescription from the pharmacy as soon as the initial laboratory data (WBC?s >3500) is reviewed by psychiatrist. The Clozapine National Registry will send a registry number confirmation letter within the week. A copy of form B along with the letter of confirmation will be placed in the patient?s chart.

4. Pharmacist calls Clozapine Registry to verify existence of authorization code number and to give results of first WBC test. Then the first prescription can be filled. The pharmacist will send the first form D to the Registry.

5. Psychiatrist writes standing order for weekly blood counts and titration schedule prescription for the initial medication trial period. Complete vital signs are required frequently during the first three weeks of clozapine treatment as clinically indicated. Full liver function panel should be ordered every six months.

6. In order to continue dispensing weekly supplies to the patient, the pharmacist must continue to send WBC and dosage information weekly to the Clozapine National Registry. WBC reports must be submitted to the Clozapine National Registry within 7 days of collection.

7. Weekly or bi-weekly supplies of clozapine are dispensed by the pharmacist pursuant to the physician's order, and only after receiving results of the corresponding weekly WBC count. If the WBC is over 3500, the pharmacist fills the 7-day prescription. If the WBC is between 2000 and 3500, the pharmacist checks with the physician about filling the prescription. If the WBC count is below 2000, the pharmacist must not dispense the next week's supply.

8. If laboratory WBC results are below 3500 at any point, a second WBC should be ordered by the physician and performed immediately. If the repeat results are still below 3500, physician should re-evaluate the patient for clozapine. Therapy should be interrupted when the WBC is below 3000. If the WBC results are between 3500 and 3000, therapy may be continued and WBC with differentials are required twice weekly. If WBC rises to normal, therapy can be continued. If the WBC results are between 3000 and 2000 or granulocyte counts are between 1500 and 1000, therapy will be interrupted and frequent WBC with differential is recommended. If WBC counts ever fall below 2000 or granulocyte counts below 1000, the following should be done:

A. Therapy must be discontinued and frequent WBC with differentials done until count rises to normal.

B. The pharmacist will be notified to discontinue dispensing medication immediately.

C. Form D with WBC information is to be sent to the Clozapine National Registry.

D. Consultation with a hematologist or internist is recommended along with consideration for reverse isolation and bone marrow evaluation procedures. Any opportunistic infections should be aggressively treated.

9. If the psychiatrist or patient discontinues therapy, four more weekly blood tests are required, with WBC information (Form D) sent to Clozapine National Registry. Copies of this form, which also specifies the patient's clozapine status, will be placed in the patient's chart.

Length of Trial on Clozapine:

1. Thirty percent of patients show some response in the first 4-6 weeks.

2. There is a second group of responders who will show a gradual change in the first 4-6 months and who will present the biggest dilemma in deciding whether clozapine should be continued.

3. There is a third group of responders who will show a gradual decrease in negative symptoms with increased social functioning despite positive symptoms.

4. A six month trial of clozapine should be sufficient to evaluate the patient's response. Clozapine will be discontinued for patients showing no or minimal response during this six month trial. Consultation with Quality Improvement Psychiatrist should be requested on questionable cases.

5. Termination from clozapine can be abrupt for medical reasons. Abrupt termination should be closely evaluated for medical symptoms, including cholinergic rebound.

6. Planned termination from clozapine should include a tapering-off period, lasting 2-3 weeks. Patients should be monitored closely for any medical symptoms.

7. Patients who are to continue taking clozapine beyond the six month trial must have a progress note in the chart clearly documenting the specific areas of improvement.

8. Patients who are maintained on clozapine must have a detailed summary progress note in the chart every six months clearly documenting the continued areas of improvement.