~
Clozapine: Nursing Care Considerations
Nancy Jaretz, RN, MEd, Ellen Flowers, RN, BSN, and Lisa Millsap, RN, BSN, C
Since its release for clinical use in Februa y of 1990, an ever-growing number of psychiatrists
are beginning to use clozapine to treat clients whose psychoses have been refractory to conventional measures. While clozapine has been shown to have superior antipsychotic efficacy without the standard extrapyramidal side effects, it also has some potentially fatal side effects. The unpredictability in client response poses a number of issues for nursing, which has an essential role in assuring that treatment occurs accurately and safely. The authors share their experience in working with clients ,families, and staff over the past two years who have been actively involved with clozapine.
T h e rise, fall, and reemergence of interest in clozapine has been well documented (Green & Salzman, 1990; Lieberman, Kane, & Johns, 1989). From its initial testing in 1962 through the mid-’70s, clozapine was heraldtd as ”a unique new neuroleptic” that held promise for clients who had not responded to conventional neuroleptics. However, despite its use with some 3,000 clients, the full extent of its risks had not been recognized (Ayd, 1974). The hatus that occurred in the use of clozapine because of deaths due to agranulocytosis allowed time for an analysis of its potential to cause that condition, as well as seizures and less severe side effects. The belief that dotapine might have the potential to effect signifjcant, t’ven dramatic, improvement in some treatment-resistant clients kept it from being dismissed entirely. Another added impetus has been the hope that clozapine would prove ”that the capacity to cause extrapyramidal reactions is not absolutely necessary to be an effective neuroleptic” (Ayd). When subsequent studies (Claghorn et al., 1987; Meltzer, Burnett, Bastini, & Ramirez, 1990; N a b w & Hippius, 1990) confirmed clozapine’s efficacy writh treatment-resistant clients, the focus shifted from whether it could be used to how it could be used saftily. Clarification of clozapine’s side-effect profile led to the present policy of weekly monitoring of WBC in all US. clients, as well as the establishment of a nationwide network to ensure the practice (Salzman, 1990). The challenge for nursing is to help keep the benefitto-risk ratio balanced toward the positive side for the client. Using the nursing process model, such assistance involves assessing the client’s response to the medication, planniug for response to side effects and to issues of noncompliance, implementing drug titration, and evaluating the effectiveness of approaches taken.
Nursing Assessment and Planning: Actual and Potential Problems Relevant nursing assessments for clients on clozapine include vital signs, weights, subjective reports by clients, and observations of behavior, mental status, and clinical Perspectivesin psychiatricCare Vol. 28, No. 3, July-Sept.,1992
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Clozapine: Nursing Care Considerations
Table 1.Nursing Assessment of ActuaVFotentialProblems
Frequency
Potential Problem
Postural BP
Daily or prior to dosing if clinically indicated
Orthostatic hypertension
Need to establish parameters to dosing if for seeking medical consultation and holding drug. May be severe and cause dizziness or falls. Will govern rate of medication dose increase.
Postural pulse
Daily or clinically indicated
Tachycardia
Need to establishparameters. May cause palpitations Severity may govern rate of increase. Low pulse rates may indicate non-compliance.
Temperature
Daily
Hyperthermia
May be initial, idiosyncraticreaction to drug. May be evidence of infection, agranulocytosisor neuroleptic malignant syndrome.
Weight
Weekly
Weight gain
May be accompaniedby increased appetite and feeling heavier. May become a safety issue with concomitant physical conditions,eg., sialorrhea, sleep apnea.
Patient's subjective report and nursing observations
ongoing
Sialorrhea
May necessitate blotting with tissues, frequent change of pillow cases or use of absorbent towels.
Nursing Assessment
Implications
Can prove embarrassing for patient. May become a safety issue re: aspiration.
Report /Observations
ongoing
Sedation
Likely to be most prominent during initiation of treatment. May govern dose titration. Necessitates careful use of pm medications.
Report/Obsemations
ongoing
Alteration in GI functioning
Maybe evidenced as nausea,constipation and/or diarrhea. Need to rule out other causes. May be sign of hepatic dysfunction
Report/Obsemations
ongoing
Report/Obsemations and laboratory data
ongoing/weekly
20
Seizureactivity
May present as pre-seizme activity, e.g. mydonic jerks. R e q M immediate medical consultation. May necessitate reconsideration of drug's use. Early signs and symptom may include sore throats, "flu"-like feelings, skin rashes,sores/ulcerations, evidence of infection. May q u i r e immediate cessation of drugsuse. Confirmed condition precludes futureuse of drug for that patient.
Perspectives in Psychiatric Care Vol. 28, No. 3, July-Sept,1992
well-being. As basic as these activities are to client care, they can reveal the presence of the major side effects reported with the use of the drug. In addition, close observation during the initiation phase may reveal individual or idiosyncratic concerns not previously identified. Commonly reported side effects and their management are outlined in Table 1. Orthostatic hypotension. Since clozapine can produce severe postural hypotension, postural vital signs are taken daily during titration and stabilization. They may be taken more frequently if significant changes or associated symptoms (such as dizziness) are noted. Data provided by vital signs serves as a guide for adjusting administrationtimes and dosages. Tachycardia. Pulses taken in conjunction with blood pressures routinely reveal rates over 100. Failure to observe a rise in the pulse rate over 90 may signify noncompliance in taking the medication, especially at the time of dose increases. While experience shows eventual development of tolerance, rates greater than 130 warrant medical consultation. If the pulse is 140, the dose should be held. The clienvs awareness (palpitations)also affects the actions taken. Hyperthermia. Although less frequently seen (up to 13%reported; Lieberman et al., 1980), hyperthermia is more likely to occur at the beginning of treatment. An elevated temperature is troublesome since it may indicate an early sign of infection, agranulocytosis, or neuroleptic malignancy syndrome. Therefore, temperature elevations warrant a fever workup and should be communicated to the physician. Weight gain. Routine weight monitoring and the client‘s report often reveal increased appetite and weight gain. While generally this factor is of greatest concern to the client, it may also become a safety issue. A client with a history of sleep apnea in the authors’ setting developed profound sialorrhea and weight gain on clozapine; both could compromise her physical condition. Thus, diet monitoring and education have become an important nursing concern. Sialorrhea (hypersalivation). While this side effect has been documented in some 13%of clients on clozapPerspectivesin Psychiatric Care VoL 28, No. 3, July-Sept, 1992
ine (Lieberman et al., 1980), the authors have seen it in a majority of clients. Some have had severe sialorrhca, with impaired speech and the necessity for constant blotting with tissue or towels. Others gave evidence of a more minor condition, e.g., a wet pillow at night. While not generally considered a serious side effect, excess salivation is extremely troublesome for the client. One client who became well enough to live independently related her embarrassment at falling asleep on the train to awaken with a pool of saliva on her clothes. The need for nursing support is obvious.
Pulses taken in conjunction with blood pressures routinely reveal rates over 100. Failure to observe a rise in the pulse rate over 90 may signify noncompliance in taking the medication.
Sedation. The most frequently occurring side effect, sedation is particularly evident during initiation and dose titration. While it usually subsides over time, care must be taken to monitor drowsiness, level of consciousness, and arousability, especially if prn medication is used concurrently. Even later in treatment clients may complain of fatigue and may need assistance in setting aside rest periods during what may be an increasingly busy schedule for them. Alterations in GI functioning. Nausea, constipation, and diarrhea have all been reported in association with clozapine initiation. Differing individual responses demand careful attention to the client’s complaints and some detective work to rule out other potential sources of the symptoms. Due to the aura surrounding treatment with this new and “different” drug, some clients 21
Clozapine: Nursing Care Considerations
attribute any somatic symptoms to the drug, and at times incorporate changes into their somatic delusions. Most GI problems can be handled symptomatically. However, since nausea and vomiting, along with decreased appetite, may also suggest hepatic dysfunction, such symptoms merit a further medical workup. Seizures. Observations of seizure-like or preseizure activity must be reported to the physician immediately. Whle treatment of the seizure itself is handled by usual clinical procedures, consideration must be given to further treatment with clozapine. Since the incidence of seizures is apparently dose related, the dose may be reduced or the clozapine discontinued altogether. (Risk = 1%-2%below 300 mg/day, 3%-4%below 600 mg/day, 5% above 600 mg/day; the cumulative rise over a year is 10%) (Kane, Honigfeld, Singer, & Meltzer, 1988).
~
~~~~~
A 1977 review of reported cases indicated
that 90% of the time agranulocytosis occurred during the first 18 weeks of treatment (Amsler, Teerenhovi, Barth, Harjula, & Vuopio, 1977). More recent research suggests that the risk may be greatest from six weeks to six months (Ayd, 1980; Claghorn et al., 1987).
Agranulocytosis. Clearly, agranulocytosis is the primary concern with clozapine use because of its potential lethality. Agranulocytosis is characterized by leukopenia (WBC
Clozapine: Nursing Care Considerations
Nancy Jaretz, RN, MEd, Ellen Flowers, RN, BSN, and Lisa Millsap, RN, BSN, C
Since its release for clinical use in Februa y of 1990, an ever-growing number of psychiatrists
are beginning to use clozapine to treat clients whose psychoses have been refractory to conventional measures. While clozapine has been shown to have superior antipsychotic efficacy without the standard extrapyramidal side effects, it also has some potentially fatal side effects. The unpredictability in client response poses a number of issues for nursing, which has an essential role in assuring that treatment occurs accurately and safely. The authors share their experience in working with clients ,families, and staff over the past two years who have been actively involved with clozapine.
T h e rise, fall, and reemergence of interest in clozapine has been well documented (Green & Salzman, 1990; Lieberman, Kane, & Johns, 1989). From its initial testing in 1962 through the mid-’70s, clozapine was heraldtd as ”a unique new neuroleptic” that held promise for clients who had not responded to conventional neuroleptics. However, despite its use with some 3,000 clients, the full extent of its risks had not been recognized (Ayd, 1974). The hatus that occurred in the use of clozapine because of deaths due to agranulocytosis allowed time for an analysis of its potential to cause that condition, as well as seizures and less severe side effects. The belief that dotapine might have the potential to effect signifjcant, t’ven dramatic, improvement in some treatment-resistant clients kept it from being dismissed entirely. Another added impetus has been the hope that clozapine would prove ”that the capacity to cause extrapyramidal reactions is not absolutely necessary to be an effective neuroleptic” (Ayd). When subsequent studies (Claghorn et al., 1987; Meltzer, Burnett, Bastini, & Ramirez, 1990; N a b w & Hippius, 1990) confirmed clozapine’s efficacy writh treatment-resistant clients, the focus shifted from whether it could be used to how it could be used saftily. Clarification of clozapine’s side-effect profile led to the present policy of weekly monitoring of WBC in all US. clients, as well as the establishment of a nationwide network to ensure the practice (Salzman, 1990). The challenge for nursing is to help keep the benefitto-risk ratio balanced toward the positive side for the client. Using the nursing process model, such assistance involves assessing the client’s response to the medication, planniug for response to side effects and to issues of noncompliance, implementing drug titration, and evaluating the effectiveness of approaches taken.
Nursing Assessment and Planning: Actual and Potential Problems Relevant nursing assessments for clients on clozapine include vital signs, weights, subjective reports by clients, and observations of behavior, mental status, and clinical Perspectivesin psychiatricCare Vol. 28, No. 3, July-Sept.,1992
19
-~~~
~~
~
~
Clozapine: Nursing Care Considerations
Table 1.Nursing Assessment of ActuaVFotentialProblems
Frequency
Potential Problem
Postural BP
Daily or prior to dosing if clinically indicated
Orthostatic hypertension
Need to establish parameters to dosing if for seeking medical consultation and holding drug. May be severe and cause dizziness or falls. Will govern rate of medication dose increase.
Postural pulse
Daily or clinically indicated
Tachycardia
Need to establishparameters. May cause palpitations Severity may govern rate of increase. Low pulse rates may indicate non-compliance.
Temperature
Daily
Hyperthermia
May be initial, idiosyncraticreaction to drug. May be evidence of infection, agranulocytosisor neuroleptic malignant syndrome.
Weight
Weekly
Weight gain
May be accompaniedby increased appetite and feeling heavier. May become a safety issue with concomitant physical conditions,eg., sialorrhea, sleep apnea.
Patient's subjective report and nursing observations
ongoing
Sialorrhea
May necessitate blotting with tissues, frequent change of pillow cases or use of absorbent towels.
Nursing Assessment
Implications
Can prove embarrassing for patient. May become a safety issue re: aspiration.
Report /Observations
ongoing
Sedation
Likely to be most prominent during initiation of treatment. May govern dose titration. Necessitates careful use of pm medications.
Report/Obsemations
ongoing
Alteration in GI functioning
Maybe evidenced as nausea,constipation and/or diarrhea. Need to rule out other causes. May be sign of hepatic dysfunction
Report/Obsemations
ongoing
Report/Obsemations and laboratory data
ongoing/weekly
20
Seizureactivity
May present as pre-seizme activity, e.g. mydonic jerks. R e q M immediate medical consultation. May necessitate reconsideration of drug's use. Early signs and symptom may include sore throats, "flu"-like feelings, skin rashes,sores/ulcerations, evidence of infection. May q u i r e immediate cessation of drugsuse. Confirmed condition precludes futureuse of drug for that patient.
Perspectives in Psychiatric Care Vol. 28, No. 3, July-Sept,1992
well-being. As basic as these activities are to client care, they can reveal the presence of the major side effects reported with the use of the drug. In addition, close observation during the initiation phase may reveal individual or idiosyncratic concerns not previously identified. Commonly reported side effects and their management are outlined in Table 1. Orthostatic hypotension. Since clozapine can produce severe postural hypotension, postural vital signs are taken daily during titration and stabilization. They may be taken more frequently if significant changes or associated symptoms (such as dizziness) are noted. Data provided by vital signs serves as a guide for adjusting administrationtimes and dosages. Tachycardia. Pulses taken in conjunction with blood pressures routinely reveal rates over 100. Failure to observe a rise in the pulse rate over 90 may signify noncompliance in taking the medication, especially at the time of dose increases. While experience shows eventual development of tolerance, rates greater than 130 warrant medical consultation. If the pulse is 140, the dose should be held. The clienvs awareness (palpitations)also affects the actions taken. Hyperthermia. Although less frequently seen (up to 13%reported; Lieberman et al., 1980), hyperthermia is more likely to occur at the beginning of treatment. An elevated temperature is troublesome since it may indicate an early sign of infection, agranulocytosis, or neuroleptic malignancy syndrome. Therefore, temperature elevations warrant a fever workup and should be communicated to the physician. Weight gain. Routine weight monitoring and the client‘s report often reveal increased appetite and weight gain. While generally this factor is of greatest concern to the client, it may also become a safety issue. A client with a history of sleep apnea in the authors’ setting developed profound sialorrhea and weight gain on clozapine; both could compromise her physical condition. Thus, diet monitoring and education have become an important nursing concern. Sialorrhea (hypersalivation). While this side effect has been documented in some 13%of clients on clozapPerspectivesin Psychiatric Care VoL 28, No. 3, July-Sept, 1992
ine (Lieberman et al., 1980), the authors have seen it in a majority of clients. Some have had severe sialorrhca, with impaired speech and the necessity for constant blotting with tissue or towels. Others gave evidence of a more minor condition, e.g., a wet pillow at night. While not generally considered a serious side effect, excess salivation is extremely troublesome for the client. One client who became well enough to live independently related her embarrassment at falling asleep on the train to awaken with a pool of saliva on her clothes. The need for nursing support is obvious.
Pulses taken in conjunction with blood pressures routinely reveal rates over 100. Failure to observe a rise in the pulse rate over 90 may signify noncompliance in taking the medication.
Sedation. The most frequently occurring side effect, sedation is particularly evident during initiation and dose titration. While it usually subsides over time, care must be taken to monitor drowsiness, level of consciousness, and arousability, especially if prn medication is used concurrently. Even later in treatment clients may complain of fatigue and may need assistance in setting aside rest periods during what may be an increasingly busy schedule for them. Alterations in GI functioning. Nausea, constipation, and diarrhea have all been reported in association with clozapine initiation. Differing individual responses demand careful attention to the client’s complaints and some detective work to rule out other potential sources of the symptoms. Due to the aura surrounding treatment with this new and “different” drug, some clients 21
Clozapine: Nursing Care Considerations
attribute any somatic symptoms to the drug, and at times incorporate changes into their somatic delusions. Most GI problems can be handled symptomatically. However, since nausea and vomiting, along with decreased appetite, may also suggest hepatic dysfunction, such symptoms merit a further medical workup. Seizures. Observations of seizure-like or preseizure activity must be reported to the physician immediately. Whle treatment of the seizure itself is handled by usual clinical procedures, consideration must be given to further treatment with clozapine. Since the incidence of seizures is apparently dose related, the dose may be reduced or the clozapine discontinued altogether. (Risk = 1%-2%below 300 mg/day, 3%-4%below 600 mg/day, 5% above 600 mg/day; the cumulative rise over a year is 10%) (Kane, Honigfeld, Singer, & Meltzer, 1988).
~
~~~~~
A 1977 review of reported cases indicated
that 90% of the time agranulocytosis occurred during the first 18 weeks of treatment (Amsler, Teerenhovi, Barth, Harjula, & Vuopio, 1977). More recent research suggests that the risk may be greatest from six weeks to six months (Ayd, 1980; Claghorn et al., 1987).
Agranulocytosis. Clearly, agranulocytosis is the primary concern with clozapine use because of its potential lethality. Agranulocytosis is characterized by leukopenia (WBC
