Clozapine Research Papers
Drug Name: Clozapine (Brand name Clozaril)
Medication Class: Anti-psychotic, atypical, second generation.
History of Use:
Clozapine was used in Europe first in the early 1970s to treat schizophrenia. It was withdrawn in 1975 when it was shown to cause a dangerous drop in white blood cells (agranulocytosis). It was later approved for limited use in the United States (1989), specifically for treatment-resistant Schizophrenia, as long as weekly blood tests were monitored for low white cell counts. Further FDA approvals came in 2002, as it was shown to be effective in lower the risk of suicide for those in high risk categories.
As a result, Clozapine is generally used where other medications have failed. Several newer atypicals have been released …show more content…
that are attempting to overcome the limitations of Clozapine and other related anti-psychotics (Preston, O’Neal, & Talaga, 2013). These are documented in our text.
Benefits, concerns:
• Besides helping to treat the positive symptoms of Schzophrenia, Clozapine, and other atypicals, also treat negative symptoms, although the success rate of atypicals is generally no higher than 30 percent for negative symptoms (Preston, O’Neal, & Talaga, 2013).
• One group of researchers attributed the positive impact on negative symptoms to both the effect of treating the positive symptoms, as well as to the direct treatment of the causes responsible for the negative symptoms (Miller, Perry, Cadoret, & Andreasen, 1994).
• The seriousness of some side-effects (see below) have limited the use of this drug. To ensure that strict blood testing is followed, the distribution system has been set up to ensure white blood cell counts have been tested (retrieved from http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/019758s062lbl.pdf).
Delivery:
• The medication can be delivered by a pill that is swallowed or a pill that is dissolved in the mouth.
How/why does it work?
According to the text (Preston, O’Neal, & Talaga, 2013), Clozapine, along with other second-generation antipsychotics, block serotonin, while having a lower impact on dopamine blockage (the primary action of first-generation drugs).
The mechanism of Clozapine-induced agranulocytosis is unknown; nonetheless, it is possible that causative factors may interact synergistically to increase the risk and/or severity of bone marrow suppression (retrieved from http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/019758s062lbl.pdf).
Side effects:
• Clozapine carries a five-box FDA warning for agranulocytosis (low white blood counts), seizures (e..g grand mal), myocarditis (inflammation of the heart muscle), other adverse cardiovascular and respiratory effects (including cardiac arrest and orthostatic hypotension), and increased mortality rates when used with older dementia patients with psychosis (retrieved from http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/019758s062lbl.pdf).
• Sedation can also be quite bothersome to some patients (Preston, O’Neal, & Talaga, 2013).
• One benefit is that the drug has lower extrapyramidal side effects than other second generation anti-psychotic medications (Parkinsonian, Dystonic, Akathisia).
• The text has a full list of side effects on page 233 (Preston, O’Neal, & Talaga, 2013).
Strengths and Weaknesses:
• The key strength is the success rate with treatment-resistant schizophrenia and the lowering of suicidal tendency in high risk patients.
• This drug can cost as much as $10,000/month (Preston, O’Neal, & Talaga, 2013).
• This drug can also kill you, in some cases, even if you are being carefully monitored by your doctor.
• Ideally, the next generation of drugs (some of which are already in use) will remove the most egregious side-effects.
Known Contraindications:
• Clozapine should not be prescribed if there is a history of sensitivity to the drug, epilepsy that is not well controlled, certain blood disorders (myeloproliferative), paralytic ileus (intestinal blockage caused by nerve and muscle malfunction), or a history agranulocytosis.
• Clozapine is not advised if a patient is suffering from a comatose state or depression of the central nervous system.
• It should not be used in conjunction with other drugs which can impact some of the same mechanisms, such as lowering white blood cell count (retrieved from http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/019758s062lbl.pdf)
Age/gender/cultural concerns:
• While animal studies were negative for effects on pregnant animals, caution should be taken when considering prescribing to pregnant mothers.
• Clozapine may be excreted in breast milk, so women using this drug should not breast-feed.
• Clozapine has not been tested for use with children.
Feedback from prescribers and
consumers:
• In one study, prescribers overestimated prevalence of side effects as compared to consumers.
• Consumers were most concerned about drooling mouth, compared to impacts on sleep for prescribers (Hodge & Jespersen, 2008).
Consumer Psychoeducation:
• Carefully lay out the pros and cons. A client needing to take Clozapine has likely already been through significant efforts to manage their symptoms.
Medication Class: Anti-psychotic, atypical, second generation.
History of Use:
Clozapine was used in Europe first in the early 1970s to treat schizophrenia. It was withdrawn in 1975 when it was shown to cause a dangerous drop in white blood cells (agranulocytosis). It was later approved for limited use in the United States (1989), specifically for treatment-resistant Schizophrenia, as long as weekly blood tests were monitored for low white cell counts. Further FDA approvals came in 2002, as it was shown to be effective in lower the risk of suicide for those in high risk categories.
As a result, Clozapine is generally used where other medications have failed. Several newer atypicals have been released …show more content…
that are attempting to overcome the limitations of Clozapine and other related anti-psychotics (Preston, O’Neal, & Talaga, 2013). These are documented in our text.
Benefits, concerns:
• Besides helping to treat the positive symptoms of Schzophrenia, Clozapine, and other atypicals, also treat negative symptoms, although the success rate of atypicals is generally no higher than 30 percent for negative symptoms (Preston, O’Neal, & Talaga, 2013).
• One group of researchers attributed the positive impact on negative symptoms to both the effect of treating the positive symptoms, as well as to the direct treatment of the causes responsible for the negative symptoms (Miller, Perry, Cadoret, & Andreasen, 1994).
• The seriousness of some side-effects (see below) have limited the use of this drug. To ensure that strict blood testing is followed, the distribution system has been set up to ensure white blood cell counts have been tested (retrieved from http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/019758s062lbl.pdf).
Delivery:
• The medication can be delivered by a pill that is swallowed or a pill that is dissolved in the mouth.
How/why does it work?
According to the text (Preston, O’Neal, & Talaga, 2013), Clozapine, along with other second-generation antipsychotics, block serotonin, while having a lower impact on dopamine blockage (the primary action of first-generation drugs).
The mechanism of Clozapine-induced agranulocytosis is unknown; nonetheless, it is possible that causative factors may interact synergistically to increase the risk and/or severity of bone marrow suppression (retrieved from http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/019758s062lbl.pdf).
Side effects:
• Clozapine carries a five-box FDA warning for agranulocytosis (low white blood counts), seizures (e..g grand mal), myocarditis (inflammation of the heart muscle), other adverse cardiovascular and respiratory effects (including cardiac arrest and orthostatic hypotension), and increased mortality rates when used with older dementia patients with psychosis (retrieved from http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/019758s062lbl.pdf).
• Sedation can also be quite bothersome to some patients (Preston, O’Neal, & Talaga, 2013).
• One benefit is that the drug has lower extrapyramidal side effects than other second generation anti-psychotic medications (Parkinsonian, Dystonic, Akathisia).
• The text has a full list of side effects on page 233 (Preston, O’Neal, & Talaga, 2013).
Strengths and Weaknesses:
• The key strength is the success rate with treatment-resistant schizophrenia and the lowering of suicidal tendency in high risk patients.
• This drug can cost as much as $10,000/month (Preston, O’Neal, & Talaga, 2013).
• This drug can also kill you, in some cases, even if you are being carefully monitored by your doctor.
• Ideally, the next generation of drugs (some of which are already in use) will remove the most egregious side-effects.
Known Contraindications:
• Clozapine should not be prescribed if there is a history of sensitivity to the drug, epilepsy that is not well controlled, certain blood disorders (myeloproliferative), paralytic ileus (intestinal blockage caused by nerve and muscle malfunction), or a history agranulocytosis.
• Clozapine is not advised if a patient is suffering from a comatose state or depression of the central nervous system.
• It should not be used in conjunction with other drugs which can impact some of the same mechanisms, such as lowering white blood cell count (retrieved from http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/019758s062lbl.pdf)
Age/gender/cultural concerns:
• While animal studies were negative for effects on pregnant animals, caution should be taken when considering prescribing to pregnant mothers.
• Clozapine may be excreted in breast milk, so women using this drug should not breast-feed.
• Clozapine has not been tested for use with children.
Feedback from prescribers and
consumers:
• In one study, prescribers overestimated prevalence of side effects as compared to consumers.
• Consumers were most concerned about drooling mouth, compared to impacts on sleep for prescribers (Hodge & Jespersen, 2008).
Consumer Psychoeducation:
• Carefully lay out the pros and cons. A client needing to take Clozapine has likely already been through significant efforts to manage their symptoms.