Effects of clozapine: A Synthesis of Findings from 13 Studies

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Original Abstract of the Article

Major Research Findings

Clozapine has been shown to be more effective than other antipsychotics in reducing hostility among patients with schizophrenia. 5 Clozapine has also been shown to be effective in reducing positive, negative, and affective symptoms of schizophrenia. 4 Furthermore, clozapine has been associated with fewer side effects and shorter hospital stays compared to other antipsychotics. 1 Clozapine is often considered the drug of choice for treatment-resistant schizophrenia. 8 However, clozapine is also associated with potentially life-threatening side effects, including agranulocytosis and myocarditis. 8

Clozapine can induce changes in the electroencephalogram (EEG) and these changes can vary depending on the serum levels. 2 A clozapine serum level between 350 and 450 ng/mL is associated with more frequent and severe slowing on EEG. 2 These changes may be linked to drowsiness. 2

Benefits and Risks

Benefit Summary

Clozapine has been shown to be more effective than other antipsychotics in reducing hostility among patients with schizophrenia. 5 Clozapine has also been shown to be effective in reducing positive, negative, and affective symptoms of schizophrenia. 4 Furthermore, clozapine has been associated with fewer side effects and shorter hospital stays compared to other antipsychotics. 1

Risk Summary

Clozapine is associated with potentially life-threatening side effects, including agranulocytosis and myocarditis. 8 Clozapine can induce changes in the electroencephalogram (EEG) and these changes can vary depending on the serum levels. 2 A clozapine serum level between 350 and 450 ng/mL is associated with more frequent and severe slowing on EEG. 2 These changes may be linked to drowsiness. 2 Clozapine can also cause fever and flu-like symptoms in up to 50% of patients during the first month of treatment. 8

Comparison Across Studies

Commonalities Across Studies

Many studies have shown that clozapine is effective in treating schizophrenia symptoms, including positive, negative, and affective symptoms. 5 4 1 7 9 However, clozapine can also cause serious side effects. 8 2 Therefore, clozapine should be used with caution.

Differences Across Studies

There are some differences in the findings of studies on clozapine, such as variations in the patient populations and evaluation methods. 5 4 1 7 9 12 For example, while some studies suggest clozapine is significantly more effective than other antipsychotics, others find no such significant differences. 12 Further research is needed to better understand clozapine's effects.

Consistency and Contradictions in Findings

There is a mix of consistency and contradictions in the findings on clozapine's effects. 5 4 1 7 9 12 Some studies suggest clozapine is more effective than other antipsychotics, but others find no significant differences. 12 Additionally, clozapine has been shown to cause serious side effects. 8 2 Further research is required to gain a more complete understanding of clozapine's effects.

Considerations for Real-World Application

Clozapine may be effective for patients with treatment-resistant schizophrenia. 1 However, clozapine can cause serious side effects, so it should be used cautiously. 8 2 It is important to consult with a doctor to assess the individual patient's symptoms and risk factors when considering clozapine treatment.

Limitations of Current Research

There are still some limitations in research on clozapine's effects. 5 4 1 7 9 12 For example, studies may have limited patient populations or short follow-up periods. 12 Further research is needed to address these limitations and gain a more complete understanding of clozapine's effects.

Future Research Directions

Further research is needed to better understand the effects of clozapine. 5 4 1 7 9 12 Specifically, research comparing clozapine's effects to other antipsychotics and exploring ways to mitigate clozapine's side effects are important. 12 Additionally, research examining how clozapine's effects relate to specific patient characteristics is valuable. 11 10 13

Conclusion

Clozapine may be more effective than other antipsychotics in reducing hostility in patients with schizophrenia. 5 Clozapine has also been shown to be effective in reducing positive, negative, and affective symptoms of schizophrenia. 4 However, clozapine can cause serious side effects, including agranulocytosis and myocarditis, so it should be used cautiously. 8 2 It is important to consult with a doctor to assess the individual patient's symptoms and risk factors when considering clozapine treatment.

Literature analysis of 13 papers
Positive Content
12
Neutral Content
0
Negative Content
1
Article Type
9
2
3
3
13
1.

Clozapine's effectiveness for patients in state hospitals: results from a randomized trial.

Author: EssockS M, HargreavesW A, CovellN H, GoetheJ

Reduced hospitalization
Reduced side effects

Clozapine was associated with significantly greater reductions in side effects, disruptiveness, and hospitalization, but was not more effective in reducing symptoms or improving quality of life.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.
Research Support, U.S. Gov't, P.H.S.Research funding provided by the Public Health Service (PHS).

Language : English

2.

Clozapine-induced electroencephalogram changes as a function of clozapine serum levels.

Author: FreudenreichO, WeinerR D, McEvoyJ P

EEG slowing
Seizures
Sleepiness

Clozapine therapy was found to cause EEG changes in 53% of patients with schizophrenia. 6% of patients experienced seizures, 13% developed spikes, and 53% developed slowing. Higher clozapine serum levels (350-450 ng/mL) led to more frequent and severe slowing compared to lower levels.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.

Language : English

3.

A comparison of clozapine and haloperidol in hospitalized patients with refractory schizophrenia. Department of Veterans Affairs Cooperative Study Group on Clozapine in Refractory Schizophrenia.

Author: RosenheckR, CramerJ, XuW, ThomasJ, HendersonW, FrismanL, FyeC, CharneyD

Reduced extrapyramidal side effects
Agranulocytosis

Clozapine is a widely used antipsychotic drug for patients with refractory schizophrenia, with a low risk of extrapyramidal side effects but potential for agranulocytosis. Long-term effects on symptoms, social functioning, healthcare utilization, and cost need further investigation.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Multicenter StudyResearch conducted in collaboration with multiple research institutions. It aims to collect a wide range of data and obtain more generalizable results.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, U.S. Gov't, Non-P.H.S.Research funding provided by US government agencies other than the Public Health Service.

Language : English

4.

Positive and negative symptom response to clozapine in schizophrenic patients with and without the deficit syndrome.

Author: BuchananR W, BreierA, KirkpatrickB, BallP, CarpenterW T

Improved symptoms

This study investigated the effectiveness of clozapine for treating both positive and negative symptoms of schizophrenia, including those with and without the deficit syndrome. The researchers also looked at the long-term effects of clozapine on various aspects of the illness, including social and occupational functioning, and quality of life.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.
Research Support, U.S. Gov't, P.H.S.Research funding provided by the Public Health Service (PHS).

Language : English

5.

Effects of clozapine, olanzapine, risperidone, and haloperidol on hostility among patients with schizophrenia.

Author: CitromeL, VolavkaJ, CzoborP, SheitmanB, LindenmayerJ P, McEvoyJ, CooperT B, ChakosM, LiebermanJ A

Anti-hostility effect

Clozapine demonstrated a specific antiaggressive effect, showing significantly greater improvement than haloperidol or risperidone in patients with schizophrenia or schizoaffective disorder.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Multicenter StudyResearch conducted in collaboration with multiple research institutions. It aims to collect a wide range of data and obtain more generalizable results.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.
Research Support, U.S. Gov't, P.H.S.Research funding provided by the Public Health Service (PHS).

Language : English

6.

Does clozapine decrease smoking?

Author: de LeonJose, DiazFrancisco J, JosiassenRichard C, CooperThomas B, SimpsonGeorge M

May reduce smoking

Clozapine is a drug that is often used to treat schizophrenia. Studies on the effects of clozapine on smoking in patients with schizophrenia have yielded inconsistent results. This study found no significant effects of clozapine on smoking.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.
Research Support, U.S. Gov't, P.H.S.Research funding provided by the Public Health Service (PHS).

Language : English

7.

A randomized double-blind comparison of ziprasidone vs. clozapine for cognition in patients with schizophrenia selected for resistance or intolerance to previous treatment.

Author: HarveyPhilip D, SacchettiEmilio, GalluzzoAlessandro, RomeoFabio, GoriniBarbara, BilderRobert M, LoebelAntony D

schizophrenia treatment

This study compared the cognitive benefits of clozapine and ziprasidone in schizophrenia patients who had failed to respond to or were intolerant of other antipsychotics.

Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Multicenter StudyResearch conducted in collaboration with multiple research institutions. It aims to collect a wide range of data and obtain more generalizable results.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

8.

Immunomodulatory effects of clozapine and their clinical implications: what have we learned so far?

Author: RøgeRasmus, MøllerBjarne K, AndersenChristian R, CorrellChristoph U, NielsenJimmi

Treat schizophrenia
Agranulocytosis
Myocarditis

Clozapine, an antipsychotic drug for treatment-resistant schizophrenia, exhibits immunomodulatory effects. While its efficacy is well-established, further research is needed to understand its immunomodulatory mechanisms and to develop safer and more effective therapies.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.
Systematic ReviewA review that systematically collects, evaluates, and integrates relevant research to answer a specific research question.

Language : English

9.

Comparative efficacy between clozapine and other atypical antipsychotics on depressive symptoms in patients with schizophrenia: analysis of the CATIE phase 2E data.

Author: NakajimaShinichiro, TakeuchiHiroyoshi, FervahaGagan, PlitmanEric, ChungJun Ku, CaravaggioFernando, IwataYusuke, MihashiYukiko, GerretsenPhilip, RemingtonGary, MulsantBenoit, Graff-GuerreroAriel

Clozapine antidepressant
Clozapine schizophrenia
Clozapine not superior MDE

Clozapine demonstrated superior antidepressant effects to quetiapine and comparable effects to olanzapine and risperidone in chronic schizophrenia.

Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

10.

Structural and functional neuroimaging findings associated with the use of clozapine in schizophrenia: a systematic review.

Author: GarciaGiovana J, ChagasMarcos H, SilvaCarlos H, Machado-de-SousaJoão P, CrippaJosé A, HallakJaime E

Schizophrenia treatment

This study reviewed the available literature on the structural and functional neuroimaging findings associated with use of clozapine.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.
Systematic ReviewA review that systematically collects, evaluates, and integrates relevant research to answer a specific research question.

Language : English

11.

The clinical potentials of adjunctive fluvoxamine to clozapine treatment: a systematic review.

Author: PolcwiartekChristoffer, NielsenJimmi

Increased clozapine levels
Reduced clozapine side effects
Agranulocytosis risk
Increased clozapine side effects

This study reviews the pharmacodynamic effects and adverse effect profile of changing the clozapine/N-desmethylclozapine (NDMC) ratio with adjunctive fluvoxamine. Evidence supports that adjunctive fluvoxamine increases clozapine plasma levels, which may improve response in patients who do not achieve sufficient clozapine levels. Fluvoxamine also reduces metabolic adverse effects of clozapine, but not agranulocytosis risk.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Meta-AnalysisA statistical technique that integrates the results of multiple studies to draw more general conclusions about a particular issue.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.
Systematic ReviewA review that systematically collects, evaluates, and integrates relevant research to answer a specific research question.

Language : English

12.

Efficacy, Acceptability, and Tolerability of Antipsychotics in Treatment-Resistant Schizophrenia: A Network Meta-analysis.

Author: SamaraMyrto T, DoldMarkus, GianatsiMyrsini, NikolakopoulouAdriani, HelferBartosz, SalantiGeorgia, LeuchtStefan

Reduced schizophrenia symptoms
Clozapine side effects

Insufficient evidence exists on which antipsychotic is more efficacious for patients with treatment-resistant schizophrenia. Blinded RCTs-in contrast to unblinded, randomized effectiveness studies-provide little evidence of the superiority of clozapine compared with other second-generation antipsychotics.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Meta-AnalysisA statistical technique that integrates the results of multiple studies to draw more general conclusions about a particular issue.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

13.

N-acetylcysteine (NAC) in schizophrenia resistant to clozapine: a double blind randomised placebo controlled trial targeting negative symptoms.

Author: RossellSusan L, FrancisPaul S, GalletlyCherrie, HarrisAnthony, SiskindDan, BerkMichael, BozaogluKiymet, DarkFrances, DeanOlivia, LiuDennis, MeyerDenny, NeillErica, PhillipouAndrea, SarrisJerome, CastleDavid J

Effective for clozapine-resistant SZ

Clozapine is an effective treatment for a proportion of people with schizophrenia (SZ) who are resistant to the beneficial effects of other antipsychotic drugs. 40-60% of people on clozapine experience residual symptoms even on adequate doses of the medication, and thus could be considered 'clozapine resistant'. A large scale clinical trial of NAC in the treatment of clozapine-resistant SZ is being conducted to improve the lives of individuals with clozapine-resistant SZ.

Clinical Trial, Phase IVPost-marketing surveillance. Monitors long-term safety/efficacy after approval.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Multicenter StudyResearch conducted in collaboration with multiple research institutions. It aims to collect a wide range of data and obtain more generalizable results.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.

Language : English

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