Side Effects of clozapine: A Synthesis of Findings from 21 Studies

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Original Abstract of the Article

Key Research Findings

Clozapine is an effective treatment for treatment-resistant schizophrenia, but it has been reported to have many side effects. There is often a discrepancy between clinician and patient ratings of clozapine-induced side effects, highlighting the need for patient-reported side effects in addition to clinician-based assessments. 10 ,

Clozapine side effects range from subjectively unpleasant to clinically serious, which can affect treatment adherence. 18

Effective clozapine administration may be influenced by polymorphisms in the CYP1A2 gene, which affects drug metabolism. 20

Reasons for Side Effects

Clozapine is a second-generation antipsychotic drug effective for treatment-resistant schizophrenia. However, clozapine can affect metabolic regulation, potentially leading to metabolic disorders. This explains why clozapine can cause metabolic side effects such as weight gain, diabetes, and dyslipidemia. 6

Common Side Effects

Agranulocytosis

Clozapine can cause a serious side effect called agranulocytosis. 13 , 14 , 1

Metabolic Disorders

Clozapine can cause metabolic disorders such as weight gain, diabetes, and dyslipidemia. 21 , 12 , 15 , 2 , 6 , 3 , 9

Cardiovascular Side Effects

Clozapine can cause cardiovascular side effects such as myocarditis, orthostatic hypotension, and tachycardia. 9 ,

Others

Clozapine can cause side effects such as constipation, excessive salivation, drowsiness, urinary incontinence, tremors, blurred vision, and loss of appetite. 13 , 19 , 3 , 7 , 17 , 4

Side Effects Management

Agranulocytosis

Regular blood tests are recommended to prevent agranulocytosis. 14

Metabolic Disorders

A healthy diet and exercise are recommended to prevent metabolic disorders such as weight gain, diabetes, and dyslipidemia. 6

Cardiovascular Side Effects

Regular monitoring of blood pressure and heart rate is recommended to prevent cardiovascular side effects such as myocarditis, orthostatic hypotension, and tachycardia. 9

Others

A diet rich in fiber and sufficient water intake are recommended to prevent constipation. 19

Rinsing the mouth or chewing gum is recommended to reduce excessive salivation. 19

Avoiding caffeine is recommended to reduce drowsiness. 19

Increasing the frequency of toilet trips is recommended to reduce urinary incontinence. 19

Comparison of Studies

Commonalities

Many studies have shown that clozapine can cause side effects such as agranulocytosis, weight gain, and diabetes. These side effects can affect a patient's quality of life.

Differences

Clozapine side effects can vary from person to person and may be affected by genetic factors and interactions with other drugs. 20 , 15

Practical Implications

Clozapine is an effective medication, but it is important to understand the risk of side effects and follow your doctor's instructions. Consult your doctor if you are concerned about side effects.

Limitations of Current Research

There is still a lack of research on clozapine side effects. More research is needed, especially on the long-term effects of side effects and research considering individual differences.

Future Directions for Research

Research on the mechanisms of side effect development and new treatments to reduce side effects is needed to better understand clozapine side effects.

Conclusion

Clozapine is an effective treatment for treatment-resistant schizophrenia, but various side effects have been reported. It is important to follow your doctor's instructions for taking clozapine, detect side effects early, and take appropriate action.

Literature analysis of 21 papers
Positive Content
12
Neutral Content
2
Negative Content
7
Article Type
0
0
0
3
20
4.

Clozapine-induced gastroesophageal rumination in 22q11.2 Deletion Syndrome. A case report on gastroesophageal side effects management without renouncing clozapine's effectiveness.

Author: AccinniTommaso, FrascarelliMarianna, GhezziFrancesco, PanzeraAlessia, BuzzancaAntonino, FanellaMartina, Di BonaventuraCarlo, CarloneLuca, GirardiNicoletta, PasquiniMassimo, Di FabioFabio

Treatment-resistant schizophrenia
Severe side effects

Despite potential side effects in patients with 22q11.2 deletion syndrome, clozapine should still be considered the gold standard for treatment-resistant schizophrenia in this population.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.

Language : English

6.

A Focused Review of the Metabolic Side-Effects of Clozapine.

Author: YuenJessica W Y, KimDavid D, ProcyshynRic M, PanenkaWilliam J, HonerWilliam G, BarrAlasdair M

Effective for treatment-resistant psychosis
Low extrapyramidal symptoms
Low hyperprolactinemia
Metabolic side-effects
Metabolic syndrome

Clozapine is the most effective treatment for treatment-resistant psychosis but is associated with significant metabolic side effects, including glucose and lipid dysregulation. This review discusses the underlying mechanisms of these side effects and treatment options.

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.

Language : English

7.

Reliability of the Glasgow Antipsychotic Side-effects Scale for Clozapine Japanese version (GASS-C-J).

Author: KitagawaKohei, SoRyuhei, NomuraNobuyuki, MizunoYuya, MisawaFuminari, KodamaMasafumi, UchidaHiroyuki, MimuraMasaru, TakeuchiHiroyoshi

Clozapine side effect assessment

The Glasgow Antipsychotic Side effects Scale for Clozapine Japanese version (GASS-C-J) was found to be a reliable scale for assessing clozapine-related side effects with an internal consistency of 0.78 (95% CI: 0.72 to 0.84) and 0.82 (95% CI: 0.76 to 0.88) and a weighted kappa coefficient ranging from 0.45 to 0.88.

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.

Language : English

11.

Clozapine-related extrapyramidal side effects: a case report.

Author: GalloMariana, SquarcioneChiara, BersaniFrancesco Saverio, MinichinoAmedeo, FojanesiMarta, BiondiMassimo

Clozapine
EPS risk

Clozapine is a medication used to treat schizophrenia. While it is generally considered to have fewer side effects than other antipsychotic medications, this case report shows that long-term use can still lead to extrapyramidal side effects, which are movement problems.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

12.

Genetic Determinants of Clozapine-Induced Metabolic Side Effects.

Author: VasudevKamini, ChoiYun-Hee, NormanRoss, KimRichard B, SchwarzUte I

Metabolic side effects
Weight gain

A high prevalence of metabolic side effects was found in patients on 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.

Language : English

15.

Pharmacogenetics of clozapine treatment response and side-effects in schizophrenia: an update.

Author: SriretnakumarVenuja, HuangEric, MüllerDaniel J

Reduces aggression
Reduces suicide risk
Treatment-resistant schizophrenia
Agranulocytosis
Weight gain

Clozapine is the most effective treatment for treatment-resistant schizophrenia, but its high risk of agranulocytosis, weight gain, and metabolic dysregulation limits its use. Pharmacogenetics offers the potential for personalized treatment by predicting patient response and risk of adverse effects based on genetics.

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.

Language : English

16.

Glasgow Antipsychotic Side-effects Scale for Clozapine - Development and validation of a clozapine-specific side-effects scale.

Author: HynesCaroline, KeatingDolores, McWilliamsStephen, MadiganKevin, KinsellaAnthony, MaidmentIan, FeetamCelia, DrakeRichard J, HaddadPeter M, GaughranFiona, TaylorMark, ClarkeMary

Clozapine treatment

A study of 110 clozapine outpatients found that the GASS-C (Glasgow Antipsychotic Side-effects Scale for Clozapine) is a valid and reliable clinical tool to assess the subjectively unpleasant side-effects of clozapine.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Validation StudyResearch to assess the validity and reliability of new measurement methods or diagnostic tests.

Language : English

17.

The ocular surface side effects of an anti-psychotic drug, clozapine.

Author: CeylanErdinç, OzerMuhammet Derda, YilmazYusuf Cem, KartalBaki, Yildiz EkinciDilbade, ÇiniciEmine, Aksu CeylanNihan

Corneal alterations
Dry eye syndrome

Long-term clozapine usage was found to induce dry eye syndrome and lead to morphological alterations in corneal parameters, such as reduced corneal thickness and tear film stability. These changes may impact glaucoma patients and candidates for corneal refractive surgery.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

18.

Factors associated with subjective side-effects during clozapine treatment.

Author: SeppäläNiko, LeinonenEsa, ViikkiMerja, SolismaaAnssi, NuolivirtaTimo, KampmanOlli

Side effects

Clozapine, a medication for schizophrenia, can cause unpleasant side effects. This study examined the association between clozapine serum concentration and subjective side effects in patients with schizophrenia.

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.

Language : English

19.

Pharmacological and behavioral management of some often-overlooked clozapine-induced side effects.

Author: SagyRoi, WeizmanAbraham, KatzNachum

Clozapine treatment
Constipation
Hypersalivation
Nocturnal enuresis
Tachycardia

Clozapine, an effective treatment for schizophrenia, can cause hypersalivation, constipation, tachycardia, and nocturnal enuresis.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

20.

CYP1A2 polymorphism -1545C > T (rs2470890) is associated with increased side effects to clozapine.

Author: ViikkiMerja, KampmanOlli, SeppäläNiko, MononenNina, LehtimäkiTerho, LeinonenEsa

Antipsychotic side effects

Polymorphisms in the CYP1A2 gene have been linked to increased side effects of antipsychotics. This study examined the association between a specific CYP1A2 polymorphism and side effects in patients undergoing long-term clozapine treatment.

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.

Language : English

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