Therapeutic Options in the Treatment of Clozapine-Induced Adverse Effects

Iqbal, Mohammad; Aneja, Alka; Rahman, Atiq; Megna, James L; Yasmin, Laila; Schwartz, Thomas L.; Osmany, Saabry; Alam, Mohammed Adnan

doi:10.1177/875512250402000303

Cited by 5 publications

(5 citation statements)

References 101 publications

(96 reference statements)

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“…While some authors advised that CLZ shouldn't be used with other drugs known to potentially affect bone marrow including carbamazepine, phenytoin, phenobarbital, captopril, and sulphonamides, 21,[72][73][74] our study didn't prove increased risk of CLZ-induced bone marrow toxicity by concomitant captopril administration.…”

Section: Discussionmentioning

confidence: 62%

Evaluation of the role of captopril on clozapine-induced cardiotoxicity and hematotoxicity in adult male albino rats

Hamid

Ahmed

Hassaneine

et al. 2017

Toxicology Research and Application

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Clozapine (CLZ) is considered the most effective drug in treatment of resistant schizophrenia. However, its cardiotoxic effect has raised concerns about its safety. Captopril is a well-known angiotensin-converting enzyme inhibitor with unique antioxidant properties. The aim of this study was to investigate the protective effect of captopril against CLZ-induced myocarditis, and since both drugs have hematotoxic effects, this study aimed to clarify the effect of their combined use on the bone marrow. The study was conducted for 4 weeks on 50 adult male albino rats divided into five groups: group I (negative control), group II (positive control), group III treated with captopril 5 mg/kg/day, group IV treated with CLZ 25 mg/kg/day, and group V treated with captopril (5 mg/kg) 1 hour before CLZ (25 mg/kg/day). CLZ group showed a significant increase in serum troponin I, marked histopathological changes, and immunohistochemical staining of DNA degradation product 8-hydroxy-2-deoxy guanosine (8-OHdG). It significantly increased malondialdehyde level and decreased glutathione peroxidase. Captopril coadministration decreased the histopathological hallmarks and biochemical marker of myocarditis and attenuated CLZ effects on the oxidative stress parameters and 8-OHdG, suggesting its protective action against CLZ-induced myocarditis. Complete blood count and bone marrow evaluation was normal indicating that captopril, in the protective dose given, didn't increase the risk of CLZ-induced hematotoxicity

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Section: Discussionmentioning

confidence: 62%

Evaluation of the role of captopril on clozapine-induced cardiotoxicity and hematotoxicity in adult male albino rats

Hamid

Ahmed

Hassaneine

et al. 2017

Toxicology Research and Application

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“…Hence, the prevalence of seizures was 5% for those patients treated with 600–900 mg/day; 3–4% for patients on 300–599 mg/day; and 1–2% for those on less than 300 mg/day. 8 In 1990, Haller and Bindr 33 reported ictal activity in three patients taking clozapine ≥ 600 mg/day. One of the patients was concomitantly treated with a very high dose of haloperidol (60 mg/day), which decreases seizure threshold as well as increases clozapine level by inhibition of 2D6 and 3A4.…”

Section: Literature Search Findingsmentioning

confidence: 99%

“…Amongst antipsychotics, clozapine has been associated with the highest incidence of seizures (1–5%) and the risk increases with high dose (≥ 600 mg/day) 8–10 as well as with high serum concentration (≥ 1300 ng/ml). 11–13…”

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confidence: 99%

“…1 Although good response may occur at any dose/serum concentration, for most patients the best clinical results appear to occur at 600 mg/day, 2 or at clozapine serum concentrations >350 ng/ml. [3][4][5][6][7] Amongst antipsychotics, clozapine has been associated with the highest incidence of seizures (1-5%) and the risk increases with high dose (≥ 600 mg/day) [8][9][10] as well as with high serum concentration (≥ 1300 ng/ml). [11][12][13] In 1991 Devinsky et al 9 recommended as one (but not the only) strategy that patients taking > 600 mg/day of clozapine be commenced on anticonvulsant therapy as a primary prophylaxis for seizures.…”

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confidence: 99%

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Use of anticonvulsants as prophylaxis for seizures in patients on clozapine

Caetano

2013

Australas Psychiatry

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Clozapine-induced seizures may occur at any dose; the risk increases with dose and goes up to 4% at ≥ 600 mg/day. Some authors have advocated that patients on that dose regimen have anticonvulsant added as a primary prophylactic measure. The author discusses the pitfalls of this recommendation and highlights that seizures are better predicted from serum concentration (1300 ng/ml) rather than dose alone, and that serum concentration is strongly influenced by sex, age, smoking habit, drug-drug interactions and variations in the 1A2, 2D6 and 3A4 genotypes. Anticonvulsants are not recommended as a primary prophylaxis for clozapine-induced seizures. When deemed necessary as secondary prophylaxis, the clinician's choice should consider drug-drug interactions that may increase/decrease clozapine serum concentration and lead to more side effects, including neutropenia/agranulocytosis and seizures, or compromise therapeutic response. Recommendations for primary and secondary prophylaxis of clozapine related-seizures are provided.

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“…Clozapine, the first SDA (serotonin–dopamine antagonist) to be approved, remains the treatment of choice for refractory schizophrenia. Weight gain is a frequent side effect of clozapine with between 20% and 80% of patients gaining greater than 10% baseline body weight (Iqbal et al, 2004; Young et al, 1998).…”

mentioning

confidence: 99%