Clozapine dose for schizophrenia

Subramanian, Selvizhi; Völlm, Birgit; Huband, Nick

doi:10.1002/14651858.cd009555.pub2

Cited by 42 publications

(47 citation statements)

References 74 publications

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“…We used 0.45 mg/kg of CNO in our experiment so the equivalent dose of clozapine would be 0.005 mg/kg because the clozapine dose required to induce behavioral change in vivo through hM3Dq was 100 times more potent than CNO 25 . The clinical dose of clozapine is 12.5-600 mg/day 28 , which corresponds to 0.2-10 mg/kg when assuming a human body weight of 60 kg. Therefore, the dosing of CNO in this study was far lower (1/40-1/2000) than that which might induce cataplexy-like behavior.…”

Section: Discussionmentioning

confidence: 99%

Involvement of the Nucleus Accumbens in Chocolate-induced Cataplexy

Yamashita

et al. 2020

Sci Rep

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Happiness is key for both mental and physical well-being. To further understand the brain mechanisms involved, we utilized the cataplexy that occurs in narcoleptic animal models as a quantitative behavioral measure because it is triggered by actions associated with happiness, such as laughter in humans and palatable foods in mice. Here we report that the rostral part of the nucleus accumbens (NAc) shell is strongly activated during the beginning of chocolate-induced cataplexy in orexin neuron-ablated mice. We made a local lesion in the NAc using ibotenic acid and observed the animals' behavior. The number of cataplexy bouts was negatively correlated to the lesion size. We also examined the hedonic response to palatable food by measuring the number of tongue protrusions in response to presentation of honey, which was also found to be negatively correlated to the lesion size. Next, we used clozapine N-oxide to either activate or inactivate the NAc through viral DREADD expression. As expected, the number of cataplexy bouts increased with activation and decreased with inactivation, and saline control injections showed no changes. Hedonic response in the DREADD experiment varied and showed both increases and decreases across mice. These results demonstrated that the rostral part of the NAc plays a crucial role in triggering cataplexy and hedonic orofacial movements. Since the NAc is also implicated in motivated behavior, we propose that the NAc is one of the key brain structures involved in happiness and is a driving force for positive emotion-related behaviors.

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Section: Discussionmentioning

confidence: 99%

Involvement of the Nucleus Accumbens in Chocolate-induced Cataplexy

Yamashita

et al. 2020

Sci Rep

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“…It should be noted that as clozapine duration increased, so did the patient's dose of clozapine. Current research associates dose and serum concentration with clozapine induced weight gain and metabolic side effects, however, these effects can also occur at doses considered "very low" [30][31][32].…”

Section: Discussionmentioning

confidence: 99%

Implications of Clozapine Complications in Geriatric Patients with Type II Diabetes Mellitus

Chehovich¹,

Demler²

2019

obm geriatr

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Second-generation antipsychotics, have known metabolic side effects; specifically, clozapine is implicated in worsening or causing hyperglycemia, hypercholesterolemia and weight gain. Recently, there has been an increased interest in the safe use of clozapine in patients with diabetes. In March 2018, a 65-year-old female with a diagnosis of schizophrenia was admitted for inpatient hospitalization to a psychiatric hospital in Buffalo, NY for further stabilization after receiving two months of treatment at a comprehensive psychiatric emergency program (CPEP). Her medical diagnoses included type 2 diabetes mellitus (T2DM), vitamin D deficiency, hyperlipidemia, glaucoma, and constipation. Upon admission, the patient was continued on clozapine, and fluphenazine for treatment of schizophrenia. Her medical medications upon admission included acetaminophen, cholecalciferol, multivitamin, and timolol maleate eye drops. Low blood glucose results at the beginning of her hospitalization led to discontinuation of fingerstick blood glucose readings as the patient was

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“…A recent article on clozapine dosing published using the Cochrane methodology [20] is excellent proof of how using EBM methodology can provide results that make no sense in the context of pharmacokinetics. Indeed, if you know pharmacokinetics, you know that the question of which clozapine dose is best is essentially nonsensical.…”

Section: Lack Of Understanding the Limitations Of Traditional Statistmentioning

confidence: 99%

“…The authors of this EBM clozapine review concluded, "It is unclear, however, what dose of clozapine is most effective with the least side effects." [20]. In reality, there is no need to make the effort to complete such a review to reach that conclusion; a pharmacokinetic scientist without completing any EBM review can explain that the only way to establish the clozapine dosage for a specific patient is to complete TDM and then reference the AGNP clozapine therapeutic reference range.…”

Section: Lack Of Understanding the Limitations Of Traditional Statistmentioning

confidence: 99%

“…In reality, there is no need to make the effort to complete such a review to reach that conclusion; a pharmacokinetic scientist without completing any EBM review can explain that the only way to establish the clozapine dosage for a specific patient is to complete TDM and then reference the AGNP clozapine therapeutic reference range. Unfortunately, these experts on Cochrane methodology [20] are much less sophisticated in their knowledge of TDM and do not know that the 2004 [9] or 2011 AGNP guidelines [11] exist; they preferred to quote a 1995 study on clozapine's therapeutic reference range.…”

Section: Lack Of Understanding the Limitations Of Traditional Statistmentioning

confidence: 99%

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A Critical Commentary on the 2017 AGNP Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology

León

2017

Pharmacopsychiatry

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In 2004, 2011, and 2017, the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP), a group of German-speaking psychiatric researchers and psychiatrists, published successive versions of therapeutic drug monitoring (TDM) expert group consensus guidelines. The 2017 version has as a major strength its encyclopedic nature, including 1358 references. The guideline has 3 major sections: 1) theoretical aspects of TDM, 2) drug concentration levels in blood to guide neuropsychopharmacotherapy, and 3) practical aspects of TDM in psychiatry and neurology. The writer hopes the time is right for a TDM guideline in psychiatry, which is indicated for: 1) psychiatric researchers ready to value how TDM can contribute to moving psychopharmacology forward, 2) flexible clinicians ready to improve their patient care by personalizing dosing, and 3) today’s psychiatry residents prepared as a new generation ready to be trained in TDM and willing to continue incorporating TDM as new psychiatric drugs are marketed.

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Clozapine dose for schizophrenia

Abstract: Analysis 3.1. Comparison 3 CLOZAPINE: LOW DOSE (150 to 300 mg/day) versus STANDARD DOSE (301 to 600 mg/day), Outcome 1 Mental state: 1a. Clinically important response as (BPRS score > 30% change

Cited by 42 publications

References 74 publications

Involvement of the Nucleus Accumbens in Chocolate-induced Cataplexy

Involvement of the Nucleus Accumbens in Chocolate-induced Cataplexy

Implications of Clozapine Complications in Geriatric Patients with Type II Diabetes Mellitus

A Critical Commentary on the 2017 AGNP Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology

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