Effects on monotherapy and reduction of antipsychotic drugs by clozapine therapy in Japanese patients with treatment‐resistant schizophrenia

2021 ◽  
Author(s):  
Yumiko Akamine ◽  
Yuka Kikuchi ◽  
Masatomo Miura
Keyword(s):  
Antipsychotic Drugs ◽  
Japanese Patients ◽  
Treatment Resistant ◽  
Clozapine Therapy

The Novel Antipsychotic Drug Cariprazine and Cognition Enhancing Drugs: Indications for Their Use as an Add-on Therapy in Schizophrenia

2020 ◽  
Vol 26 ◽  
Author(s):  
Felix-Martin Werner ◽  
Rafael Coveñas
Keyword(s):  
Clinical Trials ◽  
Maintenance Therapy ◽  
Antipsychotic Drug ◽  
Cognitive Functions ◽  
Antipsychotic Drugs ◽  
Psychotic Disorders ◽  
Therapeutic Effects ◽  
Treatment Resistant ◽  
Long Acting ◽  
Novel Antipsychotic

Background: Schizophrenia and schizoaffective disorder are treated with antipsychotic drugs. Some patients show treatment-resistant forms of psychotic disorders and, in this case, they can be treated with clozapine. In these patients and based on previous reviews on novel antipsychotic drugs, it is important to know whether an add-on therapy with new drugs can ameliorate the positive and negative schizophrenic scale (PANSS) total score. Objective: The aim of this review is to suggest an appropriate treatment for patients with treatment-resistant forms of psychotic disorders. A combination of current available antipsychotic drugs with novel antipsychotic or modulating drugs might improve negative schizophrenic symptoms and cognitive function and thereby social functioning and quality of life. Results: The mechanisms of action, the therapeutic effects and the pharmacokinetic profiles of novel antipsychotic drugs such as cariprazine, brexipiprazole and lumateperone are up-dated. Published case reports of patients with treatmentresistant psychoses are also discussed. These patients were treated with clozapine but a high PANSS total score was observed. Only an add-on therapy with cariprazine improved the score and, above all, negative schizophrenic symptoms and cognitive functions. To ensure a constant antipsychotic drug concentration, long-acting injectable antipsychotic drugs may be a choice for a maintenance therapy in schizophrenia. New modulating drugs, such as receptor positive allosteric modulators (N-methyl-D-aspartate receptor; subtype 5 of the metabotropic glutamatergic receptor) and encenicline, an alpha7 nicotinic cholinergic receptor agonist, are being investigated in preclinical and clinical trials. Conclusion: In clinical trials, patients with treatment-resistant forms of psychosis should be examined to know whether a combination therapy with clozapine and a novel antipsychotic drug can ameliorate the PANSS total score. In schizophrenia, long-acting injectable antipsychotic drugs are a safe and tolerable maintenance therapy. In further clinical studies, it should be investigated whether patients with treatment-resistant forms of psychoses can improve negative schizophrenic symptoms and cognitive functions by an add-on therapy with cognition enhancing drugs.

scholarly journals Efficacy and safety of fixed doses of intranasal Esketamine as an add-on therapy to Oral antidepressants in Japanese patients with treatment-resistant depression: a phase 2b randomized clinical study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Nagahide Takahashi ◽  
Aya Yamada ◽  
Ayako Shiraishi ◽  
Hiroko Shimizu ◽  
Ryosuke Goto ◽  
...  
Keyword(s):  
Nasal Spray ◽  
Japanese Patients ◽  
Controlled Study ◽  
Induction Phase ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Madrs Total Score ◽  
Link Type ◽  
Randomized Clinical Study ◽  
Resistant Depression

Abstract Background Esketamine nasal spray (Spravato) in conjunction with oral antidepressants (ADs) is approved in the European Union, United States, and other markets for treatment-resistant depression (TRD). Efficacy, safety, and tolerability of esketamine nasal spray in Japanese patients with TRD needs to be assessed. Methods This Phase 2b, randomized, double-blind (DB), placebo-controlled study was conducted in adult Japanese patients with TRD meeting the Diagnostic and Statistical Manual of Mental Disorders (fifth edition) criteria of major depressive disorder with nonresponse to ≥ 1 but < 5 different ADs in the current episode at screening. Patients were treated with a new oral AD for 6 weeks (prospective lead-in phase); nonresponders were randomized (2:1:1:1) to placebo or esketamine (28-, 56-, or 84-mg) nasal spray along with the continued use of AD for 4 weeks (DB induction phase). Responders (≥50% reduction from baseline in the Montgomery-Asberg Depression Rating Scale [MADRS] total score) from the DB induction phase continued into the 24-week posttreatment phase and patients who relapsed could participate in a 4-week open-label (OL) second induction (flexibly-dosed esketamine). The primary efficacy endpoint, change from baseline in the MADRS total score at Day 28 in the DB induction phase, was based on mixed-effects model using repeated measures pairwise comparisons using a Dunnett adjustment. Results Of the 202 patients randomized in the DB induction phase (esketamine [n = 122] or placebo [n = 80]), the MADRS total scores decreased from baseline to Day 28 of the DB induction phase (− 15.2, − 14.5, − 15.1, and − 15.3 for esketamine 28 mg, 56 mg, 84 mg, and placebo groups, respectively), indicating an improvement in depressive symptoms; however, the difference between the esketamine and placebo groups was not statistically significant. The most common treatment-emergent adverse events during the DB induction phase in the combined esketamine group (incidences ranging from 12.3 to 41.0%) were blood pressure increased, dissociation, dizziness, somnolence, nausea, hypoaesthesia, vertigo, and headache; the incidence of each of these events was > 2-fold higher than the corresponding incidence in the placebo group. Conclusions Efficacy of esketamine plus oral AD in Japanese TRD patients was not established; further investigation is warranted. All esketamine doses were safe and tolerated. Trial registration ClinicalTrials.gov Identifier: NCT02918318. Registered: 28 September 2016.

scholarly journals Response to antipsychotic drugs in treatment-resistant schizophrenia: Conclusions based on systematic review

2016 ◽  
Vol 178 (1-3) ◽  
pp. 64-67 ◽  
Author(s):  
C. Molins ◽  
A. Roldán ◽  
I. Corripio ◽  
M. Isohanni ◽  
J. Miettunen ◽  
...  
Keyword(s):  
Systematic Review ◽  
Antipsychotic Drugs ◽  
Treatment Resistant

scholarly journals Clozapine-Induced Late Agranulocytosis and Severe Neutropenia Complicated withStreptococcus pneumonia, Venous Thromboembolism, and Allergic Vasculitis in Treatment-Resistant Female Psychosis

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Christina Voulgari ◽  
Raphael Giannas ◽  
Georgios Paterakis ◽  
Anna Kanellou ◽  
Nikolaos Anagnostopoulos ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Second Generation ◽  
Causal Relation ◽  
Antipsychotic Agent ◽  
Iliac Vein ◽  
Severe Neutropenia ◽  
Caucasian Woman ◽  
Treatment Resistant ◽  
Clozapine Therapy ◽  
Allergic Vasculitis

Clozapine is a second-generation antipsychotic agent from the benzodiazepine group indicated for treatment-resistant schizophrenia and other psychotic conditions. Using clozapine earlier on once a case appears to be refractory limits both social and personal morbidity of chronic psychosis. However treatment with second-generation antipsychotics is often complicated by adverse effects. We present a case of a 33-year-old Caucasian woman with a 25-year history of refractory psychotic mania after switching to a 2-year clozapine therapy. She presented clozapine-induced absolute neutropenia, agranulocytosis, which were complicated byStreptococcus pneumoniaand sepsis. Clozapine-induced thromboembolism of the common femoral and right proximal iliac vein, as well as allergic vasculitis, was diagnosed. She achieved full remission on granulocyte-colony stimulating factor and specific antibiotic treatment. Early detection of severe clozapine-induced absolute neutropenia and agranulocytosis enabled the effective treatment of two among its most severe complications. Additional evidence to the previously reported possible causal relation between clozapine and venous thromboembolism is offered. Finally, clozapine-induced allergic vasculitis is confirmed as a late adverse effect of clozapine therapy.

Clozapine: Serious Adverse Side Effects, Drug Interactions, and Other Complications of Therapy

1996 ◽  
Vol 9 (2) ◽  
pp. 118-129 ◽  
Author(s):  
Deanna M. Guith
Keyword(s):  
Side Effects ◽  
Health Care Professionals ◽  
Elderly Population ◽  
Adverse Reactions ◽  
Psychotic Disorders ◽  
Antipsychotic Agent ◽  
The Elderly ◽  
Pharmacological Properties ◽  
Treatment Resistant ◽  
Clozapine Therapy

Clozapine (Clozaril®, Sandoz, East Hanover, NJ), an atypical antipsychotic agent with pharmacological properties considerably different from standard neuroleptics, has been found to be of great benefit especially to patients with treatment-resistant psychotic disorders. However, it is these unique pharmacological properties that have also been associated with mul tiple side effects ranging from the relatively benign (ie, sialorrhea during sleep, dizziness) to the potentially fatal (ie, agranulocytosis, seizures, and respiratory depression) which have limited its use. These untoward side effects are particularly problematic in the elderly population who often have concomitant medi cal illnesses requiring multiple medication regimens, including psychotropics that may interact with cloza pine (ie, benzodiazepines, cimetidine, fluoxetine). Because even the most benign of side effects has the potential of becoming fatal in certain circumstances if left unaddressed, it is imperative for patients, clinicians, pharmacists, and all health care professionals to be aware of adverse reactions and possible complica tions of clozapine therapy to prevent significant morbidity and mortality. Copyright © 1996 by W.B. Saunders Company

Precise pharmacogenetic pharmacometabolomic (PPP) guided clozapine therapy in treatment resistant schizophrenia: Insights from one ethnicity experiment

2021 ◽  
Vol 237 ◽  
pp. 26-28
Author(s):  
Amol N. Patil ◽  
Kripa Shanker Kasudhan ◽  
M. Naveen ◽  
Gurpreet Kaur Batra ◽  
Subho Chakrabarti ◽  
...  
Keyword(s):  
Treatment Resistant ◽  
Clozapine Therapy

Combination of amisulpride and olanzapine in treatment-resistant schizophrenic psychoses

2004 ◽  
Vol 19 (1) ◽  
pp. 56-58 ◽  
Author(s):  
Mathias Zink ◽  
Fritz A. Henn ◽  
Johannes Thome
Keyword(s):  
Side Effects ◽  
Antipsychotic Drugs ◽  
Therapeutic Option ◽  
Treatment Resistant ◽  
Combined Application ◽  
Drug Doses

AbstractTreatment-resistant schizophrenia often leads to combined application of antipsychotic drugs. We report first experience with the combination of olanzapine and amisulpride. Improvement of psychopathological state and side effects could be achieved, and drug doses were lower than under monotherapy. We thus conclude that this approach represents a useful therapeutic option.

Efficacy and tolerability of high dose olanzapine in Japanese patients with treatment-resistant schizophrenia

2013 ◽  
Vol 6 (1) ◽  
pp. 86-87 ◽  
Author(s):  
Taro Kishi ◽  
Tatsuyo Suzuki ◽  
Hirotaka Sekiguchi ◽  
Masatsugu Moriwaki ◽  
Akiko Okuda ◽  
...  
Keyword(s):  
Japanese Patients ◽  
High Dose ◽  
Treatment Resistant
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