Newer atypical antipsychotic medication versus clozapine for schizophrenia

Tuunainen, Arja; Wahlbeck, Kristian

doi:10.1002/14651858.cd000966

Cited by 74 publications

(53 citation statements)

References 63 publications

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“…There is a growing body of evidence, including both efficacy and more recently effectiveness studies 17,22,55,77 that collectively make a compelling case for clozapine's clinical superiority in treatment-resistant schizophrenia. [78][79][80] Clozapine has also demonstrated a unique role vis-à-vis suicidality 59,60,81,82 that led to its FDA indication for patients with schizophrenia or schizoaffective disorder who are judged to be at chronic risk for re-experiencing suicidal behaviour.…”

Section: Efficacy and Effectivenessmentioning

confidence: 99%

Where to Position Clozapine: Re-Examining the Evidence

et al. 2010

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Objective: To review clozapine's position in treatment algorithms for schizophrenia.Method: Clozapine's status is reviewed in the context of its initial discovery and unique clinical and (or) pharmacological profile, withdrawal and link with hematologic concerns, reintroduction with monitoring guidelines, prototype for atypicality, positioning in treatment algorithms, and current evidence regarding efficacy, effectiveness, and side effects. Results:The hematologic monitoring implemented with clozapine's reintroduction here in North America has proven successful in preventing clozapine-related deaths secondary to agranulocytosis. While its other side effects are not without concern, present evidence does not link clozapine to increased mortality rates; indeed, it appears better than other antipsychotics in this regard. Moreover, its clinical superiority compared with all other antipsychotics has been confirmed both in efficacy and in effectiveness trials.Conclusions: Schizophrenia continues to represent a treatment challenge, with many people demonstrating suboptimal response and poor functional outcome. Clozapine is routinely positioned as a third-line treatment in schizophrenia, but in light of existing evidence this warrants re-examination.Can J Psychiatry. 2010;55(10):677-684. Clinical Implications· Although clozapine has demonstrated superiority to other antipsychotics in refractory schizophrenia, it remains underprescribed and delayed in its use.· A large body of recent data, in combination with current safety measures, confirms that clozapine-induced agranulocytosis and related deaths are very rare.· Clozapine's unique clinical profile in refractory schizophrenia challenges delayed access to its use. Limitations· The data in this review are relevant and applicable only in the countries where clozapine safety measures are in place. · Clozapine's clinical superiority appears specific to refractory schizophrenia. · Use of clozapine earlier than third-line treatment requires a re-evaluation of how refractory schizophrenia is currently defined.

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Section: Efficacy and Effectivenessmentioning

confidence: 99%

Where to Position Clozapine: Re-Examining the Evidence

et al. 2010

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“…Patented in 1960, clozapine has shown consistent and substantial superiority to several standard antipsychotic agents in a large number of head-to-head comparisons, with even more striking differences (e.g., in relapse rates and treatment compliance) occurring with prolonged treatment. 22,27,28,47 Superiority has been less consistent in comparison with other modern antipsychotic agents, 34 except that treatment adherence has been consistently greater with clozapine (60%) than with other modern (41%) or conventional (37%) antipsychotic drugs, perhaps because of the unusually close medical monitoring required for the safe use of clozapine. 48 Clozapine remains the drug of choice for treating refractory schizophrenia.…”

Section: Neuropharmacologymentioning

confidence: 99%

Modern antipsychotic drugs: a critical overview

Gardner

Baldessarini²,

Waraich³

2005

Canadian Medical Association Journal

329

250

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SynthèseA ntipsychotic drugs are useful for treating a range of severe psychiatric disorders. Applications include the short-term treatment of acute psychotic, manic and psychotic-depressive disorders as well as agitated states in delirium and dementia and the long-term treatment of chronic psychotic disorders including schizophrenia, schizoaffective disorder and delusional disorders. Newer, "second-generation" antipsychotic drugs have largely replaced older phenothiazine, thioxanthene and butyrophenone neuroleptics in clinical practice (Table 1).1,2 The development of modern antipsychotic drugs was stimulated by a landmark 1988 study that showed clozapine to be superior in efficacy to chlorpromazine in schizophrenia patients resistant to high doses of haloperidol and to have none of the adverse neurologic effects typical of older antipsychotic agents.3 Clozapine was considered "atypical" in having a very low risk of adverse extrapyramidal symptoms. This term has since been applied broadly and uncritically to antipsychotic drugs marketed in the past decade, despite their striking chemical, pharmacologic and clinical heterogeneity. 4 In this overview we consider the neuropharmacology, efficacy and adverse effects of conventional antipsychotics and specific modern antipsychotic drugs. NeuropharmacologyThe venerable hypothesis that schizophrenia is caused by increased cerebral activity of the neurotransmitter dopamine was based primarily on the finding that dopamine agonists produced or worsened psychosis and that antagonists were clinically effective against psychotic and manic symptoms. 5 Blocking dopamine D 2 receptors may be a critical or even sufficient neuropharmacologic action of most clinically effective antipsychotic drugs, especially against hallucinations and delusions, but it is not necessarily the only mechanism for antipsychotic activity. Moreover, this activity, and subsequent pharmacocentric and circular speculations about altered dopaminergic function, have not led to a better understanding of the pathophysiology or causes of the several still idiopathic psychotic disorders, nor have they provided a non-empirical, theoretical basis for the design or discovery of improved treatments for psychotic disorders.The neuropharmacodynamics of specific modern antipsychotic drugs vary greatly, with little evidence for a unifying theory of antipsychotic activity or of drug design (Table 2). Clozapine in particular is complex: it binds loosely and transiently to D 2 receptors and interacts at dopamine (D 1 , D 3 and D 4 ), histamine (H 1 ), acetylcholine muscarinic (M 1 ) and serotonin (5-HT 2A , 5-HT 2C , 5-HT 6 and 5-HT 7 ) receptors and α 1 adrenoceptors. [6][7][8] This complexity leaves the very low risk of extrapyramidal symptoms and unexcelled antipsychotic effectiveness of clozapine unexplained.9 Postural dizziness, sedation and increased appetite may reflect actions of clozapine and some other antipsychotic agents at α 1 , H 1 and 5-HT 2C receptors respectively. Olanzapine demonstrates significant anti-...

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“…There has been a large shift in favour of the use of these atypical antipsychotics [6], although the precise therapeutic value of these agents remains controversial [7,8,9,10,11,12,13]. The effect on negative symptoms has not yet been fully elucidated.…”

Section: Introductionmentioning

confidence: 99%

Short-acting parenteral antipsychotics drive choice for classical versus atypical agents

Hugenholtz

Stolker

Heerdink

et al. 2003

Eur J Clin Pharmacol

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Objective: The objective of this study was to investigate which antipsychotics (classical versus atypical) are prescribed in a psychiatric hospital and which determinants affect the choice for one of these two classes of antipsychotics in newly admitted patients. Methods: In a retrospective cohort design, 522 newly admitted patients were followed from the date of admission until discharge from the hospital. In the cohort of newly admitted patients treated with an oral antipsychotic, a nested case-control study was conducted considering recipients of an atypical agent as cases. Controls were all other cohort members. The association of patient characteristics and the choice between classical versus atypical antipsychotics was studied using logistic regression analysis. The same analysis was performed with adjustment for possible confounding factors (age group, gender, DSM-IV diagnoses, use of shortacting parenteral antipsychotic, global assessment of functioning score, involuntary admissions and involuntary measures). Results: Patients treated with classical oral antipsychotics were more often previously treated with short-acting parenteral antipsychotics than patients treated with atypical antipsychotics (40.8% vs 15.2%;. No statistically significant difference was found between patients with different severities of disease.Discussion: Availability of injectable forms seems to drive the choice for oral antipsychotic agents. Future introductions of short-acting parenteral atypical antipsychotics may have a large impact on first-choice oral antipsychotic treatment.

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Newer atypical antipsychotic medication versus clozapine for schizophrenia

Cited by 74 publications

References 63 publications

Where to Position Clozapine: Re-Examining the Evidence

Where to Position Clozapine: Re-Examining the Evidence

Modern antipsychotic drugs: a critical overview

Short-acting parenteral antipsychotics drive choice for classical versus atypical agents

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