Biomaterial Database

Clozapine augmentation: safety and efficacy. 2000

S A Chong, and G Remington

Woodbridge Hospital and Institute of Mental Health, Singapore.

While clozapine has been demonstrated to be efficacious in refractory schizophrenia and possibly schizoaffective as well as bipolar disorders, a substantial number of patients still remain unresponsive. One strategy in treating these refractory patients is to augment clozapine with other somatic treatments. This article reviews the efficacy and safety of the combination of clozapine with other somatic treatments. A total of 70 articles were obtained from a manual, as well as computerized (Medline), search of the English language literature from 1978 to March 1998. Few controlled studies exist; most were case reports/series. From these data, the greatest risk of adverse effects seems to be associated with clozapine combined with benzodiazepines, valproate, or lithium, but no currently evaluated combination is absolutely unsafe. In terms of efficacy, the data suggest a number of potential augmentation strategies, although controlled data are few. Combination therapies with clozapine are common in clinical practice, despite a lack of empirical data, and the benefits and risks of these combinations need to be systematically reviewed.

UI	MeSH Term	Description	Entries
D003024	Clozapine	A tricylic dibenzodiazepine, classified as an atypical antipsychotic agent. It binds several types of central nervous system receptors, and displays a unique pharmacological profile. Clozapine is a serotonin antagonist, with strong binding to 5-HT 2A/2C receptor subtype. It also displays strong affinity to several dopaminergic receptors, but shows only weak antagonism at the dopamine D2 receptor, a receptor commonly thought to modulate neuroleptic activity. Agranulocytosis is a major adverse effect associated with administration of this agent.	Clozaril,Leponex
D004347	Drug Interactions	The action of a drug that may affect the activity, metabolism, or toxicity of another drug.	Drug Interaction,Interaction, Drug,Interactions, Drug
D004359	Drug Therapy, Combination	Therapy with two or more separate preparations given for a combined effect.	Combination Chemotherapy,Polychemotherapy,Chemotherapy, Combination,Combination Drug Therapy,Drug Polytherapy,Therapy, Combination Drug,Chemotherapies, Combination,Combination Chemotherapies,Combination Drug Therapies,Drug Polytherapies,Drug Therapies, Combination,Polychemotherapies,Polytherapies, Drug,Polytherapy, Drug,Therapies, Combination Drug
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D012559	Schizophrenia	A severe emotional disorder of psychotic depth characteristically marked by a retreat from reality with delusion formation, HALLUCINATIONS, emotional disharmony, and regressive behavior.	Dementia Praecox,Schizophrenic Disorders,Disorder, Schizophrenic,Disorders, Schizophrenic,Schizophrenias,Schizophrenic Disorder
D014150	Antipsychotic Agents	Agents that control agitated psychotic behavior, alleviate acute psychotic states, reduce psychotic symptoms, and exert a quieting effect. They are used in SCHIZOPHRENIA; senile dementia; transient psychosis following surgery; or MYOCARDIAL INFARCTION; etc. These drugs are often referred to as neuroleptics alluding to the tendency to produce neurological side effects, but not all antipsychotics are likely to produce such effects. Many of these drugs may also be effective against nausea, emesis, and pruritus.	Antipsychotic,Antipsychotic Agent,Antipsychotic Drug,Antipsychotic Medication,Major Tranquilizer,Neuroleptic,Neuroleptic Agent,Neuroleptic Drug,Neuroleptics,Tranquilizing Agents, Major,Antipsychotic Drugs,Antipsychotic Effect,Antipsychotic Effects,Antipsychotics,Major Tranquilizers,Neuroleptic Agents,Neuroleptic Drugs,Tranquillizing Agents, Major,Agent, Antipsychotic,Agent, Neuroleptic,Drug, Antipsychotic,Drug, Neuroleptic,Effect, Antipsychotic,Major Tranquilizing Agents,Major Tranquillizing Agents,Medication, Antipsychotic,Tranquilizer, Major