Related Experiment Video

Updated: Apr 16, 2026

Methods for Studying the Mechanisms of Action of Antipsychotic Drugs in Caenorhabditis elegans
07:35

Methods for Studying the Mechanisms of Action of Antipsychotic Drugs in Caenorhabditis elegans

Published on: February 4, 2014

12.0K

Schizophrenia: when clozapine fails

Seiya Miyamoto1, Lars Fredrik Jarskog, W Wolfgang Fleischhacker

  • 1aDepartment of Neuropsychiatry, St. Marianna University School of Medicine, Kawasaki, Japan bNorth Carolina Psychiatric Research Center, Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA cDepartment of Psychiatry and Psychotherapy, Medical University Innsbruck, Innsbruck, Austria.

Current Opinion in Psychiatry
|March 14, 2015
PubMed
Abstract

Insights

For treatment-resistant schizophrenia (TRS) unresponsive to clozapine, pharmacological augmentation lacks strong evidence. Electroconvulsive therapy (ECT) shows short-term promise, but more research is needed for other strategies.

Area of Science:

  • Psychiatry
  • Neuroscience
  • Pharmacology

Background:

  • Treatment-resistant schizophrenia (TRS) poses significant clinical challenges.
  • Clozapine is the gold standard, but a subset of patients remain refractory or only partially responsive.
  • Identifying effective adjunctive therapies for clozapine-resistant TRS is a critical unmet need.

Purpose of the Study:

  • To review current evidence on therapeutic strategies for patients with treatment-resistant schizophrenia (TRS) who do not respond adequately to clozapine.
  • To evaluate the efficacy of pharmacological and non-pharmacological interventions as augmentation therapies for clozapine-resistant TRS.

Main Methods:

  • Systematic review of recent clinical trials and randomized studies.
  • Analysis of pharmacological augmentation strategies.
  • Evaluation of non-pharmacological biological approaches, including electroconvulsive therapy (ECT).

Main Results:

  • Evidence for pharmacological augmentation of clozapine in TRS is limited, with modest reported benefits.
  • A recent randomized trial indicates that electroconvulsive therapy (ECT) may be effective for short-term treatment of clozapine-resistant TRS.
  • Current data on other biological and psychosocial adjuvant treatments remain inconclusive.

Conclusions:

  • Pharmacological augmentation strategies for clozapine-resistant TRS lack sufficient evidence of efficacy.
  • Electroconvulsive therapy (ECT) presents a potentially promising short-term treatment option for clozapine-resistant TRS.
  • Further controlled research is essential to validate the long-term effects of ECT and explore other adjuvant therapies for clozapine-resistant TRS.

More Related Videos

Development of a Virtual Reality Assessment of Everyday Living Skills10:32

Development of a Virtual Reality Assessment of Everyday Living Skills

Published on: April 23, 2014

19.5K
MRI-guided dmPFC-rTMS as a Treatment for Treatment-resistant Major Depressive Disorder08:20

MRI-guided dmPFC-rTMS as a Treatment for Treatment-resistant Major Depressive Disorder

Published on: August 11, 2015

14.8K

Related Concept Videos

Psychosis: Goals of Pharmacotherapy01:26

Psychosis: Goals of Pharmacotherapy

Antipsychotic drugs are a crucial treatment method for acute and chronic psychoses, bipolar illness, and behavioral disorders. The selection of these drugs depends on several factors, including the state of the disease, clinical judgment, possible drug interactions, and the patient's sensitivity to adverse effects. In immediate scenarios, such as delirium and dementia, short-term treatment with low doses of high-potency typical or atypical agents can effectively manage symptom exacerbation.
682
Psychosis and Antipsychotic Drugs: Overview01:28

Psychosis and Antipsychotic Drugs: Overview

The term "psychosis" refers to a spectrum of mental disorders characterized by abnormal thoughts, perceptions, and behaviors. It can manifest as mood disorders, dementia, delirium with psychotic features, substance-induced psychosis with psychotic features, brief psychotic disorder, delusional disorder, schizoaffective disorder, and schizophrenia. Among all these disorders, schizophrenia is the most common psychotic disorder, affecting 1% of the worldwide population. Psychotic...
1.2K
Drug Therapy01:28

Drug Therapy

The advent of drug therapy has profoundly shaped modern mental health care, providing targeted treatments for a range of psychological disorders. Psychotherapeutic drugs, classified into antianxiety, antidepressant, and antipsychotic medications, address symptoms across anxiety disorders, mood disorders, and schizophrenia. While these medications have transformed patient outcomes, they require careful management due to their potential side effects and limitations.
Antianxiety Medications
418
Antipsychotic Drugs: Typical and Atypical Agents01:21

Antipsychotic Drugs: Typical and Atypical Agents

Antipsychotic drugs are classified into first-generation (typical) drugs including phenothiazines; and second-generation (atypical) drugs. Chlorpromazine hydrochloride (Thorazine), a phenothiazine derivative, broadly impacts the central, autonomic, and endocrine systems. This drug, along with typical agents like haloperidol (Haldol), primarily works by antagonizing D2 receptors, thus reducing dopaminergic neurotransmission. However, typical antipsychotics can cause side effects such as sedation...
1.3K
Antipsychotic Drugs: Therapeutic Uses and Side Effects01:21

Antipsychotic Drugs: Therapeutic Uses and Side Effects

Antipsychotic drugs primarily block dopamine and serotonin receptors and cholinergic, adrenergic, and histaminergic receptors, thereby reducing hallucinations and delusions in conditions like schizophrenia. However, they can trigger unwanted extrapyramidal effects such as dystonias, Parkinson-like symptoms, and tardive dyskinesia.
Despite these side effects, antipsychotics are used therapeutically for various purposes, including managing schizophrenia, preventing nausea and vomiting, curbing...
1.2K
Psychological and Sociocultural Causes of Schizophrenia01:29

Psychological and Sociocultural Causes of Schizophrenia

Schizophrenia, a complex psychiatric disorder, has been historically misunderstood. Early psychological theories attributed its origins to childhood trauma and unresponsive parenting. However, contemporary research largely rejects these notions, favoring the vulnerability-stress hypothesis. This model proposes that individuals with a genetic predisposition to schizophrenia may develop the disorder following exposure to significant environmental stressors. Notably, studies on high-risk...
946