A prospective multicenter assessor-blinded randomized controlled study to compare the efficacy of short versus long protocols of electroconvulsive therapy as an augmentation strategy to clozapine in patients with ultra-resistant schizophrenia (SURECT study)

Antipsychotic treatment resistance affects up to a third of individuals with schizophrenia. Of those affected, 70–84% are reported to be treatment resistant from the outset. This raises the possibility that the neurobiological mechanisms of treatment resistance emerge before the onset of psychosis and have a neurodevelopmental origin. Neuropsychological investigations can offer important insights into the nature, origin and pathophysiology of treatment-resistant schizophrenia (TRS), but methodological limitations in a still emergent field of research have obscured the neuropsychological discriminability of TRS. We report on the first systematic review and meta-analysis to investigate neuropsychological differences between TRS patients and treatment-responsive controls across 17 published studies (1864 participants). Five meta-analyses were performed in relation to (1) executive function, (2) general cognitive function, (3) attention, working memory and processing speed, (4) verbal memory and learning, and (5) visual−spatial memory and learning. Small-to-moderate effect sizes emerged for all domains. Similarly to previous comparisons between unselected, drug-naïve and first-episode schizophrenia samples v. healthy controls in the literature, the largest effect size was observed in verbal memory and learning [dl = −0.53; 95% confidence interval (CI) −0.29 to −0.76; z = 4.42; p < 0.001]. A sub-analysis of language-related functions, extracted from across the primary domains, yielded a comparable effect size (dl = −0.53, 95% CI −0.82 to −0.23; z = 3.45; p < 0.001). Manipulating our sampling strategy to include or exclude samples selected for clozapine response did not affect the pattern of findings. Our findings are discussed in relation to possible aetiological contributions to TRS.

show abstract

Neuropsychological differences between treatment-resistant and treatment-responsive schizophrenia: a meta-analysis

Millgate

Hide

Lawrie

et al. 2021

Psychol. Med.

View full text Add to dashboard Cite

show abstract

Opţiuni terapeutice în schizofrenia ultrarezistentă. Intervenţii nonfarmacologice (II)

Vasiliu

2023

Psihiatru.ro

View full text Add to dashboard Cite

Clozapine-resistant or ultra-resistant schizophrenia represents a challenge for clinicians, given the lack of recommendations in all the major treatment guidelines regarding the next steps once clozapine has failed or cannot be tolerated. The first part of this narrative review investigated the pharmacological arsenal available to the clinician to deal with cases of clozapine-resistant schizophrenia. In the present section of the analysis, the results of research that explored the efficacy and tolerability of nonpharmacological methods for this type of schizophrenia will be presented. Ongoing or upcoming clinical trials in patients with ultra-resistant schizophrenia will also be reviewed. Searching electronic databases and clinical trial archives identified seven reports on the effects of psychotherapy and 15 reports on neuromodulation techniques that aimed at ameliorating psychotic symptoms and functionality in clozapine-resistant schizophrenia. A number of six ongoing clinical trials targeting this type of schizophrenia are also presented. In conclusion, based on the data analyzed, cognitive-behavioral therapy for psychosis, cognitive-behavioral therapy, and occupational therapy benefit from moderate-quality data to support their efficacy as add-ons to clozapine in these patients. Except for electroconvulsive therapy, the evidence for other neuromodulation techniques is, at least for now, insufficient to recommend them in ultra-resistant cases. It is necessary to carry out good quality and long-term clinical studies in order to confirm the usefulness of these adjuvant treatments.

show abstract

Clozapine: Why Is It So Uniquely Effective in the Treatment of a Range of Neuropsychiatric Disorders?

Gammon¹,

Cheng

Volkovinskaia³

et al. 2021

Biomolecules

View full text Add to dashboard Cite

Clozapine is superior to other antipsychotics as a therapy for treatment-resistant schizophrenia and schizoaffective disorder with increased risk of suicidal behavior. This drug has also been used in the off-label treatment of bipolar disorder, major depressive disorder (MDD), and Parkinson’s disease (PD). Although usually reserved for severe and treatment-refractory cases, it is interesting that electroconvulsive therapy (ECT) has also been used in the treatment of these psychiatric disorders, suggesting some common or related mechanisms. A literature review on the applications of clozapine and electroconvulsive therapy (ECT) to the disorders mentioned above was undertaken, and this narrative review was prepared. Although both treatments have multiple actions, evidence to date suggests that the ability to elicit epileptiform activity and alter EEG activity, to increase neuroplasticity and elevate brain levels of neurotrophic factors, to affect imbalances in the relationship between glutamate and γ-aminobutyric acid (GABA), and to reduce inflammation through effects on neuron–glia interactions are common underlying mechanisms of these two treatments. This evidence may explain why clozapine is effective in a range of neuropsychiatric disorders. Future increased investigations into epigenetic and connectomic changes produced by clozapine and ECT should provide valuable information about these two treatments and the disorders they are used to treat.

show abstract

scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.

Contact Info

customersupport@researchsolutions.com

10624 S. Eastern Ave., Ste. A-614

Henderson, NV 89052, USA

This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.

Blog Terms and Conditions API Terms Privacy Policy Contact Cookie Preferences Do Not Sell or Share My Personal Information

Made with 💙 for researchers

Part of the Research Solutions Family.

A prospective multicenter assessor-blinded randomized controlled study to compare the efficacy of short versus long protocols of electroconvulsive therapy as an augmentation strategy to clozapine in patients with ultra-resistant schizophrenia (SURECT study)

Cited by 3 publications

References 46 publications

Neuropsychological differences between treatment-resistant and treatment-responsive schizophrenia: a meta-analysis

Neuropsychological differences between treatment-resistant and treatment-responsive schizophrenia: a meta-analysis

Opţiuni terapeutice în schizofrenia ultrarezistentă. Intervenţii nonfarmacologice (II)

Clozapine: Why Is It So Uniquely Effective in the Treatment of a Range of Neuropsychiatric Disorders?

Contact Info

Product

Resources

About