Erfolgreich durch internationale Zusammenarbeit

NEUROLOGY AND PSYCHIATRY

Cite as: Archiv EuroMedica. 2025. 15; 4. DOI 10.35630/2025/15/4.009

Received 4 July 2025;
Accepted 18 August 2025;
Published 22 August 2025

ELECTROCONVULSIVE THERAPY AS AN AUGMENTATION STRATEGY IN CLOZAPINE-RESISTANT SCHIZOPHRENIA

Aleksandra Zagajewska¹ , Aleksandra Giba² ,
Aleksandra Krygowska² , Michał Wąsik² ,
Dorota Słupik² , Aleksandra Reda² ,
Aleksandra Śledziewska² , Magdalena Cyrkler² ,
Kamila Sieradocha³

¹Infant Jesus Clinical Hospital in Warsaw, Poland
²Military Institute of Medicine in Warsaw, Poland
³University Clinical Hospital in Poznań, Poland

download article (pdf)

  aleksandra.zagajewska@gmail.com

ABSTRACT

Aims: This narrative review evaluates the efficacy, tolerability, and clinical applicability of electroconvulsive therapy (ECT) as an augmentation strategy in clozapine-resistant schizophrenia (CRS), a particularly severe subtype of treatment-resistant schizophrenia (TRS) unresponsive to clozapine. It also aims to summarize current evidence from clinical studies and highlight unresolved challenges in the use of ECT for this population.

Methods: A comprehensive literature search was conducted in PubMed, Cochrane Library, Embase, and Web of Science for English-language publications from 2014 to 2024. The search focused on studies addressing clozapine-resistant schizophrenia and electroconvulsive therapy. Inclusion criteria comprised clinical relevance, focus on ECT as augmentation, and sufficient methodological quality. A total of 191 publications, including clinical studies, reviews, and meta-analyses, were selected and synthesized to evaluate efficacy, tolerability, and clinical application.

Results: The majority of studies suggest that ECT augmentation improves positive symptoms and overall clinical outcomes in patients with clozapine-resistant schizophrenia. Reported adverse effects are typically mild and transient, including headache and short-term cognitive impairment. Maintenance and continuation ECT (M/C-ECT) appear beneficial in sustaining remission and reducing relapse risk. Nevertheless, the overall strength of evidence is limited by methodological heterogeneity, small sample sizes, and the scarcity of randomized controlled trials.

Conclusions: ECT represents a promising adjunctive intervention for clozapine-resistant schizophrenia, particularly in cases unresponsive to pharmacological strategies alone. Despite encouraging clinical data, its routine implementation is constrained by limited high-quality evidence. Further well-designed trials are needed to define patient selection criteria, optimal treatment protocols, and long-term outcomes, and to support the integration of ECT into standardized treatment guidelines.

Keywords: schizophrenia, clozapine-resistant, electroconvulsive therapy, augmentation, antipsychotic resistance

1 INTRODUCTION

Schizophrenia – overview

Schizophrenia is a severe, chronic, and complex psychiatric disorder affecting approximately 1% of the global population over their lifetime [1,2]. This debilitating illness is characterized by a heterogeneous symptomatology encompassing positive symptoms (e.g. hallucinations and delusions), negative symptoms (e.g. social withdrawal, apathy, and blunted affect), and cognitive deficits, such as impaired memory and executive functioning [3,4]. The disorder’s course is highly variable, with some individuals experiencing full recovery after an initial episode, while most endure a relapsing-remitting course [5,6].

The etiology of schizophrenia is multifactorial and encompasses genetic predispositions [7], infections [8], autoimmune processes [9], as well as social and psychological influences [10]. Comorbid conditions, including cardiovascular, metabolic, and infectious diseases, contribute to a mortality rate 2–3 times higher than that of the general population [11,12].

Functionally, schizophrenia leads to profound disability, with 80–90% of patients unable to maintain employment and a significant proportion requiring long-term support for daily activities [13,14]. The financial burden is substantial, covering direct healthcare costs and indirect costs due to lost productivity [15,16].

Treatment strategies primarily rely on antipsychotic medications, beginning with the introduction of chlorpromazine in the 1950s, alongside non-pharmacological therapies tailored to individual patient needs [17,18]. Despite advances in pharmacotherapy, the variability in treatment response and disease trajectory highlights the ongoing challenges in managing this disabling condition [19,20].

Treatment-resistant schizophrenia and clozapine-resistant schizophrenia

While many individuals with schizophrenia achieve symptom control with antipsychotic medications, a significant proportion experience inadequate treatment response, leading to what is classified as “treatment-resistant” or “treatment-refractory” schizophrenia (TRS). The most widely accepted minimum criterion for TRS includes a failure to respond to at least two different, non-clozapine antipsychotic drugs [16,21–27]. However, various definitions have been proposed, with some suggesting stricter diagnostic criteria to ensure precision and consistency in identifying treatment resistance. In 2017, the Treatment Response and Resistance in Psychosis (TRRIP) Working Group established treatment resistance criteria based on a global expert consensus. According to their definition, TRS is characterized by at least moderate symptom severity and functional impairment linked to schizophrenia, along with insufficient improvement following two or more trials of antipsychotic medications. Each trial must meet specific standards, including an adequate dosage (equivalent to at least 600 mg of chlorpromazine daily), a minimum duration of six weeks, and a patient adherence rate of at least 80% of the prescribed doses [22].

The prevalence of TRS varies significantly across studies, ranging from 10% to 70% of individuals diagnosed with schizophrenia. Most authors agree that approximately 30% of patients with schizophrenia meet the criteria for TRS [16,26,28–41].

Clozapine, developed in 1958 as the first dibenzodiazepine atypical antipsychotic, has established itself as the most effective treatment for patients with treatment-resistant schizophrenia [42,43]. Initially withdrawn in the 1970s due to concerns about agranulocytosis [42], clozapine was reintroduced in the late 1980s following a pivotal study by Kane et al. (1988) that demonstrated its superiority in treating this challenging patient population [27]. Clozapine offers significant benefits, including symptomatic improvement in both positive and negative symptoms, reduced hospitalization and mortality rates, cost-effectiveness, and enhanced social functioning [19,21,44–47]. It also has an unique advantage of mediating addictive behaviors and reducing suicide rates in patients with comorbid substance use disorders [48]. Conversely, clozapine is associated with adverse effects such as neutropenia, agranulocytosis, sedation, constipation, sialorrhea, orthostatic hypotension, chest pain, nocturnal enuresis, increased seizure risk, and metabolic syndrome. However, most of aforementioned are monitorable and manageable [49–52]. Routine hematologic monitoring is required to mitigate the rare but serious risk of agranulocytosis [16,53–55].

“Clozapine-resistant” schizophrenia (CRS) represents a particularly challenging subset of treatment-resistant schizophrenia cases, where patients fail to respond to clozapine despite its established efficacy as the gold-standard treatment for TRS [19,21,53,56–60]. While clozapine has shown remarkable success in managing TRS, approximately 40–70% of patients either do not achieve sufficient therapeutic response or are unable to tolerate the medication due to adverse effects [27,53,56–59,61–71]. The TRRIP Working Group has proposed that CRS should be classified as a distinct subtype of TRS, termed "ultra-treatment-resistant schizophrenia" (UTRS), characterized by persistent symptoms after at least three months of clozapine treatment at adequate doses (400–500 mg/day) and therapeutic plasma levels of 350 ng/mL or higher [21,22]. This condition is also referred to as "super-refractory" or "ultra-resistant schizophrenia" in the literature [72–74].

TRS and, especially, CRS are associated with profound clinical and societal burdens. These groups of patients exhibit significantly poorer daily functioning, lower quality of life, and higher unemployment rates compared to those who respond to treatment [28,66,75–77]. Furthermore, treatment resistance substantially increases the frequency of hospitalizations, reflecting both the severity and persistence of symptoms. The financial impact is also notable [76,78]. The costs associated with TRS are estimated to be 3–11 times greater than for patients whose schizophrenia is in remission [76].

The treatment of clozapine-resistant schizophrenia remains one of the most challenging areas in psychiatry, with limited evidence-based interventions available [79]. Augmentation strategies are often employed, involving the addition of other pharmacological agents, such as antipsychotics, antidepressants, mood stabilizers, anxiolytics, or glutamatergic agents [19,21,80–85]. Despite these efforts, meta-analyses of placebo-controlled trials have demonstrated little or no consistent benefit from pharmacological augmentation in CRS [86–89]. Moreover, the use of polypharmacy carries a higher likelihood of adverse effects compared to monotherapy, highlighting the importance of investigating non-pharmacological augmentation strategies [16]. Alternative approaches, such as electroconvulsive therapy (ECT), repetitive transcranial magnetic stimulation (rTMS), and cognitive behavioral therapy (CBT), have been proposed for addressing CRS [21]. However, the overall lack of unequivocal evidence underscores the significant public health burden of managing CRS, highlighting the need for continued research and innovation in treatment approaches [63,90,91].

This narrative review aims to synthesize current evidence on the use of electroconvulsive therapy (ECT) as an augmentation strategy in clozapine-resistant schizophrenia (CRS), focusing on its clinical efficacy, tolerability, and mechanisms of action. The novelty of this paper lies in its comprehensive integration of recent clinical trials, meta-analyses, and consensus statements, providing an updated and critical perspective on the evolving role of ECT in treatment-resistant cases. Additionally, a more multifaceted view is presented than has been emphasized in prior research.

2 METHODOLOGY

A comprehensive literature search was conducted using electronic databases, including PubMed, Cochrane Library, Embase, and Web of Science. The search employed a specific query designed to identify studies focusing on clozapine-resistant schizophrenia and electroconvulsive therapy. The query comprised the keywords: "clozapine-resistant", "clozapine-refractory", "CRS", "treatment-resistant", "TRS", "schizophrenia", "electroconvulsive", "electroshock", "shock" and "ECT" in the title or abstract fields. Inclusion criteria were original clinical or observational studies, systematic reviews, and meta-analyses addressing ECT in clozapine- or treatment-resistant schizophrenia, published within the last 10 years (2014-2024). Exclusion criteria included editorials, letters, conference abstracts without full-text availability, non-English papers, and studies not involving human subjects.

The primary search yielded 53 articles that were screened based on titles and abstracts, resulting in the selection of 47 papers comprising randomized controlled trials (RCTs), cohort studies, retrospective analyses, meta-analyses, and systematic reviews. Additionally, a manual search of related references identified and reviewed 423 articles. Although no formal quality appraisal tool was applied, methodological rigor, sample size, outcome clarity, and peer-reviewed publication status were considered in evaluating the quality and relevance of each study.

Ultimately, a total of 191 studies were included in this review, and their findings were synthesized to address the objectives of the article. This multi-step process ensured a comprehensive and rigorous selection of relevant literature.

FINDINGS

3 Electroconvulsive therapy as a form of treatment

History and evolution

Electroconvulsive therapy, introduced by Cerletti and Bini in the 1930s, is the oldest biological treatment in modern psychiatry and has been used in schizophrenia treatment for nearly 90 years [80,92,93]. Its application initially declined after the introduction of antipsychotic medications in the 1950s but still continues to play a significant role in the management of schizophrenia, especially in regions with limited access to pharmacological therapies, such as Asia, Africa, and South America [80,94,95]. Since the reintroduction of clozapine in the 1990s, ECT has increasingly been explored and utilized as an augmentation strategy [96,97].

Early ECT practices often resulted in side effects, such as muscle damage, fractures and memory impairment, due to the lack of anesthesia and the use of sine-wave devices. Modern techniques, including anesthesia and brief-pulse wave devices, have markedly improved electroconvulsive therapy’s safety profile [19,98]. While now most commonly used for depression, ECT remains a key neurostimulation tool for severe psychiatric disorders, demonstrating enduring value within psychiatry's therapeutic armamentarium [80,92].

Mechanism of action

During the procedure, a controlled electrical current is delivered to the brain to induce therapeutic seizures while the patient is under anesthesia and muscle relaxation [99,100]. Depending on electrode placement, the treatment can be administered bilaterally, affecting both hemispheres of the brain, or unilaterally, targeting the non-dominant hemisphere [101]. Among the variations of bilateral ECT, bifrontal ECT has demonstrated superior clinical outcomes and fewer side effects compared to bitemporal ECT, the latter being more frequently associated with cognitive impairments [102,103]. Another term often used in the literature is "sham-ECT," which refers to the procedure involving all steps except the electrical stimulation [101].

Although the exact mechanisms remain unclear, ECT has been linked to alterations in neurotransmitter levels, increased neuroplasticity, and changes in regional cerebral blood flow [70,104–106]. It has also been suggested that enhanced blood-brain barrier permeability allows therapeutic drugs to reach the brain more effectively [107,108]. However, positive effects of ECT may partly result from placebo mechanisms, including patient expectations, attention from medical staff, or the intensive nature of the care process [109,110].

Psychiatric implications

Electroconvulsive therapy is effective in treating various psychiatric conditions but remains controversial due to potential side effects, particularly memory loss [111]. While there is no conclusive evidence linking ECT to brain damage [112,113], it can still cause cognitive impairments, prolonged seizures, and cardiovascular complications [19]. Moreover, ECT is a resource-intensive treatment that often involves multiple sessions over weeks and may require inpatient care, which adds to the financial and time-related burden for patients and their families [37,114]. Furthermore, ECT’s underutilization is influenced by factors such as stigma, negative media portrayals, and unclear treatment guidelines [111,115–118].

Before delving into considerations regarding ECT augmentation in schizophrenia treatment, the authors of this review first examined the most recent recommendations from the American Psychiatric Association (APA). The 2025 guidelines highlight ECT as a highly efficacious treatment for acute catatonia, supported by robust expert consensus and observational evidence. Regarding schizophrenia, the APA recommends ECT as a treatment option in combination with antipsychotic medications when there is a history of positive response to ECT, when symptoms are resistant to antipsychotic treatment (including clozapine), or when symptoms are severe, such as in cases of violence or significant disability [119]. These guidelines, while not exhaustive, underscore the continued relevance of ECT in managing schizophrenia in specific, often challenging, clinical scenarios.

4 Augmentation of ECT

Some studies focus on ECT augmentation in treatment-resistant schizophrenia in general, while others specifically examine cases where clozapine, the gold standard for treatment resistance, has also failed. Although this paper primarily addresses the use of ECT as an augmentation strategy in clozapine-resistant schizophrenia, it also includes an analysis of studies on TRS. This broader perspective provides valuable context for understanding the potential benefits of ECT supplementation in CRS.

ECT augmentation in TRS

To assess the effectiveness of ECT augmentation in treatment-resistant schizophrenia, various psychiatric rating scales are used, with the Positive and Negative Syndrome Scale (PANSS) being the most common. This 30-item scale measures positive, negative, and general psychopathology symptoms, with higher scores indicating greater severity [97,120]. A clinically significant reduction is typically defined as a 20% decrease, though stricter thresholds are also used [121]. Brief Psychiatric Rating Scale (BPRS), another tool for evaluating psychiatric symptoms, assesses 18 items, where higher scores again reflect more severe symptoms [122]. Both scales are essential in measuring treatment response and provide standardized means of assessing symptom changes, offering valuable insights into the efficacy of ECT as an augmentation strategy.

The literature on ECT augmentation in treatment-resistant schizophrenia generally supports the efficacy of combining ECT with pharmacological treatments. Studies consistently report that augmenting antipsychotics with ECT is often more efficacious than relying on medications alone in managing symptoms of schizophrenia [19,35,77,95,123–125], with clozapine being shown to offer superior symptom reduction and greater cost-effectiveness compared to alternative antipsychotic options [19,53,54,59]. Additionally, studies indicate that ECT may result in fewer relapses and higher rates of hospital discharge compared to sham-ECT, further supporting the potential benefit of ECT in treatment-resistant populations [17,118,126].

In studies by Pawełczyk et al. (2014) [127,128], 29 and 34 patients with prominent negative symptoms of schizophrenia, respectively, were treated with ECT and antipsychotics. Response to AP+ECT therapy was defined as a reduction of at least 25% in the total PANSS score. In the first study [127], the results showed a 32% reduction in the total PANSS score, with the most significant improvement in the positive symptom subscale (37.5%) and the least in the negative symptom subscale (23.8%). Overall, 60% of participants demonstrated a response to the treatment. The other study [128] found a 30.8% mean decrease in PANSS total scores, with a significant 38.09% reduction in positive symptoms and a 23.01% reduction in negative symptoms. 58.8% of patients responded to the AP+ECT therapy. Another study supporting the efficacy of ECT in conjunction with clozapine in TRS was conducted by Masoudzadeh and Khalilian (2007) [77], who compared ECT, clozapine, and the two treatments together. The ECT-clozapine combination was significantly more effective, showing a 71% reduction in PANSS scores, compared to 40% for ECT alone and 46% for clozapine alone. Positive symptom reduction was also greatest in the combination group, reaching 80%. Finally, Lally's systematic review and meta-analysis (2016) of 71 patients from five clinical trials found a 54% response rate to the combination of clozapine and ECT in patients with TRS, with the rate increasing to 66% when case reports and retrospective data were included [118].

However, not all studies agree on the effectiveness of ECT added to antipsychotic treatment. Nieuwdorp et al. (2015) [129] reviewed nine RCTs that compared real ECT to sham-ECT in conjunction with antipsychotic treatment. Data from seven trials, involving a total of 172 participants, were accessible. Of these, four studies reported a significant advantage of real ECT over sham-ECT, while three studies found no difference in symptom severity between the two groups.

Based on the available evidence, ECT augmentation may offer significant benefits for patients with treatment-resistant schizophrenia, particularly when combined with antipsychotic treatments, though the results across studies are not entirely consistent. Additional studies are required before ECT can be incorporated into the standard treatment protocols for TRS.

ECT augmentation in CRS

Although clozapine remains the gold standard for managing treatment-resistant schizophrenia, it fails to achieve adequate symptom control in a subset of patients, classified as having clozapine-resistant schizophrenia. While certain authors examine the role of ECT within the broader framework of treatment-resistant schizophrenia, others have concentrated specifically on its utility in clozapine-resistant schizophrenia, which constitutes the primary focus of this article. One study specifically addressed both TRS and CRS. Grover et al. (2017) [130] reported that 63% of patients with TRS, including CRS cases, achieved a significant symptom reduction of more than 30% with the combination of clozapine and ECT. In the case of clozapine non-responders, 69% benefited from the addition of ECT.

Randomized controlled trials, meta-analyses, open-label studies, case reports and reviews have been analyzed, with the vast majority of studies indicating that electroconvulsive therapy augmentation with clozapine in clozapine-resistant schizophrenia yields positive effects and demonstrates greater therapeutic benefit compared to clozapine monotherapy [70,80,85,97,131–135]. In studies by Kim et al. (2018) [134] and Kim et al. (2017) [97], response rates were 42.9% and 71.4%, respectively, both based on a 20% reduction in PANSS. Petrides et al. (2015) [80] found a 60% response rate with a 20% reduction, and Grover et al. (2017) [130] observed the highest response rate at 85% with the same threshold. Kho et al. (2004) [133] reported a 72.7% response rate, though using a more stringent 30% reduction criterion. Furthermore, studies show that electroconvulsive therapy tends to have a more pronounced impact on positive symptoms of clozapine-resistant schizophrenia than on general or negative symptoms [70,80,85,133–135]. However, it has been suggested that improvements in negative symptoms may require prolonged treatment [136]. In a comprehensive analysis of 35 randomized controlled trials, Yeh et al. (2023) [135] evaluated the most effective augmentation strategies for clozapine-resistant schizophrenia. Among the interventions, ECT emerged as one of the top three approaches for improving overall symptoms, alongside mirtazapine and memantine. Notably, for addressing positive symptoms, ECT was identified as the most effective option.

Petrides et al. (2015) [80] conducted one of the most frequently cited studies on ECT augmentation in clozapine-resistant schizophrenia. In an 8-week, single-blind, randomized controlled trial with a crossover phase, ECT plus clozapine (N=20) was compared to clozapine monotherapy (N=19). Using a stringent response criterion (≥40% reduction in psychotic symptoms on the BPRS, CGI-severity <3, and CGI-improvement ≤2), 50% of the ECT group responded, while none in the clozapine group met this threshold. This well-designed study highlights the efficacy of ECT augmentation in CRS, though no significant benefits for negative symptoms were observed.

Conversely, studies by Melzer-Ribeiro et al. have raised doubts about the efficacy of ECT as an augmentation strategy for clozapine-resistant schizophrenia. In randomized controlled trial from 2017 [137], 23 patients with partial clozapine response were randomized to receive either 12 sessions of real ECT or sham-ECT. The study found no significant differences between the groups in PANSS total scores or its subscales, indicating that ECT did not outperform sham-ECT in symptom reduction. Recently, subsequent double-blind RCT [138] further evaluated the effectiveness of 20 sessions of ECT compared to sham-ECT in CRS patients. In this study, 19 patients in the ECT group and 17 in the sham-ECT group completed the trial. Results showed that only one patient (5.26%) in the ECT group achieved a ≥50% reduction in PANSS total score, compared to none in the sham-ECT group. A similar proportion of patients in both groups experienced moderate improvements (≥20% but <40% reduction), while 42% of the ECT group and 47% of the sham-ECT group had minimal improvements of ≤10%. Moreover, increases in PANSS scores were observed in 26% of ECT patients and 23.5% of sham-ECT patients. The findings suggest that ECT may not provide a clear advantage over sham-ECT in CRS, as no significant differences were observed in total PANSS score reductions, subscale improvements, or specific symptom dimensions.

In light of the current evidence, ECT has emerged as a promising augmentation strategy for CRS, with most of studies reporting favorable outcomes, particularly for positive symptoms. However, some studies have failed to show a clear benefit over clozapine monotherapy, particularly in terms of negative symptoms. Furthermore, a subgroup of CRS patients may not respond to ECT, a phenomenon referred to as ECT-resistant schizophrenia, which remains a topic of ongoing debate. There is currently insufficient evidence to guide clinicians in selecting the optimal treatment for this subset of patients [139]. While ECT augmentation remains a promising option, further research is essential to validate its role in management of CRS.

Table 1 provides a comparative summary of selected clinical studies evaluating the efficacy and tolerability of ECT as an augmentation strategy in treatment- and clozapine-resistant schizophrenia. The table highlights differences in study design, patient populations, treatment protocols, and reported outcomes, illustrating both the therapeutic potential of ECT and the heterogeneity of existing evidence.

Predictors of response

Several studies have investigated factors that may predict response to electroconvulsive therapy in TRS/CRS. Clinical, neuroimaging, neurophysiological, and genetic markers have been proposed as potential predictors [140]. Findings from Chanpattana & Sackeim (2010) research [141] involving 138 patients with TRS suggest that younger age, shorter illness duration, absence of comorbid substance use disorder and cognitive impairments, fewer failed treatments, and the presence of prominent positive symptoms are associated with better outcomes. Negative symptoms, on the other hand, predict poorer outcomes [141,142]. In contrast, Chan et al.'s (2019) analysis [37] of 50 patients found no clear association between treatment response and factors such as age, sex, duration of untreated illness, or prior clozapine failure. While these findings provide useful insights, the connections remain inconsistent, emphasizing the need for further research to better understand predictors of ECT response.

ECT frequency and relapse prevention

Although ECT is effective in inducing remission, its effects are often transient, with many patients experiencing a return of psychotic symptoms after treatment is abruptly discontinued [143–146]. Relapse rates within one year can reach as high as 63.6%, with the majority of recurrences occurring within the first six months [133,145,147,148]. One study found a median relapse-free period of 21.5 months following acute ECT [148]. Factors that increase the risk of symptom return include a history of multiple psychotic episodes, higher post-ECT BPRS scores, and a greater number of ECT sessions [149].

One approach to reduce the risk of relapse after initial ECT (index ECT) is continuation or maintenance ECT (C/M-ECT) [150,151]. Continuation ECT (C-ECT) is administered after the acute phase to prevent relapse within the first six months, while maintenance ECT (M-ECT) is used to prevent recurrence of symptoms after six months of remission [152,153].

Maintenance ECT has been shown to maintain clinical remission and improve the quality of life for patients with TRS, and therefore, its employment is recommended by many authors [43,57,80,146,154–164]. What is more, the procedure is reported to help reduce hospital re-admissions [150,159,165–167], with one study noting an 80% decrease in annual hospitalizations for chronic schizophrenia [167].

Combining antipsychotic drugs with M/C-ECT seems to be more effective than drug-only treatment [161,168,169]; for instance, in a study of Chanpattana (1999) [168], the use of neuroleptics alongside C-ECT resulted in a relapse rate of 40% within 6 months, compared to 93% for either C-ECT or neuroleptics alone.

There is no conclusive evidence on the optimal duration of M-ECT in schizophrenia patients [134,161,163]. However, Sackeim et al. (2001) [170] suggest that to prevent symptom recurrence, M-ECT should be administered at least every two months. To determine the appropriate frequency and titration of the treatment, it is recommended to monitor symptom severity using standardized scales such as PANSS or BPRS [159]. Further research is needed to establish clearer guidelines for the long-term administration of maintenance electroconvulsive therapy and its combined use with other treatments.

Impact on quality of life

The impact of electroconvulsive therapy on the quality of life (QOL) in patients with treatment-resistant schizophrenia or clozapine-resistant schizophrenia is complex, with improvements often occurring at a slower rate than symptom reduction [37]. While some studies indicate significant QOL improvements following ECT, particularly in domains such as physical capacity, health, and environmental satisfaction [171,172], others report no significant changes in overall QOL [37,173]. This variability highlights the multifaceted nature of QOL, which is influenced by a range of factors. Notably, the relationship between cognition and QOL is inconsistent. While improvements in cognition have been linked to better QOL in some studies [174], other research suggests that cognitive gains may sometimes result in lower QOL scores, potentially due to increased insight into the illness that may lead to feelings of depression or distress [37,175,176]. Furthermore, the severity of psychotic symptoms has shown weak or no correlation with QOL outcomes in some studies [177,178]. Additionally, factors such as re-admission rates have been found to negatively impact QOL, with patients experiencing more frequent hospitalizations reporting lower satisfaction with treatment and diminished quality of life [179]. Overall, while ECT has demonstrated efficacy in reducing symptoms in TRS/CRS, its effects on QOL remain inconsistent and appear to be influenced by a variety of psychological, clinical, and contextual factors.

Impact on cognition

Cognition, alongside quality of life, is often discussed in the context of ECT. Around 80% of individuals with schizophrenia face significant neuro- and sociocognitive deficits [180,181]. At the same time, concerns about potential cognitive side effects remain a major consideration in the use of ECT [134]. Therefore, investigating the true relationship between ECT augmentation and cognitive function in schizophrenia is of particular importance.

Evidence indicates that ECT does not result in persistent cognitive impairments [146,182,183]. While temporary issues with cognition, such as disorientation of time or memory difficulties, may occur shortly after treatment, these effects are typically mild and resolve within days to weeks [85,97,128,130,184]. Notably, no significant changes in global cognition, as assessed by tools such as the MMSE, have been observed in well-designed trials [77,80]. In fact, several studies reported cognitive improvements following ECT [37,185], including enhanced verbal memory, executive functioning, and cognitive flexibility [121]. On the whole, while transient side effects related to cognition may occur, the long-term cognitive profile of ECT appears favorable.

Adverse effects

Like any treatment, ECT augmentation in TRS/CRS is associated with potential side effects, aforementioned cognitive impairments being one of them. Among identified studies, headaches [35,85,127,128,134,138,169] and indeed mild, transient cognitive impairments (particularly affecting memory) [35,85,128,130,138,169] were mentioned most commonly. Other frequently reported adverse effects include nausea [127,128,134,138] and prolonged seizures [130,186,187]. Additionally, cardiovascular manifestations like risen blood pressure, tachycardia, or bradycardia were highlighted in a few studies [130,186,188,189]. Less commonly recorded adverse effects include delirium [37,130], muscle soreness [128], drowsiness [138] and dizziness [138]. Importantly, most undesired events were manageable with conventional treatments. Furthermore, many studies found no evidence of persistent or serious adverse effects following ECT [19,21,77,80,97,127,133,146,159,163,190,191]. Based on the findings of Lally et al.'s meta-analysis, side effects may occur in up to 14% of cases, highlighting the relatively low incidence of adverse reactions to ECT augmentation in the discussed population [118]. These results suggest that incorporating ECT in TRS/CRS treatment is relatively safe and well-tolerated, with adverse effects being uncommon and generally manageable.

5 DISCUSSION AND LIMITATIONS

Treatment-refractory schizophrenia, particularly when unresponsive to clozapine, is characterized by high disability rates, frequent hospitalizations, and substantial financial strain, all of which create significant challenges for patients, their families, and healthcare providers. Managing clozapine-resistant cases is demanding. Limited evidence for the effectiveness of pharmacological augmentation and an increased risk of adverse effects from polypharmacy underscore the need of seeking alternative treatment modalities.

Electroconvulsive therapy has shown promise in augmenting antipsychotic treatments, particularly clozapine, with studies consistently reporting superior symptom reduction and cost-effectiveness compared to pharmacological monotherapy. ECT appears to be particularly effective in alleviating positive symptoms of schizophrenia, while its impact on general or negative symptoms may be less pronounced. Continuation or maintenance ECT further shows potential in reducing relapse rates and sustaining symptom remission. Importantly, ECT augmentation seems to be generally well-tolerated, with adverse effects such as headaches and mild, transient cognitive impairments being rare and manageable.

The conclusions of this review are generally consistent with previous research. Nevertheless, there are several limitations and the interpretation of the current findings requires caution. The literature on ECT augmentation in clozapine-resistant schizophrenia provides limited high-quality evidence, as only a small number of large, well-designed randomized controlled trials have been conducted. Many analyzed studies involved small samples, single-center designs, or lacked blinding, increasing the risk of bias. Moreover, the available evidence is marked by notable methodological variation across studies, including differences in patient selection, response criteria, concurrent therapeutic interventions, electrode placement, treatment frequency, and total number of sessions, which may also contribute to the differing conclusions reported in some studies. That heterogeneity limits the ability to adequately compare the results. Finally, the current work synthesizes findings narratively and without advanced statistical or visual synthesis, which constrains the ability to precisely estimate the strength of the provided evidence.

6 CONCLUSIONS AND FUTURE RESEARCH PERSPECTIVES

This review integrates current clinical data on ECT augmentation in clozapine-resistant schizophrenia and highlights unresolved aspects of its implementation.In summary, ECT represents a valuable therapeutic option for clozapine-resistant schizophrenia, yet its use should be guided by individualized risk-benefit assessment and further supported by high-quality clinical evidence.Future research should aim to:

• conduct large-scale, well-controlled trials assessing the short- and long-term efficacy and safety of ECT-clozapine combination;
• identify clinical or biological predictors of ECT response in CRS patients;
• determine the optimal frequency and duration of maintenance or continuation ECT;
• evaluate cognitive and functional outcomes over time;
• assess cost-effectiveness and quality-of-life benefits;
• and address persistent misconceptions about ECT through public health communication.

DISCLOSURES

Authors’ Contributions

Conceptualization: Aleksandra Zagajewska; methodology: Aleksandra Zagajewska, Magdalena Cyrkler; analysis and investigation: Aleksandra Zagajewska, Aleksandra Giba, Aleksandra Krygowska; resources: Aleksandra Zagajewska, Aleksandra Giba, Aleksandra Krygowska, Aleksandra Reda; data curation: Aleksandra Zagajewska, Aleksandra Giba, Michał Wąsik; writing – original draft: Aleksandra Zagajewska, Aleksandra Giba, Aleksandra Krygowska, Michał Wąsik, Dorota Słupik, Aleksandra Reda; writing – review and editing: Aleksandra Śledziewska, Magdalena Cyrkler, Kamila Sieradocha; visualization: Michał Wąsik, Dorota Słupik; supervision: Aleksandra Zagajewska; project administration: Aleksandra Zagajewska, Aleksandra Śledziewska

Artificial Intelligence Disclosure

Artificial intelligence tools (e.g., ChatGPT, OpenAI) were used to assist with language editing, structural refinement, and the formulation of selected textual segments (e.g., background synthesis, objectives, conclusions). All AI-assisted content was critically reviewed, fact-checked, and finalized by the authors.

Conflicts of Interest

Authors have no conflict of interest to declare.

Funding

This publication was prepared without any external source of funding.

REFERENCES

1. Saha S, Chant D, Welham J, McGrath J. A systematic review of the prevalence of schizophrenia. PLoS Med. 2005;2(5):0413–33. DOI: 10.1371/journal.pmed.0020141
2. Perälä J, Suvisaari J, Saarni SI, Kuoppasalmi K, Isometsä E, Pirkola S, et al. Lifetime prevalence of psychotic and bipolar I disorders in a general population. Arch Gen Psychiatry. 2007;64(1):19–28. DOI: 10.1001/archpsyc.64.1.19
3. Yu T, Pei W, Xu C, Zhang X, Deng C. Investigation of peripheral inflammatory biomarkers in association with violence in schizophrenia. BMC Psychiatry. 2024;24(1):1–8. DOI: 10.1186/s12888-024-05966-y
4. He X, Ma Q, Fan Y, Zhao B, Wang W, Zhu F, et al. The Role of Cytokines in Predicting the Efficacy of Acute Stage Treatment in Patients with Schizophrenia. Neuropsychiatr Dis Treat. 2020;16:191. DOI: 10.2147/NDT.S218483
5. Harrison G, Hopper K, Craig T, Laska E, Siegel C, Wanderling J, et al. Recovery from psychotic illness: a 15- and 25-year international follow-up study. Br J Psychiatry. 2001;178(june):506–17. DOI: 10.1192/bjp.178.6.506
6. Carpenter WT, Kirkpatrick B. The heterogeneity of the long-term course of schizophrenia. Schizophr Bull. 1988;14(4):645–52. DOI: 10.1093/schbul/14.4.645
7. Saetre P, Emilsson L, Axelsson E, Kreuger J, Lindholm E, Jazin E. Inflammation-related genes up-regulated in schizophrenia brains. BMC Psychiatry. 2007;7(1):1–10. DOI: 10.1186/1471-244X-7-46
8. Yang L, Wang B, Yang Z, Zheng S, Xin Z, Wu S, et al. Toxoplasma gondii infection positively associated with schizophrenia: Evidences from UK Biobank cohort and case-controlled studies. J Psychiatr Res. 2024;175:243–50. DOI: 10.1016/j.jpsychires.2024.05.025
9. Cullen AE, Holmes S, Pollak TA, Blackman G, Joyce DW, Kempton MJ, et al. Associations Between Non-neurological Autoimmune Disorders and Psychosis: A Meta-analysis. Biol Psychiatry. 2019;85(1):35–48. DOI: 10.1016/j.biopsych.2018.06.016
10. Ochi S, Inoue S, Yoshino Y, Shimizu H, Iga JI, Ueno SI. Efficacy of Asenapine in Schizophrenia Resistant to Clozapine Combined with Electroconvulsive Therapy: A Case Report. Clin Psychopharmacol Neurosci. 2019;17(4):559–63. DOI: 10.9758/cpn.2019.17.4.559
11. Vos T, Abajobir AA, Abbafati C, Abbas KM, Abate KH, Abd-Allah F, et al. Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet. 2017;390(10100):1211–59. DOI: 10.1016/S0140-6736(17)32154-2
12. Olfson M, Gerhard T, Huang C, Crystal S, Stroup TS. Premature Mortality Among Adults With Schizophrenia in the United States. JAMA Psychiatry. 2015;72(12):1172–81. DOI: 10.1001/jamapsychiatry.2015.1737
13. Marwaha S, Johnson S. Schizophrenia and employment - a review. Soc Psychiatry Psychiatr Epidemiol. 2004;39(5):337–49. DOI: 10.1007/s00127-004-0762-4
14. Harvey PD, Rosenthal JB. Treatment resistant schizophrenia: Course of brain structure and function. Prog Neuropsychopharmacol Biol Psychiatry. 2016;70:111–6. DOI: 10.1016/j.pnpbp.2016.02.008
15. Millier A, Schmidt U, Angermeyer MC, Chauhan D, Murthy V, Toumi M, et al. Humanistic burden in schizophrenia: a literature review. J Psychiatr Res. 2014;54(1):85–93. DOI: 10.1016/j.jpsychires.2014.03.021
16. Nucifora FC, Woznica E, Lee BJ, Cascella N, Sawa A. Treatment resistant schizophrenia: Clinical, biological, and therapeutic perspectives. Neurobiol Dis. 2019;131. DOI: 10.1016/j.nbd.2018.08.016
17. Sinclair D, Adams CE. Treatment resistant schizophrenia: A comprehensive survey of randomised controlled trials. BMC Psychiatry. 2014;14(1). DOI: 10.1186/s12888-014-0253-4
18. Patel KR, Cherian J, Gohil K, Atkinson D. Schizophrenia: Overview and Treatment Options. Pharmacy and Therapeutics. 2014;39(9):638. PMCID: PMC4159061, PMID: 25210417
19. Ahmed S, Khan AM, Mekala HM, Venigalla H, Ahmed R, Etman A, et al. Combined use of electroconvulsive therapy and antipsychotics (both clozapine and non-clozapine) in treatment resistant schizophrenia: A comparative meta-analysis. Heliyon. 2017;3(11):e00429. DOI: 10.1016/j.heliyon.2017.e00429
20. Rayikanti R, Lentowicz I, Birur B, Li L. Combined antipsychotics and electroconvulsive therapy in an acutely psychotic patient with Treatment-resistant Schizophrenia. Psychopharmacol Bull. 2017;47(2):57–62. PMCID: PMC5472173, PMID: 28626273
21. Peitl V, Puljić A, Škrobo M, Nadalin S, Fumić Dunkić L, Karlović D. Clozapine in Treatment-Resistant Schizophrenia and Its Augmentation with Electroconvulsive Therapy in Ultra-Treatment-Resistant Schizophrenia. Biomedicines. 2023;11(4). DOI: 10.3390/biomedicines11041072
22. Howes OD, McCutcheon R, Agid O, De Bartolomeis A, Van Beveren NJM, Birnbaum ML, et al. Treatment-Resistant Schizophrenia: Treatment Response and Resistance in Psychosis (TRRIP) Working Group Consensus Guidelines on Diagnosis and Terminology. Am J Psychiatry. 2017;174(3):216–29. DOI: 10.1176/appi.ajp.2016.16050503
23. Elkis H. Treatment-resistant schizophrenia. Psychiatr Clin North Am. 2007;30(3):511–33. DOI: 10.1016/j.psc.2007.04.001
24. Buckley PF, Wiggins LD, Sebastian S, Singer B. Treatment-refractory schizophrenia. Curr Psychiatry Rep. 2001;3(5):393–400. DOI: 10.1007/s11920-996-0033-z
25. Molina JD, Jiménez-González AB, López-Muñoz F, Cañas F. Evolution of the Concept of Treatment-resistant Schizophrenia: Toward a Reformulation for Lack of an Adequate Response. J Exp Clin Med. 2012;4(2):98–102. https://doi.org/10.1016/j.jecm.2012.02.003
26. National Institute for Health and Care Excellence (NICE). Psychosis and schizophrenia in adults: prevention and management. 2014. https://www.nice.org.uk/guidance/cg178
27. Kane J, Honigfeld G, Singer J, Meltzer H. Clozapine for the treatment-resistant schizophrenic. A double-blind comparison with chlorpromazine. Arch Gen Psychiatry. 1988;45(9):789–96. DOI: 10.1001/archpsyc.1988.01800330013001
28. Meltzer HY. Treatment-resistant schizophrenia – the role of clozapine. Curr Med Res Opin. 1997;14(1):1–20. DOI: 10.1185/03007999709113338
29. Roshni Mangalore MK. Cost of schizophrenia in England. 2007;10(1):23-41. PMID: 17417045.
30. Brenner HD, Dencker SJ, Goldstein MJ, Hubbard JW, Keegan DL, Kruger G, et al. Defining treatment refractoriness in schizophrenia. Schizophr Bull. 1990;16(4):551–61. DOI: 10.1093/schbul/16.4.551
31. Van Sant SP, Buckley PF. Pharmacotherapy for treatment-refractory schizophrenia. Expert Opin Pharmacother. 2011;12(3):411–34. DOI: 10.1517/14656566.2011.528200
32. Gillespie AL, Samanaite R, Mill J, Egerton A, MacCabe JH. Is treatment-resistant schizophrenia categorically distinct from treatment-responsive schizophrenia? A systematic review. BMC Psychiatry. 2017;17(1). DOI: 10.1186/s12888-016-1177-y
33. Conley RR, Buchanan RW. Evaluation of treatment-resistant schizophrenia. Schizophr Bull. 1997;23(4):663–74. DOI: 10.1093/schbul/23.4.663
34. Suzuki T, Remington G, Mulsant BH, Uchida H, Rajji TK, Graff-Guerrero A, et al. Defining treatment-resistant schizophrenia and response to antipsychotics: a review and recommendation. Psychiatry Res. 2012;197(1–2):1–6. DOI: 10.1016/j.psychres.2012.02.013
35. Zheng W, Cao XL, Ungvari GS, Xiang YQ, Guo T, Liu ZR, et al. Electroconvulsive therapy added to non-clozapine antipsychotic medication for treatment resistant schizophrenia: Meta-analysis of randomized controlled trials. PLoS One. 2016;11(6). DOI: 10.1371/journal.pone.0156510
36. Nitesh Painuly NGAA. Concept and Management of Treatment Resistant Schizophrenia (TRS). 2004;46(2):125-134. PMCID: PMC2949927, PMID: 21408038
37. Chan CYW, Abdin E, Seow E, Subramaniam M, Liu J, Peh CX, et al. Clinical effectiveness and speed of response of electroconvulsive therapy in treatment-resistant schizophrenia. Psychiatry Clin Neurosci. 2019;73(7):416–22. DOI: 10.1111/pcn.12855
38. Ajnakina O, Horsdal HT, Lally J, MacCabe JH, Murray RM, Gasse C, et al. Validation of an algorithm-based definition of treatment resistance in patients with schizophrenia. Schizophr Res. 2018;197:294–7. DOI: 10.1016/j.schres.2018.02.017
39. Lehman AF, Lieberman JA, Dixon LB, McGlashan TH, et al. Practice guideline for the treatment of patients with schizophrenia, second edition. 2004;161(2 Suppl):1-56. PMID: 15000267.
40. Taylor M, Perera U. NICE CG178 Psychosis and Schizophrenia in Adults: Treatment and Management - an evidence-based guideline? Br J Psychiatry. 2015;206(5):357–9. DOI: 10.1192/bjp.bp.114.155945
41. Lally J, Gaughran F, Timms P, Curran SR. Treatment-resistant schizophrenia: current insights on the pharmacogenomics of antipsychotics. Pharmgenomics Pers Med. 2016;9:117–29. DOI: 10.2147/PGPM.S115741
42. Gammon D, Cheng C, Volkovinskaia A, Baker GB, Dursun SM. Clozapine: Why Is It So Uniquely Effective in the Treatment of a Range of Neuropsychiatric Disorders? Biomolecules. 2021;11(7). DOI: 10.3390/biom11071030
43. Ito M, Kunii Y, Horikoshi S, Miura I, Itagaki S, Shiga T, et al. Young patient with treatment-resistant schizophrenia drastically improved by combination of clozapine and maintenance electroconvulsive therapy: a case report. Int Med Case Rep J. 2019;12:185–8. DOI: 10.2147/IMCRJ.S198124
44. Meltzer HY. Treatment of the neuroleptic-nonresponsive schizophrenic patient. Schizophr Bull. 1992;18(3):515–42. DOI: 10.1093/schbul/18.3.515
45. Meltzer HY, Okayli G. Reduction of suicidality during clozapine treatment of neuroleptic-resistant schizophrenia: impact on risk-benefit assessment. Am J Psychiatry. 1995;152(2):183–90. DOI: 10.1176/ajp.152.2.183
46. Taipale H, Mehtälä J, Tanskanen A, Tiihonen J. Comparative Effectiveness of Antipsychotic Drugs for Rehospitalization in Schizophrenia-A Nationwide Study With 20-Year Follow-up. Schizophr Bull. 2018;44(6):1381–7. DOI: 10.1093/schbul/sbx176
47. Vermeulen JM, Van Rooijen G, Van De Kerkhof MPJ, Sutterland AL, Correll CU, De Haan L. Clozapine and Long-Term Mortality Risk in Patients With Schizophrenia: A Systematic Review and Meta-analysis of Studies Lasting 1.1-12.5 Years. Schizophr Bull. 2019;45(2):315–29. DOI: 10.1093/schbul/sby052
48. Joober R, Boksa P. Clozapine: a distinct, poorly understood and under-used molecule. J Psychiatry Neurosci. 2010;35(3):147–9. DOI: 10.1503/jpn.100055
49. Nielsen J, Correll CU, Manu P, Kane JM. Termination of clozapine treatment due to medical reasons: when is it warranted and how can it be avoided? J Clin Psychiatry. 2013;74(6):603–13. DOI: 10.4088/JCP.12r08064
50. Iqbal MM, Rahman A, Husain Z, Mahmud SZ, Ryan WG, Feldman JM. Clozapine: a clinical review of adverse effects and management. Ann Clin Psychiatry. 2003;15(1):33–48. DOI: 10.1023/a:1023228626309
51. Young CR, Bowers MB, Mazure CM. Management of the adverse effects of clozapine. Schizophr Bull. 1998;24(3):381–90. DOI: 10.1093/oxfordjournals.schbul.a033333
52. Li Q, Xiang YT, Su YA, Shu L, Yu X, Correll CU, et al. Clozapine in schizophrenia and its association with treatment satisfaction and quality of life: Findings of the three national surveys on use of psychotropic medications in China (2002-2012). Schizophr Res. 2015;168(1–2):523–9. DOI: 10.1016/j.schres.2015.07.048
53. Meltzer HY. Clozapine: balancing safety with superior antipsychotic efficacy. Clin Schizophr Relat Psychoses. 2012;6(3):134–44. DOI: 10.3371/CSRP.6.3.5
54. Cetin M. Clozaphobia: Fear of prescribers of clozapine for treatment of schizophrenia. Klinik Psikofarmakoloji Bulteni. 2014;24(4):295–301. DOI: 10.5455/bcp.20141223052008
55. Nielsen J, Young C, Ifteni P, Kishimoto T, Xiang YT, Schulte PFJ, et al. Worldwide Differences in Regulations of Clozapine Use. CNS Drugs. 2016;30(2):149–61. DOI: 10.1007/s40263-016-0311-1
56. Warnez S, Alessi-Severini S. Clozapine: a review of clinical practice guidelines and prescribing trends. BMC Psychiatry. 2014;14(1). DOI: 10.1186/1471-244X-14-102
57. Koen L, Van Den Berg CE, Niehaus DJH. Combining ECT and clozapine in the treatment of clozapine-refractory schizophrenia and schizoaffective disorder – a pilot study. South African Journal of Psychiatry. 2008;14(4):5. DOI: 10.4102/sajpsychiatry.v14i4.174
58. Kasckow J, Felmet K, Zisook S. Managing suicide risk in patients with schizophrenia. CNS Drugs. 201;25(2):129–43. DOI: 10.2165/11586450-000000000-00000
59. Chakrabarti S. Clozapine resistant schizophrenia: Newer avenues of management. World J Psychiatry. 2021;11(8):429. DOI: 10.5498/wjp.v11.i8.429
60. Samara MT, Dold M, Gianatsi M, Nikolakopoulou A, Helfer B, Salanti G, et al. Efficacy, Acceptability, and Tolerability of Antipsychotics in Treatment-Resistant Schizophrenia: A Network Meta-analysis. JAMA Psychiatry. 2016;73(3):199–210. DOI: 10.1001/jamapsychiatry.2015.2955
61. Samara M, Leucht S. Clozapine in treatment-resistant schizophrenia. Br J Psychiatry. 2017;210(4):299. DOI: 10.1192/bjp.210.4.299
62. Siskind D, Siskind V, Kisely S. Clozapine Response Rates among People with Treatment-Resistant Schizophrenia: Data from a Systematic Review and Meta-Analysis. Can J Psychiatry. 2017;62(11):772–7. DOI: 10.1177/0706743717718167
63. De Berardis D, Fornaro M, Anastasia A, Vellante F, Valchera A, Cavuto M, et al. When clozapine fails: Augmentation strategies in the management of clozapine-resistant schizophrenia. Treatment Resistance in Psychiatry: Risk Factors, Biology, and Management. 2018;349–67. DOI: 10.1007/978-981-10-4358-1_23
64. Roerig JL. Clozapine augmentation strategies. Ment Health Clin. 2019;9(6):336–48. DOI: 10.9740/mhc.2019.11.336
65. Pompili M, Lester D, Dominici G, Longo L, Marconi G, Forte A, et al. Indications for electroconvulsive treatment in schizophrenia: a systematic review. Schizophr Res. 2013;146(1–3):1–9. DOI: 10.1016/j.schres.2013.02.005
66. Iasevoli F, Giordano S, Balletta R, Latte G, Formato MV, Prinzivalli E, et al. Treatment resistant schizophrenia is associated with the worst community functioning among severely-ill highly-disabling psychiatric conditions and is the most relevant predictor of poorer achievements in functional milestones. Prog Neuropsychopharmacol Biol Psychiatry. 2016;65:34–48. DOI: 10.1016/j.pnpbp.2015.08.010
67. Barber S, Olotu U, Corsi M, Cipriani A. Clozapine combined with different antipsychotic drugs for treatment-resistant schizophrenia. Cochrane Database Syst Rev. 2017;3(3). DOI: 10.1002/14651858.CD006324.pub3
68. Taylor DM. Clozapine for Treatment-Resistant Schizophrenia: Still the Gold Standard? CNS Drugs. 2017;31(3):177–80. DOI: 10.1007/s40263-017-0411-6
69. Meltzer HY, Bastani B, Kwon KY, Ramirez LF, Burnett S, Sharpe J. A prospective study of clozapine in treatment-resistant schizophrenic patients. I. Preliminary report. Psychopharmacology (Berl). 1989;99 Suppl:S68-72. DOI: 10.1007/BF00442563
70. Havaki-Kontaxaki BJ, Ferentinos PP, Kontaxakis VP, Paplos KG, Soldatos CR. Concurrent administration of clozapine and electroconvulsive therapy in clozapine-resistant schizophrenia. Clin Neuropharmacol. 2006;29(1):52–6. DOI: 10.1097/00002826-200601000-00012
71. Muscatello MRA, Bruno A, De Fazio P, Segura-Garcia C, Pandolfo G, Zoccali R. Augmentation strategies in partial responder and/or treatment-resistant schizophrenia patients treated with clozapine. Expert Opin Pharmacother. 2014;15(16):2329–45. DOI: 10.1517/14656566.2014.956082
72. Elkis H, Buckley PF. Treatment-Resistant Schizophrenia. Psychiatr Clin North Am. 2016;39(2):239–65. DOI: 10.1016/j.psc.2016.01.006
73. Campana M, Falkai P, Siskind D, Hasan A, Wagner E. Characteristics and definitions of ultra-treatment-resistant schizophrenia - A systematic review and meta-analysis. Schizophr Res. 2021;228:218–26. DOI: 10.1016/j.schres.2020.12.002
74. Moulier V, Krir MW, Dalmont M, Bendib B, Berjamin C, Benosman C, et al. 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). 2021;22(1). DOI: 10.1186/s13063-021-05227-3
75. Kuipers E, Yesufu-Udechuku A, Taylor C, Kendall T. Management of psychosis and schizophrenia in adults: summary of updated NICE guidance. BMJ. 2014;348. DOI: 10.1136/bmj.g1173
76. Kennedy JL, Altar CA, Taylor DL, Degtiar I, Hornberger JC. The social and economic burden of treatment-resistant schizophrenia: a systematic literature review. Int Clin Psychopharmacol. 2014;29(2):63–76. DOI: 10.1097/YIC.0b013e32836508e6
77. Masoudzadeh A, Khalilian AR. Comparative study of clozapine, electroshock and the combination of ECT with clozapine in treatment-resistant schizophrenic patients. Pak J Biol Sci. 2007;10(23):4287–90. DOI: 10.3923/pjbs.2007.4287.4290
78. Hasan A, Falkai P, Wobrock T, Lieberman J, Glenthoj B, Gattaz WF, et al. World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for Biological Treatment of Schizophrenia, Part 1: Update 2012 on the acute treatment of schizophrenia and the management of treatment resistance. The World Journal of Biological Psychiatry. 2012;13:318–78. DOI: 10.3109/15622975.2012.696143
79. Remington G, Addington D, Honer W, Ismail Z, Raedler T, Teehan M. Guidelines for the Pharmacotherapy of Schizophrenia in Adults. Can J Psychiatry. 2017;62(9):604–16. DOI: 10.1177/0706743717720448
80. Petrides G, Malur C, Braga RJ, Bailine SH, Schooler NR, Malhotra AK, et al. Electroconvulsive therapy augmentation in clozapine-resistant schizophrenia: A prospective, randomized study. American Journal of Psychiatry. 2015;172(1):52–8. DOI: 10.1176/appi.ajp.2014.13060787
81. Porcelli S, Balzarro B, Serretti A. Clozapine resistance: augmentation strategies. Eur Neuropsychopharmacol. 2012;22(3):165–82. DOI: 10.1016/j.euroneuro.2011.08.005
82. Sommer IE, Begemann MJH, Temmerman A, Leucht S. Pharmacological augmentation strategies for schizophrenia patients with insufficient response to clozapine: a quantitative literature review. Schizophr Bull. 2012;38(5):1003–11. DOI: 10.1093/schbul/sbr004
83. Taylor DM, Smith L, Gee SH, Nielsen J. Augmentation of clozapine with a second antipsychotic – a meta-analysis. Acta Psychiatr Scand. 2012 Jan;125(1):15–24. DOI: 10.1111/j.1600-0447.2011.01792.x
84. Veerman SRT, Schulte PFJ, Begemann MJH, De Haan L. Non-glutamatergic clozapine augmentation strategies: a review and meta-analysis. Pharmacopsychiatry. 2014;47(7):231–8. DOI: 10.1055/s-0034-1385930
85. Wang G, Zheng W, Li X Bin, Wang S Bin, Cai D Bin, Yang XH, et al. ECT augmentation of clozapine for clozapine-resistant schizophrenia: A meta-analysis of randomized controlled trials. J Psychiatr Res. 2018;105:23–32. DOI: 10.1016/j.jpsychires.2018.08.002
86. Barbui C, Signoretti A, Mule S, Boso M, Cipriani A. Does the addition of a second antipsychotic drug improve clozapine treatment? Schizophr Bull. 2009;35(2):458–68. DOI: 10.1093/schbul/sbn030
87. Cipriani A, Boso M, Barbui C. Clozapine combined with different antipsychotic drugs for treatment resistant schizophrenia. Cochrane Database Syst Rev. 2009;(3). DOI: 10.1002/14651858.CD006324.pub2
88. Correll CU, Rummel-Kluge C, Corves C, Kane JM, Leucht S. Antipsychotic combinations vs monotherapy in schizophrenia: a meta-analysis of randomized controlled trials. Schizophr Bull. 2009;35(2):443–57. DOI: 10.1093/schbul/sbn018
89. Taylor DM, Smith L. Augmentation of clozapine with a second antipsychotic: a meta-analysis of randomized, placebo-controlled studies. Acta Psychiatr Scand. 2009;119(6):419–25. DOI: 0.1111/j.1600-0447.2011.01792.x
90. Lally J, Gaughran F. Treatment resistant schizophrenia - review and a call to action. Ir J Psychol Med. 2019;36(4):279–91. DOI: 10.1017/ipm.2018.47
91. Remington G, Saha A, Chong SA, Shammi C. Augmentation strategies in clozapine-resistant schizophrenia. CNS Drugs. 2005;19(10):843–72. DOI: 10.2165/00023210-200519100-00004
92. Fink M. The mode of action of ECT. Psychopharmacol Bull. 1994;30(3):309-12. PMID: 7878178
93. Norman S. Endler. The Origins of Electroconvulsive Therapy (ECT). 1988;4(1):5-23. PMID: 11940939
94. Leiknes KA, Schweder LJ von, Høie B. Contemporary use and practice of electroconvulsive therapy worldwide. Brain Behav. 2012 May;2(3):283–344. DOI: 10.1002/brb3.37
95. Chanpattana W, Andrade C. ECT for treatment-resistant schizophrenia: a response from the far East to the UK. NICE report. J ECT. 2006;22(1):4–12. DOI: 10.1097/00124509-200603000-00002
96. Fink M. Clozapine and electroconvulsive therapy. Arch Gen Psychiatry. 1990;47(3):290–1. DOI: 10.1001/archpsyc.1990.01810150090018
97. Kim HS, Kim SH, Lee NY, Youn T, Lee JH, Chung S, et al. Effectiveness of Electroconvulsive Therapy Augmentation on Clozapine-Resistant Schizophrenia. Psychiatry Investig. 2017;14(1):58–62. DOI: 10.4306/pi.2017.14.1.58
98. Scott AIF. The ECT handbook: the third report of the Royal College of Psychiatrists’ Special Committee of ECT. 2nd ed. London: Royal College of Psychiatrists. 2005;243.
99. Weiss A, Hussain S, Ng B, Sarma S, Tiller J, Waite S, et al. Royal Australian and New Zealand College of Psychiatrists professional practice guidelines for the administration of electroconvulsive therapy. 2019;53(7):609-623. DOI: 10.1177/0004867419839139
100. Li M, Yao X, Sun L, Zhao L, Xu W, Zhao H, et al. Effects of Electroconvulsive Therapy on Depression and Its Potential Mechanism. Front Psychol. 2020;11:80. DOI: 10.3389/fpsyg.2020.00080
101. Sinclair DJM, Zhao S, Qi F, Nyakyoma K, Kwong JSW, Adams CE. Electroconvulsive therapy for treatment-resistant schizophrenia. Schizophr Bull. 2019;45(4):730–2. DOI: 10.1002/14651858.CD011847.pub2
102. Phutane VH, Thirthalli J, Muralidharan K, Naveen Kumar C, Keshav Kumar J, Gangadhar BN. Double-blind randomized controlled study showing symptomatic and cognitive superiority of bifrontal over bitemporal electrode placement during electroconvulsive therapy for schizophrenia. Brain Stimul. 2013;6(2):210–7. DOI: 10.1016/j.brs.2012.04.002
103. Crowley K, Pickle J, Dale R, Fattal O. A critical examination of bifrontal electroconvulsive therapy: clinical efficacy, cognitive side effects, and directions for future research. J ECT. 2008;24(4):268–71. DOI: 10.1097/YCT.0b013e318168e72c
104. Singh A, Kar SK. How Electroconvulsive Therapy Works?: Understanding the Neurobiological Mechanisms. Clinical Psychopharmacology and Neuroscience. 2017;15(3):210. DOI: 10.9758/cpn.2017.15.3.210
105. Rosen Y, Reznik I, Sluvis A, Kaplan D, Mester R. The significance of the nitric oxide in electro-convulsive therapy: A proposed neurophysiological mechanism. Med Hypotheses. 2003;60(3):424–9. DOI: 10.1016/s0306-9877(02)00419-x
106. Szota AM, Radajewska I, Ćwiklińska-Jurkowska M, Lis K, Grudzka P, Dróżdż W. Changes in IL-6, IL-12, IL-5, IL-10 and TGF-β1 Concentration in Patients with Treatment-Resistant Schizophrenia (TRS) Following Electroconvulsive Therapy (ECT)-A Pilot Study. Biomedicines. 2024;12(11). DOI: 10.3390/biomedicines12112637
107. Jahangard L, Haghighi M, Bigdelou G, Bajoghli H, Brand S. Comparing efficacy of ECT with and without concurrent sodium valproate therapy in manic patients. J ECT. 2012;28(2):118–23. DOI: 10.1097/YCT.0b013e31824b64b5
108. Kales HC, Dequardo JR, Tandon R. Combined electroconvulsive therapy and clozapine in treatment-resistant schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry. 1999;23(3):547–56. DOI: 10.1016/s0278-5846(99)00015-9
109. Fox HA. Natural course, placebo effect, and sham electroconvulsive therapy. J ECT. 2010;26(1):76. DOI: 10.1097/YCT.0b013e3181aa84c5
110. Arumugham SS, Praharaj SK, Shreekantiah U, Sreeraj VS, Roy C, Shenoy S, et al. Clinical efficacy and neurobiological correlates of electroconvulsive therapy in patients with clozapine-resistant/intolerant schizophrenia: study protocol of multi-site parallel arm double-blind randomized sham-controlled study. Wellcome Open Res. 2022;7:212. DOI: 10.12688/wellcomeopenres.18028.2
111. Rose D, Wykes T, Leese M, Bindman J, Fleischmann P. Patients’ perspectives on electroconvulsive therapy: systematic review. BMJ. 2003;326(7403):1363–5. DOI: 10.1136/bmj.326.7403.1363
112. Devanand DP, Dwork AJ, Hutchinson ER, Bolwig TG, Sackeim HA. Does ECT alter brain structure? Am J Psychiatry. 1994;151(7):957–70. DOI: 10.1176/ajp.151.7.957
113. Dwork AJ, Arango V, Underwood M, Ilievski B, Rosoklija G, Sackeim HA, et al. Absence of histological lesions in primate models of ECT and magnetic seizure therapy. Am J Psychiatry. 2004;161(3):576–8. DOI: 10.1176/appi.ajp.161.3.576
114. Payne NA, Prudic J. Electroconvulsive therapy: Part I. A perspective on the evolution and current practice of ECT. J Psychiatr Pract. 2009;15(5):346–68. DOI: 10.1097/01.pra.0000361277.65468.ef
115. Kellner CH, Obbels J, Sienaert P. When to consider electroconvulsive therapy (ECT). Acta Psychiatr Scand. 2020;141(4):304–15. DOI: 10.1111/acps.13134
116. Gergel T. “Shock tactics”, ethics and fear: an academic and personal perspective on the case against electroconvulsive therapy. Br J Psychiatry. 2022;220(3):109–12. DOI: 10.1192/bjp.2021.116
117. Rose DS, Wykes TH, Bindman JP, Fleischmann PS. Information, consent and perceived coercion: patients’ perspectives on electroconvulsive therapy. Br J Psychiatry. 2005;186:54–9. DOI: 10.1192/bjp.186.1.54
118. Lally J, Tully J, Robertson D, Stubbs B, Gaughran F, MacCabe JH. Augmentation of clozapine with electroconvulsive therapy in treatment resistant schizophrenia: A systematic review and meta-analysis. Schizophr Res. 2016 Mar 1;171(1–3):215–24. DOI: 10.1016/j.schres.2016.01.024
119. American Psychiatric Association. The Practice of Electroconvulsive therapy, Third Edition: Recommendations for Treatment, Training, and Privileging. 2025;470.
120. Salehpour S, Masoodzadeh A, Khalilian AR, Setareh J. EEG Data as a Predictor Index of Efficacy of Clozapine Therapy in Resistant Schizophrenia. Journal of Mazandaran University of Medical Sciences. 2013;23(105):2–7.
121. Vuksan Cúsa B, Klepac N, Jakšić N, Bradaš Z, Božičević M, Palac N, et al. The Effects of Electroconvulsive Therapy Augmentation of Antipsychotic Treatment on Cognitive Functions in Patients with Treatment-Resistant Schizophrenia. Journal of ECT. 2018;34(1):31–4. DOI: 10.1097/YCT.0000000000000463
122. Hunter EE, Murphy M. Brief Psychiatric Rating Scale. Encyclopedia of Clinical Neuropsychology. 2011;447–9.
123. Tharyan P, Adams CE. Electroconvulsive therapy for schizophrenia. Cochrane Database Syst Rev. 2005;(2). DOI: 10.1002/14651858.CD000076.pub2
124. Rey JM, Walter G. Half a century of ECT use in young people. Am J Psychiatry.1997;154(5):595–602. DOI: 10.1176/ajp.154.5.595
125. Wang W, Pu C, Jiang J, Cao Q, Wang J, Zhao M, et al. Efficacy and safety of treating patients with refractory schizophrenia with antipsychotic medication and adjunctive electroconvulsive therapy: a systematic review and meta-analysis. Shanghai Arch Psychiatry. 2015;27(4):206. DOI: 10.11919/j.issn.1002-0829.215093
126. Cervera Enguix S, Seva Fernández A. Pharmacological treatment resistant schizophrenia. 2006;34(1):48-54. PMID: 16525905.
127. Pawełczyk T, Kołodziej-Kowalska E, Pawełczyk A, Rabe-Jabłońska J. Effectiveness and clinical predictors of response to combined ECT and antipsychotic therapy in patients with treatment-resistant schizophrenia and dominant negative symptoms. Psychiatry Res. 2014;220(1–2):175–80. DOI: 10.1016/j.psychres.2014.07.071
128. Pawełczyk T, Kołodziej-Kowalska E, Pawełczyk A, Rabe-Jabłońska J. Augmentation of antipsychotics with electroconvulsive therapy in treatment-resistant schizophrenia patients with dominant negative symptoms: A pilot study of effectiveness. Neuropsychobiology. 2014;70(3):158–64. DOI: 10.1159/000366484
129. Nieuwdorp W, Koops S, Somers M, Sommer IEC. Transcranial magnetic stimulation, transcranial direct current stimulation and electroconvulsive therapy for medication-resistant psychosis of schizophrenia. Curr Opin Psychiatry. 2015;28(3):222–8. DOI: 10.1097/YCO.0000000000000156
130. Grover S, Chakrabarti S, Hazari N, Avasthi A. Effectiveness of electroconvulsive therapy in patients with treatment resistant schizophrenia: A retrospective study. Psychiatry Res. 2017;249:349–53. DOI: 10.1016/j.psychres.2017.01.042
131. Biedermann F, Pfaffenberger N, Baumgartner S, Kemmler G, Wolfgang Fleischhacker W, Hofer A. Combined clozapine and electroconvulsive therapy in clozapine-resistant schizophrenia: clinical and cognitive outcomes. J ECT. 2011;27(4):e61–2. DOI: 10.1097/YCT.0b013e31821a8f05
132. Grover S, Shouan A, Chakrabarti S, Sahoo S, Mehra A. Comparative study of effectiveness of augmentation with ECT in clozapine resistant schizophrenia (CRS) and non-clozapine resistant schizophrenia (Non-CRS). Nord J Psychiatry. 2021;75(6):397–405. DOI: 10.1080/08039488.2021.1877349
133. Kho KH, Blansjaar BA, De Vries S, Babuskova D, Zwinderman AH, Linszen DH. Electroconvulsive therapy for the treatment of clozapine nonresponders suffering from schizophrenia – an open label study. Eur Arch Psychiatry Clin Neurosci. 2004;254(6):372–9. DOI: 10.1007/s00406-004-0517-y
134. Kim JH, Youn T, Choi JG, Jeong SH, Jung HY, Kim YS, et al. Combination of Electroconvulsive Therapy and Clozapine in Treatment-Resistant Schizophrenia. Psychiatry Investig. 2018;15(8):829–35. DOI: 10.30773/pi.2018.05.15
135. Yeh TC, Correll CU, Yang FC, Chen MH, Tseng PT, Hsu CW, et al. Pharmacological and nonpharmacological augmentation treatments for clozapine-resistant schizophrenia: A systematic review and network meta-analysis with normalized entropy assessment. Asian J Psychiatr. 2023;1;79. DOI: 10.1016/j.ajp.2022.103375
136. Schooler NR, Buchanan RW, Laughren T, Leucht S, Nasrallah HA, Potkin SG, et al. Defining therapeutic benefit for people with schizophrenia: focus on negative symptoms. Schizophr Res. 2015;162(1–3):169–74. DOI: 10.1016/j.schres.2014.12.001
137. Melzer-Ribeiro DL, Rigonatti SP, Kayo M, Avrichir BS, Ribeiro RB, Dos Santos B, et al. Efficacy of electroconvulsive therapy augmentation for partial response to clozapine: a pilot randomized ECT – sham controlled trial. Archives of Clinical Psychiatry (São Paulo). 2017;44(2):45–50. DOI: 10.1590/0101-6083.000000116
138. Melzer-Ribeiro DL, Napolitano IC, Leite SA, Alencar de Souza JA, Vizzotto ADB, Di Sarno ES, et al. Randomized, double-blind, sham-controlled trial to evaluate the efficacy and tolerability of electroconvulsive therapy in patients with clozapine-resistant schizophrenia. Schizophr Res. 2024;268:252–60. DOI: 10.1016/j.schres.2023.11.009
139. Potkin SG, Kane JM, Correll CU, Lindenmayer JP, Agid O, Marder SR, et al. The neurobiology of treatment-resistant schizophrenia: paths to antipsychotic resistance and a roadmap for future research. NPJ Schizophr. 2020;6(1). DOI: 10.1038/s41537-019-0090-z
140. Sharma P, Sharma P. Biomarkers of Electroconvulsive Therapy (ECT) Response in Treatment-resistant Schizophrenia (TRS). Kathmandu Univ Med J (KUMJ). 2024;22(85):107–11. DOI: 10.2139/ssrn.4692779
141. Chanpattana W, Sackeim HA. Electroconvulsive therapy in treatment-resistant schizophrenia: prediction of response and the nature of symptomatic improvement. J ECT. 2010;26(4):289–98. DOI: 10.1097/YCT.0b013e3181cb5e0f
142. Stenmark L, Popiolek K, Boden R, Brus O, Hammar Å, Landen M, et al. Predictors of Treatment Response to Electroconvulsive Therapy in Schizophrenia—A Nationwide Registry-Based Study. Schizophr Bull Open. 2020;1(1). DOI: 10.1093/schizbullopen/sgaa019
143. Lisanby SH, Sampson S, Husain MM, Petrides G, Knapp RG, McCall V, et al. Toward individualized post-electroconvulsive therapy care: piloting the Symptom-Titrated, Algorithm-Based Longitudinal ECT (STABLE) intervention. J ECT. 2008;24(3):179–82. DOI: 10.1097/YCT.0b013e318185fa6b
144. Kellner CH, Husain MM, Knapp RG, Mccall WV, Petrides G, Rudorfer M V., et al. A Novel Strategy for Continuation ECT in Geriatric Depression: Phase 2 of the PRIDE Study. Am J Psychiatry. 2016;173(11):1110–8. DOI: 10.1176/appi.ajp.2016.16010118
145. Braga RJ, John M, Schooler NR, Bailine SH, Malur C, Mendelowitz A, et al. Continuation Electroconvulsive Therapy for Patients with Clozapine-Resistant Schizophrenia: A Pilot Study. Journal of ECT. 2019;35(3):156–60. DOI: 10.1097/YCT.0000000000000588
146. Youn T, Jeong SH, Kim YS, Chung IW. Long-term clinical efficacy of maintenance electroconvulsive therapy in patients with treatment-resistant schizophrenia on clozapine. Psychiatry Res. 2019;273:759–66. DOI: 10.1016/j.psychres.2019.02.008
147. Suzuki K, Awata S, Matsuoka H. One-year outcome after response to ECT in middle-aged and elderly patients with intractable catatonic schizophrenia. J ECT. 2004;20(2):99–106. DOI: 10.1097/00124509-200406000-00005
148. Shibasaki C, Takebayashi M, Fujita Y, Yamawaki S. Factors associated with the risk of relapse in schizophrenic patients after a response to electroconvulsive therapy: a retrospective study. Neuropsychiatr Dis Treat. 2015;11:67–73. DOI: 10.2147/NDT.S74303
149. Grover S, Sahoo S, Rabha A, Koirala R. ECT in schizophrenia: a review of the evidence. Acta Neuropsychiatr. 2019;31(3):115–27. DOI: 10.1017/neu.2018.32
150. Choi KM, Choi SH, Hong JK, Lee MH, Jung JH, Oh SH, et al. The Effects of Continuation-Maintenance Electroconvulsive Therapy on Reducing Hospital Re-Admissions in Patients with Treatment-Resistant Schizophrenia. Clin Psychopharmacol Neurosci. 2018;16(3):339–42. DOI: 10.9758/cpn.2018.16.3.339
151. O’Connor DW, Gardner B, Presnell I, Singh D, Tsanglis M, White E. The effectiveness of continuation-maintenance ECT in reducing depressed older patients’ hospital re-admissions. J Affect Disord. 2010;120(1–3):62–6. DOI: 10.1016/j.jad.2009.04.005
152. Motohashi N, Awata S, Isse K, Ueda S, Okubo Y, et al. Recommendations for ECT Practice, Second Edition. 2013;115(6):586-600. PMID: 23944116.
153. Andrade C, Kurinji S. Continuation and maintenance ECT: a review of recent research. J ECT. 2002;18(3):149–58. DOI: 10.1097/00124509-200209000-00007
154. Suzuki K, Takano T, Ebina Y, Takamatsu K, Awata S, Matsuoka H. Continuation electroconvulsive therapy to prevent relapse of schizophrenia in relapse-prone patients. J ECT. 2007;23(3):204–5. DOI: 10.1097/YCT.0b013e3180544972
155. Weiner RD, Reti IM. Key updates in the clinical application of electroconvulsive therapy. Int Rev Psychiatry. 2017;29(2):54–62. DOI: 10.1080/09540261.2017.1309362
156. Trevino K, McClintock SM, Husain MM. A review of continuation electroconvulsive therapy: application, safety, and efficacy. J ECT. 2010;26(3):186–95. DOI: 10.1097/YCT.0b013e3181efa1b2
157. Suzuki K, Awata S, Takano T, Ebina Y, Hitoshiiwasaki, Matsuoka H. Continuation electroconvulsive therapy for relapse prevention in middle-aged and elderly patients with intractable catatonic schizophrenia. Psychiatry Clin Neurosci. 2005;59(4):481–9. DOI: 10.1111/j.1440-1819.2005.01402.x
158. Suzuki K, Awata S, Takano T, Ebina Y, Shindo T, Harada N, et al. Adjusting the frequency of continuation and maintenance electroconvulsive therapy to prevent relapse of catatonic schizophrenia in middle-aged and elderly patients who are relapse-prone. Psychiatry Clin Neurosci. 2006;60(4):486–92. DOI: 10.1111/j.1440-1819.2006.01536.x
159. Purohith AN, Chatorikar SA, Praharaj SK, Bhandary RP, Sharma PSVN. Efficacy and safety of maintenance electroconvulsive therapy (M-ECT) in treatment-resistant schizophrenia: A case series. Asian J Psychiatr. 2022;73. DOI: 10.1016/j.ajp.2022.103132
160. Chanpattana W. Maintenance ECT in mentally retarded, treatment-resistant schizophrenic patients. 1999;15(2):150-3. PMID: 10378154.
161. Ward HB, Szabo ST, Rakesh G. Maintenance ECT in schizophrenia: A systematic review. Psychiatry Res. 2018;264:131–42. DOI: 10.1016/j.psychres.2018.03.033
162. Iancu I, Pick N, Seener-Lorsh O, Dannon P. Patients with schizophrenia or schizoaffective disorder who receive multiple electroconvulsive therapy sessions: characteristics, indications, and results. Neuropsychiatr Dis Treat. 2015;11:853–62. DOI: 10.2147/NDT.S78919
163. Moeller S, Kalkwarf N, Lücke C, Ortiz D, Jahn S, Först C, et al. Achieving stable remission with maintenance electroconvulsive therapy in a patient with treatment-resistant schizophrenia. Medicine (United States). 2017;96(48). DOI: 10.1097/MD.0000000000008813
164. Chung IW, Kim HS, Kim JH, Jang JH, Kim YS. Resolution of Persistent Auditory Verbal Hallucinations after Long-term Electroconvulsive Therapy Maintenance: A Case Report of a Patient with Clozapine-resistant Schizophrenia. Clin Psychopharmacol Neurosci. 2021;19(1):170–3. DOI: 10.9758/cpn.2021.19.1.170
165. Shelef A, Mazeh D, Berger U, Baruch Y, Barak Y. Acute electroconvulsive therapy followed by maintenance electroconvulsive therapy decreases hospital re-admission rates of older patients with severe mental illness. J ECT. 2015;31(2):125–8. DOI: 10.1097/YCT.0000000000000197
166. Cosculluela A, Cobo J, Martínez-Amorós E, Paños M, et al. Effectivity and Cost-effectivity of the Maintenance Electroconvulsive Therapy: A mirror naturalistic analysis. 2017;45(6):257-67. PMID: 29199760.
167. Lévy-Rueff M, Jurgens A, Lôo H, Olié JP, Amado I. Maintenance electroconvulsive therapy and treatment of refractory schizophrenia. Encephale. 2008;34(5):526–33. DOI: 10.1016/j.encep.2007.08.008
168. Chanpattana W, Chakrabhand ML, Sackheim HA, Kitaroonchai W, et al. Continuation ECT in treatment-resistant schizophrenia: a controlled study. 1999;15(3):178-92. PMID: 10492856.
169. Mishra BR, Agrawal K, Biswas T, Mohapatra D, Nath S, Maiti R. Comparison of Acute Followed by Maintenance ECT vs Clozapine on Psychopathology and Regional Cerebral Blood Flow in Treatment-Resistant Schizophrenia: A Randomized Controlled Trial. Schizophr Bull. 2022;48(4):814–25. DOI: 10.1093/schbul/sbac027
170. Sackeim HA, Haskett RF, Mulsant BH, Thase ME, Mann JJ, Pettinati HM, et al. Continuation pharmacotherapy in the prevention of relapse following electroconvulsive therapy: a randomized controlled trial. JAMA. 2001;285(10):1299–307. DOI: 10.1001/jama.285.10.1299
171. Chanpattana W, Kramer BA. Acute and maintenance ECT with flupenthixol in refractory schizophrenia: Sustained improvements in psychopathology, quality of life, and social outcomes. Schizophr Res. 2003;63(1–2):189–93. DOI: 10.1016/s0920-9964(02)00330-4
172. Garg R, Chavan BS, Arun P. Quality of life after electroconvulsive therapy in persons with treatment resistant schizophrenia. Indian J Med Res. 2011;133(6):641. PMID: 21727663, PMCID: PMC3135992.
173. An FR, Zhang L, Zhang QE, Ungvari GS, Ng CH, Chiu HFK, et al. Electroconvulsive therapy and its relationships with clinical characteristics and quality of life in Chinese psychiatric patients. Psychiatry Res. 2016;246:246–9. DOI: 10.1016/j.psychres.2016.09.046
174. Savilla K, Kettler L, Galletly C. Relationships between cognitive deficits, symptoms and quality of life in schizophrenia. Aust N Z J Psychiatry. 2008;42(6):496–504. DOI: 10.1080/00048670802050512
175. Narvaez JM, Twamley EW, McKibbin CL, Heaton RK, Patterson TL. Subjective and objective quality of life in schizophrenia. Schizophr Res. 2008;98(1–3):201–8. DOI: 10.1016/j.schres.2007.09.001
176. Kim JH, Lee S, Han AY, Kim K, Lee J. Relationship between cognitive insight and subjective quality of life in outpatients with schizophrenia. Neuropsychiatr Dis Treat. 2015;11:2041–8. DOI: 10.2147/NDT.S90143
177. Priebe S, McCabe R, Junghan U, Kallert T, Ruggeri M, Slade M, et al. Association between symptoms and quality of life in patients with schizophrenia: a pooled analysis of changes over time. Schizophr Res. 2011;133(1–3):17–21. DOI: 10.1016/j.schres.2011.09.021
178. Wilson-d’Almeida K, Karrow A, Bralet MC, Bazin N, Hardy-Baylé MC, Falissard B. In patients with schizophrenia, symptoms improvement can be uncorrelated with quality of life improvement. Eur Psychiatry. 2013;28(3):185–9. DOI: 10.1016/j.eurpsy.2011.10.002
179. Schmidt-Kraepelin C, Janssen B, Gaebel W. Prevention of rehospitalization in schizophrenia: results of an integrated care project in Germany. Eur Arch Psychiatry Clin Neurosci. 2009;259 Suppl 2:S205-12. DOI: 10.1007/s00406-009-0056-7
180. Meesters PD, Stek ML, Comijs HC, De Haan L, Patterson TL, Eikelenboom P, et al. Social functioning among older community-dwelling patients with schizophrenia: a review. Am J Geriatr Psychiatry. 2010;18(10):862–78. DOI: 10.1097/JGP.0b013e3181e446ff
181. Raffard S, Gely-Nargeot MC, Capdevielle D, Bayard S, Boulenger JP. Learning potential and cognitive remediation in schizophrenia. Encephale. 2009;35(4):353–60. DOI: 10.1016/j.encep.2008.06.014
182. Bailine SH, Sanghani SN, Petrides G. Maintenance Electroconvulsive Therapy Is Not Acute Electroconvulsive Therapy. J ECT. 2019;35(1):1–2. DOI: 10.1097/YCT.0000000000000524
183. Ali SA, Mathur N, Malhotra AK, Braga RJ. Electroconvulsive Therapy and Schizophrenia: A Systematic Review. Mol Neuropsychiatry. 2019;5(2):75–83. DOI: 10.1159/000497376
184. Kaster TS, Daskalakis ZJ, Blumberger DM. Clinical Effectiveness and Cognitive Impact of Electroconvulsive Therapy for Schizophrenia: A Large Retrospective Study. J Clin Psychiatry. 2017;78(4):e383–9. DOI: 10.4088/JCP.16m10686
185. Tor PC, Ying J, Ho NF, Wang M, Martin D, Ang CP, et al. Effectiveness of Electroconvulsive Therapy and Associated Cognitive Change in Schizophrenia: A Naturalistic, Comparative Study of Treating Schizophrenia With Electroconvulsive Therapy. J ECT. 2017;33(4):272–7. DOI: 10.1097/YCT.0000000000000422
186. Grover S, Hazari N, Kate N. Combined use of clozapine and ECT: a review. Acta Neuropsychiatr. 2015;27(3):131–42. DOI: 10.1017/neu.2015.8
187. Cardwell BA, Nakai B. Seizure activity in combined clozapine and ECT: a retrospective view. 1995;11(2):110-3. PMID: 7552049.
188. Safferman AZ, Munne R. Combining clozapine with ECT. Convuls Ther. 1992;8(2):141-143. PMID: 11941161.
189. Bhatia SC, Bhatia SK, Gupta S. Concurrent administration of clozapine and ECT: a successful therapeutic strategy for a patient with treatment-resistant schizophrenia. 1998;14(4):280-3. https://doi.org/10.1097/00124509-199812000-00012
190. Sajatovic M, Meltzer HY. The Effect of Short-Term Electroconvulsive Treatment Plus Neuroleptics in Treatment-Resistant Schizophrenia and Schizoaffective Disorder. 1993;9(3):167-175. PMID: 11941209.
191. Ukpong DI, Makanjuola RO, Morakinyo O. A controlled trial of modified electroconvulsive therapy in schizophrenia in a Nigerian teaching hospital. West Afr J Med. 2002;21(3):237–40. DOI: 10.4314/wajm.v21i3.28039

back