Clinical impact of reducing the frequency of clozapine monitoring: controlled mirror-image cohort study.

BACKGROUND: To minimise infection during COVID-19, the clozapine haematological monitoring interval was extended from 4-weekly to 12-weekly intervals in South London and Maudsley NHS Foundation Trust. AIMS: To investigate the impact of this temporary policy change on clinical and safety outcomes. METHOD: All patients who received clozapine treatment with extended (12-weekly) monitoring in a large London National Health Service trust were included in a 1-year mirror-image study. A comparison group was selected with standard monitoring. The proportion of participants with mild to severe neutropenia and the proportion of participants attending the emergency department for clozapine-induced severe neutropenia treatment during the follow-up period were compared. Psychiatric hospital admission rates, clozapine dose and concomitant psychotropic medication in the 1 year before and the 1 year after extended monitoring were compared. All-cause clozapine discontinuation at 1-year follow-up was examined. RESULTS: Of 569 participants, 459 received clozapine with extended monitoring and 110 controls continued as normal. The total person-years were 458 in the intervention group and 109 in the control group, with a median follow-up time of 1 year in both groups. During follow-up, two participants (0.4%) recorded mild to moderate neutropenia in the intervention group and one (0.9%) in the control group. There was no difference in the incidence of haematological events between the two groups (IRR = 0.48, 95% CI 0.02-28.15, P = 0.29). All neutropenia cases in the intervention group were mild, co-occurring during COVID-19 infection. The median number of admissions per patient during the pre-mirror period remained unchanged (0, IQR = 0) during the post-mirror period. There was one death in the control group, secondary to COVID-19 infection. CONCLUSIONS: There was no evidence that the incidence of severe neutropenia was increased in those receiving extended monitoring.

Clozapine augmentation with long-acting antipsychotic injections: A case series and systematic review.

BACKGROUND: Up to 30% of patients with a diagnosis of treatment-resistant psychosis remain symptomatic despite an optimal trial with the gold standard treatment, clozapine. Emerging evidence suggests the clinical utility of long-acting injections (LAI) in such clinical scenarios. In this study, we aimed to describe clozapine augmentation with LAIs in an inner London hospital and explore the literature on the clinical effectiveness of this treatment modality. METHODS: Patients prescribed clozapine, who were commenced on a LAI between 2007 and 2023 by the United Kingdom's largest mental health trust, were identified from electronic patient records. First, routine clinical data were used to describe the use, effectiveness, and safety of this augmentation strategy. Second, we conducted a literature search up to 1st June 2023 to identify published studies describing clinical outcomes after clozapine augmentation with a LAI. Clinical outcomes were collated and presented in a table, including hospitalisation rates and quantitative clinical assessments using validated scales. RESULTS: Of the 1248 patients prescribed clozapine in SLaM, three patients (0.2%) received augmentation with the following LAIs: olanzapine embonate, paliperidone palmitate and pipotiazine palmitate. This treatment strategy was clinically effective and generally well tolerated in all three cases. Twelve published studies between 2010 and 2022 were included in the review. Eight distinct LAIs were reported (4 first and 4 second generation antipsychotics), with risperidone and paliperidone most widely studied. All the identified studies were observational including mirror-image studies, case series and case reports. Duration of follow up varied from 3 months to 3 years. There was evidence that the use of LAIs with clozapine can significantly reduce clinical symptoms, hospitalisation rates and bed days. No serious adverse effects were reported. CONCLUSION: This preliminary evidence suggests clinical utility of LAIs in alleviating residual symptoms and subsequently reducing hospitalisation rates in patients optimised on clozapine treatment. The current study warrants further investigations including a randomised controlled study to establish the clinical efficacy, tolerability, and place in therapy of this treatment modality.

The lived experience of clozapine discontinuation in patients and carers following suspected clozapine-induced neutropenia.

BACKGROUND: Clozapine is the treatment of choice in refractory psychosis. In most countries, clozapine must be stopped indefinitely if white blood cells fall below a defined threshold during routine monitoring. Despite evidence of severe adverse consequences of clozapine discontinuation, published accounts on the lived experiences and perspectives of patients and carers are scarce. METHOD: We completed semi-structured interviews with patients (n = 4) and family carers (n = 4) on experiences of clozapine cessation following suspected drug-induced neutropenia. Interviews were audio-recorded, transcribed and analysed thematically. RESULTS: The two overarching themes comprised:(i) stress of clozapine below threshold neutrophil results and (ii) patient and carer priorities. CONCLUSIONS: There is a suggested need for evidence-based pharmacological and psychological approaches to support patients and carers after clozapine cessation. Such approaches will minimise the potentially negative physical and emotional sequela in the aftermath of a below threshold neutrophil result and reduce the likelihood of experiencing additional health and social inequalities after clozapine discontinuation.

A retrospective case notes review of the effectiveness and tolerability of metoclopramide in the treatment of clozapine-induced hypersalivation (CIH).

OBJECTIVE: The objective of the study is to explore the long-term effectiveness and tolerability of metoclopramide in the treatment of CIH. METHOD: This study is a retrospective, observational cohort study of patients prescribed metoclopramide for CIH at the South London & Maudsley (SLaM) NHS Foundation Trust. RESULTS: Of the 96 patients identified, 14 patients were eligible for inclusion in our study. Five patients continued treatment with a mean duration of 27 months (SD = 17.8), and one patient continued until transfer with a duration of 3 months. Eight patients discontinued treatment after a mean duration of 8 months. CONCLUSION: Metoclopramide may be an effective and tolerated drug in CIH, but more data is required to establish its place in the pharmacotherapy of this condition.

An evaluation of the variation and underuse of clozapine in the United Kingdom.

BACKGROUND: Clozapine is the only licensed treatment for treatment refractory schizophrenia. Despite this, it remains grossly underused relative to the prevalence of refractory schizophrenia. The extent of underuse and the degree of regional variation in prescribing in the United Kingdom is unknown. It is also unclear, how the UK compares with other European countries in rates of clozapine prescribing. METHODS: We obtained data relating to all clozapine prescribing in the UK from the relevant clozapine registries. We examined regional variation in clozapine use across England, corrected for the known prevalence of severe mental illness (SMI). We also compared the UK rate of clozapine use per 100,000 population to that described in other European countries. FINDINGS: There is substantial variation in clozapine prescribing across different regions of England and only about a third of potentially eligible patients were prescribed the drug in the UK. Clozapine prescribing rate in the UK was lower than in several European countries. INTERPRETATION: There is clear regional inequity in access to the most effective treatment in refractory schizophrenia in England. Strategies to increase clozapine use, by overcoming both real and perceived barriers, are urgently necessary to reduce treatment inequity for patients with refractory schizophrenia.

Benign ethnic neutropenia: an analysis of prevalence, timing and identification accuracy in two large inner-city NHS hospitals.

BACKGROUND: Benign ethnic neutropenia (BEN) is the most common cause of chronic neutropenia seen in individuals of African, Middle Eastern and West Indian descent. This phenotype is broadly defined by an absolute neutrophil counts (ANC) below 1.8 × 109 cells/L in the absence of other causes, without an increased risk of infection. BEN has been implicated as a potential source of disparity in patients treated with clozapine, the antipsychotic of choice in treatment-resistant schizophrenia. Our main objective was to examine the current level of BEN recognition in a cohort of patients treated with clozapine and the potential impact of unidentified BEN on the initiation and maintenance of clozapine treatment. METHODS: This was an observational, retrospective analysis of patients registered with clozapine haematological monitoring systems in two large mental health trusts, chosen because they serve an ethnically diverse population. The first objective was to establish certified BEN prevalence in current users of clozapine. The second objective was to explore the stage of treatment at which BEN was identified. The third objective was to evaluate the extent of unrecognised BEN in patients registered on the Central Non-Rechallenge Database (CNRD), a database for patients whose haematological parameters fall below set thresholds when receiving clozapine treatment, meaning they cannot ordinarily be prescribed clozapine again. RESULTS: The study population comprised of 2020 patients on the clozapine register. 111 patients were monitored under BEN criteria. BEN was mostly identified after a below threshold haematological result or clozapine rechallenge (68%) compared to at clozapine initiation (32%). Eight of the 18 (42%) black patients registered on the CNRD were classified as BEN after assessment by a haematologist. Of these 8 patients, none would have met CNRD criteria again if monitored with BEN criteria at clozapine initiation. CONCLUSIONS: Current evidence suggests that BEN remains an uncommonly recognised haematological phenotype. Improved timely identification of BEN will reduce unnecessary interruption or discontinuation of clozapine treatment. Our results suggest consideration should also be given to determining BEN status prior to initiating clozapine. Moreover, adoption of current FDA BEN monitoring criteria in the UK may further reduce clozapine discontinuation due to perceived neutropenia as drug toxicity, particularly in treatment-refractory schizophrenia patients.

A retrospective study of intramuscular clozapine prescription for treatment initiation and maintenance in treatment-resistant psychosis.

BACKGROUND: Clozapine is uniquely effective in treatment-resistant psychosis but remains underutilised, partly owing to psychotic symptoms leading to non-adherence to oral medication. An intramuscular formulation is available in the UK but outcomes remain unexplored. AIMS: This was a retrospective clinical effectiveness study of intramuscular clozapine prescription for treatment initiation and maintenance in treatment-resistant psychosis over a 3-year period. METHOD: Successful initiation of oral clozapine after intramuscular prescription was the primary outcome. Secondary outcomes included all-cause clozapine discontinuation 2 years following initiation, and 1 year after discharge. Discontinuation rates were compared with a cohort prescribed only oral clozapine. Propensity scores were used to address confounding by indication. RESULTS: Among 39 patients prescribed intramuscular clozapine, 19 received at least one injection, whereas 20 accepted oral clozapine when given an enforced choice between the two. Thirty-six (92%) patients successfully initiated oral clozapine after intramuscular prescription; three never transitioned to oral. Eight discontinued oral clozapine during the 2-year follow-up, compared with 83 out of 162 in the comparator group (discontinuation rates of 24% and 50%, respectively). Discontinuation rates at 1-year post-discharge were 21%, compared with 44% in the comparison group. Intramuscular clozapine prescription was associated with a non-significantly lower hazard of discontinuation 2 years after initiation (hazard ratio 0.39, 95% CI 0.14-1.06) and 1 year after discharge (hazard ratio 0.37, 95% CI 0.11-1.24). The only reported adverse event specific to the intramuscular formulation was injection site pain and swelling. CONCLUSIONS: Intramuscular clozapine prescription allowed transition to oral maintenance in an initially non-adherent cohort. Discontinuation rates were similar to patients only prescribed oral clozapine and comparable to existing literature.

Clozapine and Norclozapine Plasma Levels in Patients Switched Between Different Liquid Formulations.

BACKGROUND AND OBJECTIVE: Clozapine is the drug of choice for treatment-resistant schizophrenia. The primary objective of this study was to compare plasma clozapine and N-desmethylclozapine levels in patients switched between 2 liquid formulations [Denzapine suspension and clozapine oral solution (St George's ZTAS)]. Secondary objectives included comparison of safety, tolerability, and patient acceptability. METHODS: This was a noninterventional, observational, prospective follow-up of patients consecutively switched between formulations of clozapine liquid in a large inner-city NHS mental health trust. The authors also performed retrospective analysis of outcomes from patient case notes. RESULTS: The authors identified 43 patients receiving Denzapine suspension in the trust. Data were available for 43 patients switched from Denzapine to clozapine oral solution (St George's ZTAS), among whom, 15 (32%) were excluded from the analysis. Of the 28 patients for whom data were available, the 90% confidence interval for the ratio of mean values for corrected Cmin 91.5 (85.2%-98.4%) and uncorrected Cmin 91.2 (84.4%-98.6%) were within the guideline range of bioequivalence (80%-125%). Safety and tolerability profiles were comparable between the 2 formulations (P = 0.10). Patient acceptability was also similar between the brands in most domains. However, there was a taste preference for Denzapine suspension. CONCLUSIONS: No significant difference in clozapine plasma levels was observed after switching from Denzapine suspension to a recently introduced clozapine solution. This study also highlights the significance of medicinal characteristics such as taste for patient acceptability and compliance.

Hearts and Minds: Real-Life Cardiotoxicity With Clozapine in Psychosis.

BACKGROUND: Schizophrenia has a 1% prevalence in the population; 30% of these patients are treatment refractory. Clozapine is the only drug licensed to treat treatment refractory psychosis, but concerns about potential adverse effects result in only a proportion of eligible patients being treated. Although a well-documented neutropenia risk is mitigated by routine blood testing, cardiac toxicity is a commonly cited reason to discontinue clozapine treatment. However, there is little data on the real-life cardiac outcomes in those receiving clozapine treatment. METHODS: Retrospective review of electrocardiogram, echocardiogram, and clinical outcomes in 39 inpatients with treatment-refractory schizophrenia, treated with clozapine and other antipsychotic medication, referred for cardiology opinion. RESULTS: Commonest reasons for referral were development of left ventricular (LV) impairment or sinus tachycardia with normal LV function. Patients were reviewed by a range of cardiologists, receiving varied interventions.Median LV ejection fraction in the clozapine group was normal (52%). Serial echocardiograms demonstrated that clozapine-treated patients with LV impairment had no change in LV ejection fraction over a 4-month follow-up. Left ventricular ejection fraction did not differ between patients treated with clozapine and other antipsychotics. However, over an 11-year follow-up period, 48% of patients had discontinued clozapine treatment. CONCLUSIONS: This naturalistic study demonstrates that clozapine is not associated with significant cardiac mortality or morbidity. There is a real need for multidisciplinary working between specialist cardiologists and psychiatrists caring for these complex patients to facilitate optimal long-term physical and mental health outcomes.

The Use of Granulocyte Colony-Stimulating Factor in Clozapine Rechallenge: A Systematic Review.

PURPOSE/BACKGROUND: Clozapine is associated with hematological abnormalities, with neutropenia and agranulocytosis of most concern. Granulocyte colony-stimulating factor (G-CSF) has been used to support clozapine rechallenge after neutropenia with the aim of maintaining the neutrophil count. This study aims to explore the practice, use, safety, and efficacy of G-CSF in this context. METHODS/PROCEDURES: We conducted a systematic review to identify all studies investigating or describing G-CSF as a prophylaxis to enable continued clozapine treatment during a rechallenge. FINDINGS/RESULTS: We identified 32 reports of patients who received G-CSF either regularly (n = 23) or as required (n = 9) to support clozapine rechallenge after an episode of neutropenia necessitating discontinuation of clozapine. Seventy-five percent (n = 24) of published cases remained on clozapine with the use of continual prophylactic G-CSF or after single G-CSF administrations (n = 8). Seventy percent (n = 16) of patients in receipt of continual prophylactic G-CSF were successfully maintained on clozapine. However, 1 of the 3 episodes of rechallenge in those with a history of severe agranulocytosis (absolute neutrophil count <0.1 × 10/L) had a recurrence of agranulocytosis at week 9. IMPLICATIONS/CONCLUSIONS: Our findings suggest that G-CSF can sometimes be safely used to support the maintenance of normal neutrophil counts and clozapine use after neutropenia. Publication bias is an important limitation, however. Also, few reports clearly documented the presence or absence of an independent nonclozapine cause of the index neutropenia, which may have increased success rates. Furthermore, adverse events were not systematically recorded. Prospective studies are needed to determine safety because if agranulocytosis occurs on clozapine while supported by G-CSF, there is no obvious alternate rescue therapy to promote granulopoiesis. From the available data, it is not possible to recommend this course of action for someone with a true clozapine agranulocytosis.

Clozapine-Associated Agranulocytosis Treatment With Granulocyte Colony-Stimulating Factor/Granulocyte-Macrophage Colony-Stimulating Factor: A Systematic Review.

PURPOSE/BACKGROUND: Clozapine is associated with hematological abnormalities, notably neutropenia, which may progress to agranulocytosis. Granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) have been used to reduce the frequency and duration of clozapine-associated neutropenia. This review aims to explore the use, efficacy, and tolerability of these cytokines in the treatment of clozapine-associated agranulocytosis. METHODS/PROCEDURES: We conducted a systematic review of published interventional and observational studies, case series, and case reports where G-CSF/GM-CSF was used to treat clozapine-associated agranulocytosis. FINDINGS/RESULTS: We identified 29 reports (40 patients). The median duration of neutrophil recovery time after stopping clozapine and starting cytokine treatment was 7 days (range, 2-13 days) for those with agranulocytosis (absolute neutrophil count < 0.5 × 10 cells/L). Ninety-four percent (n = 29) had no serious adverse reactions, and no deaths occurred. IMPLICATIONS/CONCLUSIONS: Our findings indicate that G-CSF/GM-CSF use is well tolerated and suggest that G-CSF can sometimes be safely used to reduce the duration of neutropenia associated with clozapine use. However, the interpretation of this outcome is difficult, given the likely publication bias for positive outcomes in case reports.

Understanding clozapine-related blood dyscrasias. Developments, genetics, ethnicity and disparity: it's a CIN.

Clozapine remains the gold standard intervention for treatment-resistant schizophrenia; however, it remains underused, especially for some minority groups. A significant impediment is concern about propensity to neutropenia. The aim of this article is to provide an update on current knowledge relating to: the pattern and incidence of severe blood dyscrasias; the effectiveness of current monitoring regimes in reducing harm; the mechanisms of and the distinctions between clozapine-induced neutropenia and agranulocytosis; benign ethnic neutropenia; and changes to the monitoring thresholds in the USA and other international variations. These all have implications for the practical use of clozapine; specifically, how barriers to initiating, maintaining and restarting clozapine can be understood and in many cases overcome, especially for patients from minority groups, potentially with simpler approaches than the use of lithium or G-CSF.

New approaches to antipsychotic medication adherence - safety, tolerability and acceptability.

INTRODUCTION: Antipsychotic pharmacotherapy is considered a first-line treatment in schizophrenia-related disorders and is associated with favorable prognosis and lower mortality rates. However, low adherence rates present a major clinical challenge. In this paper, we will review contemporary approaches to improve adherence to antipsychotic treatment, considering their mechanism of action, safety, tolerability and acceptability. AREAS COVERED: Novel pharmacological delivery methods included different routes of administration of registered medications (such as intramuscular clozapine preparation and transdermal asenapine), modifications of existing compounds (such as 3-monthly injectable formulation of paliperidone palmitate), and increased interest in oral long-acting medication formulations (such as with penfluridol). In addition, we reviewed innovative technology to monitor adherence, based on the use of electronic digital medicine systems and ingestible sensors. EXPERT OPINION: All of these diverse approaches were clinically relevant in enhancing treatment adherence and found to be safe and tolerable. The place of each approach is predicated on a personalized approach in each patient, and future research could usefully use large comparative studies to establish robust treatment guidelines. The implementation of new and varied approaches to antipsychotic treatment adherence is welcomed and have the potential to make a significant impact on morbidity in this often difficult-to-treat population.

Distinctive pattern of neutrophil count change in clozapine-associated, life-threatening agranulocytosis.

The wider use of clozapine is limited by the risk of agranulocytosis and the associated requirement for monitoring of neutrophil counts. We searched local electronic patient records for cases of agranulocytosis occurring during clozapine treatment during the period 2007-2020. We found 23 episodes recorded as agranulocytosis in clozapine patients. Of these, nine met pre-defined criteria and were considered episodes of life-threatening agranulocytosis (LTA). These episodes of clozapine-induced LTA exhibited a distinct pattern of continuous and rapid neutrophil count decline to zero or near zero. Mean time for neutrophils to fall from ANC > 2 to ANC <0.5 × 109/L was 8.4 days (range 2-15 days). Each event was also characterised by a prolonged nadir and delayed recovery (range 4-16 days). Non-LTA episodes were, in contrast, brief and benign. We conclude that an important proportion of cases of agranulocytosis identified in people prescribed clozapine are not life-threatening and may not even be clozapine-related. Monitoring schemes should aim to identify true clozapine-induced LTA as opposed to threshold-defined nominal agranulocytosis. Genetics studies might benefit from examining associations with clozapine-induced LTA rather than with recorded cases of agranulocytosis or neutropenia.

Clozapine augmentation with cariprazine for negative symptoms: a case series and literature review.

Only about 50% of patients with treatment-resistant schizophrenia respond to clozapine, and many more patients continue to experience ongoing and prominent negative symptoms. These negative symptoms, for which there are limited pharmacological options, may represent the greatest barrier to functional recovery. Cariprazine is a novel antipsychotic drug that is a partial agonist at dopamine D2 and D3 receptors with preferential binding to the D3 receptor, antagonism of 5HT2B receptors, and partial agonism at 5HT1A receptors. Cariprazine is currently licenced for the treatment of schizophrenia in Europe and the United States and has also been approved for bipolar disorder in the United States. There is a limited body of evidence to suggest clinical effectiveness as an augmentation strategy for negative symptoms in those treated with clozapine. In this case series, we present five cases of successful treatment of negative symptoms by clozapine combined with cariprazine in treatment-resistant psychosis.

Relaxation of the criteria for entry to the UK Clozapine Central Non-Rechallenge Database: a modelling study.

BACKGROUND: Clozapine is uniquely effective in treatment-resistant psychosis. In the UK, patients must discontinue clozapine indefinitely if they are placed on the Central Non-Rechallenge Database (CNRD) after their haematological parameters fall below particular thresholds. Under exceptional circumstances, patients can be rechallenged on clozapine under an off-licence agreement. In the USA in 2015, restrictive practice was discontinued to allow greater flexibility for clozapine maintenance. The absolute neutrophil count leading to treatment interruption was lowered from less than 1·5 × 109/L to less than 1·0 × 109/L and platelet and white cell count monitoring were ceased. We aimed to investigate the implications of a similar policy change on clozapine use in the UK. METHODS: This was a modelling study of all patients registered on the UK CNRD. First, we determined the proportion of patients placed on the database in the UK who would have had to discontinue clozapine treatment under the US Food and Drug Administration (FDA) criteria. Second, we compared the haematological characteristics of patients who did or did not meet FDA criteria for discontinuing clozapine, including the time to registration from clozapine initiation and the proportion of cases of severe neutropenia at registration. Third, we investigated the success rates of clozapine re-challenge for patients that had been placed on the CNRD. Successful rechallenge was defined as no recurrence of CNRD registration. FINDINGS: Between May 2, 2002 and March 1, 2021, 3731 patients were placed on the CNRD, with a mean age of 47 years (SD 15), including 1420 (38%) women and 2311 (62%) men, of whom 3089 (83%) were White, 360 (10%) were Black, 190 (5%) were Asian, and 92 (2%) were classified as other. 566 (15%) of 3731 patients met the equivalent criteria for clozapine discontinuation under the FDA guidelines. The median time to CNRD registration from clozapine initiation was 1·6 years (IQR 0·2-4·9). Data for 519 rechallenged patients were examined; 419 (81%) were successful. Clozapine rechallenge success rates were broadly similar between individuals who did not meet the US CNRD registration criteria (36 [78%] of 46) and those who did meet the criteria (383 [81%] of 473). INTERPRETATION: Implementing the revised FDA monitoring criteria in the UK would substantially reduce clozapine discontinuation for haematological reasons, which would greatly improve the mental health outcomes of these patients without having a major effect on their physical health. FUNDING: None.

Evaluation of the effectiveness and acceptability of the long-acting oral antipsychotic penfluridol: Illustrative case series.

AIM: In this study, we sought to determine clinical outcomes at 1 year for patients prescribed penfluridol in an inner London National Health Service Trust. Using noninterventional data, we describe the use, effectiveness and safety of this treatment modality. RESULTS: We retrospectively followed up 17 patients prescribed penfluridol as part of routine clinical practice. All patients took penfluridol once weekly. Of these patients, 12 (70.6%) were considered treatment resistant. The average duration of illness for this cohort was 10 years (SD = 6.7). At 1 year, nine (53%) patients remained on treatment. Median survival time was not reached at 1-year follow-up; mean time on penfluridol was 251 days (95% confidence interval (CI), 184-318). The mean number of admissions to hospital in the year following penfluridol initiation was 0.6 compared with 0.8, 1 year before initiation (p = 0.465). The median number of bed days 1 year before penfluridol initiation was 24, whereas in the year following penfluridol initiation, it was 0 (p = 0.514). CLINICAL IMPLICATIONS: Although penfluridol is unlicensed in the United Kingdom, limited data suggest that this long-acting oral therapy has the potential to be used safely and effectively for the treatment of psychotic disorders. However, more data are required to establish the place of penfluridol and other potential long-acting oral antipsychotic formulations in the treatment of psychotic disorders.

Vortioxetine as adjunctive therapy in the treatment of schizophrenia.

Background: The evidence for safe and effective interventions to treat the negative and cognitive symptoms of schizophrenia is lacking. Objectives: Vortioxetine is a novel antidepressant that has been used as adjunctive therapy for the treatment of psychosis; however, its effectiveness in clinical practice is relatively unknown. In this study, we aimed to determine the potential clinical effectiveness and safety and tolerability of vortioxetine in psychosis. Design: This is a non-interventional, retrospective study on the add-on use of vortioxetine in a group of people with schizophrenia-spectrum disorders in a large UK NHS mental health trust. Methods: Clinical effectiveness of vortioxetine was retrospectively assessed through the Clinical Global Impression - Severity (CGI-S) scale at 3 months. Safety and tolerability were evaluated through treatment discontinuation rates at 3, 6, and 12 months, and clinical reasons were evaluated at the primary endpoint of 3 months. Results: Data were available for 40 subjects with a diagnosis of schizophrenia or schizoaffective disorder-prescribed vortioxetine treatment; 30 (75%) remained on treatment at 3 months. At CGI-S assessment, 15 of the 35 evaluated subjects reported at least a 1-point improvement, from 5 at baseline to 4 after 3 months of treatment. Twenty-six (65%) remained on treatment at 1-year follow-up. The main reasons for those discontinuing treatment were inadequate response (10%) and manic switch (7.5%), while one subject refused treatment. Tolerability to treatment was good, and 36 subjects (90%) reported no adverse events specific to vortioxetine treatment. Conclusion: Schizophrenia is a complex illness, and there is insufficient treatment response in many individuals. A significant proportion of whom may require adjunctive treatments depending on the nature of the residual symptoms. Vortioxetine could be a potentially safe and effective option in such people, but further controlled studies are required.