Latest news with #clozapine
Medscape
4 days ago
- Health
- Medscape
Clozapine Shows Better Results in Schizoaffective Disorder
TOPLINE: A real-world trial showed that in adults with dual psychosis, clozapine was effective in alleviating psychotic and affective symptoms, with better outcomes being observed in schizoaffective disorder (SZD) than in treatment-resistant schizophrenia (TRS). METHODOLOGY: Researchers conducted a prospective, pragmatic clinical trial from 2021 to 2024 in Spain and included 127 participants with refractory psychosis (mean age, 38.5 years; 74.8% men). Participants were divided into three arms: those with TRS receiving clozapine (TRS-clozapine; n = 43), those with TRS receiving optimised standard antipsychotics (TRS-control; n = 42), and those with SZD receiving clozapine (SZD-clozapine; n = 42; non-randomised due to low prevalence). Monthly assessments over 3 months included the use of the Positive and Negative Syndrome Scale (PANSS), Young Mania Rating Scale (YMRS), Montgomery-Åsberg Depression Rating Scale (MADRS), Calgary Depression Scale for Schizophrenia (CDSS), Clinical Global Impression (CGI) scale, and Udvalg für Kliniske Undersogelser (UKU) scale. Researchers evaluated the efficacy of clozapine in patients with TRS, the effect of clozapine on real-world SZD psychotic and affective symptoms, and the response and tolerability to clozapine in patients with TRS vs SZD. TAKEAWAY: Compared with the TRS-control group, the TRS-clozapine group had greater 3-month reductions in PANSS positive, negative, and total (P/N/T) scores (P < .001 for all) and CDSS (P < .001), CGI (P < .001), and MADRS (P = .003) scores, whereas the SZD-clozapine group showed rapid, significant improvements in psychotic scale scores (PANSS-P, P = .027; PANSS-N, P = .002; and PANSS-T, P = .005) and YMRS, MADRS, and CDSS scores (P < .001 for all) from month 1 to month 3. The SZD-clozapine group showed greater reductions in the following scores than the TRS‐clozapine group at 3 months: PANSS-P (-23.4 vs -19.3), PANSS-T (-68.7 vs -63.0), YMRS (-15.3 vs -4.9), MADRS (-8.4 vs -6.0), and CDSS (-5.4 vs -4.1). Patients receiving clozapine reported better subjective treatment perception (P < .01) and required fewer adjunct antipsychotics and sedatives, and clozapine emerged as the sole independent predictor of superior symptom and substance use outcomes. Clozapine was well tolerated in both groups, with no serious treatment-related adverse events. Mild drowsiness or asthenia was observed, which was managed by lowering co-medication doses. UKU side effect scores also reduced from month 2 onwards. IN PRACTICE: "[The study] findings have direct clinical implications, reinforcing the evidence supporting the use of CLZ [clozapine] in dual psychosis and expanding therapeutic options for SZD," the authors wrote. "Moving forward, efforts to improve clozapine use should focus on enhancing clinician education, standardising knowledge sources and promoting best practices in its management. Additionally, the development of well-designed long-term studies will be essential," they added. SOURCE: This study was led by Marc Peraire, Consorci Hospitalari Provincial de Castelló, Castellón de la Plana, Spain. It was published online on August 1 in the Journal of Psychopharmacology. LIMITATIONS: This study was limited by incomplete patient histories and the absence of antisuicidal efficacy measures. Additional constraints were the lack of comparison between dual-disorder and pure psychosis cohorts, unstable diagnostic labels, gender imbalance, a single-site design, potential overfitting in regression models, and a relatively short follow-up period. DISCLOSURES: This study received financial support from the Research Foundation of the Provincial Hospital of Castellón. The authors reported having no conflicts of interest. This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
Medscape
01-08-2025
- Health
- Medscape
SSRIs and SNRIs Boost Clozapine Treatment Response
TOPLINE: Standard doses of selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) reduced the risk for relapse when added to clozapine in treatment-resistant schizophrenia, unlike other antidepressants, according to a new study. Sertraline, duloxetine, and escitalopram were particularly effective, and high-dose antidepressant use increased both psychiatric and somatic hospital admission risks. METHODOLOGY: Researchers analysed and then meta-analysed data from two register-based, nationwide cohort studies in Finland (1996-2017) and Sweden (2006-2023) and included 23,206 patients with schizophrenia (mean age, 41.3 years; 9531 women) who were followed up from first clozapine use until death or the end of data linkage. This study had a within-individual cohort design in which each person served as their own control and compared clozapine augmentation with specific antidepressants against clozapine use alone. Researchers categorised antidepressant use into four dose categories: low (< 0.6 defined daily doses [DDDs] per day), standard (0.6 to < 1.1 DDDs per day), medium-high (1.1 to < 2.1 DDDs per day), and high (≥ 2.1 DDDs per day), with specific milligrams per day ranges for each medication. The primary outcome was schizophrenia relapse, defined as hospital admission with psychotic disorder; the secondary outcome was somatic hospital admission. The mean follow-up duration was 12.1 years for the Finnish cohort and 11.4 years for the Swedish cohort. TAKEAWAY: A total of 65.8% of patients in the Finnish cohort and 51.0% in the Swedish cohort had a relapse during follow-up. Additionally, 52.6% of patients in the Finnish cohort and 41.2% in the Swedish cohort experienced hospital admission because of somatic reasons during follow-up. The lowest risk for relapse was observed with sertraline (adjusted hazard ratio [aHR], 0.76), followed by duloxetine (aHR, 0.78) and escitalopram (aHR, 0.85; P < .001 for all). Antidepressants other than SSRIs and SNRIs were associated with an increased risk for relapse without achieving statistical significance. Standard doses showed optimal effectiveness, with sertraline 30-54 mg/d (aHR, 0.49; 95% CI, 0.27-0.89), escitalopram 6-10 mg/d (aHR, 0.57; 95% CI, 0.37-0.88), and duloxetine 18-32 mg/d (aHR, 0.59; 95% CI, 0.46-0.75) showing the lowest risk for relapse. Augmentation with antidepressants was not associated with an increased risk for somatic hospital admission at low or standard doses; however, high-dose use was linked to elevated risks for both relapse and somatic hospital admission. IN PRACTICE: "[The study] findings support the use of SSRIs and SNRIs as viable augmentation strategies for clozapine-treated patients with schizophrenia, particularly at standard doses," the authors wrote. "The same finding was not observed with other, non-SSRI and non-SNRI antidepressants," they added. "The findings have important clinical implications, emphasising the potential utility of antidepressant augmentation in specific subgroups of patients with TRS [treatment-resistant schizophrenia], such as those with persistent negative symptoms, comorbid depression, or suicidal ideation. Given the increased risks associated with high-dose antidepressant use, clinicians should carefully balance the potential benefits with the risk of adverse outcomes," they concluded. SOURCE: This study was led by Heidi Taipale, PhD, University of Eastern Finland, Niuvanniemi Hospital, Kuopio, Finland. It was published online in the August 2025 issue of The Lancet Psychiatry. LIMITATIONS: This study was limited by its observational design, the lack of randomisation, and the low number of users for some exposures. This study lacked information on why antidepressants were started or stopped, symptom severity fluctuations, social support or non-pharmacologic interventions, and confirmation of treatment resistance. Additionally, dose categorisation on the basis of DDDs was not optimal for some drugs. Schizophrenia relapse was broadly defined as hospital admission with psychotic disorder without symptom specificity, and major depressive disorder was rarely recorded. Furthermore, the findings were limited to long-term risks in low-cost healthcare settings, and people with lived experience were not involved. DISCLOSURES: This study received funding from the Sigrid Jusélius Foundation and the Finnish Ministry of Social Affairs and Health. This project used data from the REWHARD consortium supported by the Swedish Research Council. Several authors reported having financial ties with various sources including pharmaceutical companies. Details are provided in the original article. This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
Medscape
14-07-2025
- Health
- Medscape
EU to Ease Clozapine Monitoring Frequency After First Year
The European Medicines Agency's (EMA) Pharmacovigilance Risk Assessment Committee has recommended easing routine blood count monitoring for patients on clozapine, citing new data that show that the risk for severe neutropenia and agranulocytosis declines significantly after the first year of treatment. Under the updated guidelines, monitoring for patients without a history of neutropenia can be reduced to once every 12 weeks after the first year, and to once annually after 2 years. In addition, absolute neutrophil count (ANC) will now be the sole parameter used for hematologic monitoring, replacing the previous requirement to also measure white blood cell count. The revised recommendations are supported by a joint expert statement from the European Clozapine Task Force, published this year, which called for changes to the monitoring protocol due to the very low incidence of late-onset agranulocytosis. Additional evidence comes from a large-scale study involving more than 26,000 patients, which found that clozapine-induced severe neutropenia peaked around week 9 (0.128% weekly incidence) and declined sharply after week 18, with rates becoming negligible — 0.001% per week — after 2 years of continuous use. Mechanism and Risk Profile Clozapine is an atypical antipsychotic indicated for treatment-resistant schizophrenia and for patients who cannot tolerate other antipsychotics due to neurologic side effects. It is also used to manage psychosis associated with Parkinson's disease when standard treatments fail. Clozapine works by antagonizing dopamine D2 and serotonin 5-HT2A receptors, contributing to its unique efficacy in refractory schizophrenia. However, it carries a known risk for drug-induced neutropenia and its most severe form, agranulocytosis. Research suggests that a reactive metabolite of clozapine, the nitrenium ion, may bind to neutrophil proteins. This complex is then thought to act as a hapten, triggering an immune response that leads to the destruction of neutrophils, a process for which certain individuals may have a genetic predisposition. All clozapine-containing products in the European Union will be updated to reflect the new ANC-based monitoring schedule and thresholds for treatment initiation and continuation. The direct healthcare professional communication will be distributed by the marketing authorization holders in coordination with national authorities, and published on EMA and national regulatory websites. Clinicians are encouraged to review and update monitoring protocols accordingly and continue reporting suspected adverse events through established pharmacovigilance channels.
Medscape
14-07-2025
- Health
- Medscape
New Clozapine Consensus Guidelines Drop ANC Monitoring
Monitoring absolute neutrophil count (ANC) levels beyond 2 years of clozapine treatment is no longer necessary, new international guidelines stated. While low ANC levels — associated with severe neutropenia — pose a significant risk early in treatment, evidence shows that the risk drops substantially over time. Still, many patients continue to undergo routine blood tests well beyond the high-risk period, lead guideline author Dan Siskind, MD, PhD, professor of psychiatry, The University of Queensland, Brisbane, Australia, told Medscape Medical News. 'What we're saying is that after 2 years of monitoring, you can stop doing blood tests to monitor ANC levels, which is a massive change,' he added. The expert panel also provides detailed suggestions for monitoring other adverse drug reactions (ADRs) related to clozapine, including constipation and sialorrhea. And the group recommends an ANC of 1.0 × 109 cells/L as a threshold at which to consider stopping clozapine. The guidelines were published online on July 2, 2025 in Lancet Psychiatry . An Underutilized Treatment Clozapine is the only FDA-approved drug for treatment-resistant schizophrenia. An estimated 814,000 to 1.2 million Americans have this condition. Although clozapine is widely regarded as a superior antipsychotic, many clinicians remain hesitant to prescribe it due to concerns about ADRs — most notably, severe neutropenia, in which dangerously low neutrophil levels increase the risk for infection and even death. Despite estimates that 25%-30% of Americans with schizophrenia could benefit from clozapine, only about 4% receive it. The concern over severe neutropenia has led to stringent ANC monitoring protocols in some jurisdictions. Until recently, a risk evaluation and mitigation strategies (REMS) program in the US required physicians and pharmacists to provide documentation of a patient's ANC. However, after lobbying by relevant professional organizations including the American Psychiatric Association (APA), which argued the program poses unnecessary barriers to accessing a potentially life-saving medication, the FDA made the decision to discontinue the REMS program. Some experts insist the risk for severe neutropenia is low in patients taking clozapine. As previously reported by Medscape Medical News a study presented at the 2024 APA annual meeting showed the risk for moderate-to-severe neutropenia is low to minimal in patients with treatment-resistant schizophrenia. Siskind agreed. He points to other research showing the rate of severe neutropenia at initiation of clozapine is around 0.9%, but after peaking, the risk then 'drops over time' and after about 18 weeks, 'it's very low, and after about 2 years, it's negligible.' Yet patients who have been on clozapine for 10 years still receive blood tests every 4 weeks. 'We felt that's probably low value healthcare that creates impediments to people on clozapine,' said Siskind. No Current Consensus The guideline authors noted there's currently no international consensus on ANC thresholds for considering clozapine cessation. In some jurisdictions, an ANC of fewer than about 2.0 × 109 cells/L is the threshold but in other areas, the threshold is 1.5 × 109 cells/L. And when the REMS program was initiated, it set a lower ANC threshold (1.0 × 109 cells/L), which is in-line with that commonly used in hematology. 'What we're calling for is a global consensus; there should be one threshold,' said Siskind. Aside from neutropenia, there is a host of other clozapine-related ADRs, many of which are under-reported and some can be lethal. The consensus guidelines were developed using a global Delphi process. A steering committee — including a hematologist with expertise in clozapine-associated severe neutropenia — designed a questionnaire focused on ANC and ADR monitoring. The questionnaire was distributed to an international expert panel comprising psychiatrists and pharmacists. Recommendations were formulated based on their responses, with consensus defined as at least 75% agreement. The experts developed a clozapine monitoring algorithm that includes: Weekly ANC monitoring for the first 18 weeks after initiation Monthly monitoring from week 19 through year 2 Annual complete blood counts thereafter to screen for hematologic malignancies The algorithm includes a recommended ANC cessation threshold of 1.0 × 109 cells/L — or 0.5 × 109 cells/L for individuals with benign ethnic neutropenia who are Duffy antigen receptor for chemokines-null. In addition to clozapine, the new guidance advises clinicians to consider other potential causes of a low ANC, said Siskind. 'If it's 2 weeks after starting clozapine and there's a sudden, precipitous drop, it's likely related to the medication,' he explained. 'But if it's 18 months after initiation and you see a drop in neutrophil count, it's probably due to something else — and worth investigating.' Other causes of transient neutropenia could be chemotherapy treatment or a concomitant infection, he added. Side Effect Checklist Panel members developed a detailed checklist for regular and comprehensive ADR monitoring. The checklist includes pharmacological and nonpharmacological recommendations for each ADR where present. For example, in the category of constipation, which Siskind said is 'the number one cause of mortality' in patients taking clozapine, the experts suggest asking patients about bowel movement frequency and presence of blood and pain, and using the Bristol Stool Chart to determine if there's a health issue. Given the high prevalence of gastrointestinal hypomotility, prophylactic laxatives are recommended, the panel said. Sialorrhea occurs in up to 92% of patients taking clozapine and this can cause pneumonia, which is the second highest cause of death in people on clozapine, said Siskind. Here, the panel noted pharmacological strategies could include adding amisulpride or ipratropium sublingual spray while chewing sugar-free gum or placing a towel over the pillow when sleeping. Panel members also provided management guidelines for weight gain and metabolic syndrome, gastro-esophageal reflux, sedation, sleep apnea, nocturnal enuresis and urinary incontinence, and tachycardia. The panel stressed ADR monitoring should occur in partnership with primary care physicians. Annual ECGs did not reach consensus for routine use, so the expert panel does not recommend them. They concluded that cardiomyopathy in clozapine patients is more likely related to comorbidities such as obesity, diabetes, and tachycardia. Removing Barriers to an Optimal Treatment Commenting on the new guidance for Medscape Medical News , Frederick Nucifora Jr, PhD, DO, associate professor, Department of Psychiatry, Johns Hopkins School of Medicine, and director of the clozapine clinic at Johns Hopkins Bayview Medical Center, Baltimore, said it is sensible, reasonable, and could help remove 'troubling' barriers to accessing clozapine. He welcomed the ADR monitoring suggestions as clozapine-related side effects can be life-threatening and are the reason patients don't stay on the drug. 'There's so much confusion around using clozapine and the side effects and how to address them that people don't use the medicine, so it's very useful to have something to help guide us,' he said. He said it's deeply unfortunate that clozapine remains underused, particularly given its status as the most effective treatment available. In his experience, the drug has had a transformative impact on his patients. To increase physician comfort in prescribing clozapine, Nucifora suggests creating centers of excellence that could offer consultations on using the drug. Also commenting for Medscape Medical News , Mahavir Agarwal, MD, PhD, associate professor, Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada who heads a clozapine clinic at the Centre for Addiction at Mental Health (CAMH), said the paper's 'mini flow chart' to manage side effects is a valuable tool for physicians to review with patients. He noted that the guideline authors are recognized leaders in the field and fully agrees that lifetime monitoring of ANC levels is likely unnecessary. Clozapine has had a huge impact on patients at the CAMH clinic, said Agarwal. 'Among our clientele are people who work full–time in very, very high-capacity roles; we have scientists, teachers, all manner of professions, who are able to lead meaningful lives after they found clozapine.' 'Other antipsychotics may do that, but the beauty of clozapine is that it can completely turn life around for somebody who has not responded to other antipsychotics.'
BBC News
26-05-2025
- Health
- BBC News
Mental health patient treated with clozapine via virtual ward
An NHS hospital trust has said it could be the first in England to have treated a patient with an anti-psychotic medication while monitoring them mental health trust for Cambridgeshire and Peterborough said it treated the patient for schizophrenia with the drug were being monitored via a so-called virtual ward, where clinicians in the hospital keep track of the patient while they are at Dr Rajeev Krishnadas said the patient was "doing very well". The treatment was the result of a partnership between the Cambridgeshire and Peterborough NHS Foundation Trust (CPFT) - which oversees mental health services in the area - and the North West Anglia NHS Foundation Trust (NWAFT).Dr Krishnadas, from CPFT, said clozapine was "hugely under-prescribed" because it was usually difficult to monitor the patient after they had begun treatment."If this initial project continues to be a success, even more people will be able to access clozapine and get the help and support they need," he Deyo Okubadejo, clinical director for virtual wards at NWAFT, said: "This may also release some capacity for other patients who require urgent admission to a mental health ward from home or from an emergency department." Mixed success Virtual wards make use of video and other technology, such as wearable a patient receiving clozapine would need to stay in scheme was first trialled at Peterborough City Hospital in Health Foundation charity has pointed to the mixed success of virtual wards, with some areas struggling to access the right technology and one study finding that these "beds" could cost twice as much as a real hospital NHS describes psychosis as when people lose some contact with might involve seeing or hearing things that other people cannot see or hear – hallucinations - and believing things that are not actually true, known as delusions. Follow Peterborough news on BBC Sounds, Facebook, Instagram and X.
