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MMW Fortschritte Der Medizin May 2022
Review
Topics: Antipsychotic Agents; Humans; Schizophrenia
PubMed: 35585398
DOI: 10.1007/s15006-022-1194-3 -
The Lancet. Psychiatry Dec 2023TV-46000 is a long-acting, subcutaneous, antipsychotic agent that combines risperidone and an innovative, copolymer-based drug delivery technology in a suspension that... (Randomized Controlled Trial)
Randomized Controlled Trial
Efficacy and safety of TV-46000, a long-acting, subcutaneous, injectable formulation of risperidone, for schizophrenia: a randomised clinical trial in the USA and Bulgaria.
BACKGROUND
TV-46000 is a long-acting, subcutaneous, antipsychotic agent that combines risperidone and an innovative, copolymer-based drug delivery technology in a suspension that was approved in April, 2023 for subcutaneous use. The aim of the phase 3 Risperidone Subcutaneous Extended-release (RISE) study was to evaluate the efficacy of TV‑46000 in schizophrenia.
METHODS
The RISE study consisted of two treatment stages: a 12-week, open-label stabilisation phase with oral risperidone (stage 1), and an open-ended, randomised, double-blind, placebo-controlled, relapse-prevention phase with subcutaneous TV-46000 (stage 2) done at 69 clinical sites across the USA and Bulgaria. Patients diagnosed with schizophrenia more than 1 year before screening by DSM-5 criteria and confirmed at screening by the Structured Clinical Interview for DSM-5 and who had at least one relapse within 24 months before screening were eligible for enrolment. Patients who were outpatients and stabilised in stage 1 continued to stage 2 and were randomly assigned 1:1:1 by a computer-generated randomisation list to receive either subcutaneous TV-46000 once monthly, TV-46000 once every 2 months, or placebo until relapse, early discontinuation, or the study was stopped because the prespecified stopping criterion of at least 90 relapse events was met. The primary endpoint was time to impending relapse of the intention-to-treat patient population in stage 2. This study is registered with ClinicalTrials.gov, number NCT03503318, and is complete.
FINDINGS
The study enrolled the first patient on June 1, 2018, and the last patient completed on Dec 3, 2020. 1267 patients were screened, 863 enrolled, and 544 (male, n=332 [61%], female, n=212 [39%]; mean [SD] age, 49·3 [10·98] years; Black or African American, n=322 [59%]; White, n=206 [38%]; Asian, n=7 [1%]; Native Hawaiian or other Pacific Islander, n=2 [<1%]; race not reported, n=3 [<1%]; other race, n=4 [<1%]; Hispanic or Latinx, n=117 [22%]) randomly assigned to subcutaneous TV-46000 once monthly (n=183), TV-46000 once every 2 months (n=180), or placebo (n=181). Time to impending relapse was significantly prolonged by 5·0 times with TV-46000 once monthly (hazard ratio, 0·200 [95% CI 0·109-0·367]; p<0·0001) and by 2·7 times with TV-46000 once every 2 months (0·375 [0·227-0·618]; p<0·0001) versus placebo. Most frequently reported treatment-related adverse events (ie, ≥5% of patients in either TV-46000 group) that occurred more often in patients receiving TV-46000 (once monthly or once every 2 months) versus placebo were injection site nodules (7% for TV-46000 once monthly, 7% for TV-46000 once every 2 months, 3% for placebo), weight increased (4%, 6%, 2%, respectively), and extrapyramidal disorder (5%, 3%, 0% respectively). Serious adverse events were reported for eight (4%) patients in the TV-46000 once-monthly group, ten (6%) patients in the TV-46000 once-every-2-months group, and 14 (8%) patients in the placebo group. The safety profile of TV-46000 was consistent with other approved formulations of risperidone. No new safety signals were identified.
INTERPRETATION
In patients with schizophrenia, subcutaneous TV-46000 once monthly and once every 2 months significantly delayed impending relapse versus placebo. TV-46000 is an effective long-acting, subcutaneous, antipsychotic agent treatment option in adult patients with schizophrenia, with a favourable benefit-risk profile.
FUNDING
Teva Branded Pharmaceutical Products R&D.
Topics: Adult; Humans; Male; Female; Middle Aged; Risperidone; Schizophrenia; Antipsychotic Agents; Bulgaria; Treatment Outcome; Chronic Disease; Double-Blind Method; Recurrence
PubMed: 37924833
DOI: 10.1016/S2215-0366(23)00288-2 -
Der Nervenarzt Jan 2020Schizophrenia is a severe psychiatric disorder with variable therapeutic responses, the etiology and pathophysiology of which require further elucidation. (Review)
Review
BACKGROUND
Schizophrenia is a severe psychiatric disorder with variable therapeutic responses, the etiology and pathophysiology of which require further elucidation.
OBJECTIVE
To review which pharmacological options are effective and safe and for which treatment goals in schizophrenia.
MATERIAL AND METHODS
Narrative review of the pharmacological therapy of adults diagnosed with schizophrenia.
RESULTS
Despite heterogeneous therapeutic responses, to date only dopamine antagonists or partial agonists are approved for the treatment of schizophrenia. The efficacy of antipsychotic agents differs only gradually, with the exception of clozapine for treatment-resistant schizophrenia, whereas undesired adverse effects are more variable. Those antipsychotic agents that show gradual efficacy advantages in meta-analyses of acute and maintenance treatment (clozapine, amisulpride, olanzapine, risperidone) are also those where at least one undesired adverse effect is most severely expressed. Antipsychotic adverse effects occur in subgroups of patients and are generally tolerable or treatable, whereas the "side effect" of untreated schizophrenia affects almost all patients, including relapses, psychosocial deterioration, secondary treatment resistance and increased mortality. Therefore, in patients with a confirmed diagnosis of schizophrenia, a lifelong continuous therapy is currently most likely indicated, ideally with antipsychotic agents for which adherence is directly measurable and improved. In the case of treatment resistant clozapine is the agent of choice, followed by electroconvulsive therapy, which also has the best evidence as augmentation treatment in cases of clozapine resistance.
CONCLUSION
New therapeutic agents with improved efficacy and tolerability as well as effectiveness for negative symptoms and cognitive disturbance are needed.
Topics: Adult; Antipsychotic Agents; Clozapine; Humans; Olanzapine; Risperidone; Schizophrenia
PubMed: 31919550
DOI: 10.1007/s00115-019-00858-z -
The Psychiatric Quarterly Mar 2020The effect of antipsychotic medication is poor in 30-40% of patients with schizophrenia; treatment resistance is usually met with shifts to new drugs or drug... (Review)
Review
The effect of antipsychotic medication is poor in 30-40% of patients with schizophrenia; treatment resistance is usually met with shifts to new drugs or drug augmentation strategies or a trial of clozapine. The purpose of this review was to examine the potential role of intestinal bacteria in the bioavailability of antipsychotic medication and the possibility that parenterally administered antipsychotics might be able to overcome treatment resistance. Databases were searched with appropriate terms to locate relevant papers dealing with the effect of antipsychotic drugs on the gut microbiome and the effect of bacterial metabolizing enzymes on antipsychotic drugs. Also searched were papers addressing the various current parenteral formulations of antipsychotic drugs. Sixty-five recent pertinent papers were reviewed and the results are suggestive of the premise that there is a drug refractory form of psychosis for which the composition of gut bacteria is responsible, and that parenteral drug administration could overcome the problem.
Topics: Antipsychotic Agents; Gastrointestinal Microbiome; Humans; Psychotic Disorders; Schizophrenia
PubMed: 31781943
DOI: 10.1007/s11126-019-09695-4 -
MMW Fortschritte Der Medizin May 2024
Topics: Humans; Antipsychotic Agents; Dementia; Aged
PubMed: 38693357
DOI: 10.1007/s15006-024-3895-2 -
Ugeskrift For Laeger May 2024Long-acting injectable antipsychotics (LAI) is a frequently used treatment modality which has advantages over oral antipsychotics regarding hospitalization or relapse... (Review)
Review
Long-acting injectable antipsychotics (LAI) is a frequently used treatment modality which has advantages over oral antipsychotics regarding hospitalization or relapse prevention. However, the pharmacokinetic properties of LAI greatly differ from oral antipsychotics. This necessitates an increased knowledge about LAI among clinicians, especially when commencing treatment, changing doses and discontinuing treatment. In this review, we summarize an array of clinically important characteristics of LAI and give a conceptual framework for understanding the pharmacokinetics of LAI.
Topics: Humans; Antipsychotic Agents; Delayed-Action Preparations; Injections; Injections, Intramuscular
PubMed: 38808759
DOI: 10.61409/V12230776 -
The Journal of Clinical Psychiatry May 2024Schizophrenia is a major mental illness that is managed with long-term antipsychotic medication as a standard of care. Antipsychotic medications, however, are associated... (Review)
Review
Schizophrenia is a major mental illness that is managed with long-term antipsychotic medication as a standard of care. Antipsychotic medications, however, are associated with many subjective and objective adverse effects. These adverse effects have driven the study of risk-mitigation strategies such as targeted intermittent therapy and dose reduction and drug discontinuation. Randomized controlled trials (RCTs) of these strategies have been synthesized in meta-analysis; both strategies have been associated with no functional benefits and with an increased risk of relapse. The RCTs, however, have been criticized because, in many, patients were abruptly switched to the target dose or too rapidly tapered, thereby predisposing the RCT to failure of the intervention. Two important RCTs examined gradual individualized dose reduction and discontinuation. One, conducted in first-episode psychosis patients who were free from positive symptoms for 6 months, found that, at 18-month follow-up, dose reduction was associated with a higher risk of relapse (number needed to harm [NNH] = 5) and with no functional benefits. However, after return to routine clinical care, at a 7-year follow-up, the dose reduction group had better functional outcomes and similar clinical outcomes relative to the maintenance treatment group. The other RCT, conducted in patients with relapsing psychosis, found that, at a 2-year follow-up, dose reduction was associated with a higher risk of relapse (NNH = 5) and with no improvements in social, cognitive, quality of life, satisfaction, and other domains. Many large nationwide observational studies have found that antipsychotic discontinuation by patients with first-episode psychosis and schizophrenia is associated with increased relapse, rehospitalization, suicide mortality, cardiovascular mortality, and all-cause mortality. There is also the ethical matter that attempts to identify the few who may benefit from antipsychotic dose reduction and discontinuation may compromise the health and stability of the many who require long-term maintenance treatment.
Topics: Humans; Antipsychotic Agents; Schizophrenia; Psychotic Disorders; Drug Tapering; Randomized Controlled Trials as Topic; Recurrence
PubMed: 38767930
DOI: 10.4088/JCP.24f15363 -
Acta Psychiatrica Scandinavica Aug 2020
Topics: Antipsychotic Agents; Clozapine; Humans; Schizophrenia
PubMed: 32812234
DOI: 10.1111/acps.13224 -
Acta Psychiatrica Scandinavica Sep 2022Drugs can be divided into two major categories, symptomatic and disease modifying. This review explores whether and how psychiatric drugs fall into one or the other of... (Review)
Review
OBJECTIVE
Drugs can be divided into two major categories, symptomatic and disease modifying. This review explores whether and how psychiatric drugs fall into one or the other of those categories, and the implications of those results for clinical practice and research in psychopharmacology.
METHOD
Narrative review.
RESULTS
Most psychiatric drugs have only short-term effects of improving active symptoms. They do not show long-term benefits for the underlying disease, such as improving the course of illness and improving mortality. Evidence is provided for this claim in the treatment literature of antidepressants for depressive illness and antipsychotics for schizophrenia. Developing truly beneficial drugs for disease modification also is limited by the poor clinical and biological validity of Diagnostic and Statistical Manual diagnoses as well as the use of invalid falsely positive maintenance efficacy randomized discontinuation trial designs.
CONCLUSIONS
Current psychopharmacology is limited mostly to symptomatic effects, not transformative treatments for the diseases underlying those symptoms. A change in approach is needed in psychopharmacology practice and research, focusing on long-term disease modification rather than short-term symptom improvement.
Topics: Antidepressive Agents; Antipsychotic Agents; Diagnostic and Statistical Manual of Mental Disorders; Humans
PubMed: 35653111
DOI: 10.1111/acps.13459 -
Clinica Chimica Acta; International... Oct 2020Accurate identification and measurement of antipsychotic drugs in in-vivo and in-vitro environment has a key role in the development and design of drugs, as any slight... (Review)
Review
Accurate identification and measurement of antipsychotic drugs in in-vivo and in-vitro environment has a key role in the development and design of drugs, as any slight change in their dosage can affect the treatment process. Determination of antipsychotics in physiological fluids such as blood, plasma and urine are important in drug tablets and medical approaches. Chromatography is the main method used in the determination of antipsychotic drugs but this technique, despite its relative sensitivity, is a costly and complicated method. Biosensors, as simple, low-cost and highly sensitive and specific tools, can be the best alternative to eliminate the drawbacks of routine methods. For this purpose, various biosensors have been extensively developed in the recent years. The main objective of the present study is to introduce and collect recently developed biosensors for the measurement and detection of antipsychotic drugs. Therapeutic drug monitoring (TDM) is a fundamental principle in pharmaceuticals, with the primary goal being to reduce and eliminate the side effects of drugs. This study shows that biosensors can be a modern and novel approach in the field of TDM.
Topics: Antipsychotic Agents; Biological Assay; Biosensing Techniques; Drug Monitoring; Humans
PubMed: 32504638
DOI: 10.1016/j.cca.2020.05.025