lurasidone-hydrochloride and Chronic-Disease

Topics: Chronic Disease; Depressive Disorder, Major; Double-Blind Method; Humans; Lurasidone Hydrochloride; Treatment Outcome; Vortioxetine

Schizophrenia is a serious mental health condition characterised by distortions in thought processes, perception, mood, sense of self, and behaviour. Lurasidone, a second-generation atypical antipsychotic, represents an additional treatment option alongside existing antipsychotics for adolescents and adults with schizophrenia. An economic model was developed to evaluate the incremental costs of lurasidone as a first-line treatment option compared to existing antipsychotics.. A Markov model was developed to estimate the cost impact of lurasidone as a first-line treatment option for both adolescents and adults. The sequence-based model incorporated the following health states: stable (no relapse or discontinuation), discontinuation (due to adverse events or other reasons), and relapse. Data used to determine the movement of patients between health states were obtained from network meta-analyses (NMAs). The time horizon ranged from three to five years (depending on the patient population) and a six-weekly cycle length was used. Unit costs and resource use were reflective of the UK NHS and Personal Social Services and consisted of the following categories: outpatient, adverse events, primary and residential care. Extensive deterministic sensitivity analysis was undertaken to assess the level of uncertainty associated with the base case results.. Lurasidone is demonstrated to be cost-saving as a first-line treatment within the adolescent and adult populations when compared to second-line and third-line respectively. Lurasidone is more expensive in terms of treatment costs, resource use (in the stable health state) and the treatment of adverse events. However, these costs are outweighed by the savings associated with the relapse health state. Lurasidone remains cost-saving when inputs are varied in sensitivity analysis and scenario analysis.. Lurasidone is a cost-saving first-line treatment for schizophrenia for both adolescents and adults.

Topics: Adolescent; Adult; Antipsychotic Agents; Chronic Disease; Cost-Benefit Analysis; Humans; Lurasidone Hydrochloride; Recurrence; Schizophrenia; United Kingdom

Schizophrenia is a low-prevalence mental disorder with a global age-standardized prevalence of 21 million people (2016). Second-generation antipsychotics (lurasidone and quetiapine XR) are recommended as the first-line treatment for schizophrenia. It is interesting to investigate how the results of clinical studies translate into direct medical costs. The objective of this analysis was to assess the direct medical costs related to pharmaceutical treatments and the management of relapses in patients affected with schizophrenia treated with lurasidone (74 mg) vs quetiapine XR (300 mg) assuming the Italian and Spanish National Health Service perspective.. A health economic model was developed based on a previously published model. The analysis considered direct medical costs related to the pharmacological therapies and inpatient or outpatient management of relapses (direct medical costs referred to 2019). The probability of relapses and related costs were derived from two systematic reviews. A deterministic sensitivity analysis was implemented to test the robustness of the results.. The use of lurasidone (74 mg) compared with quetiapine XR (300 mg) would lead to a reduction in direct medical costs in Italy and Spain, with a lower cost per patient of - 163.7 € (- 9.0%) and - 327.2 € (- 22.7%), respectively. In detail, it would lead to an increase in the cost of therapy of + 53.8% and of + 30.5% in Italy and Spain, respectively, to a decrease in the cost of relapses with hospitalization of - 135.7%, and to an increase in the cost of relapses without hospitalization of + 24.5%.. The use of lurasidone (74 mg) for the treatment of patients affected with schizophrenia, compared with quetiapine XR (300 mg), would be a cost-saving strategy in the two contexts investigated assuming the National Health Service point of view.

Topics: Adult; Antipsychotic Agents; Chronic Disease; Cost-Benefit Analysis; Female; Hospitalization; Humans; Italy; Lurasidone Hydrochloride; Middle Aged; Models, Economic; Quetiapine Fumarate; Recurrence; Schizophrenia; Spain; State Medicine

Psychiatric disorders are associated with altered function of inhibitory neurotransmission within the limbic system, which may be due to the vulnerability of selective neuronal subtypes to challenging environmental conditions, such as stress. In this context, parvalbumin-positive GABAergic interneurons, which are critically involved in processing complex cognitive tasks, are particularly vulnerable to stress exposure, an effect that may be the consequence of dysregulated redox mechanisms.. Adult Male Wistar rats were subjected to the chronic mild stress procedure for 7 weeks. After 2 weeks, both control and stress groups were further divided into matched subgroups to receive chronic administration of vehicle or lurasidone (3 mg/kg/d) for the subsequent 5 weeks. Using real-time RT-PCR and western blot, we investigated the expression of GABAergic interneuron markers and the levels of key mediators of the oxidative balance in the dorsal and ventral hippocampus.. Chronic mild stress induced a specific decrease of parvalbumin expression in the dorsal hippocampus, an effect normalized by lurasidone treatment. Interestingly, the regulation of parvalbumin levels was correlated to the modulation of the antioxidant master regulator NRF2 and its chaperon protein KEAP1, which were also modulated by pharmacological intervention.. Our findings suggest that the susceptibility of parvalbumin neurons to stress may represent a key mechanism contributing to functional and structural impairments in specific brain regions relevant for psychiatric disorders. Moreover, we provide new insights on the mechanism of action of lurasidone, demonstrating that its chronic treatment normalizes chronic mild stress-induced parvalbumin alterations, possibly by potentiating antioxidant mechanisms, which may ameliorate specific functions that are deteriorated in psychiatric patients.

Topics: Animals; Antipsychotic Agents; Chronic Disease; Disease Models, Animal; GABAergic Neurons; Gene Expression; Hippocampus; Interneurons; Kelch-Like ECH-Associated Protein 1; Lurasidone Hydrochloride; Male; NADPH Oxidase 2; NF-E2-Related Factor 2; Oxidation-Reduction; Parvalbumins; Rats, Wistar; RNA, Messenger; Stress, Psychological

Major depression is associated with several alterations, including reduced neuronal plasticity and impaired synaptic function, which represent an important target of pharmacological intervention.. In the present study, we have investigated the ability of the antipsychotic drug lurasidone to modulate behavioral and neuroplastic alterations in the chronic mild stress model of depression.. Rats that show reduced sucrose consumption after 2 weeks of chronic mild stress have reduced expression of the pool of Bdnf transcripts with the long 3' untranslated region (3'-UTR) that may be targeted to the synaptic compartment, suggesting the contribution of the neurotrophin to the behavioral dysfunction produced by chronic mild stress. The downregulation of Bdnf expression persisted also after 7 weeks of chronic mild stress, whereas chronic lurasidone treatment improved anhedonia in chronic mild stress rats and restored Bdnf mRNA levels in the prefrontal cortex. Moreover, chronic lurasidone treatment was able to normalize chronic mild stress-induced defects of Psd95 and Gfap as well as changes in molecular regulators of protein translation at the synapse, including mTOR and eEF2.. These results demonstrate that lurasidone shows antidepressant properties in the chronic mild stress model through the modulation of synaptic and neuroplastic proteins. Such changes may contribute to the amelioration of functional capacities, which are deteriorated in patients with major depression and stress-related disorders.

Topics: Animals; Antidepressive Agents; Brain-Derived Neurotrophic Factor; Chronic Disease; Depressive Disorder; Disease Models, Animal; Disks Large Homolog 4 Protein; Elongation Factor 2 Kinase; Excitatory Amino Acid Transporter 2; Excitatory Amino Acid Transporter 3; Gene Expression; Glial Fibrillary Acidic Protein; Intracellular Signaling Peptides and Proteins; Lurasidone Hydrochloride; Male; Membrane Proteins; Prefrontal Cortex; Random Allocation; Rats, Wistar; RNA, Messenger; Stress, Psychological; TOR Serine-Threonine Kinases; Vesicular Glutamate Transport Protein 1