P.575 Long-term functional improving effects of cariprazine: post-hoc analyses of acute and predominant negative symptom schizophrenia patient data

Laszlovszky, István; Acsai, K.; Born, Christoph; Sebe, B.; Szatmári, B.; Vass, G.; Earley, Willie; Németh, György

doi:10.1016/j.euroneuro.2020.09.421

Cited by 3 publications

(6 citation statements)

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“…In longer-term treatment, functional improvement was also investigated via post hoc analyses of PSP total and subdomain outcomes in the relapse prevention trial [ 46 ]. Marked and clinically relevant PSP total score improvement was noted for patients who were stabilized on cariprazine during the open-label phase of the trial (+19 point) versus patients who did not stabilize during open-label treatment (+8 points) [ 75 ]. After stabilized patients entered double-blind treatment, those randomized to placebo experienced worsening of PSP outcomes, while cariprazine-treated patients remained basically unchanged, with statistically significant differences in favor cariprazine seen in PSP total score ( P < 0.001) and each subdomain score (self-care, socially useful activity, personal and social relationships, aggressive behavior; P < 0.01).…”

Section: Post Hoc Efficacy Analysesmentioning

confidence: 99%

Cariprazine, A Broad-Spectrum Antipsychotic for the Treatment of Schizophrenia: Pharmacology, Efficacy, and Safety

2021

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Schizophrenia is characterized by positive, negative, cognitive, and affective symptoms. Antipsychotic medications, which work by blocking the dopamine D 2 receptor, are the foundation of pharmacotherapy for schizophrenia to control positive symptoms. Cariprazine is a dopamine D 3 receptor-preferring D 3 /D 2 partial agonist antipsychotic that is approved for the treatment of schizophrenia (USA and European Union [EU]) and manic and depressive episodes associated with bipolar I disorder (USA). Partial agonist agents have a lower intrinsic activity at receptors than full agonists, so they act as either functional agonists or functional antagonists depending on the surrounding neurotransmitter environment. Beyond efficacy against positive symptoms, the unique D 3 -preferring partial agonist pharmacology of cariprazine suggests potential advantages against negative symptoms, and cognitive and functional impairment, which are challenging to treat. The efficacy and safety of cariprazine in adult patients with schizophrenia have been demonstrated in four short-term randomized, double-blind, placebo-controlled clinical trials, two long-term open-label studies, one relapse prevention study, and one prospective negative symptom study versus the active comparator risperidone. Additional post hoc investigations have supported efficacy across individual symptoms and domains in schizophrenia, as well as in diverse areas of interest including cognition, functioning, negative symptoms, hostility, and global well-being. This comprehensive review of cariprazine summarizes its pharmacologic profile, clinical trial evidence, and post hoc investigations. Collective evidence suggests that the pharmacology of cariprazine may offer broad-spectrum efficacy advantages for patients with schizophrenia, including effects against difficult-to-treat negative and cognitive symptoms, as well as functional improvements. Cariprazine was generally safe and well tolerated in patients with short-and long-term exposure and no new safety concerns were associated with longerduration treatment. Trial registration ClinicalTrials.gov identifiers,

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Section: Post Hoc Efficacy Analysesmentioning

confidence: 99%

Cariprazine, A Broad-Spectrum Antipsychotic for the Treatment of Schizophrenia: Pharmacology, Efficacy, and Safety

2021

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“…Current "dopamine modulators" (e.g., aripiprazole, brexpiprazole, blonaserin) differ depending on their predominant site of action at dopamine and serotonin receptors, with consequent differences in the spectrum of psychopathology they reduce and their side effect profile (55). Among them, cariprazine has a D3 receptor preferring affinity, with functional selectivity according to the prevailing neuronal environment, thus contributing to its efficacy across an array of symptoms of schizophrenia, bipolar disorder, and major depressive disorder (27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(63)(64)(65)(66). Importantly, cariprazine also exhibits a favorable side effect profile with no higher incidence on metabolic parameters, ECG abnormalities, vital sign and prolactin levels changes compared to placebo (27-37, 63, 65, 66).…”

Section: Discussionmentioning

confidence: 99%

“…Among them, cariprazine has a D3 receptor preferring affinity, with functional selectivity according to the prevailing neuronal environment, thus contributing to its efficacy across an array of symptoms of schizophrenia, bipolar disorder, and major depressive disorder ( 27 – 37 , 63 – 66 ). Importantly, cariprazine also exhibits a favorable side effect profile with no higher incidence on metabolic parameters, ECG abnormalities, vital sign and prolactin levels changes compared to placebo ( 27 – 37 , 63 , 65 , 66 ). Its efficacy in long term use in schizophrenia is also confirmed ( 31 , 32 , 37 ).…”

Section: Discussionmentioning

confidence: 99%

“…Cariprazine was also found to be uniquely effective in treating primary negative symptoms of schizophrenia, due to its predominant preference for D3 receptors, as well as its considerable affinity for 5-HT 1A receptors (33)(34)(35)(36)(37). In a randomized, double-blind multicenter study which compared the efficacy of cariprazine and risperidone in patients with schizophrenia with predominantly negative symptoms, cariprazine in the mean dose of 4.2 mg/d showed a superiority over risperidone (mean dose 3.8 mg/d) at Week 14, which was continued until Week 26 (end of trial) (33).…”

Section: Cariprazine Efficacy Across the Wide Range Of Symptoms Of Schizophreniamentioning

confidence: 99%

“…An observational study by Rancans et al ( 34 ) showed the effectiveness of cariprazine in ‘real-life' clinical settings when treating negative symptoms. In a post-hoc analysis of long-term treatment, studies have shown that cariprazine also improved everyday functioning and social skills which influence quality of life ( 37 ). This is a potentially significant advantage, considering that recovery should include not only symptom reduction but also functional improvement across various aspects of life ( 38 , 39 ).…”

Section: Cariprazine Efficacy Across the Wide Range Of Symptoms Of Schizophreniamentioning

confidence: 99%

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Treatment of Symptom Clusters in Schizophrenia, Bipolar Disorder and Major Depressive Disorder With the Dopamine D3/D2 Preferring Partial Agonist Cariprazine

et al. 2021

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Cariprazine is currently approved for the treatment of patients with schizophrenia (USA and EU), and for manic, depressive, and episodes with mixed features in bipolar I disorder (USA): several randomized controlled studies have also explored its efficacy in patients with major depressive disorder. This review summarizes its current therapeutic uses and potential advantages for treating the main symptoms of schizophrenia, bipolar I and major depressive disorder, considering its pharmacodynamic properties, efficacy, and tolerability. Its predominantly D3 receptor preferring affinity, with functional selectivity according to the prevailing neuronal environment, contributes to its efficacy across a wide array of psychopathological symptoms (including reality distortion, disorganized thought, negative symptoms, mood disturbance, anhedonia, and cognitive impairment), and to a favorable side effect profile. Cariprazine may be a “drug of choice” in patients with predominant negative and cognitive symptoms of schizophrenia, as well as those with metabolic syndrome. Further investigation of its relative efficacy when compared to aripiprazole or other active comparators is warranted. Its effectiveness in the treatment of bipolar mania, bipolar I depression and bipolar I episodes with mixed features, with minimal accompanying metabolic changes is well-established. The longer half-life and delayed time to relapse in patients diagnosed with schizophrenia when compared to other second-generation antipsychotics represent other advantages, given the high rates of non-adherence and frequent relapses seen in clinical practice. Its efficacy in overlapping symptom domains in other major psychiatric disorders appears promising.

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A Systematic Review of the Effects of Antipsychotics on Anhedonia by Using Knowledge Graph Approach

Cheng,

Qin,

Yuan

et al. 2023

Proceedings of the 2023 4th International Symposium on Artificial Intelligence for Medicine Science

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P.575 Long-term functional improving effects of cariprazine: post-hoc analyses of acute and predominant negative symptom schizophrenia patient data

Cited by 3 publications

References 0 publications

Cariprazine, A Broad-Spectrum Antipsychotic for the Treatment of Schizophrenia: Pharmacology, Efficacy, and Safety

Cariprazine, A Broad-Spectrum Antipsychotic for the Treatment of Schizophrenia: Pharmacology, Efficacy, and Safety

Treatment of Symptom Clusters in Schizophrenia, Bipolar Disorder and Major Depressive Disorder With the Dopamine D3/D2 Preferring Partial Agonist Cariprazine

A Systematic Review of the Effects of Antipsychotics on Anhedonia by Using Knowledge Graph Approach

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