An update of safety of clinically used atypical antipsychotics

Orsolini, Laura; Tomasetti, Carmine; Valchera, Alessandro; Vecchiotti, Roberta; Matarazzo, Ilaria; Vellante, Federica; Iasevoli, Felice; Ef, Buonaguro; Fornaro, Michele; Al, Fiengo; Martinotti, Giovanni; Mazza, Monica; Perna, Giampaolo; Carano, Alessandro; Bartolomeis, Andrea de; M, Di Giannantonio; Berardis, Domenico De

doi:10.1080/14740338.2016.1201475

Cited by 121 publications

(90 citation statements)

References 149 publications

(174 reference statements)

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“…No safety data are so far available for children and adolescents 42. Other previous studies, systematic reviews and meta-analyses showed that iloperidone is an acceptable drug, even when compared to placebo or other antipsychotics, especially in terms of modest weight gain, no medically important changes in lipid and glucose levels and little in the way of prolactin elevation and EPS 31,39,52,63…”

Section: Resultsmentioning

confidence: 99%

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Iloperidone in the treatment of schizophrenia: an evidence-based review of its place in therapy

Tonin¹,

Wiens²,

Fernández-Llimós³

et al. 2016

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IntroductionSchizophrenia is a chronic and debilitating mental disorder that affects the patient’s and their family’s quality of life, as well as financial costs and health care settings. Despite the variety of available antipsychotics, optimal treatment outcomes are not always achieved. Novel drugs, such as iloperidone, can provide more effective, tolerable and safer strategies.AimTo review the evidence for the clinical impact of iloperidone on the treatment of patients with schizophrenia.Evidence reviewClinical trials, observational studies and meta-analyses reached a common consensus that iloperidone is as effective as haloperidol, risperidone and ziprasidone in reducing schizophrenia symptoms. Similar amounts of adverse events and discontinuations were observed with iloperidone compared to placebo and active treatments. Common adverse events are mild and include dizziness, hypotension, dry mouth and weight gain. Iloperidone can induce extension of QTc interval, and clinicians should be aware of its contraindications. In long-term trials, iloperidone also showed promising safety and tolerability profiles. The low propensity to cause akathisia, extrapyramidal symptoms (EPS), increased prolactin levels or changes to metabolic laboratory parameters support its use in practice. Results showed that iloperidone prevents relapse in stabilized patients, with a time to relapse superior to placebo and similar to haloperidol. Patients using a prior antipsychotic (eg, risperidone and aripiprazole) can easily switch to iloperidone with no serious impact on safety or efficacy. However, the acquisition costs of iloperidone may hamper its use. Further evidence comparing iloperidone with other antipsychotics, and pharmacoeconomic studies would be welcome.Place in therapyConsidering just the clinical profile of iloperidone, it represents a promising drug for treating schizophrenia, particularly in patients who are intolerant to previous antipsychotics, as well as being suitable as first-line therapy. Cost-effectiveness comparisons are needed to justify its use in clinical practice.

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Section: Resultsmentioning

confidence: 99%

“…This pharmacodynamic profile with low affinity to H1 and M1 receptors would lead to minimal sedation, cognitive impairment and mild weight gain. The extremely low binding at cholinergic receptors suggests a low risk of anticholinergic symptoms (eg, blurred vision and dry mouth), as well as a lower EPS liability 42,43…”

Section: Resultsmentioning

confidence: 99%

Iloperidone in the treatment of schizophrenia: an evidence-based review of its place in therapy

Tonin¹,

Wiens²,

Fernández-Llimós³

et al. 2016

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“…Substantial consensus exists about the pharmacological signature of lurasidone hydrochloride across sources assessing either preclinical or clinical studies on the matter [60–64], as briefly synthesized below.…”

Section: Resultsmentioning

confidence: 99%

“…Moreover, its lack of affinity for some receptors (e.g., histamine H1, acetylcholine M1) would predict improved (metabolic and cognitive) tolerability with respect to alternative SGAs options approved by the FDA for BD in adults [61, 63]. Favorable D2/5-HT2A balance would predict lower propensity for extrapyramidal symptoms [64]. …”

Section: Resultsmentioning

confidence: 99%

“…Thus, early bipolar antidepressant activity excreted by lurasidone has been correlated with disinhibitory norepinephrinergic effects of agonistic activity at 5-HT1A (which may play a core mechanism in bipolar depression [78] beyond major depressive disorder [79]) and antagonism at alpha-1 norepinephrine and serotonin 5-HT2A receptors, though the presence of norepinephrine reuptake inhibition (lurasidone is also weak alpha-2a (autoinhibitory, presynaptic) antagonist (Ki = 10.8 nM) for lurasidone [64]) is essential in order to sustain it [61], whereas dopaminergic activity overall may likewise play a major role [80]. …”

Section: Resultsmentioning

confidence: 99%

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Lurasidone in the Treatment of Bipolar Depression: Systematic Review of Systematic Reviews

Fornaro

Berardis²,

Perna

et al. 2017

BioMed Research International

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Introduction A burgeoning number of systematic reviews considering lurasidone in the treatment of bipolar depression have occurred since its Food and Drug Administration extended approval in 2013. While a paucity of available quantitative evidence still precludes preliminary meta-analysis on the matter, the present quality assessment of systematic review of systematic reviews, nonetheless, aims at highlighting current essential information on the topic. Methods Both published and unpublished systematic reviews about lurasidone mono- or adjunctive therapy in the treatment of bipolar depression were searched by two independent authors inquiring PubMed/Cochrane/Embase/Scopus from inception until October 2016. Results Twelve included systematic reviews were of moderate-to-high quality and consistent in covering the handful of RCTs available to date, suggesting the promising efficacy, safety, and tolerability profile of lurasidone. Concordance on the drug profile seems to be corroborated by a steadily increasing number of convergent qualitative reports on the matter. Limitations Publication, sponsorship, language, citation, and measurement biases. Conclusions Despite being preliminary in nature, this overview stipulates the effectiveness of lurasidone in the acute treatment of Type I bipolar depression overall. As outlined by most of the reviewed evidence, recommendations for future research should include further controlled trials of extended duration.

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Synthesis and Biological Evaluation of Five‐Atom‐Linker‐Based Arylpiperazine Derivatives with an Atypical Antipsychotic Profile

Wang

Yang

et al. 2019

ChemMedChem

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Herein we describe a focused set of new arylpiperazine derivatives as potential broad-spectrum antipsychotics. The general structure contains a quinolinone-like moiety, an arylpiperazine moiety, and a five-atom linker. Among them,isothiazol-4-yl)piperazin-1-yl)pentyl)quinolin-2(1H)-one (S6) shows a promising preclinical profile. Compound S6, characterized by partial D 2 R agonism, 5-HT 1A R agonism, 5-HT 2A R antagonism, and blockade of SERT activities, was found to decrease psychosis-and depressive-like symptoms in rodents. The polypharmacological profile of S6 could provide opportunities for the treatment of various other central nervous system disorders such as anxiety, depression, and psychoses associated with dementia. Furthermore, S6 demonstrated acceptable safety, toxicology, and pharmacokinetic profiles, and has been selected as a preclinical candidate for further evaluation in schizophrenia.[a] Dr.previous SAR studies on antipsychotic drugs indicated that an appropriate linker is of great importance for desired multireceptor activity, we also explored the influence of linker flexibility of the new derivatives on receptor function profiles. [18] Among the derivatives prepared, compound S6 manifested a unique polypharmacological antipsychotic profile. It displayed much higher potency for the desired targets (D 2 , 5-HT 1A , 5-HT 2A , and SERT) than other off-target receptors (α 1A , H 1 , 5-HT 2C , M 3 , hERG). Thus, compound S6 was developed as an atypical antipsychotic candidate to treat schizophrenia based on the D 2 R, 5-HT 1A R, 5-HT 2A R and SERT multi-target profile. 2 3 4 5 6 7 8

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An update of safety of clinically used atypical antipsychotics

Cited by 121 publications

References 149 publications

Iloperidone in the treatment of schizophrenia: an evidence-based review of its place in therapy

Iloperidone in the treatment of schizophrenia: an evidence-based review of its place in therapy

Lurasidone in the Treatment of Bipolar Depression: Systematic Review of Systematic Reviews

Synthesis and Biological Evaluation of Five‐Atom‐Linker‐Based Arylpiperazine Derivatives with an Atypical Antipsychotic Profile

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