Safety, tolerability, and risks associated with first-and second-generation antipsychotics: A state-of-the-art clinical review

Nicola Veronese, Juan Undurraga, Nicola Veronese, Andrea Murru, André F. Carvalho, Mary Vseeman, Brendon Stubbs, Francesco Monaco, Isabella Pacchiarotti, Marco Solmi, Christoph U Correll, Michele Fornaro, Eduard Vieta

Research output: Contribution to journalArticlepeer-review

132 Citations (Scopus)

Abstract

Since the discovery of chlorpromazine (CPZ) in 1952, first-generation antipsychotics (FGAs) have revolutionized psychiatric care in terms of facilitating discharge from hospital and enabling large numbers of patients with severe mental illness (SMI) to be treated in the community. Second-generation antipsychotics (SGAs) ushered in a progressive shift from the paternalistic management of SMI symptoms to a patient-centered approach, which emphasized targets important to patients-psychosocial functioning, quality of life, and recovery. These drugs are no longer limited to specific Diagnostic and Statistical Manual of Mental Disorders (DSM) categories. Evidence indicates that SGAs show an improved safety and tolerability profile compared with FGAs. The incidence of treatment-emergent extrapyramidal side effects is lower, and there is less impairment of cognitive function and treatment-related negative symptoms. However, treatment with SGAs has been associated with a wide range of untoward effects, among which treatment-emergent weight gain and metabolic abnormalities are of notable concern. The present clinical review aims to summarize the safety and tolerability profile of selected FGAs and SGAs and to link treatment-related adverse effects to the pharmacodynamic profile of each drug. Evidence, predominantly derived from systematic reviews, meta-analyses, and clinical trials of the drugs amisulpride, aripiprazole, asenapine, brexpiprazole, cariprazine, clozapine, iloperidone, lurasidone, olanzapine, paliperidone, quetiapine, risperidone, sertindole, ziprasidone, CPZ, haloperidol, loxapine, and perphenazine, is summarized. In addition, the safety and tolerability profiles of antipsychotics are discussed in the context of the “behavioral toxicity” conceptual framework, which considers the longitudinal course and the clinical and therapeutic consequences of treatment-emergent side effects. In SMI, SGAs with safer metabolic profiles should ideally be prescribed first. However, alongside with safety, efficacy should also be considered on a patient-tailored basis. © 2017 Solmi et al.
Original languageEnglish
Pages (from-to)757-777
Number of pages21
JournalTHERAPEUTICS AND CLINICAL RISK MANAGEMENT
Volume13
Publication statusPublished - 2017

All Science Journal Classification (ASJC) codes

  • Safety Research
  • General Pharmacology, Toxicology and Pharmaceutics
  • Pharmacology (medical)
  • Chemical Health and Safety

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