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

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.

A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study of Adjunctive Pimavanserin in Patients With Major Depressive Disorder and an Inadequate Response to Therapy (CLARITY)

“…In contrast, use of atypical antipsychotics may be limited by weight gain, metabolic disturbances (glucose intolerance, diabetes, lipid disorders, hyperprolactinemia), and daytime sleepiness. 10,[46][47][48] In addition, most conventional antidepressants are well known to cause sexual dysfunction in at least 50% of patients with MDD. 49 Limitations of this study include a relatively short length of treatment as well as a small sample size, particularly in Stage 2.…”

Rediscovery of penicillin of psychiatry: haloperidol decanoate

“…Although clozapine is an effective therapeutic option in treatment-resistant schizophrenia, only 40% of patients benefit from this agent. The search for a novel drug continues because clozapine is associated with several undesirable effects, including agranulocytosis, myocarditis, thromboembolism, ileus, and pneumonia [16,17]. Furthermore, the presence of intramuscular formulations of haloperidol, which is suitable for patients resistant to treatment during acute episodes, represents an important advantage over clozapine and other oral antipsychotics because it provides rapid tranquilization.…”

“…The next 4 interviews (interview 2-5) were conducted as a weekly follow-up. The interviews were conducted every two weeks (interview 6-7) in next month and then subsequent interviews were conducted monthly [8][9][10][11][12][13][14][15][16][17][18]. In this way, one-year follow-up was completed with the follow-up patients over time.…”

Possibilities of Partial D3-Receptor Agonists Usage in Addictive Pathology

“…Напротив, при оценке долгосрочной переносимости и безопасности приема препарата на протяжении 48 недель регистрировалось незначительное снижение уровня пролактина вне зависимости от дозы [12,25]. О подобном пролактин-регу-лирующем действии уже известно из ряда исследований применения частичных агонистов дофаминовых рецепторов, таких как арипипразол и брекспипразол [28][29][30][31]. Проблема повышения массы тела зачастую негативно влияет на приверженность пациентов к терапии.…”