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Treatment of Psychological Disorders
Published in Mohamed Ahmed Abd El-Hay, Understanding Psychology for Medicine and Nursing, 2019
Later on, another class of antipsychotics, the prototypical agent of which was clozapine, was developed with less potential for extrapyramidal side effects and tardive dyskinesia. This class is called the second generation antipsychotics or atypical antipsychotics. It produces less D2 receptors blockage and has serotonin (5HT2A) antagonistic activity. An increased ratio of 5-HT2A to D2 receptor antagonism has been proposed as responsible for the efficacy and tolerability of atypical antipsychotics. This group includes risperidone and olanzapine, quetiapine, ziprasidone, amisulpride, zotepine, and sertindole. Atypical antipsychotics are marked by its metabolic side effects (e.g., weight gain, dysglycemia, dyslipidemia). Aripiprazole is an atypical antipsychotic that exceptionally acts as partial DA agonist.
Efficacy, safety, and tolerability of ulotaront (SEP-363856, a trace amine-associated receptor 1 agonist) for the treatment of schizophrenia and other mental disorders: a systematic review of preclinical and clinical trials
Published in Expert Opinion on Investigational Drugs, 2023
Gia Han Le, Emily S. Gillissie, Taeho Greg Rhee, Bing Cao, Yazen Alnefeesi, Ziji Guo, Joshua D. Di Vincenzo, Muhammad Youshay Jawad, Andrew M. March, Ranuk Ramachandra, Leanna M.W. Lui, Roger S. McIntyre
To overcome the limitations of typical antipsychotic drugs, second generation/atypical antipsychotic drugs were developed. In a double-blind study examining clozapine’s effectiveness for treatment-resistant schizophrenia, 30% of clozapine-treated patients experienced significantly greater improvements to positive and negative symptom scores. In contrast, only 4% of chlorpromazine-treated patients experienced these improvements [18]. Despite some degree of effectiveness, results from a meta-analysis comparing first- and second-generation antipsychotics indicate that only some of the studied second-generation antipsychotics displayed improved overall efficacy compared to first-generation antipsychotics, including amisulpride, clozapine, olanzapine, and risperidone [19]. First-generation drugs that yielded higher efficacy than second-generation drugs for the treatment of both positive and negative symptoms of schizophrenia include aripiprazole, quetiapine, sertindole, ziprasidone, and zotepine [19]. Case studies also suggest cariprazine – a third-generation antipsychotic – and brexpiprazole to be candidate atypical antipsychotics to reduce both the positive and negative symptoms of schizophrenia; however, further research with larger sample sizes is required to examine the long-term effects of these agents as the results from these clinical cases are not generalizable [20,21].
How do we address treating the negative symptoms of schizophrenia pharmacologically?
Published in Expert Opinion on Pharmacotherapy, 2021
Pharmacological treatment of schizophrenia is highlighted by antipsychotics, which all share in common blockade or partial agonism of the dopamine type 2 receptor (D2R) and are primarily effective on positive symptoms. Compared to overall symptoms, meta-analysis of antipsychotics shows attenuated standardized mean difference (SMD) effect sizes for negative symptom improvement [6], with the largest SMDs for clozapine (−0.62), zotepine (−0.54), amisulpride (−0.5) and olanzapine (−0.45). The studies included in this meta-analysis were of acutely exacerbated schizophrenia without a specific focus on patients with high levels (prominent) or treatment-resistant (persistent) negative symptoms. Nor did they focus on predominant negative symptoms, which in addition to having both prominent and persistent negative symptoms, requires low levels of positive symptoms [2]. Thus, these studies did not distinguish between primary and secondary negative symptoms, suggesting potential pseudospecificity of improvement in extrapyramidal side effects, paranoia-induced withdrawal or depression.
Drugs that increase the risk of community-acquired pneumonia: a narrative review
Published in Expert Opinion on Drug Safety, 2018
Adamantia Liapikou, Catia Cilloniz, Antoni Torres
Gambassi et al. [60], estimating the risk-benefit ratio for prescribing APs, suggested that there was 1 hospitalization for pneumonia for every 2–5 patients showing any clinical improvement in symptoms in response to treatment with APs. In a nested case-control study that followed patients aged 18–65 years with schizophrenia over eight years, Kuo et al. [61] found that the use of second-generation antipsychotic drugs was associated with a 69% greater risk (adjusted RR = 1.69) of developing pneumonia, after taking into account confounding factors, with the magnitude of the association being the highest for clozapine. Although quetiapine, olanzapine, zotepine, and risperidone were also associated with an increased risk, there was no clear dose-dependent association. Wang et al. [62] reported that the risk for pneumonia was the highest within the first 30 days of treatment with APs (HR, 1.1; 95% CI: 0.76–1.38), decreasing after 60 days (HR, 1.03; 95% CI: 0.76–1.38) and disappearing after 120 days of treatment (HR, 0.84; 95% CI: 0.66–1.05). Likewise, Trifiró and colleagues [57] demonstrated that the risk for CAP lasted only in the first week of treatment (OR, 4.62; 95% CI: 2.05–10.38), decreasing thereafter. Similarly, Pratt et al. [63] observed a reduced risk with continuous treatment in a self-controlled case series, but only for AAPs.