The Effect of Atypical Anti-psychotic Agents on Obesity and Glucose Metabolism

Atypical antipsychotics are more effective than typical antipsychotics and have fewer side effects such as tardive dyskinesia and extrapyramidal symptoms; therefore, prescriptions of atypical antipsychotics are increasing. However, recently, it has been reported that atypical antipsychotics have a higher incidence of diabetes, hyperglycemia, and obesity than typical antipsychotics. Atypical antipsychotics induce obesity-inhibiting appetite-related receptors such as serotonin and dopamine. Decreased exercise due to improving psychotic symptoms, and genetic characterictics can also cause weight gain. Hyperglycemia and hypoglycemia were another metabolic problem related to treatment with atypical antipsychotics. The mechanisms of hyperglycemia were mainly related obesity, decreased anorexigenic hormones, and increased insulin resistance in multiple organs. There are also reports that genes related to diabetes have an effect on the incidence of diabetes mellitus treated with atypical antipsychotics. On the other hand, although it is not clear why hypoglycemia occurs, it documented in case reports all over the world. There are more reports of atypical antipsychotics than typical antipsychotics and these are frequently reported in Asians. Further research on the mechanism of hypoglycemia related to atypical antipsychotics is strongly recommended.

Use of antipsychotics and long-term risk of parkinsonism

Introduction Few epidemiological studies have assessed the risk of parkinsonisms after prolonged use of neuroleptics. We aimed to examine the long-term risk of degenerative parkinsonisms (DP) associated with previous use of neuroleptics. Methods All residents in Piedmont, Northern-west Italy, older than 39 years (2,526,319 subjects), were retrospectively followed up from 2013 to 2017. Exposure to neuroleptics was assessed through the regional archive of drug prescriptions. The development of DP was assessed using the regional archives of both drug prescriptions and hospital admissions. We excluded prevalent DP cases at baseline as well as those occurred in the first 18 months (short-term risk). The risk of DP associated with previous use of neuroleptics was examined through Cox regression, using a matched cohort design. Results The risk of DP was compared between 63,356 exposed and 316,779 unexposed subjects. A more than threefold higher risk of DP was observed among subjects exposed to antipsychotics, compared to those unexposed (HR = 3.27, 95% CI 3.00–3.57), and was higher for exposure to atypical than typical antipsychotics. The risk decreased after 2 years from therapy cessation but remained significantly elevated (HR = 2.38, 95% CI 1.76–3.21). Conclusions These results indicate a high risk of developing DP long time from the start of use and from the cessation for both typical and atypical neuroleptics, suggesting the need of monitoring treated patients even after long-term use and cessation.

Effectiveness Study of Typical and Atypical Antipsychotics on Patients with Schizophrenia using WHO Disability Assessment Schedule (WHODAS 2.0)

Background and Objectives: Schizophrenia is the commonest and one of the best known mental disorder which usually starts before 25 years of age, leading to significant disability in both behavioural and social life. Usually the person with any mental disability has to face social ignorance, this further leads to deterioration of their health and productivity. The deterioration of the health is not only due to the course of the disease but also may be due to treatment by some of the antipsychotics, which are the main drugs for the schizophrenia management. So, the present study has been designed to determine the effectiveness of typical and atypical antipsychotics in patients with schizophrenia in terms of disability reduction caused by them using WHODAS 2.0. Methods: After taking ethics committee approval and informed consent from study participants this prospective, observational, questionnaire based study has been conducted in the Department of Psychiatry and Pharmacology of V. S.S. Institute of Medical Sciences and Research, Burla, Odisha using WHODAS 2.0 in patients suffering from schizophrenia. Results: Atypical antipsychotics lead to more reduction in disability in patients with schizophrenia than typical antipsychotics both at 6 and 12 month duration. On comparing the various atypical antipsychotics used in the study, there was no significant difference among them. Conclusion: Based on the above findings, it can be concluded that atypical antipsychotics are more effective than typical antipsychotics in terms of disability reduction. The findings may help clinicians to get better insight in the management of schizophrenia.

Typical Antipsychotics Increase Risk of Severe Exacerbation in Asthma Patients– A Nationwide Population-Based Cohort Study

Background:Severe asthma exacerbation reduces patients’ life quality, results in visits to the emergency department (ED) and hospitalization, and incurs additional medical costs. Antipsychotics block receptors with bronchodilation function; however, the effects of antipsychotics use on severe asthma exacerbation are unknown. This study aimed to investigate the effects of antipsychotics on asthma-related ED visits and hospitalizations.Methods:This study used a case-crossover design. Using the 2003-2017 Taiwan National Health Insurance Reimbursement Database, we established a cohort of 18,657 adults with severe asthma exacerbation leading to ED visits or hospitalization. Univariate and multivariate conditional logistic regressions were conducted to explore the association of antipsychotics use with severe asthma exacerbation. Subgroup analyses of different classes, doses, receptor functions of antipsychotics and schizophrenia were also performed.Results:Antipsychotics use was associated with a higher risk of severe asthma exacerbation (adjusted odds ratio (OR): 1.27; 95% confidence interval (CI): 1.05-1.54; P = 0.013) compared with no use of antipsychotics. Use of typical antipsychotics increased the risk of severe asthma exacerbation (adjusted OR: 1.40, 95% CI: 1.10-1.79, P = 0.007), whereas use of atypical antipsychotics did not. There was a dose-dependent effect of antipsychotics (test for trend: P =0.025). Antipsychotics that block the M2 muscarinic or D2 dopaminergic receptor were associated with an increased risk of severe asthma exacerbation (adjusted OR: 1.39, 95% CI: 1.10-1.76, P = 0.007 and adjusted OR: 1.33, 95% CI: 1.08-1.63, P = 0.008, respectively).Conclusions: Use of typical antipsychotics is associated with a dose-dependent increased risk of severe asthma exacerbation. Physicians should thus weight the risk and benefit of prescribing high-dose typical antipsychotics for asthma patients.

Effect of medication on risk of traumatic brain injury in patients with bipolar disorder: A nationwide population-based cohort study

Background: Increased traumatic brain injury (TBI) risk was found in patients with bipolar disorder (BPD). Whether the medications for BPD and dosage moderate the risk of TBI is not clear. Aim: This study aimed to determine whether an association exists between BPD and TBI and whether the prescription of psychotropics moderates TBI risk. Methods: A total of 5606 individuals who had received diagnoses of BPD between January 1, 1997 and December 31, 2013 and 56,060 matched controls without BPD were identified from Taiwan’s National Health Insurance Research Database. Cases and controls were followed until the date of TBI diagnosis. Results: BPD was associated with a high risk of TBI (adjusted hazard ratio (aHR): 1.85; 95% CI: 1.62–2.11). Patients with BPD, with or without a history of psychiatric hospitalization, had increased risks of TBI (aHR: 1.94, 95% CI: 1.57–2.4 and aHR: 1.82, 95% CI: 1.55–2.1, respectively). The prescription of typical antipsychotics (0 < defined daily dose (DDD) < 28: hazard ratio (HR) = 1.52, 95% CI: 1.19–1.94; ⩾28 DDD: HR = 1.54, 95% CI: 1.15–2.06) and tricyclic antidepressants (TCAs) (0 < DDD < 28: HR = 1.73, 95% CI: 1.26–2.39; ⩾28 DDD: HR = 1.52, 95% CI: 1.02–2.25) was associated with higher TBI risk. Patients receiving higher doses of benzodiazepines (BZDs) (cumulative dose ⩾28 DDD) had a higher TBI risk (HR = 1.53, 95% CI: 1.13–2.06). Conclusion: Patients with BPD have a higher risk of TBI. The use of typical antipsychotics, TCAs, or high-dose BZDs increases the risk of TBI in BPD.

Mechanism of Action of Atypical Antipsychotic Drugs in Mood Disorders

Atypical antipsychotic drugs were introduced in the early 1990s. Unlike typical antipsychotics, which are effective only against positive symptoms of schizophrenia, atypical antipsychotics are effective against negative and cognitive symptoms as well. Furthermore, they are effective not only in psychotic but also in affective disorders, on their own or as adjuncts to antidepressant drugs. This review presents the neural mechanisms of currently existing atypical antipsychotics and putative antipsychotics currently being investigated in preclinical and clinical studies and how these relate to their effectiveness in mood disorders such as depression, anxiety, and post-traumatic stress disorder (PTSD). Typical antipsychotics act almost exclusively on the dopamine system. Atypical drugs, however, modulate serotonin (5-HT), norepinephrine, and/or histamine neurotransmission as well. This multimodal mechanism of action putatively underlies the beneficial effect of atypical antipsychotics in mood and anxiety disorders. Interestingly, novel experimental drugs having dual antipsychotic and antidepressant therapeutic potential, such as histamine, adenosine, and trace amine-associated receptors (TAAR) ligand, are also characterized by a multimodal stimulatory effect on central 5-HT, norepinephrine, and/or histamine transmission. The multimodal stimulatory effect on central monoamine neurotransmission may be thus primarily responsible for the combined antidepressant and antipsychotic therapeutic potential of certain central nervous system (CNS) drugs.

Use of Antipsychotics in Patients with Behavioral and Psychological Symptoms of Dementia: Results of a Spanish Delphi Consensus

<b><i>Background:</i></b> Behavioral and psychological symptoms of dementia (BPSD) are difficult to manage and associated with poor outcome. <b><i>Objectives:</i></b> The aim of this study was to reach consensus on the use of antipsychotics in patients with BPSD in Spain. <b><i>Methods:</i></b> A qualitative, multicenter, two-round Delphi study was carried out, with the participation of specialists involved in the care of dementia patients throughout Spain. They completed a 76-item questionnaire related to the identification of BPSD, treatment with antipsychotics, follow-up of patients, barriers for the use of atypical antipsychotics, and effects of antipsychotics on quality of life. <b><i>Results:</i></b> A total of 162 specialists in neurology, psychiatry, and geriatrics (61% men) with a mean (SD) age of 45.9 (10) years participated in the study. Almost all participants (96.9%) strongly agreed that atypical antipsychotics are safer and better tolerated than typical antipsychotics. There was agreement on the importance to review the indication and dose of the antipsychotic drug at least every 3 months. There was consistent high rate of agreement on the beneficial impact of atypical antipsychotics on the quality of life of patients with dementia and their caregivers. A consensus was also reached on the need of detecting BPSD in patients with dementia as it decreases the quality of life of both patients and caregivers, and the need to routinely screen for dementia in elderly patients with no previous psychiatric history in the presence of suggestive symptoms of BPSD. Finally, the participants in the study agreed that administrative barriers for the prescription of atypical antipsychotics in Spain hinder the access to this drug group and favor the prescription of typical antipsychotics. <b><i>Conclusions:</i></b> The participants in the study agreed that atypical antipsychotics should be preferred to typical antipsychotics in the management of BPSD. Wide consensus was reached about the importance of early identification of BPSD in persons with cognitive impairment, the use and management of atypical antipsychotic drugs and their favorable impact on patients and caregiver’s quality of life.

Medication-precipitated Seizure in Psychiatric Patients: Typical vs. Atypical Antipsychotics

Backgrounds: It is unknown whether second-generation antipsychotics are safer than first-generation antipsychotics in terms of seizure induction. Objective: In the present assessment, the relationships between the incidence of seizure attacks among a great sample of non-western psychiatric inpatients and prescribed typical and atypical antipsychotics have been probed and analyzed based on the existing data in the literature. Methods: Razi psychiatric hospital, as one of the largest and oldest public psychiatric hospitals in the Middle East, had been selected as the field of study in the present retrospective estimation. For assessment, all inpatients that had suffered a seizure during the last sixtyfour months had been included in the current study. Results: Among seventy-four patients who had experienced seizure attack during the inpatient management, and had been prescribed antipsychotics for symptomatic management of primary psychiatric disorders, 67.56% had received atypical antipsychotic and the remaining (32.43%) had received typical antipsychotics, which revealed a significant quantitative difference between them (p<0.000). Among atypical antipsychotics, olanzapine was the most recommended antipsychotic (33.78%), followed by risperidone (34%), quetiapine (9.45%), and clozapine (n=1, 1.35%). Among typical antipsychotics, too, haloperidol (28.37%) was significantly more prescribed than chlorpromazine (2.70%) and thioridazine (1.35%) (p<0.000). By the way, there was no significant difference, quantitatively, between olanzapine and haloperidol in the present evaluation (p<0.47). Conclusion: Atypical antipsychotics have comparable potentiality, as typical antipsychotics, for triggering seizure attacks, which demands indispensable cautiousness by clinicians when prescribing such a group of medications for epileptic and neuropsychiatric patients.

Mechanism of Action of Atypical Antipsychotic Drugs in Mood Disorders

Atypical antipsychotic drugs were introduced in the early 1990th. Unlike typical antipsychotics, which are effective only against positive symptoms of schizophrenia, atypical antipsychotics show effectiveness against negative and cognitive symptoms as well. Furthermore, they are effective not only in psychotic, but also in affective disorders, by their own or as adjuncts to antidepressant drugs. While typical antipsychotics act, almost exclusively, via dopamine-2 (D2) receptors, atypical target serotonin-1A/1B/2A/2C (5-HT1A/1B/2A/2C), &alpha;1/2-adrenergic, and/or histamine-1 (H1) receptors as well. Blocking of 5-HT1A/1B autoreceptors, inducing their early desensitization, and/or activation of &alpha;1-adrenoceptors, allow some atypical drugs to enhance 5-HT transmission. Blocking of 5-HT2A/2C and/or &alpha;2-adrenoceptors enable some atypical antipsychotics to stimulate catecholamine transmission and/or diminish the inhibition of catecholamine neurons induced by some antidepressants. It is possible, that the activation of H1 and/or blocking of H3 boost monoamine transmission as well, via a mechanism involving stimulation of firing activity of dopamine neurons. The experimental drugs with antipsychotic potential, acting on adenosine and trace amino associated (TAAR) receptors, might be effective in mood disorders as well, because of the ability to modulate the excitability of monoamine-secreting neurons and to potentiate extracellular concentrations of monoamines in the limbic areas of the brain.