New Antipsychotic Drugs Research Articles

A cross-sectional study to assess the drug utilization pattern and pharmacotherapeutic adherence among patients with schizophrenia and quality of life of patient’s caregiver in a tertiary care teaching hospital

Background: Schizophrenia is a chronic severe psychiatric illness affecting nearly 0.4 to 1.4% of people in India. Many newer anti-psychotic drugs are used now-a-days in schizophrenia. Poor adherence to the treatment given to patients of schizophrenia is observed very often. Although, the quality of life of schizophrenia patients is very much compromised; at the same time, quality of life of the caregiver is also compromised. Methods: A cross-sectional Observational study was conducted among patients already diagnosed with Schizophrenia and on treatment, after ethical approval. Data relevant to study variables was collected in a pre-designed case record form. Evaluation of drug utilization pattern was done by WHO core drug prescribing indicators. Medication adherence was assessed through modified Morisky scale. Quality of life of relative or caregiver was assessed through WHO-QOL BREF questionnaire scale. Results: Patients of 18 years and above were enrolled. Among them, average age was 35.8±5.5 years. In my study, female patients were 64.7% and male patients were 35.3%. Average number of drugs per prescription was 3.8. Drugs prescribed by generic name were around 86.2%. Around 56.9% of drugs were prescribed from national list of essential medicines. Atypical antipsychotics were prescribed in 32% of all prescriptions for Schizophrenia; Whereas Benzodiazepines were prescribed in 19% of all prescriptions. Average Medication adherence score using MMS scale was 3.7±2.2. Patients with high adherence to the medications prescribed were nearly 71% and patients with low adherence to the medications prescribed were 29%. Mean total WHOQOL-BREF score was 75.2±6.5 out of 120. Conclusions: Most prescribed class of drugs was atypical anti-psychotics. Pharmacotherapeutic adherence among patients with schizophrenia was relatively high. Quality of life of patients’ relative or caregiver was impaired to some extent, more impaired in physical health and social relationships domain.

High dose antipsychotic polypharmacy and dopamine partial agonists - time to rethink guidelines?

Guidelines for the treatment of schizophrenia limit the use of antipsychotic agents to clinically-established maximum doses. This acknowledges both the absence of additional efficacy of dopamine D2 receptor antagonists above a receptor occupancy threshold, and the increases in side effects that can occur at higher doses. These limits restrict the dosing of combinations of antipsychotics as they do single agents; drugs sharing the major antipsychotic mechanism of D2 receptor antagonism will act additively in blocking these receptors.Several newer antipsychotic drugs, including aripiprazole and cariprazine, act as partial agonists at the D2 receptor site and avoid action at several other receptors, effects at which are responsible for some non-dopaminergic adverse effects. This pharmacology imparts different characteristics to the drugs resulting often in a more favourable side effect profile. Their partial agonism, along with high affinities for the D2 receptor, also means that these drugs given adjunctively may in part replace, rather than enhance, the D2 antagonism of other antipsychotic agents. This can result in an improvement in certain side effects without loss of antipsychotic efficacy.This article makes the case for distinguishing the D2 partial agonists from antagonists in defining maximum doses of combined treatments, which would increase the options available to the prescriber, emphasising that pharmacological mechanisms need to be understood in identifying optimal treatments for psychotic illness.

A Novel Antipsychotic

In December 2019, the FDA approved the new antipsychotic drug lumateperone tosylate. In an industry-sponsored, 1-month, randomized clinical trial,

Preclinical pharmacokinetics and biodistribution studies of asenapine maleate using novel and sensitive RP-HPLC method.

Asenapine maleate (ASPM) is a newer antipsychotic drug available as a sublingual tablet in the market. To investigate the pharmacokinetic and tissue distribution study of ASPM following oral administration in rats, reversed-phase HPLC method was developed and validated. ASPM was extracted from plasma and tissue matrix by liquid-liquid extraction technique and analyzed using mobile phase consisted of phosphate buffer pH 3.0 and acetonitrile (65:35% v/v). The method showed good linearity (10-500 ng/ml) with recovery 83-102%. In pharmacokinetics study, half-life was 32.74 ± 7.51 h due to slow elimination of drug. The biodistribution study indicated preferential distribution of ASPM to highly perfused organs. The current method can be successfully applied for estimating the drug in various biological matrices.

Chlorpromazine versus atypical antipsychotic drugs for schizophrenia.

Chlorpromazine versus atypical antipsychotic drugs for schizophrenia.

Chlorpromazine-induced severe exfoliative photoallergic reaction

Despite the availability of newer antipsychotic drugs, chlorpromazine is still widely used due to its cost-utility and effectiveness in many parts of India, particularly for patients in whom marked psychomotor excitement and sleep disturbances are present. The side effects of chlorpromazine include photo-induced skin reactions. Chlorpromazine causes both phototoxic as well as photoallergic cutaneous reactions. We present the case report of an adult male who developed severe photoallergic skin reactions to chlorpromazine. The skin lesions largely resolved on stopping the drug, but reappeared in a more severe form when the drug was inadvertently restarted by the patient. This highlights the need for awareness and education of patients about the skin effects of psychotropics such as chlorpromazine.

Metabolic Challenges in Schizophrenia

Schizophrenia is a psychiatric disorder requiring constant vigilance and lifelong intervention with psycho therapeutic counseling and administration of Antipsychotic drugs. Metabolic aberrations are documented to occur more frequently in subjects with Schizophrenia (SCH) prior to treatment and the prevalence of these metabolic alterations is significantly raised following administration of Antipsychotic drugs especially the newer ones. Adiposity in SCH prior to drug therapy is significantly increased in comparison to age matched healthy subjects (N) as documented by several indices. Body Mass Index, kg/m2 (26.7 for SCH vs. 22.8 for N, p<0.003); Waist/Hip Ratio (0.99 for SCH vs. 0.86 for N, p<0.005); Total Body Fat, mm2 (34681 in SCH vs. 27692 in N, p<0.01) and Intraabdominal fat, mm2 (13232 in SCH vs. 3880 in N, p<0.005). Squealed of obesity involve almost every organ and system in the body and contribute to increase both morbidity and mortality in SCH. Thus, the prevalence of other disorders constituting metabolic syndrome e.g. Hypertension, Pre Diabetes or Type 2 Diabetes and Dyslipidemia rise markedly and presence of these disorders more than double the relative risks of mortality in SCH in comparison to general population. The mortality risk is likely to be increased further with recent documentation of rising prevalence of cancer amongst subjects with obesity and diabetes. In several subjects with SCH, the initial manifestation of Diabetes is Diabetic Ketoacidosis or Hyperglycemic Hyperosmolar State resulting in hospitalization with obtundation and coma. Moreover, the severity of these metabolic changes is more pronounced at diagnosis in subjects with SCH as compared to non SCH subjects due to lack of recognition of symptoms and/or neglect on part of the subjects with SCH, leading to a far greater mortality. Moreover, increased frequency of smoking in subjects with SCH induces even greater risks of morbidity and mortality via rise in infectious and respiratory disorders. Finally, some of the newer antipsychotic drugs especially Olanzapine and Quetiapine are well documented to cause a rise in prevalence of all disorders constituting Metabolic Syndrome. Therefore, we concur with the recommendations for management of subjects with Schizophrenia formulated by the consensus development conference conducted by several organizations They include Metabolic risk considerations prior to and at initiation of atypical antipsychotics: 1) Patient, family, and caregiver education, 2) Baseline screening, 3) Regular frequent monitoring at 3-6 months’ interval and 4) Referral to specialized services, when appropriate

Cost effectiveness of strategies to combat neuropsychiatric conditions in sub-Saharan Africa and South East Asia: mathematical modelling study

Objective To assess the comparative costs and effects of interventions to combat five neuropsychiatric conditions (schizophrenia, bipolar disorder, depression, epilepsy, and heavy alcohol use).Design Cost effectiveness analysis based on an...

Cress seed mucilage based buccal mucoadhesive gel of venlafaxine: in vivo, in vitro evaluation

Venlafaxine is a newer antipsychotic drug which shows first pass effect. Cress seed is also called as garden cress or green salad. This study examined the mechanical (gel strength, adhesiveness) and rheological properties of cress seed mucilage based gels that contain different ratios of carbopol 934 P (0.5-1.5%). In addition, diffusion of venlafaxine from gel formulations was evaluated. The selected formulation was further analyzed for pharmacokinetic parameters in rabbits. All formulations exhibited pseudoplastic flow with thixotropy. Formulation F5 showed the C(max) of 24.19 ± 0.72 ng/ml by buccal route of administration and 17.98 ± 1.15 ng/ml by oral route of administration. The bioavailability of F5 by buccal route was 54.44% and that of by oral route was 39.60%. A combination of the cress seed mucilage and carbopol 934 P resulted in a prolonged and higher venlafaxine delivery by buccal route of administration.

The clinical use of NAD in the treatment of children schizophrenia

Objective To compare the use of new antipsychotic drugs （NAD） including Olanzapine, Risperidone and Qutipine in the treatment for children with schizophrenia. Methods 66 children patients were included in this study, according to the case disease condition history, we evaluated the efficacy and side effects with CGI and TESS before treatment, and at the 2nd,4th ,8th weeks after the treatment. Results The response rate of Risperidone, Olazapine and Qutipine are 71%, 85.7%, and 60% respectively. The total response rate is 72.7%. The rates of side effects are 21%, 33%, 30% respectively. Conclusion It suggested that NAD is effective and safe in the treatment for children schizot~hrenia patients. NAD has been widelv u.~d in children ~chi~nnhreni~ nutnnti~nt~ Key words: New antipsychotic drugs; Children schizophrenia

Biological Perspectives: Update on Newer Antipsychotic Drugs: Are They Evidence Based?

Biological Perspectives: Update on Newer Antipsychotic Drugs: Are They Evidence Based?

Effects of 5-HT 2A and 5-HT 2C receptor antagonists on acute and chronic dyskinetic effects induced by haloperidol in rats

An important limitation of classical antipsychotic drugs such as haloperidol (HAL) is their liability to induce extrapyramidal motor symptoms acutely and tardive dyskinetic syndromes when given chronically. These effects are less likely to occur with newer antipsychotic drugs, an attribute that is often thought to result from their serotonin-2 (5-HT 2) receptor antagonistic properties. In the present study, we used selected doses of the 5-HT 2A antagonist M100,907, the 5-HT 2C antagonist SB242,084 and the mixed 5-HT 2A/C antagonist ketanserin to re-examine the respective roles of 2A vs. 2C 5-HT 2 receptor subtypes in both acute and chronic motor effects induced by HAL. Acutely, SB242,084 (0.5 mg/kg) reduced HAL-induced catalepsy, while M100,907 (0.5 mg/kg) and ketanserin (1 mg/kg) were without effect. None of the drugs reduced HAL-induced Fos expression in the striatum or frontal cortex, and M100,907 actually potentiated HAL-induced Fos expression in the n. accumbens. In rats chronically treated with HAL, both ketanserin and SB242,084 attenuated vacuous chewing movements, while M100,907 had no effect. In addition, 5-HT 2C but not 5-HT 2A mRNA levels were altered in several brain regions after chronic HAL. These results highlight the importance of 5-HT2 2C receptors in both acute and chronic motoric side effects of HAL, and suggest that 5-HT 2C antagonism could be targeted as a key property in the development of new antipsychotic medications.

Possible Rabbit Syndrome With Amisulpride

Back to table of contents Previous article Next article LETTERFull AccessPossible Rabbit Syndrome With AmisulprideDattatreya Namdeorao Mendhekar D.P.M., M.D.,Dattatreya Namdeorao Mendhekar D.P.M., M.D.Search for more papers by this author,Published Online:1 Jul 2010https://doi.org/10.1176/jnp.2010.22.3.352.e23AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: Recently, rabbit syndrome has been reported with newer antipsychotic drugs such as clozapine, risperidone, olanzapine, and aripiprazole. 1 We report the case of an elderly man with depressive disorder who developed rabbit syndrome as an acute extrapyramidal side effect after addition of amisulpride to ongoing mianserin therapy. To our knowledge, this is the first case report in the existing literature of rabbit syndrome associated with amisulpride. Case ReportMr. A, a 78-year-old man, presented with a history of depression, diurnal variation of mood, nihilistic delusion, and disturbed biological functions of 4 months’ duration. His brother had bipolar disorder; however, there was no family history of movement disorder. Mr. A’s hypertension was well stabilized with amlodipine, 5 mg/day, for the last 5 years. The diagnosis of major depression with psychotic features was established according to DSM-IV criteria. All his routine investigations were within normal limits except lipid profile. Initially, he was treated with mianserin, 15 mg/day, and olanzapine, 2.5 mg/day, but olanzapine was stopped due to drowsiness and the dose of mianserin was gradually increased to 30 mg per day. Since there was no improvement in his depressive and psychotic symptoms even after taking this medicine for 4 weeks, 50 mg of amisulpride was added and subsequently increased to 150 mg/day over a period of 10 days. In addition, he was also taking alprazolam, 0.5 mg/day, and lorazepam, 1 mg/day. On the fifth day of amisulpride therapy, an abrupt onset of abnormal perioral movements was noticed. These were rapid, fine, and rhythmic involuntary movements of lip and jaw on a vertical axis. Detailed examination also revealed mild parkinsonian symptoms in the form of rigidity, bradykinesia, tremor, and salivation but no dystonic reaction. Estimation of abnormal movements by abnormal involuntary movement scale provided a score of 9. An MRI scan of his head and an EEG were within normal limits. A diagnosis of rabbit syndrome was made, and amisulpride was replaced by trihexyphenidyl, 4 mg/day. On the sixth day of trihexyphenidyl therapy, all perioral movements as well as parkinsonian symptoms subsided. Trihexyphenidyl was gradually withdrawn over the next 2 weeks. A further 2 weeks later, the patient did not report for his scheduled appointment and was subsequently lost to follow-up.Discussion As noticed in our case, a large majority of cases with rabbit syndrome also have other signs of drug-induced parkinsonism. 2 One can argue that mianserin might have been a contributory factor in the emergence of rabbit syndrome as there was a single report of oral dyskinesia and torticollis associated with mianserin. 3 It is also possible that mianserin might have potentiated the motor side effects of amisulpride by increasing the amisulpride level. However, our case did not developed rabbit syndrome while he was on mianserin as a monotherapy. Further, amisulpride is substituted benzamides with high affinity and selectivity for the dopamine D2 and D3 receptors mainly responsible for dyskinesia, 4 whereas mianserin has no or little effect on the dopaminergic system. 3 Clinicians who prescribe amisulpride ought to be aware of this adverse effect. Department of Psychiatry, Neuropsychiatry and Headache Clinic, Delhi, India

Antipsychotic Drug Treatment for Patients with Schizophrenia: Theoretical Background, Clinical Considerations and Patient Preferences

The cornerstone in treatment of psychosis is antipsychotic drugs. Treatment options have increased over the years; newer antipsychotic drugs with a proposed increased efficacy regarding negative and cognitive symptoms, but also a shift in side-effects from neurological side-effects to metabolic side-effects have arisen as the new challenge. The basis of successful pharmacological treatment is a fundamental understanding of the mechanisms of action, the desired effects and side-effects of antipsychotic drugs, a good relationship with the patient and a thorough monitoring of the patient before and during treatment. The clinically relevant aspects of antipsychotic drug treatment are reviewed; mechanism of antipsychotic drug action, clinical considerations in treatment, switching antipsychotic drugs, polypharmacy, safety and patient preference.

Psychiatric Issues in Parkinson's Disease

Psychiatric Issues in Parkinson's Disease

Schizophrenia treatment in the developing world: an interregional and multinational cost-effectiveness analysis.

Schizophrenia is a highly disabling disease and is costly to treat. We set out to establish what are the most cost-effective interventions applicable to developing regions and countries. Analysis was undertaken at the level of three WHO subregions spanning the Americas, Africa and South-East Asia, and subsequently in three member states (Chile, Nigeria and Sri Lanka). A state transition model was used to estimate the population-level health impact of older and newer antipsychotic drugs, alone or in combination with psychosocial intervention. Total population-level costs (in international dollars or local currencies) and effectiveness (measured in disability-adjusted life years averted) were combined to form cost-effectiveness ratios. The most cost-effective interventions were those using older antipsychotic drugs combined with psychosocial treatment, delivered via a community-based service model (I$ 2350-7158 per disability-adjusted life year averted across the three subregions, I$ 1670-3400 following country-level contextualisation within each of these subregions). The relative cost-effectiveness of interventions making use of newer, "atypical" antipsychotic drugs is estimated to be much less favourable. By moving to a community-based service model and selecting efficient treatment options, the cost of substantially increasing treatment coverage is not high (less than I$ 1 investment per capita). Taken together with other priority-setting criteria such as disease severity, vulnerability and human rights protection, this study suggests that a great deal more could be done for persons and families living under the spectre of this disorder.

Torsade de pointes in a patient with complex medical and psychiatric conditions receiving low‐dose quetiapine

Describe potential cardiac complications of low-dose quetiapine and other atypical antipsychotic drugs. We present a case report of a 45-year-old Black woman with multiple medical and psychiatric problems taking low-dose quetiapine. Coincident with a generalized seizure, the patient developed 'ventricular fibrillation'. She was countershocked with restoration of normal sinus rhythm. The initial electrocardiogram showed QT interval prolongation. Shortly thereafter, classical torsade de pointes appeared, lasted 10 min, and resolved spontaneously. Hypomagnesemia was present. A cardiac electrophysiologist was concerned that the very slow shortening of the prolonged QTc interval after magnesium replacement implicated quetiapine as a risk factor for QTc interval prolongation and torsade de pointes. A psychosomatic medicine consultant asserted that the fragmented medical and psychiatric care almost certainly contributed to the patient's medical problems. We discuss other cases of QT interval prolongation by newer antipsychotic drugs and previous reports by our group concerning the association of psychotropic drugs, QT interval prolongation, and torsade de pointes. Atypical antipsychotic drug administration, when accompanied by risk factors, may contribute to cardiac arrhythmias including torsade de pointes.

Diabetes Associated with Atypical Antipsychotic Drugs

Several newer atypical antipsychotic drugs appear to be associated with increased risk for development of diabetes. In this partially industry-sponsored analysis of the U.S. Veterans Affairs database, researchers identified nearly 57,000 nondiabetic schizophrenic …

New Generation Antipsychotic Drugs and QTc Interval Prolongation.

BACKGROUND: Recent regulatory and clinical concerns have brought into sharp focus antipsychotic drug-induced QTc interval prolongation, torsades de pointes, and sudden cardiac death. Several new generation (atypical) antipsychotic drugs have either been withdrawn from clinical use or delayed in reaching the marketplace due to these concerns. Because torsades de pointes is rarely found, QTc interval prolongation serves as a surrogate marker for this potentially life-threatening arrhythmia. Current methods of calculating this electrocardiographic parameter have limitations. The primary care physician is a key member of the team managing a patient who requires administration of antipsychotic drugs. This article focuses on new generation antipsychotic drugs and principles useful to both the primary care physician and the psychiatrist. METHOD: PubMed was searched in September 2002 using the terms antipsychotic drug and QT interval. References were examined from review articles describing antipsychotic drugs and the QT interval. The author's files gathered over the past 20 years on the QT interval were also reviewed. RESULTS: Nine cases were available in which drug-induced QTc interval prolongation was associated with new generation antipsychotic drug administration. Eight cases were taken from the literature, and the author added one additional report. The newer agents involved were risperidone, quetiapine, and ziprasidone. In at least 8 cases, there was evidence of other risk factors associated with QTc interval prolongation. In one case frequently referenced in the literature, the authors misunderstood their own data showing that QTc interval prolongation did not relate to delayed ventricular repolarization. In another instance, 2 authors reported on the same patient, with important information missing from both articles. No evidence of torsades de pointes appeared in any of the 9 cases. CONCLUSIONS: No evidence is currently available in the literature implicating new generation antipsychotic drugs in the production of torsades de pointes. However, the absence of such evidence does not prove that newer antipsychotic drugs do not cause torsades de pointes. Among patients free of risk factors for QTc interval prolongation and torsades de pointes, current literature does not dictate any specific consultative or laboratory intervention before administering new generation antipsychotic drugs. When risk factors are present, evaluation and intervention specific to those risk factors should dictate the clinician's course of action. More specific guidelines for monitoring the QT interval and risk of torsades de pointes await improved methods of measuring the QTc interval relevant to each patient.

The Effects of Excitotoxic Hippocampal Lesions in Rats on Risperidone- and Olanzapine-Induced Locomotor Suppression

Previous studies have shown that excitotoxic hippocampal lesions in rats attenuate the ability of different doses of haloperidol, but not of clozapine, to suppress locomotor activity. The purpose of the present study was to determine if kainic acid-induced hippocampal damage reduces the degree of locomotor suppression produced by two relatively newer antipsychotic drugs, risperidone and olanzapine. Young adult male rats received bilateral intracerebroventricular infusions of the excitotoxin, kainic acid (KA), or vehicle and were tested for locomotor responses to drug treatment 30 days later. Infusions of KA produced neuronal loss in the CA3 region of the dorsal hippocampus in every rat. As reported previously, KA lesions reduced the ability of haloperidol (0.35 mg/kg) to completely suppress the locomotor activity elicited by amphetamine (1.5 mg/kg) relative to the effect of haloperidol in non-lesioned controls. Lesioned animals treated with a moderate dose of risperidone (1.4 mg/kg) also exhibited significantly more locomotor activity after amphetamine treatment in comparison to control animals. A trend toward greater activity was also observed in the lesioned group relative to the control group after olanzapine (3.0 mg/kg) injection (p = .09, 2-tailed). The locomotor effects of lower and higher doses of risperidone and olanzapine were not altered by kainic acid lesions. These data suggest that the locomotor-suppressive effects of moderate doses of risperidone and, perhaps, olanzapine involve hippocampal neurons, but that higher doses of each drug can suppress activity in a hippocampal-independent manner.