High-potency Agents Research Articles

IgA Nephropathy – Current and Future Perspectives in Treatment

Abstract Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulopathy in our adult population and is associated with a high lifetime risk of kidney failure. Recent years have succeeded in describing the pathogenesis of IgAN at the molecular level, where immune complexes containing specific galactose deficient IgA1 play an essential role. The gold standard in the diagnosis of IgAN remains renal biopsy followed by determination of a prognostic score using the Oxford classification. A fundamental goal in the management of patients with IgAN is to optimize supportive therapy involving active lifestyle modification and renoprotective medications. The reno-protective drug menu has recently been expanded to include effective sodium-glucose cotransporter 2 inhibitors (SGLT2i), and additional agents are on the way. However, despite maximal supportive therapy, a wide range of patients remain at high risk of disease progression and require the deployment of immunomodulatory drugs. To date, however, we do not have high potency agents that are well tolerated and safe. This has led to the initiation of many studies to target the inflammatory process at different pathogenetic levels. In this article, we summarize the current standards in the treatment of IgAN and present new promising options in the management of this disease.

Antiplatelet Therapy and Bleeding Outcomes With CYP2C19 Genotyping.

The impact of antiplatelet therapy with availability of CYP2C19 genotyping on bleeding in a real-world setting has not been extensively studied. Prospective, single-center, cohort study conducted between December 2015 and October 2019 with 1-year follow-up. Patients underwent percutaneous coronary intervention (PCI), CYP2C19 genotyping, and received P2Y12 inhibitor therapy. The primary outcome was time to first bleed of any severity using Bleeding Academic Research Consortium criteria. Secondary outcomes included time to first major bleed and rates of antiplatelet switching. The primary outcome occurred in 697 of 2091 (33%) participants at a median of 15 days. Major bleeding occurred in 176 (8%) of patients. Compared to clopidogrel, treatment with ticagrelor or prasugrel was associated with increased risk of any bleeding (adjusted HR [aHR] 2.04, 95% CI 1.69-2.46). For patients without CYP2C19 no function alleles, treatment with prasugrel or ticagrelor was associated with increased risk of any bleeding (aHR 2.31, 95% CI 1.83-2.90). Similar associations were observed for major bleeding. No difference in ischemic events was observed. Among patients discharged on ticagrelor or prasugrel, 199 (36%) were de-escalated to clopidogrel within 1 year. De-escalation was more likely after a bleed if patients did not have a no function allele (35.9% vs 19.1%; P = .02). Bleeding is common in post-PCI patients on antiplatelet therapy. Patients on high potency agents had higher bleeding risk in the population at-large and in non-carriers of CYP2C19 no function alleles. Genotype-guided antiplatelet de-escalation should be further explored in prospective studies.

Natalizumab administration in multiple sclerosis patients during active SARS-CoV-2 infection: a case series

BackgroundThe Coronavirus disease 2019 (COVID-19) caused by the new Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has become a pandemic, affecting the therapeutic management for Multiple Sclerosis (MS). Any decision regarding the discontinuation of high-potency agents for moderate and highly active MS should be carefully evaluated, taking into account the potential risk of rebound of the disease. In particular, no data about clinical outcome of patients with MS receiving Natalizumab (NTZ) during active COVID-19 infection have been reported yet.Cases presentationWe reported on 6 patients treated with NTZ for relapsing MS during active COVID-19 infection, who recovered without reporting any worsening or new symptoms. Most of the patients were asymptomatic, with the exception of one patient who had a slight worst COVID-19 clinical course. No patients received O2-therapy or required intensive care. No neurological complications were observed.ConclusionsThis paper reported the clinical outcome of patients with MS receiving NTZ during active COVID-19 infection. This case series suggests that treatment with NTZ during pandemic is relatively safe and might be continued in selected patients who are infected by COVID-19, thereby reducing the risk of MS disease rebound.

Multiple Sclerosis Disease-Modifying Therapy and the COVID-19 Pandemic: Implications on the Risk of Infection and Future Vaccination

The coronavirus 2019 (COVID-19) pandemic is expected to linger. Decisions regarding initiation or continuation of disease-modifying therapy for multiple sclerosis have to consider the potential relevance to the pandemic. Understanding the mechanism of action and the possible idiosyncratic effects of each therapeutic agent on the immune system is imperative during this special time. The infectious side-effect profile as well as the route and frequency of administration of each therapeutic agent should be carefully considered when selecting a new treatment or deciding on risk mitigation strategies for existing therapy. More importantly, the impact of each agent on the future severe acute respiratory syndrome coronavirus type-2 (SARS-CoV-2) vaccine should be carefully considered in treatment decisions. Moreover, some multiple sclerosis therapies may have beneficial antiviral effects against SARS-CoV-2 while others may have beneficial immune-modulating effects against the cytokine storm and hyperinflammatory phase of the disease. Conventional injectables have a favorable immune profile without an increased exposure risk and therefore may be suitable for mild multiple sclerosis during the pandemic. However, moderate and highly active multiple sclerosis will continue to require treatment with oral or intravenous high-potency agents but a number of risk mitigation strategies may have to be implemented. Immune-modulating therapies such as the fumerates, sphinogosine-1P modulators, and natalizumab may be anecdotally preferred over cell-depleting immunosuppressants during the pandemic from the immune profile standpoint. Within the cell-depleting agents, selective (ocrelizumab) or preferential (cladribine) depletion of B cells may be relatively safer than non-selective depletion of lymphocytes and innate immune cells (alemtuzumab). Patients who develop severe iatrogenic or idiosyncratic lymphopenia should be advised to maintain social distancing even in areas where lockdown has been removed or ameliorated. Patients with iatrogenic hypogammaglobulinemia may require prophylactic intravenous immunoglobulin therapy in certain situations. When the future SARS-CoV-2 vaccine becomes available, patients with multiple sclerosis should be advised that certain therapies may interfere with mounting a protective immune response to the vaccine and that serological confirmation of a response may be required after vaccination. They should also be aware that most multiple sclerosis therapies are incompatible with live vaccines if a live SARS-CoV-2 vaccine is developed. In this article, we review and compare disease-modifying therapies in terms of their effect on the immune system, published infection rates, potential impact on SARS-CoV-2 susceptibility, and vaccine-related implications. We propose risk mitigation strategies and practical approaches to disease-modifying therapy during the COVID-19 pandemic.

Nucleoside analog monotherapy for prophylaxis in Hepatitis B liver transplant patients is safe and efficacious.

Combination therapy with HBIG and NAs has reduced HBV recurrence post LT. Despite its efficacy, costs of HBIG remain prohibitive. With high-potency NAs, HBIG's use has been questioned. We aim to evaluate the efficacy and safety of HBIG-free regimens in patients transplanted for HBV-related liver disease. A review of LT patients at the National University Hospital, Singapore from 2001 to 2015 was performed. Patients transplanted for HBV were divided by antiviral treatment received: high- or low-potency NAs, or a combination of HBIG with high-potency NAs. Post-transplant outcomes were reviewed till data censure. Primary outcome was recurrence of HBV viremia post-transplant, while secondary outcomes were HBsAg sero-clearance, graft survival and mortality. Among 58 patients, 51 (88%) had persistent HBV viral suppression. Patients on a high-potency agent had significantly higher viral suppression compared to those on a low-potency agent (97% vs 72%, p = 0.02). This was also seen in patients with VL detectable at transplant (100% vs 50%, p < 0.01). None of the 16 patients with VL detectable at transplant and treated with high-potency agents developed recurrence. 42 patients (72%) achieved persistent HBsAg sero-clearance. Although this was higher in the high-potency NA-only group, it was not statistically significant (p = 0.56). There were no graft failures or mortalities attributed to HBV recurrence. With the use of high-potency agents, HBIG may not be necessary in the treatment of patients transplanted for HBV-related liver disease, even in the presence of detectable VL at time of transplant.

Paradoxical psoriasiform inflammatory reaction during the use of tumor necrosis factor-alpha inhibitors in patients with Crohn’s disease (a review of the literature and presentation of two clinical cases)

Psoriasiform rash (paradoxical inflammation) induced by tumor necrosis factor-alpha (TNFα) inhibitors is observed in about 5–10% of patients with inflammatory bowel diseases treated by these genetically engineered agents. Its predictors include gender (mostly female), smoking, higher body mass index, and formation of anti-neutrophil antibodies. There is no correlation between the paradoxical inflammation and specific agent; the rash can develop with the use of any TNFα inhibitor, such as infliximab, adalimumab, or certolizumab pegol. The first line of treatment for pharmacologically induced psoriasis includes topical corticosteroids (mostly, high potency agents clobetasol and betamethasone) and combination steroid-containing agents (betamethasone + calcipotriol). If this treatment is ineffective or the rash recurs during the use of TNFα inhibitors, the rash is qualified as a class-specific effect, with consideration of switching the patient to a genetically engineered product with another mechanism of action. In such a case, there is a strong indication for ustekinumab. Despite a relatively high incidence of the paradoxical inflammation with TNFα inhibitors and a bulk of published data, some questions remain unanswered. In particular, further studies are required into the time intervals between the achievement of a clinically significant effect of TNFα inhibitors on the symptoms of inflammatory bowel diseases and the skin rash formation, which means the possibility of treatment withdrawal and change of the treatment strategy, as well as studies on the long-term prognosis of the skin lesions. In this context, clinical case presentation and the accumulated experience would subsequently help to formulate actual clinical recommendations on the management of this patient category.

Synthesis, spectroscopic, molecular orbital calculation, cytotoxic, molecular docking of DNA binding and DNA cleavage studies of transition metal complexes with N-benzylidene-N′-salicylidene-1,1-diaminopropane

Eight mononuclear chromium(III), manganese(II), iron(III), cobalt(II), nickel(II), copper(II), zinc(II) and cadmium(II) complexes of Schiff’s base ligand were synthesized and determined by different physical techniques. The complexes are insoluble in common organic solvents but soluble in DMF and DMSO. The measured molar conductance values in DMSO indicate that the complexes are non-electrolytic in nature. All the eight metal complexes have been fully characterized with the help of elemental analyses, molecular weights, molar conductance values, magnetic moments and spectroscopic data. The analytical data helped to elucidate the structure of the metal complexes. The Schiff base is found to act as tridentate ligand using N2O donor set of atoms leading to an octahedral geometry for the complexes around all the metal ions. Quantum chemical calculations were performed with semi-empirical method to find the optimum geometry of the ligand and its complexes. Additionally in silico, the docking studies and the calculated pharmacokinetic parameters show promising futures for application of the ligand and complexes as high potency agents for DNA binding activity. The interaction of the complexes with calf thymus DNA (CT-DNA) has been investigated by UV absorption method, and the mode of CT-DNA binding to the complexes has been explored. Furthermore, the DNA cleavage activity by the complexes was performed. The Schiff base and their complexes have been screened for their antibacterial activity against bacterial strains [Staphylococcus aureus (RCMB010027), Staphylococcus epidermidis (RCMB010024), Bacillis subtilis (RCMB010063), Proteous vulgaris (RCMB 010085), Klebsiella pneumonia (RCMB 010093) and Shigella flexneri (RCMB 0100542)] and fungi [(Aspergillus fumigates (RCMB 02564), Aspergillus clavatus (RCMB 02593) and Candida albicans (RCMB05035)] by disk diffusion method. All the metal complexes have potent biocidal activity than the free ligand.

Synthesis, spectroscopic characterization, potentiometric studies, cytotoxic studies and molecular docking studies of DNA binding of transition metal complexes with 1,1-diaminopropane–Schiff base

A new series of Schiff base transition metal complexes with N,N′-bis(2-hydroxybenzylidene)-1,1-diaminopropane (H2BHBDAP) have been prepared and characterized by elemental analysis, spectroscopic and magnetic measurements. Protonation constants of Schiff base and stability constants of their binary metal complexes have been determined potentiometrically in 50% DMSO–water media at 25°C and ionic strength 0.10M sodium perchlorate. Quantum chemical calculations were performed with semi-empirical method to find the optimum geometry of the ligand and its complexes. Additionally in silico, the Docking studies and the calculated pharmacokinetic parameters show promising futures for application of the ligand and complexes as high potency agents for DNA binding activity.

Perphenazine Suspension: A New, Old Treatment, Side Effects and Continuous Use

A number of innovative delivery systems for acute antipsychotic pharmacotherapy have been developed over the years which include oral suspensions, rapidly dissolving wafers and acute intramuscular preparations. Currently, the availability of first generation antipsychotic (FGA) formulations is limited to two high potency agents: haloperidol and fluphenazine. At Yale New-Haven Psychiatric Hospital, the hospital pharmacy was able to create perphenazine suspension, a mid-potency FGA, with a record of effectiveness and tolerability that was no worse than that of second generation antipsychotics (SGAs) in the CATIE trial. In this study we compare perphenazine suspension to other first and SGAs in the risk of extrapyramidal reactions and whether or not patients were continued on the same antipsychotic they were started with at the time of discharge. Medical records of patients who received acute pharmacotherapy in a unique form while hospitalized at Yale New Haven Psychiatric Hospital from July 2009 to December 2009 were examined. All data were collected thru a chart review using a form that was created to systematically document experiences. A total of 229 patients were included in the study. There were no significant differences between treatment groups on gender, age, race or diagnosis. In the entire samples 1.75% had pseudo-parkonisnism, 1.31% had acute dystonia, 0.04% had tardive dyskinesia, 1.31% akithesia, and 4.8% any neurological side effects. There were no significant differences between agents in the likelihood of any of these side effects or of having any side effect. Higher use of anticholinergics was found in patients treated with FGAs. We also found that 77% were discharged on the same antipsychotic agent they received when they were initially hospitalized. A wide range of acute oral pharmacoptherapy in non-tablet formulations of first and SGAs should be available in psychiatric hospital formularies. FGAs seems to be as well tolerated as SGAs.

Patterns and Trends in Antipsychotic Prescribing for Parkinson Disease Psychosis

Antipsychotic (AP) use is common in Parkinson disease (PD), but APs can worsen parkinsonism, evidence for efficacy is limited, and use in patients with dementia increases mortality. To examine the frequency and characteristics, including changes over time, of AP use in a large cohort of patients with PD. Using Veterans Affairs data from fiscal year (FY) 2008, rates and predictors of AP prescribing were determined for patients with PD and psychosis stratified by dementia status (N = 2597) and a comparison group of patients with dementia and psychosis without PD (N = 6907). Fiscal year 2008 and FY2002 data were compared to examine changes in AP prescribing over time. Department of Veterans Affairs outpatient facilities. Outpatients with PD and psychosis and outpatients without PD with dementia and psychosis, all receiving care at Veterans Affairs facilities in FY2002 and FY2008. Antipsychotic prescribing, including overall, class, and specific medications. In FY2008, 50% of patients with PD having a diagnosis of psychosis were prescribed an AP. Among treated patients, the atypical AP quetiapine was most frequently prescribed (66%), but approximately 30% received high-potency APs. Clozapine was rarely prescribed (<2%). In multivariate models, diagnoses of PD and dementia were associated with AP use. Comparing FY2008 with FY2002, AP use in PD was unchanged, with decreases in risperidone and olanzapine use offset by an increase in quetiapine prescribing and the introduction of aripiprazole. Half of the patients with PD and psychosis receive APs, not uncommonly high-potency agents associated with worsening parkinsonism, and frequency of use has been unchanged since the "black box" warning for AP use in patients with dementia was issued. Recent trends are a shift to quetiapine use and the common use of aripiprazole. As psychosis and dementia are frequently comorbid in PD, safety risks associated with AP use in this population need to be assessed.

Aripiprazole as the Causative Agent of Neuroleptic Malignant Syndrome

Aripiprazole as the Causative Agent of Neuroleptic Malignant Syndrome

A new concept for bisphosphonate therapy: a rationale for the development of monthly oral dosing of ibandronate

Oral daily and weekly bisphosphonates represent the current mainstay of treatment for postmenopausal osteoporosis (PMO). However, the inconvenience of frequent dosing is known to negatively affect adherence to therapy in the long term. This has prompted the development of convenient oral bisphosphonate regimens that feature simple, less frequent dosing schedules. Such regimens require high potency agents, which can be given at low effective doses and that also have good tolerability. Ibandronate is a potent, nitrogen-containing bisphosphonate with proven efficacy when given intermittently to estrogen-depleted beagle dogs, rats and cynomolgus monkeys. Clinically, a pivotal prospective study has established that oral ibandronate has significant vertebral fracture efficacy in PMO, whether given daily (2.5 mg) or intermittently (20 mg every other day for 12 doses every 3 months; extended between-dose interval>2 months). Both oral regimens were well tolerated, which is noteworthy as patients with a history of gastrointestinal (GI) disturbance were not specifically excluded. As a result of these findings, a large, multinational, randomized, double-blind study (Monthly Oral iBandronate In LadiEs: MOBILE) is currently exploring the non-inferiority of once-monthly oral ibandronate (100 or 150 mg) to the oral daily ibandronate (2.5 mg) regimen with proven anti-fracture efficacy, in terms of lumbar spine bone mineral density (BMD) change. As with the trials investigating the weekly administration of other bisphosphonates, vertebral fracture efficacy will be inferred if the study demonstrates the non-inferiority of once-monthly ibandronate to the proven oral daily regimen in terms of spinal BMD change. The availability of this once-monthly ibandronate regimen is expected to offer benefits in terms of convenience (by having to follow dosing recommendations once a month vs. once daily or weekly) and potentially tolerability (by reducing the potential for upper GI irritation that can result from frequent, repeated exposure). Greater convenience and tolerability may enhance the therapy adherence and, hence, improve long-term therapeutic outcomes in PMO.

Clinical correlates of antipsychotic polytherapy in patients with schizophrenia in Singapore.

The purpose of the present study wa to determine the prevalence of antipsychotic polytherapy (use of more than one antipsychotic drug at one time) and its clinical correlates among 300 hospitalized psychotic Asian patients diagnosed with schizophrenia. It was hypothesized that such treatment would be associated with more severe illness than in comparable monotherapy patients, and with higher chlorpromazine-equivalent (CPZ) total daily doses. Clinical and demographic details were obtained from the medical records and direct clinical examinations. Polytherapy was encountered in 215 of the 300 patients (71.7%), with an average number of 1.8 antipsychotics (range 1-4) prescribed at a mean CPZ daily dose of 612 +/- 528 mg (median: 464 mg, range: 25-2500 mg). The 215 patients prescribed more than one antipsychotic agents were younger, ill longer, more likely to be taking at least one high-potency agent, in receipt of higher average daily CPZ doses, and more likely to be prescribed anticholinergic agents but with similar admission illness severity rating (Brief Psychiatric Rating Scale) scores compared to the 85 patients given only one antipsychotic drug at one time. The high rate of antipsychotic polytherapy that appeared to be unrelated to current illness severity suggests that this practice may not consistently be based on rational therapeutic principles.

Antipsychotic dosing and concurrent psychotropic treatments for Medicaid-insured individuals with schizophrenia.

Antipsychotic medications have been first line treatment for schizophrenia for half a century, yet few studies have assessed outpatient maintenance treatment in large populations. This article describes oral antipsychotic dosing patterns and psychotropic treatments using computerized Medicaid claims data for individuals who were diagnosed with schizophrenia and received treatment on an outpatient basis during 1991. The findings show that the mean daily oral antipsychotic dose was 729 +/- 586 chlorpromazine equivalents (CPZ-EQ) for high-potency agents and 304 +/- 328 CPZ-EQ for low-potency agents. Males, younger individuals, and African-Americans received larger mean daily doses of high-potency agents, ranging from 747 to 800 CPZ-EQ. Antiparkinsonian agents were prescribed for over 90 percent of the outpatient antipsychotic treatment exposure. In summary, young adults, males, and African-Americans were given high-potency antipsychotic medications at outpatient maintenance doses that exceeded the maximum recommended levels, despite well-established evidence that high-dose treatment offers no additional benefit. Likewise, concurrent antiparkinsonian treatment exceeded the 1990 World Health Organization recommendations.

Antipsychotic use in pregnancy. What are the best treatment options?

Both the rapid emergence of new antipsychotic medications and the increasing fertility rate among women with psychotic disorders have contributed to the growing clinical importance of the treatment of pregnant women who have psychotic illnesses. The treatment of this patient population must always take into consideration the effect of that treatment on the fetus. With regard to the high risk of decompensation during pregnancy and postpartum, continuous antipsychotic medication is needed using the minimum effective dose. The use of high-potency agents appears to be preferable for first-line management, as there are few data regarding the use of atypical agents such as clozapine in pregnancy. Guidelines for treating pregnant women with psychoses vary little from those for nonpregnant patients. Clinicians must always carefully weigh up the risks and benefits for each patient on an individual basis.

Cognitive effects of antipsychotic agents in persons with traumatic brain injury

Over 1 million survivors of traumatic brain injury receive maintenance pharmacotherapy, of which a substantial number receive antipsychotic agents for the treatment of psychoses, agitation and aggres sion, and other maladaptive behaviours. In spite of the common clinical uses of antipsychotics, the cognitive risks versus benefits are unclear. The purpose of this study was to assess differences in cognitive functioning before, during, and after discontinuation of antipsychotic agents in inpatients undergoing rehabilitation for traumatic brain injury. Neuropsychiatric tests Reys Auditory-Verbal Learning, Trail Making A B, Digit Span Forwards and Backwards evaluating cognitive skills of verbal ability, visuomotor speed, memory, learning, attention, and spatial ability were administered to each subject at baseline immediately prior to tapering or discontinuing antipsychotic, when taper reached 50 of baseline dose, 1 week after antipsychotic discontinuation, and 3 weeks after discontinuation. These data suggest that select areas of cognition improve after antipsychotic discontinuation in subjects with traumatic brain injury. The magnitude of improvement appeared to be greater after discontinua tion with thioridazine, a low potency agent, compared to haloperidol, a high potency agent. Results, although very preliminary, support the hypothesis of cholinergic involvement in regulating cognitive processes, and this underscores the need for more systematic research in this area.

Hospital use of antipsychotic agents in 1989 and 1993: stable dosing with decreased length of stay

This study evaluated recent and current use of antipsychotics by psychiatric inpatients. Computer-based hospital pharmacy records identified prescriptions for antipsychotics in 1993. Medical records were reviewed to verify prescription and clinical data, and these were compared with similar data from 1989. In 1993, antipsychotics were prescribed for 299 (42%) of 709 hospitalized patients. Treatment usually started within 24 hours of admissions averaging 18 days. High-potency agents were used 2.4 times more frequently than low-potency drugs; 13% received clozapine. The mean chlorpromazine-equivalent daily dose, corrected for as-needed supplements, was 305 mg; peak doses were 32% higher. Doses of the most potent agents (fluphenazine and haloperidol) were only 22%-33% above the overall mean. Rarely were two neuroleptics given simultaneously, but cotreatment with an anticonvulsant (84% of patients, 92% of whom received valproate), a potent benzodiazepine (81%), lithium (70%), one CNS depressant (84%), or more (45%) was common. Doses averaged 20% higher for men, 42% lower at age > 50 years versus 20-30 years, and 53% greater for schizophrenia or schizoaffective disorder versus other conditions. Comparison with 1989 admissions (N = 50) averaging 73 days indicated few differences in use of neuroleptics or benzodiazepines but less frequent use of anticonvulsants and lithium. High-potency antipsychotic agents and clozapine were used most often in 1993; doses of high-potency agents were only slightly higher than doses of low-potency agents, but combinations with mood stabilizers were more common in 1993, when length of stay was one-fourth that in 1989.

Drug distribution between blood and brain as a determinant of antipsychotic drug effects

Concentrations of the neuroleptics haloperidol, bromperidol, fluphenazine, chlorpromazine and its metabolites nor-1- and nor-2-chlorpromazine, thioridazine and its metabolites mesoridazine, sulforidazine, and northioridazine, and promazine were estimated is serum and brain of rats by high performance liquid chromatography (HPLC) with electrochemical detection following 5 days of chronic administration of drug at typical doses (haloperidol, bromperidol, and fluphenazine 1 mg/kg/day; chlorpromazine, promazine, and thioridazine 25 mg/kg/day). The observed ration of brain-to-serum concentration of drug varied widely (0.18–62.5) among neuroleptics studied. High potency agents had more favorable brain-to-blood distribution than low potency agents, and a strong correlation (r = 0.734, p < 0.05) was observed between the brain-to-serum ratios of the neuroleptics and standard clinical doses of drug. This finding suggests that drug distribution is a significant determinant of clinical potency. For most neuroleptics, including drugs with high (fluphenazine, haloperidol) and low potency (thioridazine) such as dopamine D2 antagonists, concentration of drug in the brain was similar. If the results are applicable to patients, they suggest that the degree of dopamine D2 blockade achieved during treatment may vary by drug. Chlorpromazine and promazine were notable for producing high concentrations of drug in the brain at typical doses, suggesting that optimal doses might be lower than those in common use. These results may be important in designing and interpreting studies of the effects of neuroleptic drugs in animals and patients.

Neuroleptic Prescription for Chinese Schizophrenics in Hong Kong

There are very few studies on the pattern of neuroleptic prescription for schizophrenics in Asia. 106 schizophrenic patients in a psychiatric unit of a general teaching hospital in Hong Kong were surveyed. The mean daily dose (in chlorpromazine equivalent) was low (568.5mg). The mean daily dose of high potency agents was four times that of low potency agents. A high frequency of use of anticholinergic drugs may indicate that Chinese are more susceptible to acute extrapyramidal side-effects.

Antipsychotics in the elderly

Neuroleptics are commonly prescribed medications in the geriatric population and have a broader spectrum of indications than in younger patients. In spite of the frequent use of neuroleptics in elderly patients with organic brain syndromes, there are relatively few studies that use double-blind, placebo-controlled methodology. The results of these studies are conflicting; however, there is sufficient evidence that symptoms of agitation, behaviourial dyscontrol, and psychosis are often responsive to neuroleptic treatment. Elderly patients with schizophrenia or other psychotic disorders may also benefit from neuroleptic treatment. As there is a potential for overuse of these medications among the elderly, clear definition of checklist symptoms is imperative. Furthermore, periodic reduction of dose and possible discontinuation of the drug should be considered since many of the checklist symptoms in this age group are environmentally related and time-limited. There has so far been little evidence to support the use of one neuroleptic over another. Side-effect profiles suggest that low doses of the high potency agents are safer and better tolerated in the elderly. Both therapeutic effects and side effects should be assessed at regular intervals.