Antipsychotics In Clinical Practice Research Articles

Changing vistas of psychosis and antipsychotic drug dosing toward personalized management of antipsychotics in clinical practice.

To discuss current evidence on tapering antipsychotic drugs in view of changing vistas of psychosis, suggesting a provisional framework for safely tapering antipsychotic drugs to an optimal low dose, in collaboration with patients and their relatives, to promote functional recovery while preventing relapse. Paradigm shifts during recent years regarding the nature of psychotic disorders and the role of the dopamine system are discussed, including the positive effects of dopamine blockade in acute psychosis and the limitations and drawbacks of dopamine blockade regarding negative and cognitive symptoms after remission of positive symptoms. Recent advances in tapering strategies and upcoming ways to solve the dilemma between the need to prevent relapses with antipsychotics on the one hand and the need to minimize side effects by tapering these drugs on the other are presented. Modern tapering strategies appear to reduce relapse risk to acceptable levels and offer a feasible personalized option to find the least effective dose to treat and prevent positive symptoms without redundant side effects and functional incapacity. These findings need replication, and several trials that might provide more certainty are on their way. Preliminary evidence and clinical experience indicate that personalized dose reduction of antipsychotics is feasible and safe if carried out in close collaboration with patients and their relatives, according to a provisionally suggested framework presented here. These preliminary directions still must be confirmed, revised, and adjusted according to upcoming trial results. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

The neutrophil-lymphocyte ratio in first-episode medication-naïve patients with schizophrenia: A 12-week longitudinal follow-up study

Inflammation has been related to schizophrenia (SZ). The neutrophil-to-lymphocyte ratio (NLR) is an inexpensive inflammatory marker, however, its potential predictive value in patients with SZ has not been extensively investigated. This study aimed to examine whether NLR could predict the clinical response to antipsychotics in this population. One hundred and ninety-five medication-naïve first-episode schizophrenia (MNFES) patients were recruited and received treatment with risperidone for 12 weeks in the present study. Clinical symptoms were evaluated at week 0 and the end of 12 weeks of treatment using the PANSS scales. Complete blood counts were determined at baseline. We found that baseline NEU counts and NLR were positively associated with improvements in clinical symptoms in patients. In addition, MNFES patients with higher baseline NLR values showed a better treatment response to antipsychotics. Linear regression analysis revealed a predictive role of baseline NLR for the improvements of clinical symptoms in SZ patients. Our findings demonstrate that higher NLR was related to better improvements in symptoms after 12 weeks of treatment with antipsychotics, which renders it a promising biomarker of the response to antipsychotics in clinical practice.

Lower Risks of Gastrointestinal Perforation and Intestinal Obstruction in Patients with Atypical Antipsychotics in Comparison with Typical Antipsychotics Based on Real-World Data from the MID-NET® in Japan

Intestinal perforation and obstruction are known to be one of the adverse events caused by antipsychotics; however, warning information on package inserts varies among antipsychotics. To investigate the risks of gastrointestinal perforation and intestinal obstruction in patients prescribed atypical antipsychotics compared with those in patients prescribed typical antipsychotics, a nested case–control study was conducted utilizing real-world data from the MID-NET® medical information database in Japan. The study period spanned from January 1, 2009, to December 31, 2018. We found that the risks of gastrointestinal perforation and intestinal obstruction in patients prescribed atypical antipsychotics were significantly lower than those in patients prescribed typical antipsychotics (adjusted odds ratio, 0.48; 95% confidence interval, 0.29–0.80). This finding was supported with prolonged periods for the exposure definition in the sensitivity analyses. In addition, no major differences in the risks of atypical antipsychotics, such as risperidone, quetiapine, olanzapine, and aripiprazole, were identified in this study. The safety profile regarding the lower risks of gastrointestinal perforation and intestinal obstruction in patients prescribed atypical antipsychotics should be considered when choosing antipsychotics in clinical practice in terms of the proper use of such drugs.

Second-generation long-acting injectable antipsychotics in clinical practice

On the example of 5 clinical cases of paranoid schizophrenia at different stages of the development of the disease, the therapeutic tactics of using drugs from the group of second-generation injectable prolong antipsychotics to solve problems that arise during anti-relapse therapy are shown. The research data substantiating these approaches are presented. Various combination therapy options are discussed, including at the stage of drug replacement and the appointment of a second-generation long-acting injectable antipsychotic.

Switching antipsychotics: Results of 16-month non-interventional, prospective, observational clinical research of inpatients with schizophrenia spectrum disorders

The study aims to identify prescribing and switching patterns of antipsychotics in clinical practice. A 16-month, prospective study was conducted at the Psychiatric Hospital Idrija, Slovenia. Inpatients (N = 311) with schizophrenia spectrum disorders were observed. The causes for switching antipsychotics and switching strategies were analyzed. Analyzing a total of 3954 prescriptions, the collected data confirmed that treatment strategies in this psychiatric hospital are very complex. It was found that 37 percent of inpatients had at least one switch. Moreover, switches that included three or more antipsychotics were detected. The most common causes for switching antipsychotics were adverse reactions and inefficacy or lack of efficacy. Among switching options, abrupt switch was recorded several times. As some patients are receiving several antipsychotics at the same time, it is possible that unusual switching occurs in clinical practice. It seems that the choice of switching strategy is also affected by the cause and urgency for switching an antipsychotic.

Effectiveness of long-acting antipsychotics in clinical practice: 2. Effects of antipsychotic polypharmacy on risperidone long-acting injection and zuclopenthixol decanoate.

Antipsychotic polypharmacy (APP) is common clinical practice. Theoretically, APP runs the risk of additional side effects, drug interactions, adherence and cost. A limited evidence base is emerging to support the effectiveness of APP in clinical practice. Our companion paper highlighted the extent of APP alongside commonly prescribed long-acting antipsychotic injections (LAIs). We aimed to examine the effects of APP on discontinuation rates and Clinical Global Impression (CGI) outcomes in patients commenced on risperidone long-acting injection (RLAI) and zuclopenthixol decanoate. LAI-naïve patients commenced on RLAI (n = 102) and zuclopenthixol decanoate(n = 105) were identified using our electronic patient record (running from 2002) within NHS Lanarkshire, Scotland, UK. This was a retrospective, electronic case note review with an 18-month follow up. Patient groups were divided into those receiving the LAI as the sole antipsychotic and those who were receiving additional oral antipsychotic polypharmacy (APP) for at least 50% of the duration of the treatment with their LAI. Kaplan-Meier statistics were calculated for discontinuation rates. CGI severity and improvement scores were retrospectively assigned by the investigating team. Antipsychotic polypharmacy occurred with RLAI (37%) and zuclopenthixol decanoate (46%) and was associated with lower discontinuation rates (statistical significant with zuclopenthixol for any cause and adverse effects discontinuation). APP had no adverse outcomes on hospital admissions or CGI ratings. Patients on APP did not have more severe, chronic or treatment resistant illnesses. For RLAI and zuclopenthixol decanoate, APP had some favourable outcomes when examining discontinuation rates for any cause, and adverse effects. This was unexpected as we had considered APP would signal illness chronicity and severity and be associated with increased adverse effects resulting in early discontinuation. APP had no adverse outcomes on assigned CGI improvement or mean end-point severity ratings for RLAI and zuclopenthixol decanoate.

Effectiveness of long-acting antipsychotics in clinical practice : 1. A retrospective, 18-month follow up and comparison between paliperidone palmitate, risperidone long-acting injection and zuclopenthixol decanoate.

In the UK, nine different compounds are available as long-acting antipsychotic injections (LAIs). There are few clinical guidelines for determining which LAIs are most effective in specific patient groups. To measure the clinical effectiveness of LAIs we aimed to determine the now-established concept of antipsychotic discontinuation rates and measure Clinical Global Impression (CGI) outcomes. The population (n was approximately 560,000) was a secondary care NHS adult mental health service in Lanarkshire, Scotland, UK. This was a retrospective, electronic case note search of LAI-naïve patients commenced on paliperidone palmitate (n = 31), risperidone long-acting injection (RLAI) (n = 102) or zuclopenthixol decanoate (n = 105), with an 18-month follow up. Kaplan-Meier survival statistics for discontinuation rates and hospital admission were calculated. CGI severity and improvement scores were retrospectively assigned by the investigating team. Paliperidone palmitate performed less favourably than risperidone long-acting injection (RLAI) or zuclopenthixol decanoate. Paliperidone palmitate had higher discontinuation rates due to any cause, inefficacy and increased hospitalization risk. Paliperidone palmitate had the smallest proportion of patients assigned a clinically desirable CGI-I score of 1 (very much improved) or 2 (much improved). Paliperidone palmitate had less favourable discontinuation and CGI outcomes compared with RLAI and zuclopenthixol decanoate. This could not be adequately explained by patients in the paliperidone group being more chronically or severely unwell, nor by the presence of comorbidities such as alcohol or substance misuse, or by the use of lower mean dosages compared with RLAI or zuclopenthixol decanoate. We considered that prescribers are familiarizing themselves with paliperidone and outcomes may improve over time.

Non-adherence to medication in patients with psychotic disorders: epidemiology, contributing factors and management strategies

Although non-adherence is common across all branches of medicine, psychotic disorders pose additional challenges that increase its risk. Despite the importance of non-adherence, clinicians generally spend too little time on assessing and addressing adherence attitudes and behaviors. Importantly, how adherence is measured significantly impacts the findings, and the most frequently employed methods of asking patients or judging adherence indirectly based on efficacy or tolerability information have poor validity. Novel technologies are being developed that directly assess adherence and that can also be used to both provide real-time feedback to clinicians and serve as an intervention with patients. Several treatments are available that can positively impact adherence. Among psychosocial interventions, those combining multiple approaches and involving multiple domains seem to be most effective. Although long-acting injectable antipsychotics are theoretically a very powerful tool to assure adherence and signal non-adherence, recent results from randomized controlled trials failed to show superiority compared to oral antipsychotics. These data are in contrast to nationwide cohort studies and mirror-image studies, which arguably include more representative patients receiving long-acting antipsychotics in clinical practice. This disconnect suggests that traditional randomized controlled trials are not necessarily the best way to study interventions that are thought to work via reducing non-adherence. Clearly, non-adherence is likely to remain a major public health problem despite treatment advances. However, increasing knowledge about factors affecting adherence and leveraging novel technologies can enhance its early assessment and adequate management, particularly in patients with psychotic disorders.

1152 – Formalized consensus guidelines for use and management of antipsychotic depots

Introduction As part of a process to improve the quality of care, the Association for Biological Psychiatry and Neuropsychopharmacology (AFPBN) developed recommendations for the use and management of Long Acting Injectable (LAI) Antipsychotics in clinical practice. Methods Based on a literature review, a written survey was prepared that asked about 539 options in 32 specific clinical situations. We contacted 64 national experts, 42 (65,6%) completed the survey. According to the answers for each situation based on a 9-points scale, a categorical rank (first-line/preferred choice, second-line/alternate choice, third-line/usually inappropriate) was assigned to each option. First-line option was defined as a strategy rated as 7–9 (extremely appropriate) by at least 50% of the experts. Results For French experts, LAI Antipsychotics are indicated in patients with schizophrenia, schizoaffective disorder and bipolar disorder. According to their efficacy and tolerability risperidone LAI then olanzapine LAI are recommended as first line for maintenance treatment in schizophrenia, even after the first episode. Depot neuroleptics are recommended as second line for maintenance treatment in schizophrenia. LAI Second Generation Antipsychotics are recommended as second line in bipolar disorder. Several clusters of patients are identified, characterizing a specific profile for the use of LAI. Recommendations for the use of LAI and switch from oral to injectable formulations are suggested. Conclusion The use of LAI has advantages as maintenance treatment but their prescription rate is generally below 30% in different countries. Specific guidelines for the use and management of this formulation could improve their use in clinical practice.

Evaluation of the Incidence of Leukopenia and Agranulocytosis in Patients Receiving Combined Clozapine and Other Antipsychotics

ABS TRACT: Evaluation of the incidence of leukopenia and agranulocytosis in patients receiving combined clozapine and other antipsychotics Objective: In this study, we aimed to evaluate of the incidence of leukopenia and agranulocytosis in patients receiving a combination of clozapine and other antipsychotics in clinical practice. Methods: The data for this study were collected by retrospective analysis of the charts of patients with a diagnosis of schizophrenia at the Samsun Mental Health and Diseases Hospital in 2011. The dose of clozapine and the doses of other antipsychotics, the ages and genders of the patients, the duration of follow up (weeks) and leukocyte counts during follow up were recorded. The relationship between the use of clozapine and other antipsychotics and the categorical classification of leukocyte counts (3500-4000/µL, 3000-3499/µL or 4000/µL in patients receiving a combination of these different antipsychotics and clozapine. Leukocyte counts were decreased to lower than 3500/µL in 3 (3.2%) patients. Two (2.1%) of these patients who had leukocyte counts of 3000-3499/ µL were followed without any problem and one patient (1.1%), who had a leukocyte count of < 2000 µL followed a fatal course due to agranulocytosis and complicating infections. Conclusions: No difference was detected with respect to the risk of leukopenia and agranulocytosis with different antipsychotic combinations with clozapine. These findings must be confirmed by further studies.

Reprise: The effect of metformin on anthropometrics and insulin resistance in patients receiving atypical antipsychotic agents: A meta-analysis

ABSTRACT Atypical antipsychotics are well-established agents for the treatment of various psychiatric illnesses, although they are associated with adverse metabolic effects. There have been a few methodologically sound studies that have assessed the approach of adding metformin to atypical antipsychotics to reduce body weight. A systematic literature review of MEDLINE, EMBASE, and Cochrane was performed from the earliest possible dates to December 31, 2008. Metformin was found to be associated with a decrease in weight, waist circumference, bmi, and insulin resistance (p&amp;lt;0.005). The data supports the consideration of metformin for the reduction of metabolic effects developed from the atypical antipsychotics in clinical practice. Ultimately, additional rigorous controlled trials with the various antipsychotics and at different time points in the development of the metabolic effects are needed.

The Impact of FDA's Warning on the Use of Antipsychotics in Clinical Practice: A Survey

Determine the influence of warnings from the Food and Drug Administration (FDA) regarding antipsychotic use for the management of dementia-related psychosis on clinical practice. A survey of health care professionals specializing in geriatrics was conducted with the use of a Web-based software program. The questions focused on practitioners' familiarity with recent FDA warnings, perceptions of their validity, and changes in antipsychotic use patterns. Sixty-five geriatric practitioners belonging to major national geriatric organizations completed the survey. Responses were reviewed once the survey was closed, six weeks after Web posting. Changes in prescribing practices for the management of dementia-related psychosis in light of the antipsychotic FDA warnings. The majority of participants responded that they were "very familiar" with the FDA warnings. The results indicated that 68% of participants reported using antipsychotic medications in elderly patients with known cerebral/cardiovascular diseases. Forty-nine percent of participants reported that they changed the way they managed elderly patients with dementia-related psychosis based on this notification. The most commonly reported barriers for not taking into consideration the FDA warnings were: no alternative treatment available, lack of guidance, lack of evidence, and poor availability of data. The majority of participants reported the use of atypical antipsychotics more frequently than the typical antipsychotics. Despite FDA warnings, antipsychotics are still being used for the management of dementia-related psychosis; management of behaviors associated with dementia either through drug therapy or nonpharmacologic interventions remains a challenge.

Combination Therapy in the Treatment of Schizophrenia

Although the international guidelines for the treatment of schizophrenia recommend antipsychotic monotherapy as the treatment of choice, many schizophrenia patients receive two or more antipsychotics in clinical practice, while co-treatment with antidepressants, mood stabilizers and benzodiazepines is also common. The aim of the present review is to summarize the results of the randomized controlled trials of combination therapy versus monotherapy in schizophrenia and to discuss possible implications of these results. Altogether, recommendations are based upon theoretical assumptions rather than upon evidence-based knowledge regarding the combination of different antipsychotics or antipsychotics with other psychotropic agents in schizophrenia treatment, since the available studies reveal conflicting results. The augmentation with antidepressants for the treatment of persisting negative symptoms and with mood stabilizers in patients with additional affective symptoms seems to be a successful strategy. Further randomized controlled trials are warranted to provide substantial evidence and to suggest combination strategies for treatment-resistant schizophrenia.

Comparing the Use and Discontinuation of Antipsychotics in Clinical Practice

There are few independent studies comparing atypical or second-generation antipsychotics (SGAs). To compare the patterns of use and discontinuation of commonly used SGAs. Retrospective review of 11,250 case records (2002-2005) of all mental health care contacts in a discrete geographical setting in Scotland. Patterns of use, mean dose, psychotropic co-prescription, duration of treatment, discontinuation rates, and admission rates were examined for amisulpride, clozapine, olanzapine, quetiapine, and risperidone. Clozapine had a significantly lower discontinuation rate in individuals with schizophrenia, compared to the other 4 SGAs. Off-license prescribing and polypharmacy were common. SGAs are variously used for schizophrenia and mood disorder and have heterogeneous outcomes, with clozapine being most effective in this study. Independent observational studies such as this complement randomized controlled trials.

Children with Schizophrenia

Awareness of childhood-onset schizophrenia is rapidly increasing, with a more precise definition now available of the clinical picture and early signs, the outcome and the treatment strategies. Premorbid developmental impairments, including language, motor and social deficits, are more frequent and more pronounced in earlier- than in later-onset forms of schizophrenia. This 'pan-dysmaturation' is reported from the first months of life in more than half of the children who will develop childhood-onset schizophrenia, and it suggests a more severe and early disruption of brain development compared with the adolescent- and adult-onset disorder. The insidious onset in at least 75% of children, the high rates of premorbid problems and the hesitancy on the part of clinicians to make a diagnosis of schizophrenia in a child usually delay the recognition of the syndrome. Elementary auditory hallucinations are the most frequent positive symptom, while visual and tactile hallucinations are rarer. Delusions are less complex than in adolescents and are usually related to childhood themes. Negative symptoms are largely predominant, namely flat or inappropriate affect. A marked deterioration from the previous level of functioning is present in all these children, and an impaired outcome is reported in approximately 50-60% of them. The main diagnostic challenges are with differentiating childhood-onset schizophrenia from affective disorders (both depression and bipolar disorder) with psychotic symptoms, pervasive developmental disorders and severe personality disorders. Post-traumatic stress disorder and obsessive-compulsive disorder without insight may also be misdiagnosed as schizophrenia. Furthermore, approximately 10% of children from the community report nonpsychotic hallucinations or delusions. Finally, children with atypical psychotic features that do not strictly fit diagnostic criteria for schizophrenia have been described, and new labels have been proposed to categorise these clinical patterns, such as multidimensionally impaired disorder and multiple complex developmental disorder. In the context of a multimodal approach, including behavioral, social, scholastic and familial interventions, a pharmacological treatment is usually the core treatment. Available experience from the few controlled studies, open studies and case reports on pharmacotherapy in children with schizophrenia aged <12 years is critically analysed in this review, with particular reference to the use of atypical antipsychotics in clinical practice. To date, the major evidence supports the efficacy of risperidone and olanzapine, while clozapine seems an effective option in treatment-refractory cases. Published experience with newer atypical antipsychotics (quetiapine, ziprasidone, aripiprazole) is still lacking in this age range. Safety data (namely extrapyramidal symptoms, weight gain, hyperprolactinaemia, haematological adverse effects, seizures, hepatotoxicity, metabolic effects, neuroleptic malignant syndrome and cardiovascular effects) are reviewed and discussed, along with strategies for management.

Antipsychotics in clinical practice: guidelines for safe and effective use.

Antipsychotic drugs have made a significant contribution to the treatment of schizophrenia but the older drugs in particular have significant side-effects. The newer atypical drugs are effective for the treatment of both positive and negative symptoms and they also have significantly fewer serious side-effects. However, these drugs are considerably more expensive that the older drugs and this has generated intense debate about their cost effectiveness. There is now good evidence that when all factors are taken into consideration the atypical drugs are both cost effective and improve the quality of life of patients with schizophrenia. Despite the importance of these drugs there is widespread variation in their use and a national consensus on this important issue is long overdue.