Long-acting Antipsychotic Therapy Research Articles

Neutrophil-Lymphocyte Ratio Values in Schizophrenia: A Comparison between Oral and Long-Acting Antipsychotic Therapies.

Schizophrenia is a mental disorder affecting approximately 0.32% of the global population, according to the World Health Organization. Antipsychotic medications are used to treat this condition by inhibiting D2 dopamine and 5HT2 serotonin receptors. The selection of the appropriate mode of delivery for these drugs is based on factors such as patient adherence, clinical presentation, and patient preferences. However, additional drivers of treatment selection are required in clinical practice. Mounting evidence suggests that neuroinflammation plays a crucial role in the pathogenesis of schizophrenia. NLR, a cost-effective biomarker of inflammation, has increased in several psychiatric conditions and may represent a valid method for studying the inflammatory stage in schizophrenia, relapse, and the first episode of psychosis. The aim of this study is to evaluate whether there are any variations in NLR values between patients given oral antipsychotics and those given long-acting antipsychotics. The study included 50 individuals with schizophrenia, either acute or in the follow-up phase. NLR was obtained by calculating the ratio of absolute neutrophil count (cells/μL) and absolute lymphocyte count (cells/μL). Patients on long-acting antipsychotics exhibited significantly lower mean NLR scores (1.5 ± 0.7) compared to those on oral antipsychotics (2.2 ± 1.3) (p < 0.05). NLR appears promising as a neuroinflammatory biomarker. This study reveals significantly lower NLR values in patients on long-acting antipsychotics, which may signify reduced systemic inflammation and improved adherence.

Antipsychotic prescribing patterns in Australia: a retrospective analysis

BackgroundTo examine real-world patterns of antipsychotic use in patients with schizophrenia Australia.MethodsThis retrospective cohort analysis was conducted using the Australian Commonwealth Department of Human Services Pharmaceutical Benefits Scheme (PBS) 10% sample data. Included data were for patients aged 16-years or older who initiated treatment for the first time with a PBS-reimbursed antipsychotic medication for schizophrenia between July 2013 and September 2017. Patterns of treatment usage were summarised descriptively. Differences in prescribing patterns by age and prescribing year were reported. Treatment persistence was estimated using Kaplan-Meier methods, with differences explored using log-rank tests. Values of p < 0.05 were considered statistically significant.Results6,740 patients, representing 8,249 non-unique patients, received prescriptions for antipsychotic medications. Patients were aged 16 years to over 85 years (54.5% were < 55 years) and two-thirds of patients were male (61%). The majority of treatment episodes (62%, n = 5,139/8,249) were prescribed an atypical oral antipsychotic. Typical long-acting antipsychotic therapies (LATs) were prescribed 19% of the treatment episodes (n = 1,608/8,249. There was a small increase in prescribing of atypical LAT and typical LAT and a small decrease in atypical oral and clozapine prescribing over the study period. Treatment persistence was greatest in patients treated with clozapine, than in those treated with atypical LATs.ConclusionsWhile the majority of patients receive atypical antipsychotic medications, one in five continue to use older typical LAT therapies. Patient age and time on therapy may be associated with choice of therapy. Persistence to atypical LAT therapy is better than for other treatment modalities in this real-world cohort.

APPLICATION OF ANTIPSYCHOTICS OF LONG-TERM ACTION IN SCHIZOPHRENIA

This literature review addresses the effectiveness and safety of long-acting antipsychotic therapy for schizophrenia. The results of randomized trials of recent years are described in detail. The efficacy of taking drugs at the following key research points was examined: the general clinical impression of the severity of the condition (CGI-S), the general clinical impression of the change in state during treatment (CGI-I), and the positive and negative syndrome scale (PANSS). A systematic literature search was conducted using the Scopus, Web of Science, MedLine, elibrary, and other databases.

Adding Suicide Prevention to the Triple Advantages of Injectable Long-Acting Second-Generation Antipsychotics

With the advent of new treatment perspectives for schizophrenic patients, long-acting injectable antipsychotics promise to provide relapse prevention, neuroprotection, and lower mortality rates (1). In preliminary studies, scholars have also indicated that such treatments could play a central role in suicide prevention in patients (2, 3) for whom suicide is the most likely cause of premature death, in addition to repercussions for caregivers and clinicians. Both Kraepelin (4) and Bleuler (5) highlighted the issue of suicide risk among patients suffering from schizophrenia. Modern studies provided an intricate list of risk factors for suicide, pointing to numerous issues in the management and treatment of schizophrenic patients. Individuals at higher risk are generally unmarried young white males who achieved proper functioning before the onset of the disorder (6). Such patients may easily be overwhelmed by hopelessness and depression, as well as becoming demoralized and being aware that their previous lifestyle cannot be maintained. Such patients feel socially isolated, fear further mental deterioration, have higher rates of substance abuse, and may lose faith in the treatments. Suicide attempts and hospitalizations are frequent, and each time they may realize that both medical and family support is limited; moreover, ad hoc interventions are not available or are difficult to implement. There are also further risk factors for suicide in schizophrenia, such as post-psychotic depression, agitation or motor restlessness, poor adherence to treatment, and command hallucinations (although not well ascertained in terms of statistical significance). However, risk factors often yield too many false positives, pointing to the need for suicide assessments based on factors such as an understanding of mental pain and demoralization, as well as therapeutic relationships, foreseeable life events that may impact the patient, social support, and the available resources. Furthermore, suicide risk is indirectly related to relapse, illness progression, the number of hospitalizations, and plans for rehabilitation after discharge (7). Each admission to a psychiatric ward may represent a further loss of hope and faith in the treatments. The risk of suicide seems to peak not only shortly after discharge, as reported routinely in the literature, but also shortly after admission (7). This fact points to the implementation of human–environmental factors for providing ward safety and close supervision in both inpatient and community settings, especially in the cases of reduced adherence to treatment. Among the various risk factors, preventative actions should be directed over those factors that are modifiable and can be targeted by proper treatment actions (8). Furthermore, suicide risk seems to be higher when patients develop demoralization syndrome, in which repeated exacerbations of psychotic symptoms, functional deterioration compared with premorbid abilities, and a non-delusional awareness of the effects of an illness can lead to feelings of hopelessness, depression, and, ultimately, suicide. Suicidal behavior is also a major issue among patients with first-episode psychosis (9, 10). It is noteworthy that integrated compared with typical treatment proved to be effective in reducing both suicide and other causes of death; the Opus Study (9) demonstrated the effectiveness of this strategy. Such an intervention involved a) assertive community treatment (ACT); b) antipsychotic medication; c) psychoeducational family treatment; and d) social skills training. It resulted in lower mortality for any cause and lower suicide rates. Mortality in Schizophrenia and Pharmacological Treatment A recent study by Bitter et al. (11) highlighted the reduction in life expectancy among patients with schizophrenia. Of note is the fact that, compared with the controls, 20-year-old males with schizophrenia had their life expectancy reduced by 11.5 years and females by 13.7 years; the analogous numbers for 45-year-old schizophrenics were 8.1 and 9.6 years, respectively. Taipale et al. (12) explored mortality in a large sample of approximately 30,000 patients and found that second-generation long-acting antipsychotic therapies [SG LATs; ranking: paliperidone palmitate > oral aripiprazole > long-acting injection (LAI) risperidone > LAI haloperidol > LAI perphenazine > oral perphenazine > LAI olanzapine > LAI zuclopenthixol] were associated with the lowest cumulative mortality rate. In 7.5 years, a follow-up SG LAT observation revealed the lowest cumulative mortality rate as compared with first-generation (FG) and SG oral and with no antipsychotic use. The use of LATs reduces the risk of death by 33% when compared to the corresponding oral equivalent. Such results are in line with further investigations by the same group of researchers (13), who reported their observations over 8 years. They observed that the risk of treatment failure or relapse after discontinuing antipsychotics does not decrease over time and that patients maintaining long-term antipsychotic treatment had increased survival rates.

Once-monthly paliperidone palmitate in early stage schizophrenia - a retrospective, non-interventional 1-year study of patients with newly diagnosed schizophrenia.

BackgroundLong-acting antipsychotic therapy may be best suited for patients in the early stage of schizophrenia, when the most can be done before disease progression associated with poor adherence occurs. We explored the patterns of use of once-monthly paliperidone palmitate (PP1M), concomitant medication use, hospitalization, and clinical outcomes of adult, newly diagnosed patients with schizophrenia receiving continuous treatment with PP1M for at least 12 months.MethodsThis was an international, multicenter, exploratory, retrospective chart review of medical records of adult patients who were newly diagnosed (not more than 1 year before initiation of PP1M treatment) with schizophrenia and who had received continuous treatment with PP1M for ≥12 months in naturalistic clinical settings.ResultsA total of 84 (93.3%) patients were included in the analysis. All but one patient (98.8%, n=83) had received oral antipsychotic medication at least during the last month before the first PP1M administration. Three patients (3.6%) were newly hospitalized during the 12-month documentation period. The reason for hospitalization for all three was management of episode/relapse. A total of 79.2% of patients had a ≥20% improvement and 47.2% had a ≥50% improvement in Positive and Negative Syndrome Scale total score from baseline to endpoint. Half of patients (53.3%) showed a significant improvement, as reflected by an increase in Personal and Social Performance (PSP) total score of at least 7 points from baseline to endpoint (mean [SD] 11.9 [15.0] points; P<0.001). One quarter of patients (24.4%, n=11) moved from a PSP score of 31–70 (ie, moderate to marked functional impairment) at baseline to a PSP score of mild to no functional impairment (PSP score ≥71) at endpoint. Most adverse drug reactions were mild or moderate in severity.ConclusionContinuous treatment with PP1M over 12 months was associated with statistically significant and clinically meaningful improvements in psychotic symptoms, disease severity, and functional outcomes in patients with schizophrenia.

PMH43 - Three-Monthly Long-Acting Antipsychotic Therapy Results in A Better Treatment Continuity Compared to A One-Monthly or Bi-Weekly Treatment In Schizophrenia

PMH43 - Three-Monthly Long-Acting Antipsychotic Therapy Results in A Better Treatment Continuity Compared to A One-Monthly or Bi-Weekly Treatment In Schizophrenia

Cost effectiveness of paliperidone palmitate versus risperidone long-acting injectable and olanzapine pamoate for the treatment of patients with schizophrenia in Sweden

Objective:To model the cost effectiveness of paliperidone palmitate (paliperidone long-acting injectable; PLAI), a new once-monthly long-acting antipsychotic therapy, compared with risperidone long-acting injectable (RLAI) and olanzapine pamoate (OLAI), in multi-episode patients (two or more relapses) with schizophrenia in Sweden.Methods:A Markov decision analytic model was developed to simulate the history of a cohort of multi-episode patients transitioning through different health states on a monthly basis over a 5-year time horizon from the perspective of the Swedish healthcare system. Therapeutic strategies consisted of starting treatment with RLAI (mean dose 37.5 mg every 2 weeks), PLAI (mean dose 75 mg equivalent (eq.) every month) or OLAI (150 mg every 2 weeks or 300 mg every 4 weeks). Probability of relapse, level of adherence, side-effects (extrapyramidal symptoms, tardive dyskinesia, weight gain and diabetes) and treatment discontinuation (switch) were derived from long-term observational data when feasible. Incremental cost-effectiveness outcomes, discounted at 3% annually, included cost per quality-adjusted life-year (QALY) and cost per relapse avoided (expressed in 2009 Swedish Krona SEK).Results:Relative to RLAI and OLAI, PLAI is economically dominant: more effective (additional QALYs, less relapses) and less costly treatment option over a 5-year time horizon. The results were robust when tested in sensitivity analysis.Limitations:The impact of once-monthly treatment on adherence levels is not yet known, and not all variables that could impact on real-world outcomes and costs were included in this model.Conclusion:PLAI was cost saving from a Swedish payer perspective compared with RLAI and OLAI in the long-term treatment of multi-episode (two or more relapses) schizophrenia patients.

Treatment of schizophrenia with long-acting fluphenazine, haloperidol, or risperidone.

Objective: This study compares 3 cohorts of patients with schizophrenia before, during, and after initiating treatment with fluphenazine decanoate (FD), haloperidol decanoate (HD), or long-acting injectable risperidone (LAR). Methods: Administrative data are analyzed from California Medicaid (Medi-Cal) beneficiaries with schizophrenia who initiated FD, HD, or LAR treatment. Patients were required to have been continuously enrolled in Medi-Cal for 180 days before and 180 days after the start of the new episode of long-acting antipsychotic therapy. Results: There were few demographic and clinical differences among patients initiating FD, HD, and LAR. During the 180 days before starting long-acting injections, most patients initiating FD (53.5%), HD (58.5%), and LAR (61.2%) received oral antipsychotic medications for <80% of the days in this period (medication possession ratio: <0.80). The mean duration of depot treatment episodes was 58.3 days (SD = 53.6) for FD, 71.7 days (SD = 56.4) for HD, and 60.6 days (SD = 48.8) for LAR (F = 18.3, df = 2, 2694, P < .0001, HD > FD). Few patients who started on FD (5.4%), HD (9.7%), or LAR (2.6%) continued for at least 180 days. Most patients in each group (FD [77.4%], HD [78.9%], and LAR [75.5%]) received oral antipsychotic medications during the 45 days after discontinuing long-acting injections. Coprescription with antidepressants, mood stabilizers, and benzodiazepines was common. Conclusions: Patients treated with long-acting antipsychotic injections tend to have complex pharmacological regimens and recent medication nonadherence. A great majority of patients initiating long-acting antipsychotic medications discontinue use within the first few months of treatment.