Long-acting Injectable Antipsychotic Drugs Research Articles

Overview of approved psychiatric medications 2008-2023: A systematic review

Objective: The purpose of this systematic review is to enumerate the psychiatric medications approved by the Food and Drug Administration (FDA) over the past 15 years, from 2008 to 2023, and describe their mechanism of action, approved indications, dosing ranges, and adverse effects. Methods: Studies published from 2008 to 2023 were identified from the PubMed database, using the keywords: ‘psychiatric’ OR ‘psychopharm*” AND ‘medic*’ OR ‘pharm*’. An independent focused analysis was conducted, and a consensus was reached on the studies for approved medications to be included in this systematic review. Key findings were derived from the full-text and tables of the selected studies. Results: From 2008-2023, the FDA approved 118 medications including: 26 for Schizophrenia, 12 for Bipolar Disorders, 16 for Depressive Disorders, two for Anxiety Disorders, one for Feeding and Eating disorders, 13 for Sleep-Wake Disorders, five for Sexual Dysfunctions, 16 for Substance Use Disorders, six for Neurocognitive Disorders, and 18 for Neurodevelopmental Disorders (specifically, Attention-Deficit/Hyperactivity Disorder, ADHD), in addition to three for Psychiatric Medication-Related Movement Disorders. It is important to note that 37 out of the 118 medications were New Drug Application (NDA) approvals by the FDA, i.e., they have not been previously approved for another indication. We also noted that nine medications were discontinued by the manufacturer, with no reported safety or effectiveness concerns. Over the past fifteen years, several novel treatment approaches and modalities have been introduced, such as monoclonal antibodies for the treatment of Alzheimer’s Disease, very long-acting injectable antipsychotic drugs, targeting the glutamate neurochemical system for depression and depressive symptoms in other disorders, medications for conditions without any previously approved medicines (e.g., Binge Eating Disorder), and tablets with sensors to monitor treatment adherence. Of note, no new medications were approved from 2008-2023 for: Anxiety Disorders (with the exception of two extended-release preparations of previously approved agents), Obsessive-Compulsive Disorder, Trauma- and Stressor-Related Disorders, Dissociation Disorders, Somatic Symptom Disorders, and Disruptive, Impulse-Control, and Conduct Disorders. Conclusion: Approved psychiatric medications from 2008-2023 show substantial promise in the treatment of psychiatric conditions. More than 100 psychiatric medications were approved over the past 15 years for the major psychiatric conditions including a combination of newly introduced medications and new indications and drug formulations for already approved medications. It behooves psychiatric clinicians to keep up to date with this ever evolving and fast changing field. As the overview article, this manuscript will be followed by in-depth, disorder-based descriptions of approved medications, as well as those currently under development in Phase III.

Long-Acting Injectable Second-Generation Antipsychotics vs Placebo and Their Oral Formulations in Acute Schizophrenia: A Systematic Review and Meta-Analysis of Randomized-Controlled-Trials.

Long-acting injectable antipsychotic drugs (LAIs) are mainly used for relapse prevention but could also be advantageous for acutely ill patients with schizophrenia. We conducted a systematic review and meta-analysis of randomized-controlled-trials (RCTs) comparing the second-generation long-acting injectable antipsychotics (SGA-LAIs) olanzapine, risperidone, paliperidone, and aripiprazole with placebo or their oral counterparts in acutely ill patients with schizophrenia. We analyzed 23 efficacy and tolerability outcomes, with the primary outcome being overall symptoms of schizophrenia. The results were obtained through random effects, pairwise meta-analyses, and subgroup tests. The study quality was assessed using the Cochrane-Risk-of-Bias-Tool version-1. Sixty-six studies with 16 457 participants were included in the analysis. Eleven studies compared second-generation long-acting injectable antipsychotics (SGA-LAIs) with a placebo, 54 compared second-generation oral antipsychotics (SGA-orals) with a placebo, and one compared an SGA-LAI (aripiprazole) with its oral formulation. All 4 SGA-LAIs reduced overall symptoms more than placebo, with mean standardized differences of -0.66 (95% CI: -0.90; -0.43) for olanzapine, -0.64 (-0.80; -0.48) for aripiprazole, -0.62 (-0.76; -0.48) for risperidone and -0.42 (-0.53; -0.31) for paliperidone. The side-effect profiles of the LAIs corresponded to the patterns known from the oral formulations. In subgroup tests compared to placebo, some side effects were less pronounced under LAIs than under their oral formulations. SGA-LAIs effectively treat acute schizophrenia. Some side effects may be less frequent than under oral drugs, but due to the indirect nature of the comparisons, this finding must be confirmed by RCTs comparing LAIs and orals head-to-head.

Profile of patients undergoing treatment with long-acting injectable antipsychotic drugs in a psychiatry hospital in Portugal

IntroductionThe treatment with long-acting injectable antipsychotics (LAIAs) is more and more frequent and it shows advantages regarding adherence, effectiveness and tolerance.ObjectivesTo describe and compare the profile of patients under treatment with LAIAs in a psychiatric hospital in Portugal.MethodsAn observational and retrospective study was carried out with the collection of data referring to patients hospitalized with a first psychotic episode between 01/01/2019 and 30/06/2022 in a psychiatric hospital in Portugal and the respective evaluation of sociodemographic and clinical data through the information recorded in the clinical files.ResultsDuring the 42 months of the study, we selected 78 patients who presented psychotic symptoms on admission. Patients with a history of previous psychotic episodes and prescription of antipsychotic therapy prior to hospitalization were excluded.Of 78 patients hospitalized with a first psychotic episode, 34 - which corresponds to approximately 44% - were discharged with LAIAs.Patients receiving LAIAs had an average age of 39 years. The average number of days of hospitalization was 28 days; 41% were female (n=14) and 59 were male (n=20); 35% (n=12) consumed psychoactive substances previously on admission to hospital; 62% (n=21) were discharged under the compulsive treatment regimen. Regarding the diagnosis at discharge, based on the international classification of disease-11 (ICD-11), the most common were schizophrenia, psychotic disorder induced by psychoactive substances and acute and transient psychotic disorder.From the statistical analysis carried out, no correlation was observed between the rate of readmissions and the administration of LAIAs, nor was there any correlation between the rate of readmissions and compulsive outpatient treatment.ConclusionsDespite what is described in the literature, in the sample under study, the LAIAs were not superior in the variables studied, namely in reducing the readmission rate. Possible explanations for the results obtained may be justified by the size of the sample under study and the follow-up time of the cases.Disclosure of InterestNone Declared

The Novel Antipsychotic Drug Cariprazine and Cognition Enhancing Drugs: Indications for their Use as the Add-on Therapy in Schizophrenia.

Schizophrenia and schizoaffective disorder are treated with antipsychotic drugs. Some patients show treatment-resistant forms of psychotic disorders, and in this case, they can be treated with clozapine. Based on the previous reviews on novel antipsychotic drugs, it is important to know whether the add-on therapy with the new drugs can ameliorate the positive and negative schizophrenic scale (PANSS) total score. The aim of this review is to suggest an appropriate treatment for patients with treatment-resistant forms of psychotic disorders. A combination of the currently available antipsychotic drugs with novel antipsychotic or modulating drugs might improve negative schizophrenic symptoms and cognitive function and thereby social functioning and quality of life. The mechanisms of action, the therapeutic effects, and the pharmacokinetic profiles of novel antipsychotic drugs such as cariprazine, brexipiprazole, and lumateperone have been updated. Published case reports of patients with treatment-resistant psychoses have also been discussed in this study. These patients were treated only with clozapine, as a result of which a high PANSS total score was observed. Only the add-on therapy with cariprazine improved the score, and above all, the negative schizophrenic symptoms and cognitive functions were improved. For the ensurance of a constant antipsychotic drug concentration, long-acting injectable antipsychotic drugs might be a choice for the maintenance therapy in schizophrenia. New modulating drugs, such as receptor positive allosteric modulators (N-methyl-D-aspartate receptor; subtype 5 of the metabotropic glutamatergic receptor) and encenicline, an alpha7 nicotinic cholinergic receptor agonist, have been investigated in preclinical and clinical trials. In clinical trials, patients with treatment-resistant forms of psychosis should be examined to know whether combination therapy with clozapine and a novel antipsychotic drug can ameliorate the PANSS total score. In schizophrenia, long-acting injectable antipsychotic drugs are safe and tolerable maintenance therapy. In further clinical studies, it should be investigated whether patients with treatment-resistant forms of psychoses can improve negative schizophrenic symptoms and cognitive functions by the add-on therapy with cognitionenhancing drugs.

Risperidone for Extended-Release Injectable Suspension (Perseris)


 CADTH recommends that Perseris should be reimbursed by public drug plans for the treatment of schizophrenia in adults if certain conditions are met.
 Perseris should be covered by public drug plans in a similar manner to other long-acting injectable atypical antipsychotic drugs for the treatment of adults with schizophrenia.
 Perseris should only be reimbursed if the total monthly dose is not more than 120 mg and is not used in combination with other long-acting injectable antipsychotic drugs. Perseris should not cost more than other long-acting injectable (LAI) atypical antipsychotic drugs.

Efficacy of long-acting injectable versus oral antipsychotic drugs in early psychosis: A systematic review and meta-analysis.

Long-acting injectable antipsychotic drugs (LAIs) are often used as an alternative to oral antipsychotics (OAPs) in individuals with psychosis who demonstrate poor medication adherence. Previous meta-analyses have found mixed results on the efficacy of LAIs, compared to OAPs, in patients with psychotic disorders. The objective of this meta-analysis was to compare the effectiveness of using LAIs versus OAPs in the early stages of psychosis. Major electronic databases were used to search for any studies examining the comparative effectiveness (i.e., relapse, adherence, hospitalization, and all-cause discontinuation) of any LAIs versus OAPs in early stages of psychosis. Studies published up to 6 June, 2019 were included and no language restriction was applied. Inclusion criteria were a diagnosis of schizophrenia or related disorder, where patients were in their first episode or had a duration of illness ≤5 years. Data were analysed using a random-effects model. Fifteen studies (n=10 584) were included, of which were 7 RCTs, 7 observational studies, and 1 post-hoc analysis. We found that LAIs provided advantages over OAPs in terms of relapse rates. No significant differences were found between LAI and OAP groups in terms of all-cause discontinuation, hospitalization, and adherence rates. However, considering only RCTs revealed advantages of LAIs over OAPs in terms of hospitalization rates. LAIs may provide benefits over OAPs with respect to reducing relapse and hospitalization rates in early psychosis patients. There is a need for larger and better-designed studies comparing OAPs and LAIs specifically in early psychosis patients.

Descriptive analysis of the admission of minors into a psychiatric unit

IntroductionThe admission of minors into adult psychiatric units is a problem due to the lack of adequate resources and epidemiology data. ObjectiveThe aim of this study is to describe and analyse the sociodemographic and clinical characteristics of minors that were admitted into the Short-Stay Psychiatric Hospitalisation Unit of Caceres, Spain. Materials and methodsA retrospective, observational, and descriptive study was conducted on a sample of patients between 12 and 18 years-old admitted to the Psychiatric Unit. The study period was between 1 January 2014 and 31 December 2018. ResultsA total of 79 patients, with a mean age of 15.72 (±1.65) years, were included. Almost all of them (93.6%) had a personal psychiatric history. The most common diagnoses at discharge in males were disruptive, impulse-control and conduct disorders, and mood disorders in females. A history of substance consumption was present in 40.6%, and was more common in males, which led to a worse prognosis. The mean stay was 5.4 (±4.7) days. Prolongation of the mean stay was associated with a history of previous psychiatric admissions, the number of diagnoses at discharge, a greater number of drugs at discharge, and those that received long-acting injectable antipsychotic drugs (P < .005 in all cases). ConclusionsThe study identified the sociodemographic and clinical profile of the minor admitted to the Psychiatric Unit, and how the hospital stay was associated with previous psychiatric history, as well as diagnostic and clinical complexity.

The effects of adding long-acting injectable antipsychotic drugs to clozapine on relapse and hospitalization in patients with treatment-resistant schizophrenia: a mirror-image retrospective study.

The literature assessing the addition of long-acting injectable antipsychotics (LAIs) to clozapine is limited. The aim of this retrospective study was to determine the safety and effectiveness of adding LAIs to clozapine in patients with treatment-resistant schizophrenia (TRS). Patients aged 18-65 years with TRS, who were treated with first-generation (FGA-LAIs) and second-generation (SGA-LAIs) for at least 1 year after clozapine use, were included retrospectively by registration system scanning. Effectiveness measures included relapses and hospitalizations and days of hospitalization. Safety outcomes included levels of neutrophils, fasting blood sugar, total cholesterol, triglycerides, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and prolactin. The data of 29 patients who met the study criteria were evaluated. The numbers and days of hospitalizations and the numbers of relapses significantly decreased after LAI addition. Comparisons of the neutrophil counts and the total cholesterol, triglyceride, HDL, LDL, prolactin, and fasting blood glucose levels as safety indicators of the clozapine and LAI combination revealed no statistically significant change in these values before and after LAI addition. Adding LAIs to clozapine is apparently well tolerated in patients with TRS and may have a positive effect on the course of the disease.

Patterns of long acting injectable antipsychotic use and associated clinical factors in schizophrenia among 15 Asian countries and region.

Patterns of clinical use of long-acting injectable (LAI) antipsychotic drugs in many countries, especially in Asia, for treatment of patients diagnosed with chronic psychotic disorders including schizophrenia are not well established. Within an extensive research consortium, we evaluated prescription rates for first- (FGA) and second-generation antipsychotic (SGA) LAI drugs and their clinical correlates among 3557 subjects diagnosed with schizophrenia across 15 Asian countries and region. Overall, an average of 17.9% (638/3557; range: 0.0%-44.9%) of treated subjects were prescribed LAI antipsychotics. Those given LAI vs orally administered agents were significantly older, had multiple hospitalizations, received multiple antipsychotics more often, at 32.4% higher doses, were more likely to manifest disorganized behavior or aggression, had somewhat superior psychosocial functioning and less negative symptoms, but were more likely to be hospitalized, with higher BMI, and more tremor. Being prescribed an FGA vs SGA LAI agent was associated with male sex, aggression, disorganization, hospitalization, multiple antipsychotics, higher doses, with similar risks of adverse neurological or metabolic effects. Rates of use of LAI antipsychotic drugs to treat patients diagnosed with schizophrenia varied by more than 40-fold among Asian countries and given to an average of 17.9% of treated schizophrenia patients. We identified the differences in the clinical profiles and treatment characteristics of patients who were receiving FGA-LAI and SGA-LAI medications. These findings behoove clinicians to be mindful when evaluating patients' need to be on LAI antipsychotics amidst multifaceted considerations, especially downstream adverse events such as metabolic and extrapyramidal side effects.

Descriptive analysis of the admission of minors into a psychiatric unit

The admission of minors into adult psychiatric units is a problem and is due to the lack of adequate resources and epidemiology data. The aim of this study is to describe and analyse the sociodemographic and clinical characteristics of minors that were admitted into the Short-Stay Psychiatric Hospitalisation Unit of Caceres, Spain. A retrospective, observational, and descriptive study was conducted on a sample of patients between 12 and 18 years-old admitted to the Psychiatric Unit. The study period was between January 1, 2014 and December 31, 2018. A total of 79 patients, with a mean age of 15.72 (±1.65) years, were included. Almost all of them (93.6%) had a personal psychiatric history. The most common diagnoses at discharge in males were disruptive, impulse-control and conduct disorders, and mood disorders in females. A history of substance consumption was present in 40.6%, and was more common in males, which led to a worse prognosis. The mean stay was 5.4 (±4.7) days. Prolongation of the mean stay was associated with a history of previous psychiatric admissions, the number of diagnoses at discharge, a greater number of drugs at discharge, and those that received long-acting injectable antipsychotic drugs (p<0.005 in all cases). The study identified the sociodemographic and clinical profile of the minor admitted to the Psychiatric Unit, and how the hospital stay was associated with previous psychiatric history, as well as diagnostic and clinical complexity.

Accidental Overdose of Paliperidone Palmitate

Long-acting injectable (LAI) antipsychotics first introduced in 1960s are useful in the treatment of schizophrenic patients with poor medication adherence due to their maintaining feature of therapeutic plasma level without daily administration. Paliperidone Palmitate is one of such LAI antipsychotic drugs used due to its benefit of maintaining a therapeutic plasma level with four-week interval of injections. We report the case of a 21-year-old male with a history of mental illness that presented with selective mutism, disorganized speech, thought process and behavior, and auditory hallucinations who accidentally received 624 mg Paliperidone Palmitate intramuscularly with no reported side effects after 2 weeks of monitoring and observation. Paliperidone is a D2, 5HT2A receptor antagonist with additional antagonist activity at α-1 and α-2, H-1 receptor sites, and four metabolic pathways identified for its metabolism. Studies have reported adverse effects such as acute dystonia, acute renal failure, and cardiovascular abnormalities with Paliperidone overdose; however there is no reported literature on Paliperidone Palmitate overdose, though there have been reported cases of Paliperidone Palmitate side effects of hypersexuality and angioedema with the standard dose.

Hyperprolactinemia in psychotic patients treated in monotherapy with long-acting injectable antipsychotics

Objectives: Hyperprolactinemia (HPRL), defined as plasma prolactin (PRL) >25 ng/ml, is a frequent adverse effect of the treatment with some antipsychotics. The objectives of this study were to determine the prevalence of HPRL among schizophrenic patients treated with long-acting injectable (LAI) antipsychotic drugs at our hospital, and to estimate gender effects in PRL levels in these patients.Methods: This cross-sectional, retrospective, study analyzed 165 psychotic patients treatment with LAI antipsychotics in monotherapy from February to May of 2017 at the Psychiatry Specialized Care Units of the Elche General Hospital (Spain).Results: The prevalence of antipsychotic-derived HPRL in our hospital was 52.41%. Patients treated with LAI formulations of paliperidone and risperidone presented the highest levels of HPRL. A linear regression model showed that female patients presented 24.95 ng/ml (CI95 = 16.85, 33.05) higher levels of PRL than male patients (p < .0001). For women, age >45 years was associated to reduced levels of PRL with respect to younger patients (mean= −18.86 ng/ml, CI95 = −35.59, −2.13, p < .05).Conclusions: Our study confirmed the effects of LAI paliperidone and risperidone on PRL levels. Sex and age were significantly associated with PRL levels in patients treated with LAI antipsychotics, with younger women presenting higher rates of HPRL than men.Key pointsHPRL is a common adverse effect of the treatment with antipsychotics, detectable in over half of the patients treated in our hospital.Our study showed that treatment with LAI formulations of paliperidone and risperidone resulted in the highest levels of HPRL.Sex and age were significantly associated with PRL levels in patients treated with LAI antipsychotic drugs, with younger women presenting higher rates of HPRL than men.

First-generation versus second-generation long-acting injectable antipsychotic drugs and time to relapse.

The development of long-acting injectable formulations (LAIs) of second-generation antipsychotic drugs (SGAs) has been suggested as having advantage over first-generation antipsychotic (FGA) LAIs. In this study, we investigated the hypothesis that there was a longer time to relapse in patients with schizophrenia started on SGA LAI versus FGA LAI. Patients with a diagnosis of schizophrenia or schizoaffective disorder who were started on an SGA LAI while on an inpatient ward were identified through searching of the anonymised historical medical records at the South London and Maudsley NHS Foundation Trust. Patients starting FGA LAIs matched for diagnosis, age and date of hospital admission were identified. Time to readmission, discontinuation of LAI or death were identified. Kaplan-Meier plots were generated for each group, and the difference between groups analysed using log-rank methods. There were 157 patients identified in each group. There was no difference in time to readmission, medication discontinuation or death in patients on SGA LAI versus FGA LAI. We found no evidence of advantage in terms of maintaining response in SGA LAI versus FGA LAI. Prescriber choice should be guided by other factors such as side-effect profile, patient acceptability and price.

Long-term Administration of Antipsychotic Drugs in Schizophrenia and Influence of Substance and Drug Abuse on the Disease Outcome.

Many schizophrenic patients with a long-term administration of antipsychotic drugs do not regularly adhere to the prescribed pharmacotherapy. Antipsychotic drugs constitute a palliative, but not a curative treatment, and the long-term effect of these drugs is not secure. Patients tend to consume nicotine and alcohol, as well as some patients consume drugs such as cannabis and amphetamines. The objective of this mini-review is to examine the reasons for the high tendency of schizophrenic patients to consume alcohol, nicotine and drugs and in addition to suggest measures to reduce the abuse of substances and drugs. The effects of substances such as alcohol and nicotine and drugs such as cannabis and amphetamines on the disease outcome will be mentioned. Previous reviews on the psychotic disorders and the pharmacological treatment were used to examine the effects of substances and drugs on schizophrenic symptoms and to investigate appropriate measures to improve medication adherence and the renouncement of consuming substances and drugs. A possible coherence between the function of single susceptibility genes and the alteration of neurotransmitters is mentioned. The mechanism of action of the most important secondgeneration antipsychotic drugs and their indications are described. The tendency of schizophrenic patients to consume alcohol and nicotine and in addition the effect of both substances to possibly worsen psychotic symptoms are pointed out. The effect of nicotinergic agonists to support smoking cessation is described. The different compounds of cannabis, tetrahydrocannabidiol (a psychotomimetic) and cannabidiol (exerts antipsychotic actions), are mentioned. Because a reduced adherence to the pharmacotherapy is frequently combined with the abuse of substances, additional drugs, psychoeducation and the administration of long-acting injectable antipsychotic drugs could reduce the abuse of substances and drugs; these strategies could help to maintain the antipsychotic administration. The abuse of drugs and substances might be combined with a reduced adherence to the antipsychotic pharmacotherapy. Drugs and substances might in some cases worsen the psychotic symptoms. Appropriate measures to reduce substance and drug abuse as well as to improve the adherence to the antipsychotic pharmacotherapy are cognitive behavioral therapy, psychoeducation and the administration of long-acting injectable antipsychotic drugs. Some new drugs, for example the cannabis compound cannabidiol that shows antipsychotic properties and ß-varenicline, a nicotinergic cholinergic agonist, might be administered when substance abuse (cannabis, nicotine) occurs.

Dose and dosing frequency of long-acting injectable antipsychotics: a systematic review of PET and SPECT data and clinical implications.

Brain imaging data of antipsychotics have mainly been derived from oral antipsychotic drugs, which hampers our understanding of the requirement of dose/dosing frequency of long-acting injectable (LAI) antipsychotics for the maintenance treatment of schizophrenia. A systematic literature search was performed to identify positron emission tomography (PET) and single-photon emission computed tomography (SPECT) studies that assessed dopamine D2 receptor occupancy levels with LAI antipsychotic drugs in humans, using PubMed, EMBASE, and PsycINFO (last search, February 2013). Twenty studies (15 PET and 5 SPECT studies) were identified. The most investigated drug in these PET and SPECT studies was haloperidol decanoate (44 subjects; 11 studies), followed by risperidone LAI (24 subjects; 3 studies), olanzapine pamoate (14 subject; 1 study), and fluphenazine decanoate (12 subjects; 3 studies). The data have demonstrated high and continuous D2 receptor blockade with LAIs; the effects of LAI first-generation antipsychotics on the central nervous system may persist for several months. The prospective and cross-sectional studies showed that continuous dopamine D2 receptor blockade above 65% (ie, the lower end of the established therapeutic window for the acute phase treatment) was not always necessary for maintenance treatment for at least some of the patients. In conclusion, because of the limited brain imaging data on LAI antipsychotics, we still do not know the best way to dose them. Still, the currently available brain imaging data raises a possibility that the dosing interval of LAI antipsychotics may be extended beyond the currently indicated range in some patients.

Efficacy of Long-acting, Injectable Antipsychotics in the Treatment of Bipolar Disorders

Objective: Long-acting injectable (LAI) antipsychotic drugs have been used to treat bipolar disorders, especially in patients with poor medication adherence. We used copies of a questionnaire and chart reviews to investigate the outcome of long-term use of LAI antipsychotic drugs in bipolar patients. Methods: In this study, the use of LAI antipsychotics, including first-generation LAI (FLAI) antipsychotic drugs and second-generation LAI (SLAI) antipsychotic drugs were studied, to determine their efficacy and side effects. The study group comprised patients with bipolar disorder who were recruited from outpatient clinics at Taipei City Psychiatric Center: 27 patients who received FLAI antipsychotics and 14 patients who received risperidone one of the SLAI antipsychotics. Self-report copies of the questionnaire were gathered, and information from patients' medical records was reviewed and analyzed (n ¼ 41). Results: The frequencies (number of times per year) of mood episodes were found to be significantly different before and after the administration of LAI antipsychotic drugs (0.71 ± 0.65 and 0.23 ± 0.43, respectively, p < 0.001). The frequency of hospitalizations was also significantly different (0.57 ± 0.69 and 0.11 ± 0.26, respectively, p < 0.001). Conclusion: LAI treatment may decrease the frequency of mood episodes and number of hospitalizations in patients with bipolar disorder.

Long-acting injectable formulations of antipsychotic drugs for the treatment of schizophrenia

Antipsychotic drugs have been used to treat patients with schizophrenia and other psychotic disorders. Long-acting injectable antipsychotic drugs are useful for improving medication compliance with a better therapeutic option to treat patients who lack insight or adhere poorly to oral medication. Several long-acting injectable antipsychotic drugs are clinically available. Haloperidol decanoate and fluphenazine decanoate are first-generation depot drugs, but the use of these medicines has declined since the advent of second-generation depot agents, such as long-acting risperidone, paliperidone palmitate, and olanzapine pamoate. The second-generation depot drugs are better tolerated and have fewer adverse neurological side effects. Long-acting injectable risperidone, the first depot formulation of an atypical antipsychotic drug, was prepared by encapsulating risperidone into biodegradable microspheres. Paliperidone palmitate is an aqueous suspension of nanocrystal molecules, and olanzapine pamoate is a microcrystalline salt of olanzapine and pamoic acid suspended in aqueous solution. This review summarizes the characteristics and recent research of formulations of each long-acting injectable antipsychotic drug.

Adherence Challenges and Long-Acting Injectable Antipsychotic Treatment in Patients with Schizophrenia

Medication nonadherence has been associated with persistence of psychotic symptoms, relapse, and hospitalization in patients with schizophrenia. Patients with untreated psychosis are significantly less likely to achieve remission, whereas antipsychotic drug adherence has been associated with recovery. As such, adherence to antipsychotic drug treatment is a key issue for nurses and treatment team members caring for patients who typically are on chronic, progressive disease course. Long-acting injectable (LAI) anti-psychotic drugs, developed to improve adherence and provide and alternative antipsychotic drug treatment fro schizophrenia, have been associated with improved treatment outcomes including reduction of relapse rates approximately 30% and reduction in hospitalizations. However, LAI antipsychotic drugs remain underutilized in the United States despite a growing body of literature supporting positive outcomes of LAI versus oral antipsychotic drugs. Mental health nurses are in a key position to support improved adherence inpatients with schizophrenia through use of practical educational strategies that help patients, family members, and health care providers better understand and manage treatment.

Long-acting antipsychotic drugs for the treatment of schizophrenia: use in daily practice from naturalistic observations

BackgroundCurrent guidelines suggest specific criteria for oral or long-acting injectable antipsychotic drugs (LAIs). This review aims to describe the demographic and clinical characteristics of the ideal profile of the patient with schizophrenia treated with LAIs, through the analysis of nonrandomized studies.MethodsA systematic review of nonrandomized studies in English was performed attempting to analyze the factors related to the choice and use of LAIs in daily practice. The contents were outlined using the Cochrane methods for nonrandomized studies and the variables included demographic as well as clinical characteristics. The available literature did not allow any statistical analysis that could be used to identify the ideal profile of patients with schizophrenia to be treated with LAIs.ResultsEighty publications were selected and reviewed. Prevalence of LAI use ranged from 4.8% to 66%. The only demographic characteristics that were consistently assessed through retrieved studies were age (38.5 years in the 1970’s, 35.8 years in the 1980’s, 39.3 years in the 1990’s, to 39.5 years in the 2000’s) and gender (male > female).Efficacy was assessed through the use of various symptom scales and other indirect measurements; safety was assessed through extrapyramidal symptoms and the use of anticholinergic drugs, but these data were inconsistent and impossible to pool. Efficacy and safety results reported in the different studies yielded a good therapeutic profile with a maximum of 74% decrease in hospital admissions and the prevalence of extrapyramidal symptoms with LAIs consistently increased at 6, 12, 18, and 24 months (35.4%, 37.1%, 36.9%, and 41.3%, respectively).ConclusionsThis analysis of the available literature strongly suggests that further observational studies on patients with schizophrenia treated with LAIs are needed to systematically assess their demographic and clinical characteristics and the relationships between them and patient outcome.Besides the good efficacy and safety profile of LAIs, health care staff must also take into account the importance of establishing a therapeutic alliance with the patient and his/her relatives when selecting the most appropriate treatment. LAIs seem to be a good choice not only because of their good safety and efficacy profile, but also because they improve compliance, a key factor to improving adherence and to establishing a therapeutic alliance between patients with schizophrenia, their relatives, and their health care providers.

Movement disorders in patients treated with long-acting injectable antipsychotic drugs

The frequencies of antipsychotic drug-induced movement disorders documented by physicians and identified by researchers using standardized clinical rating scales were compared, as were the frequencies associated with use of fluphenazine decanoate and haloperidol decanoate. All outpatients at a Veterans Affairs medical center who were being maintained with intramuscular injections of fluphenazine decanoate or haloperidol decanoate and were in otherwise good health were studied. The patients were assessed by a pharmacist using the Abnormal Involuntary Movement Scale to evaluate the presence and severity of tardive dyskinesia (TD) and the Simpson-Angus EPS Rating Scale to evaluate the presence and severity of extrapyramidal symptoms (EPS). The patients' medical records for the previous two years were reviewed to determine whether a movement disorder had been documented, whether the patient's informed consent for antipsychotic drug use had been obtained, and to collect other data about the patient and his or her drug therapy. A total of 50 patients were evaluated. A neurologic examination by a physician had been documented in the chart within six months before clinical testing for 36 patients; abnormal movements had been found in 8 patients. Twenty-one subjects met the study criteria for probable TD or EPS or both. Of these patients, only six had been identified within the previous six months as having a movement disorder. Two patients with medical-record documentation of a movement disorder were not so identified by their test scores. Informed consent had been obtained from only 10 patients. Patients receiving haloperidol decanoate had a higher frequency of EPS but were also receiving higher drug dosages than patients given fluphenazine decanoate.(ABSTRACT TRUNCATED AT 250 WORDS)