Long-acting Injectable Drugs Research Articles

The Cost Effectiveness of Long-Acting/Extended-Release Antipsychotics for the Treatment of Schizophrenia

Antipsychotic medication is the mainstay of treatment in schizophrenia. Long-acting medication has potential advantages over daily medication in improving compliance and thus reducing hospitalization and relapse rates. The high acquisition and administration costs of such formulations raise the need for pharmacoeconomic evaluation. The aim of this article is to provide a comprehensive review of the available evidence on the cost effectiveness of long-acting/extended-release antipsychotic medication and critically appraise the strength of evidence reported in the studies from a methodological viewpoint. Relevant studies were identified by searching five electronic databases: PsycINFO, MEDLINE, EMBASE, the NHS Economic Evaluation Database and the Health Technology Assessment database (HTA). Search terms included, but were not limited to, 'long-acting injection', 'economic evaluation', 'cost-effectiveness' and 'cost-utility'. No limits were applied for publication dates and language. Full economic evaluations on long-acting/extended-release antipsychotics were eligible for inclusion. Observational studies and clinical trials were also checked for cost-effectiveness information. Conference abstracts and poster presentations on the cost effectiveness of long-acting antipsychotics were excluded. Thirty-two percent of identified studies met the selection criteria. Pertinent abstracts were reviewed independently by two reviewers. Relevant studies underwent data extraction by one reviewer and were checked by a second, with any discrepancies being clarified during consensus meetings. Eligible studies were assessed for methodological quality using the quality checklist for economic studies recommended by the NICE guideline on interventions in the treatment and management of schizophrenia. After applying the selection criteria, the final sample consisted of 28 studies. The majority of studies demonstrated that risperidone long-acting injection, relative to oral or other long-acting injectable drugs, was associated with cost savings and additional clinical benefits and was the dominant strategy in terms of cost effectiveness. However, olanzapine in either oral or long-acting injectable formulation dominated risperidone long-acting injection in a Slovenian and a US study. Furthermore, in two UK studies, the use of long-acting risperidone increased the hospitalization days and overall healthcare costs, relative to other atypical or typical long-acting antipsychotics. Finally, paliperidone extended-release was the most cost-effective treatment compared with atypical oral or typical long-acting formulations. From a methodological viewpoint, most studies employed decision analytic models, presented results using average cost-effectiveness ratios and conducted comprehensive sensitivity analyses to test the robustness of the results. Variations in study methodologies restrict consistent and direct comparisons across countries. The exclusion of a large body of potentially relevant conference abstracts as well as some papers being unobtainable may have increased the likelihood of misrepresenting the overall cost effectiveness of long-acting antipsychotics. Finally, the review process was restricted to qualitative assessment rather than a quantitative synthesis of results, which could provide more robust conclusions. Atypical long-acting (especially risperidone)/extended-release antipsychotic medication is likely to be a cost-effective, first-line strategy for managing schizophrenia, compared with long-acting haloperidol and other oral or depot formulations, irrespective of country-specific differences. However, inconsistencies in study methodologies and in the reporting of study findings suggest caution needs to be applied in interpreting these findings.

Race and Long-Acting Antipsychotic Prescription at a Community Mental Health Center

There has been concern that racial minorities are disproportionately prescribed long-acting injectable antipsychotic drugs. Comprehensive administrative data and clinician survey were used to identify all patients with a DSM-IV diagnosis of schizophrenia who received long-acting antipsychotic prescriptions from July 2009 to June 2010 at a community mental health center. Charts were reviewed retrospectively to validate long-acting antipsychotic prescription (eg, medication, dosage) and merged with administrative data from all center patients documenting sociodemographic characteristics (ie, age, race, gender) and comorbid diagnoses. We used bivariate χ2, t tests, and multivariate logistic regression to compare the subsample of patients receiving long-acting injectable drugs (n = 102) to patients not receiving long-acting injectable drugs (n = 799) who were diagnosed with schizophrenia for the same period. White patients were significantly less likely to receive long-acting antipsychotic prescriptions than minority patients (OR = 0.52, P < .007); ie, nonwhites were 1.89 times more likely to receive such drugs. Age, gender, and comorbid diagnoses, including substance abuse, were unrelated to long-acting injectable prescription, and race/ethnicity was not associated with use of specific agents (haloperidol decanoate, fluphenazine decanoate, or risperidone microspheres) (P = .73). Racial minorities are more likely than other patients with schizophrenia to receive long-acting injectionable antipsychotics, a finding that suggests their prescribers may consider them less adherent to antipsychotic prescriptions.

A Review of Second-Generation Antipsychotic Discontinuation in First-Episode Psychosis

"All-causes discontinuation" refers to discontinuation of treatment for any reason, and adherence to medication is an important component of this measure. Two recent landmark studies suggest that adherence is a major issue in patients with first-episode psychosis (FEP) right from the onset of treatment. In this review, the incidence, reasons for, and clinical outcomes of medication discontinuation in FEP are considered. More than 40% of patients with FEP discontinue medication during the first 9 months of treatment, at which point the chances of relapse increase dramatically. Findings concerning predictors of medication discontinuation in this patient population that have been replicated in more than one study include severity of psychopathology, lack of insight into illness, negative attitudes towards medications, comorbid substance use, and medication side effects. Interventions that have the potential to decrease discontinuation rates in patients with psychotic disorders include orally disintegrating tablets, long-acting injectable drugs, cognitive-behavioral therapy, compliance therapy, family support/intervention, and peer support, although these strategies have largely been unexplored in FEP. In addition to the question of medication discontinuation in the acute treatment of FEP, another important issue is how long patients with FEP should be treated with antipsychotics once they have achieved remission; unfortunately, little evidence is available to guide the decision as to whether medication should be discontinued or maintenance treatment provided in this situation. Studies are therefore needed to identify predictors of patients with remitted FEP who are less likely to relapse when medication is discontinued. Taken together, the findings presented in this article underscore the importance of addressing issues related to medication discontinuation as a means of preventing long-term morbidity and enhancing remission and functional recovery in FEP.

Attitudes of Psychiatrists Toward Antipsychotic Depot Medication

Since 2002, a second-generation depot antipsychotic has been available that potentially combines the advantages of depot administration and the favorable aspects of the so-called "atypical" antipsychotics. Nevertheless, long-acting injectable formulations are seldom prescribed in the treatment of schizophrenia. We surveyed 350 psychiatrists at an international conference as to their reasons for not prescribing a first- or second-generation depot antipsychotic for their patients diagnosed with schizophrenia or schizoaffective disorder. The most important factor opposing depot prescription pertaining to both classes is a presumed sufficient compliance with oral antipsychotic treatment. First-generation depots are avoided due to the threat of extrapyramidal side effects, whereas second-generation long-acting injectable drugs are considered to be associated with high treatment costs. Less than 36% of participants' patients have ever been offered antipsychotic depot treatment. Aversions to prescribing depot treatment are frequent among psychiatrists and appear to be unrelated to the antipsychotic class. The stated reasons for not prescribing depots are generally not supported by the current evidence, and further studies are urgently needed to clarify the advantages of depot treatment.

Pharmacokinetics of long-acting injectable neuroleptic drugs: clinical implications

The authors review the literature regarding the pharmacokinetics of long-acting injectable neuroleptic drugs (LINS). There are important differences between LINS and oral neuroleptics that affect their pharmacokinetics. By avoiding first pass metabolism in gut and liver, LINS result in lower circulating concentrations of metabolites than are found after oral administration. In addition, LINS take more time to reach a stable steady state than their oral counterparts. The clinical significance of these pharmacokinetic properties is discussed. The authors recommend that when patients are being changed from oral neuroleptics to LINS, that this conversion be done gradually over several months.

The Efficacy of Antipsychotic Drugs and Family Therapies in the Maintenance Treatment of Schizophrenia

The efficacy of antipsychotic drugs in both the short-term and long-term treatment of schizophrenia has been clearly demonstrated. Long-acting injectable drugs are particularly useful because of the clarity they provide about the patient's receipt of medication. The clinician can better understand the circumstances surrounding a relapse in a patient receiving long-acting antipsychotic medication because there is no uncertainty about drug compliance. Approaches to psychosocial therapy that emphasize education and involvement of family members in the treatment process also show particular promise for long-term maintenance care of schizophrenic patients. Three models of family therapy are described, and their impact on subsequent relapse rates is reviewed. Although few studies have systematically explored the interaction of drug and psychosocial treatments, the available data suggest that this treatment strategy is effective in both preventing relapse and reducing psychotic symptomatology.

The expectation of outcome from maintenance therapy in chronic schizophrenic patients.

The results from a prospective follow-up study of a group of schizophrenic patients suggest that a significant proportion (41 per cent) are likely to relapse during a two-year period despite the prescription of long-acting injectable neuroleptic drugs. Some will relapse because of a failure of the regime, but others (32-37 per cent) because the pharmacological protection of these drugs would appear to be less effective in certain patients. Even with the major advantages of the long-acting injectable neuroleptics over oral medication, the schizophrenic patient population remains a group with a high incidence of psychiatric and social morbidity which continues to require the full resources of both the hospital and community services.