Long-acting injectable versus oral antipsychotics for the maintenance treatment of schizophrenia: a systematic review and comparative meta-analysis of randomised, cohort, and pre–post studies

Kishimoto, Toshifumi; Hagi, Katsuhiko; Kurokawa, Shunya; Kane, John M.; Correll, Christoph U.

doi:10.1016/s2215-0366(21)00039-0

Cited by 218 publications

(212 citation statements)

References 130 publications

Supporting

Mentioning

202

Contrasting

Unclassified

Order By: Relevance

“…First, our study showed improvement of attitude toward medication and treatment adherence over the course of the study, alongside with improvement of psychiatric symptoms. This is in line with recent meta-analyses, showing benefits of LAIs prescription in early psychosis ( 52 ), as well as in the treatment maintenance of schizophrenia ( 18 , 20 ), not only in research settings but also in real-world clinical practice. Second, our findings support an association between the considered predictors and severity of psychiatric symptoms at the three selected timepoints, when considered independently.…”

Section: Discussionsupporting

confidence: 90%

“…It is well-known that oral and long-acting injectable (LAI) antipsychotics are similarly tolerable ( 14 ) and effective in the treatment of severe mental illnesses. Nevertheless, there is a literature debate on this topic, with randomized trials in clinically stable individuals showing a similar efficacy profile ( 15 ), and with large observational studies favoring LAI over oral antipsychotics in terms of re-hospitalizations ( 16 – 18 ). Observational studies might be less restrictive in terms of patient selection and have higher external validity, although an increased risk of detection, performance and prescribing bias may represent a relevant limitation ( 19 ).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The Role of Attitudes Toward Medication and Treatment Adherence in the Clinical Response to LAIs: Findings From the STAR Network Depot Study

et al. 2021

View full text Add to dashboard Cite

Background: Long-acting injectable (LAI) antipsychotics are efficacious in managing psychotic symptoms in people affected by severe mental disorders, such as schizophrenia and bipolar disorder. The present study aimed to investigate whether attitude toward treatment and treatment adherence represent predictors of symptoms changes over time.Methods: The STAR Network “Depot Study” was a naturalistic, multicenter, observational, prospective study that enrolled people initiating a LAI without restrictions on diagnosis, clinical severity or setting. Participants from 32 Italian centers were assessed at three time points: baseline, 6-month, and 12-month follow-up. Psychopathological symptoms, attitude toward medication and treatment adherence were measured using the Brief Psychiatric Rating Scale (BPRS), the Drug Attitude Inventory (DAI-10) and the Kemp's 7-point scale, respectively. Linear mixed-effects models were used to evaluate whether attitude toward medication and treatment adherence independently predicted symptoms changes over time. Analyses were conducted on the overall sample and then stratified according to the baseline severity (BPRS < 41 or BPRS ≥ 41).Results: We included 461 participants of which 276 were males. The majority of participants had received a primary diagnosis of a schizophrenia spectrum disorder (71.80%) and initiated a treatment with a second-generation LAI (69.63%). BPRS, DAI-10, and Kemp's scale scores improved over time. Six linear regressions—conducted considering the outcome and predictors at baseline, 6-month, and 12-month follow-up independently—showed that both DAI-10 and Kemp's scale negatively associated with BPRS scores at the three considered time points. Linear mixed-effects models conducted on the overall sample did not show any significant association between attitude toward medication or treatment adherence and changes in psychiatric symptoms over time. However, after stratification according to baseline severity, we found that both DAI-10 and Kemp's scale negatively predicted changes in BPRS scores at 12-month follow-up regardless of baseline severity. The association at 6-month follow-up was confirmed only in the group with moderate or severe symptoms at baseline.Conclusion: Our findings corroborate the importance of improving the quality of relationship between clinicians and patients. Shared decision making and thorough discussions about benefits and side effects may improve the outcome in patients with severe mental disorders.

show abstract

Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

The Role of Attitudes Toward Medication and Treatment Adherence in the Clinical Response to LAIs: Findings From the STAR Network Depot Study

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Most important, LAIs provide several therapeutic benefits over OAs that go beyond improved adherence. In a meta-analysis of studies comparing LAIs with OAs across three designs (randomized trials, mirror image studies, and cohort studies), LAIs were consistently associated with significantly lower risk of hospitalization and/or relapses [37]. Moreover, LAIs were superior to OAs in 20% of the 337 reported outcomes, whereas OAs were not superior to LAIs on any outcome, including tolerability.…”

Section: Improved Adherencementioning

confidence: 99%

“…On the other hand, perceptions about the relative safety of OAs may be influenced by poor adherence [40,41]. Importantly, SGA-LAIs have a different aqueous formulation/suspension than FGA-LAIs, and this has helped reduce the occurrence of Patients on an LAI experience breakthrough psychosis [48,49] The rate of breakthrough psychosis is similar among LAIs and OAs [49], and the benefit-risk ratio supports use of LAIs [27]; when breakthrough occurs, it is clear whether or not medication was taken X X X X Patients on LAIs can also become nonadherent to LAI use [35] Adherence rates are higher and discontinuation rates are lower for LAIs than for OAs [22,32,42], nonadherent patients can be immediately identified if a dosing appointment is missed [76], and relapses are delayed because of longer half-lives of LAIs [36] X X X Many HCPs lack experience/knowledge of LAIs; therefore, target population should remain limited [10] HCPs can be educated [78]; HCPs with LAI prescribing experience are supportive of LAI use [60] X X Dosing of an LAI is difficult to adjust, and it would be dangerous to treat patients without knowing if the most appropriate medication has been selected [59] Per drug prescribing information and recommendations, a short trial with an OA or short-duration LAI should occur to assess tolerability and efficacy, followed by a transition to the LAI formulation of the same drug [60] X X X Providers do not have the proper resources or background to set up the complicated infrastructure needed to administer LAIs [14,54,77] The long-term nature of the disease is worthy of training professionals and setting up a coordinated care team to improve outcomes, including a decrease in hospitalizations and mortality [16,22,37,51]; a coordinated care team can be organized by collaborating with experts and specialty clinics [62,63] X X X Suggesting an LAI early on in treatment will impede patient autonomy [87] Early treatment success correlates with patient acceptance of treatment and improved adherence [3,…”

Section: Greater Tolerabilitymentioning

confidence: 99%

Controversies Surrounding the Use of Long-Acting Injectable Antipsychotic Medications for the Treatment of Patients with Schizophrenia

et al. 2021

View full text Add to dashboard Cite

Schizophrenia is a serious mental illness that requires continuous and effective long-term management to reduce symptoms, improve quality of life, and prevent relapse. Oral antipsychotic medications have proven efficacy for many patients taking these medications; however, a considerable number of patients continue to experience ongoing symptoms and relapse, often due to lack of adherence. The advent of long-acting injectable (LAI) formulations of antipsychotic medications provided an opportunity to improve treatment adherence and overall patient outcomes. Despite data to support LAI efficacy, safety, and improved adherence over oral formulations, there are several misconceptions about and barriers to LAI implementation within a standard of care for patients with schizophrenia. Areas of resistance around LAIs include (1) doubts regarding their benefits outside of improved adherence, (2) questions regarding their prescribing to a broader population of patients with schizophrenia, (3) when to initiate LAIs, (4) concerns regarding the safety of LAIs in comparison with oral medication, and (5) the most effective ways to educate healthcare providers, patients, and caretakers to enable appropriate LAI consideration and acceptance. Here, we discuss these key controversies associated with LAIs and provide supportive evidence to facilitate LAI use in a manner that is constructive to the clinician-patient relationship and successful treatment. Plain Language SummarySchizophrenia is a mental condition that affects how a person acts, thinks, sees, and interprets their surroundings and expresses how they feel. Relapse can lead to hospitalization and other poor outcomes. Almost half of patients with schizophrenia tend to start and stop treatment, which can cause more relapses and make symptoms worse over time. Using antipsychotic drugs long term can reduce impairing illness symptoms and improve patient quality of life. Consistent use of antipsychotic drugs can help prevent relapse. Available antipsychotic drugs can be taken by mouth (oral) or by an injection. Oral drugs have to be taken every day, whereas long-acting injections (LAIs) of antipsychotic drugs can be given less often, such as every 2 weeks, monthly, and up to once every 3 months. In the past, LAIs were used only when oral antipsychotic drugs did not work, which was usually because patients did not take them every day. However, LAIs also work as an early treatment, which can be better for the patient. Patients taking LAIs skip fewer doses and so may have fewer relapses and hospitalizations. Because LAIs have to be given at the clinic, patients get more regular medical care and tend to keep taking their medicine for longer. Most LAI side effects are similar to those of oral antipsychotic drugs. Despite this, some clinicians hesitate to prescribe LAIs. More education for clinicians and patients about LAIs could increase interest and use. Recovery and relapse prevention are the main treatment goals for patients and their care team, and LAIs can improve both.

show abstract

“…3,4 Atypical LAI antipsychotics compared with their oral equivalents are more favorable for rate of relapse, adherence to treatment, and preventing hospitalization. [5][6][7][8] In Canada, the available LAI antipsychotics are risperidone, paliperidone palmitate, aripiprazole monohydrate, flupentixol decanoate, haloperidol decanoate, and zuclopenthixol decanoate.…”

Section: Introductionmentioning

confidence: 99%

The use of concurrent long-acting injectable antipsychotic therapy with paliperidone palmitate and aripiprazole monohydrate in a patient with schizophrenia

Evernden¹,

Giang

Anderson

2021

Mental Health Clinician

View full text Add to dashboard Cite

International schizophrenia guidelines endorse seeking the patient's preference for guiding antipsychotic therapy. There exists a small niche of patients who prefer, or are required to use, long-acting injectable antipsychotic medications due to the adherence benefit. However, they may not be able to achieve adequate symptom reduction prior to experiencing treatment-limiting adverse effects from a single agent. Here, we present a patient case prescribed concurrent long-acting injectable antipsychotic therapy with paliperidone palmitate and aripiprazole monohydrate due to patient preference in the setting of a history of nonadherence to oral medications, treatment-limiting adverse effects to long-acting injectable paliperidone, and failure to achieve adequate symptom reduction with long-acting injectable aripiprazole monotherapy.

show abstract

Long-acting injectable versus oral antipsychotics for the maintenance treatment of schizophrenia: a systematic review and comparative meta-analysis of randomised, cohort, and pre–post studies

Cited by 218 publications

References 130 publications

The Role of Attitudes Toward Medication and Treatment Adherence in the Clinical Response to LAIs: Findings From the STAR Network Depot Study

The Role of Attitudes Toward Medication and Treatment Adherence in the Clinical Response to LAIs: Findings From the STAR Network Depot Study

Controversies Surrounding the Use of Long-Acting Injectable Antipsychotic Medications for the Treatment of Patients with Schizophrenia

The use of concurrent long-acting injectable antipsychotic therapy with paliperidone palmitate and aripiprazole monohydrate in a patient with schizophrenia

Contact Info

Product

Resources

About