Depot Formulation Research Articles

Design of Highly Dispersible PLGA Microparticles in Aqueous Fluid for the Development of Long-Acting Release Injectables.

In this study, we developed highly dispersible polylactic glycolic acid (PLGA) copolymer microparticles (MRPs) in aqueous fluid. A solution containing both dissolved aripiprazole as a model drug and PLGA were spray-dried to make MRPs. The resultant MRPs were further co-processed with water-soluble additives and a surfactant to improve their dispersion behavior. The granules containing MRPs and additives, termed granulated microparticles (G-MRPs) were prepared by a newly established drop freeze-drying technique. The physicochemical properties of MRPs and G-MRPs were evaluated as a long-acting release depot injectable. The MRPs were spherical particles with diameters of approximately 1 to 20 µm and strongly assembled to one another in the aqueous phase, forming large aggregations. In contrast, the G-MRPs were spherical granules with diameters of approximately 200 to 400 µm that displayed a microparticles-in-granule structure in which small MRPs were embedded in the porous matrix inside the granules. When the G-MRPs were placed in water, the porous matrix base was immediately dissolved, and each embedded MRP was individually released, thus inducing monodispersion and significantly improved dispersibility. The excellent dispersibility was attributed to the water-soluble porous network structure mainly composed of D-mannitol and the steric hindrance effects derived from the polymeric molecular chains. These properties may give rise to the excellent passage of PLGA microparticles through needles for use in depot formulation suspensions. A crystalline evaluation of the G-MRPs suggested that the drug and PLGA molecularly interacted and that their thermodynamic stability was improved.

Development of Injectable Sustained-Release PLGA Depot Formulation with Excellent Gliding Performance

Development of Injectable Sustained-Release PLGA Depot Formulation with Excellent Gliding Performance

Exercise and Antipsychotic Drugs

Abstract Background: Exercise has been shown to reduce symptoms in patients with schizophrenia. Aim: To determine whether exercise has a corresponding effect on antipsychotic side effects. Method: The Google Scholar database was searched for references to exercise, pharmacokinetics, and antipsychotic drug side effects. Results: There are no human studies on the effect of exercise on side effects of antipsychotic medications. Clinical experience suggests that exercise increases parkinsonian side effects of intramuscular depot antipsychotics while animal experiments show that the side effects of oral antipsychotics are buffered by exercise. Conclusion: A difference in bioavailability may explain why exercise increases side effects when antipsychotic drugs are administered in intramuscular depot form, but decrease these effects when antipsychotics are given orally. Human trials are needed.

Needle-Free Injection of Vesicular Phospholipid Gels—A Novel Approach to Overcome an Administration Hurdle for Semisolid Depot Systems

Vesicular phospholipid gels (VPGs) are depot formulations for the sustained release of drugs which are characterized by a high amount of phospholipids in the formulation. They consist of physiological excipients only and therefore display high biocompatibility. Their manufacture is simple, cheap, solvent free, and ideal for the processing of proteins and peptides because of the low stress on the molecule, for example, by elevated temperatures. One major hurdle of VPGs is their high viscosity which makes them hard to almost impossible to inject with conventional, thin needles used for subcutaneous administration. However, so far no data are published to overcome this administration challenge. In the present study, needle-free injection was investigated and successfully applied as a technology for the easy and elegant administration of VPGs. VPGs with different phospholipid content were injected with a Biojector 2000 into gelatin blocks and full thickness pig skin postmortem as in vitro models and the injection depth was determined after injection. The release behavior was tested after shearing the VPG with the device to evaluate the effect of shearing on the drug release from the formulation. No differences were observed when compared to an ejection with needle and syringe.

Comparative in vitro release and clinical pharmacokinetics of leuprolide from Luphere 3M Depot, a 3-month release formulation of leuprolide acetate

A 3-month depot formulation of leuprolide acetate (Luphere 3M Depot) with a mean microsphere diameter of 22.3 μm was prepared aseptically by spray-drying glacial acetic acid solution of the drug and polylactic acid, and lyophilization in a d-mannitol solution. The encapsulation efficiency and loading content of the drug in the Luphere 3M Depot were 94.7% and 9.92% (w/w), respectively. The in vitro release of leuprolide from the depot was substantially delayed and the release profile was similar to that of Lucrin Depot (Abbott Korea, Korea). The safety and pharmacokinetics of leuprolide were investigated over a period of 42 days in 20 prostate cancer patients following a subcutaneous injection of Luphere 3M or Lucrin Depot suspensions (leuprolide acetate dose of 11.25 mg) in a multi-center, randomized, single dose, parallel study. Both formulations were well tolerated by the patients and no serious adverse effects were observed during and after the study. No significant differences were observed in the maximum serum concentration (Cmax) and area under the curve (AUClast) of leuprolide between the two formulations. The results suggest comparable safety and efficacy profiles of Luphere 3M Depot and Lucrin Depot in clinical situations.

Management of neuroendocrine tumors.

Current strategies for managing neuroendocrine tumors (NETs) in adult patients are reviewed, with a focus on medication safety concerns. NETs usually originate in the gastrointestinal or bronchopulmonary tract. Symptoms due to hormonal hypersecretion often occur in patients with foregut or midgut NETs or liver metastases. Surgical resection is recommended for most localized NETs, while systemic cytotoxic chemotherapy is typically used for high-grade and pancreatic tumors. The standard of care for metastatic NETs is somatostatin analog therapy with octreotide (available in both short- and long-acting formulations) or a depot formulation of lanreotide. Everolimus and sunitinib are targeted therapies with approved indications for use in treating advanced pancreatic NETs. Some patients with liver-predominant disease or liver metastases may undergo regional chemoembolization procedures. Pharmacists should be cognizant of differences between newer and older chemoembolization agents and procedures, as well as differences between somatostatin analog products used as medications and the radiolabelled forms used in diagnostic scintigraphy. Other medication safety issues in NET management arise during perioperative supportive care, patient education, compliance counseling, and management of adverse effects of targeted therapies and chemotherapy, including stomatitis, hyperthyroidism, and hand-foot skin reaction. Somatostatin analog therapy is the mainstay for management of locally advanced or metastatic NETs. Liver-directed therapy is an option for localized unresectable disease; platinum-based chemotherapy is the first-line treatment for poorly differentiated tumors. Optimal sequencing of these treatments and targeted therapies such as everolimus and tyrosine kinase inhibitors remains to be elucidated.

Paliperidone palmitate: factors predicting continuation with treatment at 2 years

Our aim was to determine factors relating to continuation with treatment with paliperidone palmitate long-acting injection (PP) in a 2 year, non-interventional, observational study of the use of PP in consecutive patients treated in a secondary care environment. We followed-up 300 consecutive patients; 24 (8%) were lost to follow-up (7 deceased and 17 left the care of the trust). Overall, 107 patients of the remaining 276 who were not lost to follow-up (38.7%) completed 2 years’ continuous treatment. A further 21 (7.6%) patients discontinued PP but restarted it after >2 months, 11 (4.0%) of whom were still receiving PP at 2 years. Median treatment time for PP was 465 days (95% CI 333, 583 days). Prior treatment with risperidone reduced the risk of discontinuation by 39% (RR 0.61 (95% CI −0.44, 0.86, p=0.004)); being initiated as an out-patient by 49% (RR 0.51 (95% CI 0.36, 0.73 p=0.001)). Risk of discontinuation was increased by 63% when the reason for prescribing PP was poor tolerability of prior treatment (RR 1.63 (95% CI 1.05, 2.51 p=0.028)). The rate of continuation with PP at 2 years was higher than that seen with other long acting depot formulations. Likelihood of continuation can be vastly improved by targeting PP for those most likely to benefit.

Lanreotide Depot: An Antineoplastic Treatment of Carcinoid or Neuroendocrine Tumors.

PurposePeptide drugs for antineoplastic therapies usually have low oral bioavailability and short in vivo half-lives, requiring less preferred delivery methods. Lanreotide depot is a sustained-release somatostatin analog (SSA) formulation produced via an innovative peptide self-assembly method. Lanreotide is approved in the USA and Europe to improve progression-free survival (PFS) in patients with unresectable gastroenteropancreatic neuroendocrine tumors (GEP-NETs) and also approved in Europe for symptom control in carcinoid syndrome associated with GEP-NETs. This review discusses how the distinct molecule and formulation of lanreotide depot provide advantages to patients and health care providers, as well as the most recent clinical evidence demonstrating the safety and efficacy of lanreotide depot in inhibiting tumor growth and controlling hormonal symptoms in GEP-NETs.Methodology and ResultsThe lanreotide depot formulation confers a remarkable pharmacokinetic profile with no excipients, comprised only of lanreotide acetate and water. Of note, lanreotide depot constitutes an example for peptide self-assembly based formulations, providing insights that could help future development of sustained-release formulations of other antineoplastic peptides. Most patients with GEP-NETs will present with inoperable or incurable disease; thus, medical management for symptoms and tumor control plays a crucial role. Recent long-term clinical studies have demonstrated that lanreotide depot is well tolerated, prolongs PFS in GEP-NET patients, and significantly reduces symptoms related to carcinoid syndrome.ConclusionsThe unique depot formulation and delivery method of lanreotide confer advantages in the treatment of metastatic GEP-NETs, contributing to improvements in NET-related symptoms and PFS without reducing quality of life in this patient population.

Scale-up from batch to flow-through wet milling process for injectable depot formulation

Injectable depot formulations are aimed at providing long-term sustained release of a drug into systemic circulation, thus reducing plasma level fluctuations and improving patient compliance. The particle size distribution of the formulation in the form of suspension is a key parameter that controls the release rate. In this work, the process of wet stirred media milling (ball milling) of a poorly water-soluble substance has been investigated with two main aims: (i) to determine the parametric sensitivity of milling kinetics; and (ii) to develop scale-up methodology for process transfer from batch to flow-through arrangement. Ball milling experiments were performed in two types of ball mills, a batch mill with a 30ml maximum working volume, and a flow-through mill with a 250ml maximum working volume. Milling parameters were investigated in detail by methodologies of QbD to map the parametric space. Specifically, the effects of ball size, ball fill level, and rpm on the particle breakage kinetics were systematically investigated at both mills, with an additional parameter (flow-rate) in the case of the flow-through mill. The breakage rate was found to follow power-law kinetics with respect to dimensionless time, with an asymptotic d50 particle size in the range of 200–300nm. In the case of the flow-through mill, the number of theoretical passes through the mill was found to be an important scale-up parameter.

Folate receptor targeted three-layered micelles and hydrogels for gene delivery to activated macrophages

New folic acid (FA) coupled three layered micelles (3LM) were designed to encapsulate DNA, and their application as delivery system that specifically targets activated macrophages was investigated for new treatment options in rheumatoid arthritis (RA). FA coupled poly(l-lactide)-b-poly(ethylene glycol) (FA-PEG-PLLA) was synthesized via the NHS-ester activated/amine coupling method. Fluorescein labeled folic acid was used for flow cytometric detection of the expression of functional folic receptor β in LPS-activated and resting macrophages. FA coupled 3LM were formulated in a two-step procedure and characterized regarding hydrodynamic diameters and zeta potentials. The presence of the targeting ligand was shown not to increase the size of the 3LM compared to their non-targeted counterparts. Targeted and non-targeted 3LM were used in vitro to optimize uptake conditions in the RAW 264.7 macrophage cell line. The amount of FA coupled polymer in the final formulation was found to be optimal at 75% FA-PEG-PLLA and 25% PLLA-PEG-PLLA. Subsequently, transgene expression in vitro in RAW 264.7 cells and ex vivo in primary activated and resting mouse macrophages was determined as a function of FR-mediated internalization of 3LM encapsulating GFP expressing plasmid. FR-overexpressing activated cells, as successfully identified by internalization of FA-fluorescein, showed significantly higher GFP expression in vitro and ex vivo than resting macrophages with only a basal level of FR expression. Lastly, injectable hydrogels as depot formulation were formed by stereocomplexation, and their degradation, DNA release profiles, and dissociation into intact 3LM were found to be beneficial for potential in vivo application. Our findings confirm that FA-3LM are taken up by activated macrophages via folate receptor mediated endocytosis and that their hydrogels release intact 3LM for efficient transfection of primary macrophages. Therefore, FA-3LM could become a promising delivery system for receptor-mediated drug or gene delivery and novel therapy for rheumatoid arthritis in an in situ forming gel formulation.

Evaluation of olanzapine pamoate depot in seriously violent males with schizophrenia in the community.

Olanzapine is a well established treatment for schizophrenia. The olanzapine pamoate depot (long-acting injectable) formulation improves compliance and clinical trials have shown it to be effective. However, there are no previously published reports evaluating olanzapine depot in violent patients with schizophrenia in the community. We evaluated the clinical efficacy of olanzapine depot, its effect on violence, hospitalization and incarceration in community patients with schizophrenia and prior history of serious violence. This was a retrospective service evaluation in a community forensic psychiatry service where patients had schizophrenia spectrum disorder and a significant history of violence. Treatment resistance, substance use disorders and antisocial personality disorder were common. Nine deidentified patient records were audited for 12 months pre and 12 months post olanzapine depot initiation to identify any clinical changes, breaches of (legislated) psychiatric treatment orders, hospital admission days, days incarcerated and emergency presentations. Community forensic psychiatric patients treated with olanzapine depot showed an improvement in psychotic symptoms (p = 0.008) with overall decreases in violence, supported by reductions in hospitalization days (p = 0.018) and days incarcerated (p = 0.043). Several patients had reduced psychiatric treatment order breaches and emergency presentations. Community forensic psychiatric patients with schizophrenia responded to olanzapine depot with decreased violence and reduced hostility. A depot antipsychotic medication that reduces violence and improves engagement has significant implications for greater effective community management of forensic patients with schizophrenia.

Intramuscular depot formulations of leuprolide acetate suppress testosterone levels below a 20 ng/dL threshold: a retrospective analysis of two Phase III studies.

IntroductionAndrogen deprivation therapy (ADT) with gonadotropin-releasing hormone (GnRH) analogs is a standard treatment for advanced prostate cancer. GnRH analog therapy can reduce testosterone to “castrate” levels, historically defined as <50 ng/dL. With the advent of newer assays, a lower threshold of <20 ng/dL has recently been proposed. We report the results of a retrospective analysis of two Phase III trials of 4- and 6-month depot microsphere formulations of leuprolide acetate (LA), a GnRH agonist that has previously demonstrated efficacy in testosterone suppression to <50 ng/dL in patients on ADT. This analysis investigates the ability of these LA formulations to suppress to ≤20 ng/dL levels.MethodsIn two of five AbbVie/Abbott clinical trials of microsphere formulations of LA for ADT, analytic technology permitting testosterone detection as low as 3 ng/dL was used and thus was selected for this analysis. Both trials were open-label, fixed-dose studies in prostate cancer patients, naïve to ADT. Patients received either 30 mg (4-month formulation; n=49) or 45 mg (6-month formulation; n=151) depot injections of LA microspheres. Treatment duration was up to 32 weeks for the 4-month formulation and 48 weeks for the 6-month formulation. The proportion of patients achieving the 20 ng/dL threshold was determined every 4 weeks.ResultsPooled analysis showed that 152 of 193 (79%) of patients achieved serum testosterone levels of ≤20 ng/dL at 4 weeks, and sustained the improvement at week 24 (169/189, 89%). Additionally, in the 6-month study, 127/135 (94.1%) patients were suppressed to ≤20 ng/dL at 48 weeks.ConclusionBoth 4- and 6-month intramuscular depot formulations of LA achieved and maintained mean serum testosterone levels ≤20 ng/dL in the vast majority of patients as early as 4 weeks following treatment initiation. Additional research on the clinical relevance of this lower testosterone threshold is warranted.

Dose Equivalents for Antipsychotic Drugs: The DDD Method.

Dose equivalents of antipsychotics are an important but difficult to define concept, because all methods have weaknesses and strongholds. We calculated dose equivalents based on defined daily doses (DDDs) presented by the World Health Organisation's Collaborative Center for Drug Statistics Methodology. Doses equivalent to 1mg olanzapine, 1mg risperidone, 1mg haloperidol, and 100mg chlorpromazine were presented and compared with the results of 3 other methods to define dose equivalence (the "minimum effective dose method," the "classical mean dose method," and an international consensus statement). We presented dose equivalents for 57 first-generation and second-generation antipsychotic drugs, available as oral, parenteral, or depot formulations. Overall, the identified equivalent doses were comparable with those of the other methods, but there were also outliers. The major strength of this method to define dose response is that DDDs are available for most drugs, including old antipsychotics, that they are based on a variety of sources, and that DDDs are an internationally accepted measure. The major limitations are that the information used to estimate DDDS is likely to differ between the drugs. Moreover, this information is not publicly available, so that it cannot be reviewed. The WHO stresses that DDDs are mainly a standardized measure of drug consumption, and their use as a measure of dose equivalence can therefore be misleading. We, therefore, recommend that if alternative, more "scientific" dose equivalence methods are available for a drug they should be preferred to DDDs. Moreover, our summary can be a useful resource for pharmacovigilance studies.

Biodegradable thermogelling polymers for biomedical applications

Abstract

Polymer-delivered subcutaneous leuprolide acetate formulations achieve and maintain castrate concentrations of testosterone in four open-label studies in patients with advanced prostate cancer.

To determine whether luteinising hormone-releasing hormone (LHRH) agonist, ATRIGEL® polymer-delivered, subcutaneous, leuprolide acetate (ADSC-LA), formulations suppressed serum testosterone to concentrations of ≤20ng/dL. Data from four open-label, fixed-dose studies were evaluated. Male patients aged 40-86years with advanced prostatic adenocarcinoma, whom had not undergone prior androgen-deprivation therapy (ADT), were treated with a depot formulation of ADSC-LA: 7.5mg (1-month, 120 patients), 22.5mg (3-month, 117 patients), 30mg (4-month, 90 patients), or 45mg (6-month, 111 patients). Serum testosterone was sampled at screening, baseline, 2, 4, 8h after dosing, 1, 2, 3, and 7days, and every week until the next dose, at which time, the sampling schedule repeated until the end of study (24weeks for 1- and 3-month formulations, 32weeks for 4-month, and 48weeks for the 6-month). The primary analyses were mean serum testosterone concentrations and proportion of patients who achieved concentrations of ≤20ng/dL. The mean (SE) serum testosterone concentrations at the end of study were consistently ≤20ng/dL in each study, at 6.1 (0.4), 10.1 (0.7), 12.4 (0.8), and 12.6 (2.1)ng/dL for the 1-, 3-, 4-, and 6-month formulations, respectively. A high proportion of patients (94%, 90%, 92%, 96% for the 1-, 3-, 4-, and 6-month formulations, respectively) achieved testosterone concentrations of ≤20ng/dL within 6weeks, and 90-97% of patients in all studies maintained concentrations of ≤20ng/dL from weeks 6-24. Recent studies have shown improved outcomes in patients with prostate cancer who consistently attained a more rigorous level of testosterone suppression (≤20ng/dL) with ADT than the historical standard (≤50ng/dL). All doses of ADSC-LA rapidly achieved and maintained mean serum testosterone to the more rigorous target concentration of ≤20ng/dL. These data suggest that ADSC-LA delivers equivalent testosterone suppression as achieved by surgical castration.

Risperidone (depot) for schizophrenia.

This is a copy of an article published in the Cochrane Database of Systematic Reviews © 2016 Cochrane Collaboration Publications. © The Author(s). http://www.cochranelibrary.com/

Efficacy and safety of leuprorelin acetate 6-month depot, TAP-144-SR (6M), in combination with tamoxifen in postoperative, premenopausal patients with hormone receptor-positive breast cancer: a phase III, randomized, open-label, parallel-group comparative study

BackgroundLeuprorelin acetate, a luteinizing hormone-releasing hormone agonist, is used worldwide in premenopausal women with hormone receptor-positive breast cancer. This study was conducted to assess the non-inferiority of the 6-month depot formulation, TAP-144-SR (6M) 22.5 mg to the 3-month depot formulation, TAP-144-SR (3M) 11.25 mg in postoperative, premenopausal patients with hormone receptor-positive breast cancer.MethodsThis was a 96-week phase III, randomized, open-label, parallel-group comparative study. All patients concomitantly received oral tamoxifen (20 mg daily). The primary endpoint was the suppression rate of serum estradiol (E2) to the menopausal level (≤30 pg/mL) from Week 4 through Week 48.ResultsIn total, 167 patients were randomized to receive TAP-144-SR (6M) (n = 83) or TAP-144-SR (3M) (n = 84) and the E2 suppression rate was 97.6 and 96.4 %, respectively. The estimated between-group difference was 1.2 % (95 % confidence interval −5.2 to 7.8). The non-inferiority of TAP-144-SR (6M) to TAP-144-SR (3M) for E2 suppression was confirmed. As for safety, common adverse events were hot flush and injection site reactions including induration, pain, and erythema in both treatment groups, which were of ≤Grade 2 in severity and not serious. No significant between-group differences in safety profiles and tolerability were observed.ConclusionsTAP-144-SR (6M) was not inferior to TAP-144-SR (3M) for its suppressive effect on serum E2. TAP-144-SR (6M) was also as well tolerated as TAP-144-SR (3M).

Drug Delivery Research: The Invention Cycle

Controlled drug delivery systems have been successful in introducing improved formulations for better use of existing drugs and novel delivery of biologicals. The initial success of producing many oral products and some injectable depot formulations, however, reached a plateau, and the progress over the past three decades has been slow. This is likely due to the difficulties of formulating hydrophilic, high molecular weight drugs, such as proteins and nucleic acids, for targeting specific cells, month-long sustained delivery, and pulsatile release. Since the approaches that have served well for delivery of small molecules are not applicable to large molecules, it is time to develop new methods for biologicals. The process of developing future drug delivery systems, termed as the invention cycle, is proposed, and it starts with clearly defining the problems for developing certain formulations. Once the problems are well-defined, creative imagination examines all potential options and selects the best answer and alternatives. Then, innovation takes over to generate unique solutions for developing new formulations that resolve the previously identified problems. Ultimately, the new delivery systems will have to go through a translational process to produce the final formulations for clinical use. The invention cycle also emphasizes examining the reasons for success of certain formulations, not just the reasons for failure of many systems. Implementation of the new invention cycle requires new mechanisms of funding the younger generation of scientists and a new way of identifying their achievements, thereby releasing them from the burden of short-termism.

Indication of depot antipsychotic treatment in the view of slovak psychiatrists

With the increasing number of atypical antipsychotics in depot form, there emerges question about plus and cons of their use in schizophrenia patients. We focused on the opinion of Slovak psychiatrists about use of this treatment in some specific situations of schizophrenia treatment. Research was realized via questionnaire on psychiatrists (n = 47) from ambulant and hospital care, during one conference in June 2015. First part of the questionnaire was focused on the preference of oral or depot form of antipsychotic treatment. Depot form would be indicated by psychiatrists (in more than 89%) when low compliance, anosognosia or frequent episodes. On the contrary, oral antipsychotic treatment is preferred in young patients or employed patients. The type of symptoms (e.g. positive, negative) has relatively small impact on the preference of treatment, where the preferences of each type were the lowest (fewer than 36%). According to the opinion of psychiatrists, depot antipsychotic treatment is not suitable in first episode of disorder (according to 81% of respondents), otherwise in second or third episode it would not be chosen by 6% of asked psychiatrists.From the aspects of the choice between atypical or typical depot, atypical antipsychotics in depot form were favored when presence of adverse reactions (80%), occurrence of negative symptoms (65%) and short duration of disorder (58%). Typical depot was preferred by psychiatrists in patients with chronic states.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Assessing quality of life following long-acting injection treatment: 4 cases register

IntroductionQuality of life is defined by the World Health Organization as “Individuals’ perceptions of their position in life in the context of the culture and value systems in which they live, and in relation to their goals, expectations, standards, and concerns.” Schizophrenia is a severe, disabling, lifelong disorder, associated with severe social and occupational dysfunction. Aripiprazole Long Acting Injection (LAI) is indicated for maintenance schizophrenia treatment in adult patients stabilised with oral aripiprazole. It is the fourth second-generation antipsychotic depot formulation approved for treating schizophrenia.ObjectivesAssessing quality of life in 4 patients treated with aripiprazole LAI.MethodsIn this paper, we evaluate of quality of life in 4 subjects with diagnosis of paranoid schizophrenia (less 10 years of diagnostic), male, age between 42 and 50 years, with poor adherence to oral treatment. These patients received aripirazol LAI 400 mg/month. We evaluate quality of life at baseline and after 3 months. We used the Quality of Life Scale (QOLS) and WHO-Quality of Life-Bref (WHOQOL-BREF).ResultsResults demonstrated significant greater improvements in all QLS scores. No significant changes in the WHOQOL-BREF total, but improvement in subscale scores.ConclusionQuality of life in schizophrenia is adversely influenced by the presence of clinical symptoms, especially negative and depressive. Depot medications can improve treatment adherence, however, long-term antipsychotic use can lead to irreversible adverse effects (dyskinesias), which in some cases were reduced by using newer antipsychotics (risperidone, paliperidone, aripiprazole). Aripiprazole LAI can be useful to improve quality of life. Further methodologically robust studies are needed to generate evidence-based conclusions.Disclosure of interestThe authors have not supplied their declaration of competing interest.