Oral Paliperidone Research Articles

Model-Informed Clinical Development of 6-Monthly Injection of Paliperidone Palmitate in Patients with Schizophrenia: Dosing Strategies Guided by Population Pharmacokinetic Modeling and Simulation (Part II).

Paliperidone palmitate 6-month (PP6M) intramuscular (IM) injection is the longest-acting treatment available for patients with schizophrenia. A population pharmacokinetic (popPK) modeling and simulation approach was deployed to inform dosing strategies for PP6M. The extensive analysis database included 15,932 paliperidone samples from 700 patients receiving gluteal paliperidone palmitate 3-month (PP3M) or PP6M injections in the double-blind phase of a phase-3 noninferiority study (NCT03345342). Exposure parameters for paliperidone appeared to increase dose-proportionally within each dosing schedule (PP3M/PP6M). The range of paliperidone exposures after IM administration of PP6M overlaps with that of corresponding doses of oral paliperidone extended release, PP 1-month (PP1M), and PP3M. Model-based simulations were performed to investigate paliperidone exposures in different PP6M dosing scenarios and relevant subpopulations. A dosing window of ≤ 2 weeks earlier and ≤ 3 weeks later than the target 6-month interval for maintenance treatment with PP6M dosing maintains paliperidone exposures at levels that are not expected to substantially impact its safety and efficacy. For missed-dose scenarios, tailored re-initiation regimens are proposed that should be applied before resuming PP6M maintenance dosing. Regarding subpopulations, PP6M 700 mg eq. is the highest dose recommended in mild renal-impairment patients; the paliperidone pharmacokinetics after PP6M administration is not affected by sex, body mass index, or age in a clinically meaningful way. Paliperidone concentration-time profiles after PP6M and PP3M dosing were adequately described by the popPK model. Model-based simulation results provide guidance for clinicians on initiating PP6M therapy, transitioning between paliperidone formulations, the dosing windows to use for maintenance dosing, and managing missed PP6M doses.

Male gynecomastia linked to antipsychotics: a case report

IntroductionGynecomastia refers to the abnormal development of breast tissue in males, often posing a concerning symptom. Often, gynecomastia is associated with multiple factors, including the use of various drugs, notably certain atypical antipsychotics. Gynecomastia is a significant side effect that affects the quality of life of male patients taking antipsychotic medications. Among these, risperidone and paliperidone have been identified as the most prone to causing gynecomastia, although aripiprazole has garnered attention for its superior profile in controlling prolactin and gynecomastia. The relationship between these drugs and the development of gynecomastia lies in their ability to elevate prolactin levels, a hormone that regulates reproductive function and is involved in milk production. Several studies have shown that prolactin levels are more commonly elevated with risperidone and paliperidone prescription, thus triggering gynecomastia.ObjectivesThe study aims to investigate the management of gynecomastia in male patients receiving antipsychotic medications.MethodsThis research employs a retrospective analysis of patient records to examine the association between specific antipsychotic drugs, prolactin levels, and the development of gynecomastia, while also evaluating the effectiveness of aripiprazole as an alternative treatment.ResultsWe present the case of a 21-year-old male with no prior medical history who initiated treatment with oral paliperidone and later switched to 100 mg of long-acting injectable paliperidone once monthly during his initial admission for psychotic symptoms. After six months, he developed gynecomastia, which was ruled out as breast tissue and was determined to be an increase in adipose tissue. Since his hospital discharge, he has gained 25 kg (30%) in body weight, and his baseline prolactin level has decreased. This weight gain, a common side effect of several antipsychotics, was linked to gynecomastia. However, a promising approach for gynecomastia antipsychotic-associated treatment is aripiprazole, which has a milder impact on prolactin levels. In this case, during the next appointment, a switch to 400 mg of long-acting injectable aripiprazole once-monthly was made, which led to weight loss, a reduction in breast size and blood prolactin levels in the following weeks.ConclusionsThe detection and management of gynecomastia in these patients are crucial to improving their quality of life and treatment adherence. This management encompasses changes in medication, hormonal therapy, or surgery in severe cases. Physicians must be aware of this potential complication when prescribing antipsychotics and closely monitor at-risk patients. In summary, antipsychotic-associated gynecomastia in men represents a medical challenge that requires careful attention and an individualized treatment strategy for each affected patient.Disclosure of InterestNone Declared

Paliperidone LAI-Induced Leukocytopenia: A Case Report

IntroductionAntipsychotics effectively manage psychotic symptoms but may have side effects. Patients with schizophrenia often lack insight into their condition, leading to nonadherence. Long-acting injectable (LAI) antipsychotics aim to overcome this, reducing relapse risks. Paliperidone LAI, a second-generation antipsychotic, has a lower side effect profile when compared to first-generation counterparts. Blood dyscrasias, like neutropenia and lymphopenia, increase infection susceptibility. This case report describes an instance of leukocytopenia arising during paliperidone LAI treatment, which quickly resolved after the discontinuation of the medication.ObjectivesThis case report describes an instance of leukocytopenia arising during paliperidone LAI treatment, which quickly resolved after the discontinuation of the medication.MethodsResultsCASEA 42-year-old female with schizophrenia, nonadherent to previously prescribed medication was admitted to our acute psychiatric department. She experienced positive symptoms (paranoid delusions), as well as disorganized thinking and behavior. Oral risperidone 4 mg two times a day was recommenced and titrated with mild improvement in her psychotic symptoms with the idea of switching to paliperidone LAI and eventually ceasing oral medication. Oral paliperidone was unavailable for prescription due to local restrictions. At admission her routine laboratory tests showed no abnormalities, but 5 days after receiving paliperidone LAI, routine laboratory tests showed a strong decrease in her WBC and absolute neutrophilic and lymphocytic count ( Lkc 2.89x109/L, Neut 1.57x 109/L, Lym 0.88x 109 /L ). Antipsychotic-induced blood dyscrasia was suspected and paliperidone depot was discontinued. The patient had rapid improvement in her WBC reaching the reference range in 10 days ( Lkc 4.23 x 109/L, Neut 2.51x10 9/L, Lym 0.98x 109/L). Sertindole was introduced consdering her history of a good therapeutic response to the drug, with improvement in psychotic symptoms. She is currently stable taking sertindole 16 mg/day, clonazepam 2 mg/day and alprazolam 0.5 mg/day.DISCUSSIONThe onset of neutropenia and lymphopenia post-paliperidone LAI initiation, resolving in 10 days,, indicate a direct association. Few cases report to date describe paliperidone-induced leukocytopenia, with rapid recovery post-discontinuation. Proposed mechanisms include bone marrow suppression and peripheral WBC destruction. It has been proposed that drug-induced neutropenia is often dose-dependent, which could explain why our patient exhibited tolerability to risperidone but developed cytopenia upon transitioning to depot paliperidone.ConclusionsWhile cases of agranulocytosis have been reported in association with the use of other antipsychotics these antipsychotics do not require the same monitoring as clozapine. Our case emphasizes the need for vigilant blood dyscrasia monitoring during antipsychotic therapy.Disclosure of InterestNone Declared

Clinical experience with once-monthly risperidone ISM in a mental health center. A retrospective study.

IntroductionLong-acting injectable antipsychotics have undergone a great development in recent years, becoming useful tools to facilitate therapeutic adherence. Once-monthly risperidone ISM is a new way of treatment which has been commercialized in Spain since September 2022.ObjectivesIn this study we will analyze our clinical experience with this treatment, especially in terms of tolerance and efficacy, during its first year of widespread use.MethodsLongitudinal retrospective study of monhtly risperidone users in a mental health center in the Autonomous Community of Madrid (Spain), between September 2022 and September 2023.A sample of 13 patients was selected, collecting both sociodemographic (age, gender) and clinical variables (diagnosis, dose, time elapsed, number of hospital readmissions, adverse effects and monotherapy or combined use). A descriptive analysis of the collected data was then carried out.ResultsMonthly risperidone was used in 13 patients: 15% (n=2) were women, and 85% (n=11) were male. The mean age of the patients was 43.6 years. The most frequent diganosis of these patients was “psychotic disorders” (84,6%, n= 11), with other diagnoses such as schizoaffective disorder (7,7%, n=1) and obsessive compulsive disorder (7,7%, n=1).The doses used of risperidone were 100mg every month in 61,5% of patients (n=8) and 75mg in 38,5% of patients (n=5). The mean time since the first administration was 4.35 months. Concerning monotherapy, 84,6% (n=11) of patients on monthly risperidone were on antipsychotic monotherapy, while 15,4% (n=2) required more than one antipsychotic. Among the switches made to monthly risperidone, 69,2% (n=9) were previously treated with oral risperidone, 15,4% (n=2) were treated with once-biweekly risperidone long-acting injectable, 7,9% (n=1) with oral paliperidone and 7,9% with aripiprazole monthly injectable.During the study period, hospital readmissions for psychiatric descompensations occurred in one patient (7,9%, n=1), while the rest of the patients (92,1%, n=12) did not present decompensations that required psychiatric admission.Moderate or severe effects occurred in one patient (7,9%, n=1), in the form of acute dystonia, which led to the interruption of injectable treatment. The rest of the patients (92,1%, n=12)) did not present severe adverse effects. Minor adverse effects appeared in 3 patients (25%); these adverse effects were already present in the previous treatment with oral risperidone and did not condition the suspension of the treatment.ConclusionsIn the sample analyzed, once-monthly Risperidone ISM had reasonable tolerance levels. Also, it´s shown to be effective in preventing psychotic decompensations and hospital admissions.Therefore, this new injectable of monthly risperidone represents a therapeutic alternative to consider in order to guarantee therapeutic adherence and improve the quality of life of patients with psychotic symptoms.Disclosure of InterestNone Declared

A case report of Paliperidone palmitate-induced anaphylaxis

IntroductionPaliperidone Palmitate (PP) is an atypical antipsychotic, approved by the FDA for acute and maintenance treatment of schizophrenia and schizoaffective disorder.It has a relatively safety profile, and reported cases of paliperidone palmitate-induced angioedema or anaphylaxis are uncommon.ObjectivesWe intend to present a case of paliperidone palmitate-induced anaphylaxis to alert clinicians regarding this rare, but possible complication.MethodsNon-systematic review of the literature and report of a case study.ResultsLong-acting injectable Paliperidone Palmitate (LAIPP) is a safe and effective alternative to oral Paliperidone, with less incidence of disease relapse related to medication non-compliance.Substance use disorder (SUD) is highly prevalent in first-episode psychosis (FEP), and it is associated to decreased treatment compliance, which impairs the outcomes of these patients. Therefore, several authors have been recommended long-acting injectable antipsychotics (LAI-AP), such the LAIPP, as a first line for treatment of FEP-SUD patients.The most common side effects associated with LAIPP are injection site reactions, extrapyramidal symptoms, hyperprolactinemia, sedation, hypersalivation, orthostatic hypotension, tachycardia, and weight gain. Hypersensitivity reactions have rarely been reported and may be dose-dependent.We report a case of a 20-year-old female, without medical history and no history of allergies, who was medicated with once-monthly LAIPP at dose 100 mg for the maintenance treatment of a first psychotic episode associated with cannabis abuse.Approximately 24 hours after the first monthly injection dose, she was admitted in the emergency room (ER) presenting an increasing angioedema associated with stridor, requiring endotracheal intubation and administration of adrenaline, clemastine and hydrocortisone during the assessment in the ER.After clinical stabilization, she was transferred to the internal medicine ward, and following a full recovery, she was discharged 6 days later while being medicated with Olanzapine 15 mg/day, Lorazepam 3 mg/day and Sertraline 50 mg/day. LAIPP was suspected as the etiology of the anaphylaxis reaction due to temporal relationship of its onset with therapy administration and by the exclusion of other potential causes. Consequently, LAIPP was discontinued at discharge.ConclusionsThis report shows the possibility of a late and potentially life-threatening anaphylactic reaction to LAIPP. So, all physicians should be aware of this potential complication, which requires timely recognition and management.Disclosure of InterestNone Declared

A comparison of recurrence rates after discontinuation of second-generation antipsychotic long-acting injectable versus corresponding oral antipsychotic in the maintenance treatment of bipolar disorder: A systematic review

It has been previously reported that among patients with schizophrenia that long-acting injectable (LAI) antipsychotic formulations can delay time to relapse longer when compared to their oral equivalents when patients discontinue therapy. Unanswered is whether this same pattern would be observed for patients with bipolar disorder receiving maintenance treatment. A systematic review was undertaken to identify relevant studies of LAI antipsychotics in maintenance treatment of bipolar disorder, employing a placebo-controlled randomized withdrawal design, and where equivalent studies using the corresponding oral formulation were also available. We found five studies [one aripiprazole monohydrate once monthly (AOM) study, one oral aripiprazole (OARI) study, two 2 weeks risperidone-LAI (RIS-LAI) studies, and one oral paliperidone (OPAL) study]. Numerically lower recurrence rates at 2, 4, 6, 8, 12, 16, 20, and 26 weeks were observed when AOM was discontinued when compared with discontinuation from OARI. Numerically lower recurrence rates at 2, 4, 6, 8, and 16 weeks were observed when RIS-LAI was discontinued when compared with discontinuation from OPAL. These results can be interpreted as a substantial delay in time to recurrence with a LAI antipsychotics formulation compared to the oral equivalent when medication is discontinued in patients with mania who had been stabilized on LAI antipsychotics or corresponding oral antipsychotics.

Cost-effectiveness analysis of monthly, 3-monthly, and 6-monthly long-acting injectable and oral paliperidone in adults with schizophrenia.

BACKGROUND: Paliperidone is among the most cost-effective antipsychotics in adults with schizophrenia, and it has different formulations, including oral paliperidone extended-release (ER) and long-acting injectable (LAI) paliperidone formulations administered every month (PP1M), 3 months (PP3M), or 6 months (PP6M). However, cost-effectiveness analyses comparing different paliperidone formulations were limited. OBJECTIVE: To compare the cost-effectiveness across different paliperidone formulations. METHODS: A Markov model was developed to simulate 1,000 adults aged 40 years with stable schizophrenia transitioning among stable disease-medication adherent, stable disease-medication nonadherent, relapse with hospitalization, relapse with ambulatory care, and death states every 3 months for 5 years. Drug costs were estimated using the prices listed in the Veterans Affairs Federal Supply Schedule, and costs for treating complications were estimated from published studies. All costs were estimated from the US health care system perspective and standardized to 2022 US dollars using the Consumer Price Index Inflation Calculator. Quality-adjusted life-years (QALYs) were estimated using relapse rates from randomized clinical trials and health-related quality of life scores from observational studies. The estimated future costs and QALYs were discounted at 3%. We reported incremental net monetary benefits between alternative formulations at the $50,000 willingness-to-pay (WTP) threshold with a positive value indicating cost-effectiveness. The impact of parameter uncertainty on study outcomes was assessed using 1-way deterministic and probabilistic sensitivity analyses. RESULTS: In adults with schizophrenia stabilized with paliperidone ER, switching to LAI formulations was associated with increased QALY (PP1M = 0.05, PP3M = 0.14, PP6M = 0.15) and increased cost (PP1M = 49,433, PP3M = 26,698, PP6M = 26,147), leading to a negative incremental net monetary benefit (PP1M = -$46,804, PP3M = -$19,508, PP6M = -$18,886) compared with continuing ER. Among LAI formulations, PP6M was cost-saving with the most QALYs gained (cost = $63,277, QALY = 3.731), followed by PP3M (cost = $63,828, QALY = 3.729) and PP1M (cost = $86,563, QALY = 3.638). At the $50,000 WTP threshold, the probabilities for PP1M, PP3M, and PP6M being cost-effective compared with paliperidone ER were 0.4%, 10.2%, and 9.8%, respectively. The probability of PP6M being cost-effective was 92.6% for the PP6M-PP1M pair and 55.2% for the PP6M-PP3M pair, and 91.1% of PP3M use was cost-effective in the PP3M-PP1M pair. The results were generally robust in the sensitivity analyses, even at the $190,000 WTP threshold. CONCLUSIONS: For patients with schizophrenia stabilized with paliperidone ER, switching to LAI formulations was not cost-effective, suggesting the high drug costs for LAI may not justify the improved quality of life within 5 years. Among LAI formulations, PP6M was cost-effective over PP1M and PP3M.

EE132 Cost-Utility Analysis of Long-Acting Injectable (1-, 3-, AND 6-MONTH INJECTION) and Oral Paliperidone in Adults with Stable Schizophrenia

To assess cost-effectiveness among long-acting injectable (LAI) paliperidone formulations administered every month (PP1M), 3 months (PP3M), or 6 months (PP6M) and oral paliperidone extended-release (ER).

Aripiprazole: Examining the Clinical Implications of D2 Affinity

AbstractBackgroundAripiprazole has high binding affinity for the dopamine D2 receptor, which is thought to be responsible for the antipsychotic effect, though aripiprazole is not the most potent of the second-generation antipsychotics. Theoretically, aripiprazole could displace or outcompete more potent antipsychotics, prompting decreased antipsychotic effect. We describe a case of aripiprazole potentially worsening psychiatric symptoms by blocking paliperidone.CaseMs. A is a 43-year-old woman with schizophrenia, multiple inpatient hospitalizations, and a history of court-ordered treatment. She historically has had good response to oral and long-acting formulations of risperidone and paliperidone. Ms. A requested a medication change and was transitioned to aripiprazole lauroxil injection with plan for bimonthly administration. Approximately 1 month after receiving her aripiprazole lauroxil injection, Ms. A presented to our CPEP due to symptoms of psychosis and was admitted to our inpatient unit. She was restarted on oral paliperidone, titrated up to her previously effective dose, and was transitioned to paliperidone palmitate LAI. In contrast to prior admissions, she did not respond well to paliperidone and displayed continued and worsened psychosis.DiscussionPrior studies have examined how adding aripiprazole to another, more potent D2 antagonist can cause a relapse in psychotic symptoms; however, few studies have investigated the inverse relationship or mechanism. Those that have proposed mechanisms typically refer to aripiprazole’s partial agonist activity as the causative factor, rather than an impediment to antipsychotic binding which we have described. Prescribers should be aware of this potential interaction and carefully consider initiating long-acting injectable forms of aripiprazole to avoid this phenomenon.FundingNo Funding

Alternative initiations with 6-monthly paliperidone palmitate. A retrospective study

Introduction6-monthly paliperidone palmitate features an initiation regimen through 1-monthly paliperidone palmitate or 3-monthly paliperidone palmitate. Some patients do not have sufficient adherence to treatment and it is necessary at the clinical level to start directly with 6-monthly paliperidone palmitate. There is little clinical experience with these alternative initiations and through this work those that have been carried out for 12 months at the Hospital Universitario Infanta Elena are exposed.ObjectivesThe main objective of the study is to describe the alternative initiations performed with 6-monthly paliperidone palmitate in routine clinical practice, having opted for a regimen different from the standard for clinical reasons.MethodsA retrospective selection of patients will be made through non-probabilistic consecutive sampling, including all patients who have been administered 6-monthly paliperidone palmitate with a start different from the standard during the last 4 months. To do this, the electronic medical record will be used, first selecting the patients who have started 6-monthly paliperidone palmitate through the anonymized digital records and, later, including in the study only those who have followed an alternative initiation pattern. The variables studied will be the following: age, sex, diagnosis, dose of paliperidone palmitate, initiation regimen, consumption of toxic substances, absenteeism from 6-monthly paliperidone palmitate, and visits to the emergency room and admissions.ResultsThe study included a total of 20 patients (n: 20). 80% of the patients were male and 20% were female. The mean age was 39.7 years. 75% of the patients had an associated substance use disorder. The following alternate starting schedules were performed with biannual paliperidone palmitate: monthly paliperidone palmitate on days 1 and 8, and 6-monthly paliperidone palmitate on day 38 (n: 11); monthly paliperidone palmitate 150 mg together with semi-annual paliperidone palmitate both on day 1 (n: 5); biannual paliperidone palmitate on day 1 supplemented with oral paliperidone for 45 days (n:4). A total of 0 visits to the emergency department and 0 admissions were observed after the 6-monthly paliperidone palmitate regimen.ConclusionsAlternative initiations with 6-monthly paliperidone palmitate may be a useful and safe clinical alternative in patients with very low adherence who, due to clinical needs, require starting 6-monthly paliperidone palmitate earlier in order to guarantee adherence.Disclosure of InterestNone Declared

Long-acting injectable paliperidone palmitate induced severe cutaneous allergic reaction in a patient with first episode delusional disorder tolerating oral paliperidone regimen: a case report

BackgroundPaliperidone is a second-generation antipsychotic agent that is effective in the treatment of schizophrenia and schizoaffective disorder as well as an adjunct to mood stabilizers and antidepressants for bipolar and depressive disorders. Paliperidone is available in both oral and injection forms. Here we report an unexpected case of cutaneous allergic reaction induced by paliperidone long-acting injection (LAI) following oral tolerance.Case presentationA 55-year-old man with first episode delusional disorder was treated with paliperidone tablets with tolerance. On day seven he received the paliperidone LAI and developed an allergic reaction in minutes including flushing of the face, widespread urticaria with mild airway constriction. The allergic symptoms were relived following the administration of antihistamine within several minutes.ConclusionThe allergic reaction that occurred post administration of the paliperidone LAI but not the oral tablets suggest it is likely due to the excipients in the formulation of the LAI rather than paliperidone itself. This case highlights the necessity of monitoring allergic reactions in psychiatric patients when converting from oral to LAI format of paliperidone.

Tardive Dyskinesia and Long-Acting Injectable Antipsychotics: Analyses Based on a Spontaneous Reporting System Database in Japan.

Objective: This study compared the reporting frequency of tardive dyskinesia (TD) between long-acting injectable antipsychotics (LAI-APs) and the equivalent oral antipsychotics (O-APs), LAI first-generation antipsychotics (LAI-FGAs) and LAI second-generation antipsychotics (LAI-SGAs), and individual LAI-APs.Methods: The Japanese Adverse Drug Event Report was used in this study, and data were obtained from April 2004 to February 2021. Patients who received LAI-APs available in Japan (LAI haloperidol, LAI fluphenazine, LAI aripiprazole, LAI risperidone, and LAI paliperidone) or the equivalent O-APs were included in this study. We calculated the adjusted reporting odds ratios (aRORs) to compare the reporting frequency of TD.Results: A total of 8,425 patients were included in the study. TD was reported significantly less frequently with LAI paliperidone than with oral paliperidone (aROR [95% confidence interval (CI)] = 0.13 [0.05-0.36]). Other LAI-APs were associated with a numerically lower reporting frequency of TD than the equivalent oral SGAs. The reporting frequency of TD associated with LAI-SGAs was significantly lower than that of LAI-FGAs (aROR [95% CI] = 0.18 [0.08-0.43]). All LAI-SGAs were significantly associated with a lower reporting frequency of TD than that of LAI fluphenazine (aROR [95% CI]: LAI aripiprazole, 0.11 [0.04-0.35]; LAI risperidone, 0.09 [0.03-0.32]; LAI paliperidone, 0.02 [0.005-0.09]). and LAI haloperidol, 8.58 [1.85-39.72]). LAI fluphenazine was significantly associated with a higher reporting frequency of TD than LAI haloperidol (aROR [95% CI] = 8.58 [1.85-39.72]). The reporting frequency of TD associated with LAI paliperidone was significantly lower than that with LAI aripiprazole (aROR [95% CI] = 0.18 [0.05-0.73]).Conclusions: Compared to O-APs, LAI-APs, particularly LAI-SGAs, may be associated with a lower risk of TD.

Therapeutic Drug Monitoring of Paliperidone in Patients With Schizophrenia in Taiwan.

The blood level of antipsychotics affects clinical responses to the drug; it can be influenced by race and several individual factors. This study analyzed the therapeutic plasma concentrations (Cps) of paliperidone for both oral and long-acting injectable (LAI) formulations in clinical samples from Taiwanese patients. Patients diagnosed with schizophrenia and treated with either oral paliperidone for at least 4 weeks or LAI paliperidone for at least 6 months were enrolled. Blood samples were taken before the morning dose of oral paliperidone or the injection of LAI paliperidone to obtain the trough Cps. Among the patients in this study, 51 were taking oral paliperidone, and 26 were receiving LAI paliperidone. In the oral group, the mean Cps were 40.2 ± 19.8 ng/mL in patients taking 9 mg/d and 44.2 ± 15.9 ng/mL in those taking 12 mg/d. In the LAI group, the mean Cps were 32.9 ± 12.7 ng/mL in patients receiving 100 mg per 28 days and 49.9 ± 25.9 ng/mL in those receiving 150 mg per 28 days. The mean Cps per daily dose (Cps/DD) were 4.11 ± 1.99 ng/mL/mg in the oral group and 9.24 ± 3.78 ng/mL/mg in the LAI group. Under the suggested DD for oral and LAI paliperidone treatment, most Taiwanese patients with schizophrenia can reach the suggested therapeutic Cps range. Wide interindividual differences were observed in the Cps/DD for both the oral (7-fold) and LAI paliperidone (4-fold) groups. Compared with Western reports, no difference was observed in the body weight-adjusted Cps/DD.

A case report of inhibition and severe desnutrition: negative symptoms in resistant schizophrenia

IntroductionThe appearance of inhibitory symptoms encompassed in what are known as negative symptoms is part of the usual symptoms of schizophrenia. Sometimes this inhibition reaches a significant severity, so it is essential to know its approach.ObjectivesCase report and literature review regarding the treatment of resistant schizophrenia with a predominance of negative symptomsMethodsWe present the clinical case of a 28-year-old man diagnosed with schizophrenia at 23 years old, whose onset was characterized by delusional ideas of harm (poisoning) and delusions with a mystic-religious theme that lead him to reduce his intake until requiring a first admission for severe desnutrition. Subsequently, after two more admissions, the patient presents selective reduction in food intake, decrease in daily activity and apathy without positive symptoms.ResultsThroughout the treatment, several lines of antipsychotic treatments have been tried at the maximum tolerated dose (haloperidol, oral paliperidone and depot, aripiprazole and clozapine up to a dose of 600 mg). Clozapine resistance required testing various augmentation strategies (Venlafaxine, Lamotrigine and Electroconvulsive therapy) with low results. Finally, to complement the treatment, the patient was transferred to a mid-stay unit where psychosocial treatment with a multidisciplinary approach was started. This has allowed more continuous follow-up and thus a partial improvement of the clinic.ConclusionsNumerous studies describe numerous augmentation strategies for clozapine-resistant schizophrenia with negative symptoms. However, the results are still inconclusive, needing more research. Meanwhile, we want to highlight the importance of complementing the treatment with psychosocial approaches.DisclosureNo significant relationships.

Effectiveness of oral versus long-acting antipsychotic treatment early-phase schizophrenia patients: an open-label randomized trial

IntroductionSchizophrenia is a chronic psychiatric illness with periods of remission and relapse. Patients vary in the frequency and severity of relapse, time until relapse and time in remission. Discontinuation of antipsychotic medication is by far the most important reason for relapse. A possible method to optimize medication adherence is to treat patients with long-term, depot medication rather than oral medication.ObjectivesPrimary objective is to compare all cause discontinuation rates in patients with schizophrenia randomized to either one of the two depot medications (aripiprazole depot or paliperidone palmitate) with patients randomized to either one of the two oral formulations of the same medication (aripiprazole or paliperidone) over an 19 month follow-up period.MethodsPragmatic, randomized, open label, multicenter, multinational comparative trial consisting of a 19 month treatment period. Patients aged 18 years or older, having experienced the first psychosis 1-7 years ago, currently meeting DSM-IV-R criteria for schizophrenia. Patients are randomized 1:1:1:1 to paliperidone palmitate, aripiprazole depot, oral aripiprazole or oral paliperidone. The primary outcome is all cause discontinuation.ResultsIn the Intent to Treat sample (n=511), no difference was found in time to ACD between the combined oral and combined depot treatment arms, nor between the four individual treatment arms.ConclusionsEven though the scientific evidence comparing oral and depot medication has been inconsistent, most studies were conducted in rigorous clinical settings, which may have biased those results. In contract, given the pragmatic, open label design of the current trial, the results may be more representative of common daily practice.DisclosureNo significant relationships.

Paliperidone palmitate-induced enuresis: a case report

IntroductionSchizophrenia is a severe mental illness that requires long-term treatment with antipsychotics and the intramuscular (IM) long-acting injectable (LAI) formulations may enhance treatment adherence. Some antipsychotics have been associated with enuresis, including atypical antipsychotics such as risperidone(6.2%), quetiapine(6.7%), olanzapine (9.6% ) and clozapine (20.7%) [1]. Although oral paliperidone has been related to urinary incontinence, there is only 1 report of urinary incontinence linked to monthly paliperidone palmitate [2]. [1] Harrison-Woolrych, M., Skegg, K., Ashton, J., Herbison, P., Skegg, D.C., 2011. Nocturnal enuresis in patients taking clozapine, risperidone, olanzapine and quetiapine: comparative cohort study. British Journal of Psychiatry 199, 140–144. doi:10.1192/bjp.bp.110.087478 [2] Karslıoǧlu, E.H., Özalp, E., Çayköylü, A., 2016. Paliperidone Palmitate-induced Urinary Incontinence: A Case Report. Clinical Psychopharmacology and Neuroscience 14, 96–100. doi:10.9758/cpn.2016.14.1.96ObjectivesTo establish an association between paliperidone palmitate and enuresis.MethodsCase report and a narrative review of the literature.ResultsThe patient was a 25-year-old healthy man when he was diagnosed with schizophrenia. Doctors prescribed paliperidone palmitate (LAI) 200mg monthly and he started to complain of enuresis. He was clearly suffering with this unpleasant and embarrassing adverse effect so the LAI was reduced to 150mg. Enuresis remained, so it was prescribed oxybutynin 20 mg/day and the patient improved.ConclusionsWe reported a case in which enuresis is likely to be associated with high-dose paliperidone LAI (with no clinical evidence of an organic cause). To treat it, the most effective strategy was oxybutynin 20 mg/day. This case is also important to show the impact of this symptom, which is not actively investigated.DisclosureNo significant relationships.

The combination of long-acting injectable antipsychotics, a new key in resistant schizophrenia

IntroductionSchizophrenia is a chronic disease that requires lifelong medical care and supervision. There is a high rate of relapse, mostly caused by poor adherence to oral antipsychotics. Long-acting injectable (LAI) antipsychotics have proved effective in schizophrenia and other severe psychotic disorders due to the stable blood levels, leading to a reduction of the risk of relapse. LAIs are associated with better functioning, quality of life, and patient satisfaction. In Treatment-resistant schizophrenia the combination of antipsychotics is a common practice. Nevertheless, the combination of two different long-acting injectable antipsychotics is not frequent.ObjectivesA case of a 34-year-old man is presented, previously diagnosed of Schizophrenia, with highly disabling chronic positive symptoms. With no in-sight and no will in receiving treatment. Has been stable for a year while being in treatment with paliperidone 525mg LAI/ 10 weeks, and aripiprazole 400mg LAI/28 days.MethodsThe patient was closely observed and given oral paliperidone, after 5 days long-acting paliperidone was introduced. He was discharged with mild improvement of his psychiatric symptoms. While being in treatment with Paliperidone 525mg, he kept vivid delusions and hallucinations. The patient still refused to take any oral medications. Long-acting aripiprazole 300mg was added to the treatment.ResultsHe showed clinical improvement after a month. He has been stabilized for one year.ConclusionsTreating resistant schizophrenia is among the most challenging clinical endeavors. A very helpful approach to improve adherence in schizophrenia is the use of long-acting injectable (LAI) antipsychotics. A major effort on scientific research of combination of LAI is needed.DisclosureNo significant relationships.

Precision psychiatry: The complexity of personalizing antipsychotic dosing

Recently, Salagre and Vieta commented on the complexity of implementing precision medicine in psychiatry. For 25 years, this author has focused on a circumscribed type of precision medicine: personalized dosing using pharmacokinetic mechanisms to stratified patients. This short communication focuses on personalized dosing of three oral antipsychotics (clozapine, risperidone and paliperidone) and presents their maintenance dosing in a table which provides dose-correction factors generated by pharmacokinetic studies. Inhibitors need dose-correction factors < 1 and inducers need correction factors >1. Clozapine maintenance dosing is based on the dose needed to reach 350 ng/ml (the minimum plasma therapeutic concentration in treatment-resistant schizophrenia). Clozapine maintenance dosing is influenced by 3 levels of complexity: 1) ancestry groups (Asians/Native Americans; Europeans and Blacks), 2) sex-smoking subgroups (lowest dose in female non-smokers and highest in male smokers) and 3) presence/absence of poor metabolizer status (due to genetic and non-genetic causes including co-prescription of inhibitors, obesity or inflammation). Risperidone and paliperidone maintenance dosing are based on the dose needed to reach plasma concentrations of 20–60 ng/ml. Risperidone PMs need approximately half the dose, which can be explained by genetics (CYP2D6 PMs) or co-prescription of CYP2D6 inhibitors. Fluoxetine co-prescription may require one fourth the risperidone maintenance dose. Carbamazepine co-prescription may require twice the risperidone maintenance dose. Although not well studied, two groups may need higher doses of oral paliperidone: Koreans may need 1.5 times higher doses while those taking carbamazepine may need 3 times higher paliperidone maintenance doses. Precision dosing in psychiatry requires using blood levels of individuals.

Risks of all-cause death and completed suicide in patients with schizophrenia/schizoaffective disorder treated with long-acting injectable or oral antipsychotics: A population-based retrospective cohort study in Taiwan.

Long-acting injectable (LAI) antipsychotics improve medication adherence in patients with schizophrenia and extend the duration of therapeutic drug levels but with administration of an increased dose. Real-world mortality data in patients prescribed LAIs are lacking. We conducted a population-based cohort study to estimate and compare the incidence rates of all-cause death and completed suicide in patients with schizophrenia/schizoaffective disorder exposed to LAIs and oral antipsychotics. Patients with a diagnosis of schizophrenia/schizoaffective disorder between January 1, 2015 and November 30, 2019 were enrolled from the Taiwan National Health Insurance Research Database and linked to Death Registry records. Eligible patients were new antipsychotic users. Relative risks of death for each antipsychotic compared with oral paliperidone were evaluated using a Cox proportional hazard model adjusted for age, sex, Charlson Comorbidity Index, index year, bipolar or major depressive or other mood disorders, mental disorders due to drug use, and baseline hospitalization frequency. There were 228,791.08 person-years of follow-up (mean 2.48years). The incidence rates of all-cause death in users of LAI paliperidone administered monthly (PP1M) and every 3months (PP3M) were 7.40/1,000 person-years (95% confidence interval 5.94-9.11) and 9.93 (5.88-15.79), respectively. The incidences of completed suicide were 2.03/1,000 person-years (1.32-2.99) and 3.10 (1.14-6.88), respectively. No significant associations were observed between PP1M and PP3M compared to oral paliperidone in incidences of all-cause death or for completed suicide. No increased risk of all-cause death or completed suicide was observed in users of antipsychotic LAIs, including PP1M and PP3M.

Paliperidone 3-Month Injection for Treatment of Schizophrenia: A Narrative Review.

Given the typical age onset of schizophrenia, there are tremendous economic and social impacts that extend beyond the person and their families. One critical determinant of the diseases' impact is the patient's adherence to antipsychotic drug treatment. Approved in 2015 for the treatment of schizophrenia, paliperidone palmitate (Invega Trinza, a 3-month injection, noted as PP3M) is a second-generation long-acting injectable antipsychotic medication. Among the different formulations offered for palmitate paliperidone, including the 1 and 3-month formulations, the longer duration 3-month formulation was better at preventing relapse in schizophrenic patients. To date, different formulations of palmitate paliperidone that have been studied on relapse episodes of schizophrenia include once-daily extended-release oral paliperidone (ORAL paliperidone), once-monthly paliperidone palmitate (PP1M), and once-every-3-months paliperidone palmitate (PP3M). Post-hoc analyses show that patients who were withdrawn from PP1M paliperidone had the least risk of relapse, followed by patients withdrawn from PP3M and patients withdrawn from ORAL paliperidone. PP3M was better at preventing relapse compared to ORAL paliperidone. The results demonstrated that 50% of patients who were withdrawn from ORAL paliperidone, PP1M, or PP3M remained relapse-free for ~2, 6, and 13 months, respectively. Compared to PP1M, PP3M is just as safe and effective and has the added advantage of increased adherence related to a longer dose interval, decreasing the risk of relapse.