Extended-release Injectable Suspension Research Articles

In situ forming risperidone implants: Effect of PLGA attributes on product performance

Despite the unique advantages of injectable, long-acting in situ forming implant formulations based on poly(lactide-co-glycolide) (PLGA) and N-Methyl-2-Pyrrolidone (NMP), only six products are commercially available. A better understanding of PLGA will aid in the development of more in situ forming implant innovator and generic products. This article investigates the impact of slight changes in PLGA attributes, i.e., molecular weight (MW), lactide:glycolide (L/G) ratio, blockiness, and end group, on the in vitro and in vivo performance of PLGA-based in situ forming implant formulations. Perseris (risperidone) for extended-release injectable suspension was selected as the reference listed drug (RLD). A previously developed adapter-based USP 2 method was used for the in vitro release testing of various risperidone implant formulations. A rabbit model was used to determine the in vivo pharmacokinetic profiles of the formulations (subcutaneous administration) and deconvolution (Loo–Riegelman method) was conducted to obtain the in vivo release profiles. The results showed that a 5 KDa difference in the MW (19.2, 24.2, 29.2 KDa), a 5% variation in the L/G ratio (85/15, 80/20, 75/25) and the end-cap (acid vs ester) all significantly impacted the formulation behavior both in vitro and in vivo. Higher MW, higher L/G ratio and ester end-cap PLGA all resulted in longer release durations. The formulations prepared with polymers with different blockiness values (within the blockiness range tested) did not show differences in in vitro and in vivo release. An in vitro-in vivo correlation (IVIVC) was not developed due to the different in vitro and in vivo phase separation rates, swelling tendencies and consequent significantly different release profiles. This is the first report evaluating the impact of PLGA property variation (over a narrow range) on the performance of in situ forming implants. The knowledge gained will provide a better understanding of the mechanisms underlying risperidone in situ forming implant performance and will aid the development of future products.

Preclinical development and pharmacokinetic assessment in macaques of a multipurpose long-acting injectable suspension containing medroxyprogesterone acetate for contraception and rilpivirine for HIV prevention

Depot injections comprising aqueous drug suspensions are widely marketed for long-acting administration of contraceptive progestins and antipsychotics. In recent years, there has been considerable interest in developing similar long-acting injectable products containing antiretroviral drugs for treatment or prevention of HIV infection, culminating in 2020/2021 with the approval of Cabenuva® (which combines the integrase strand transfer inhibitor cabotegravir with the non-nucleoside reverse transcriptase inhibitor rilpivirine for treatment of HIV infection) and Apretude (a cabotegravir extended-release injectable suspension for HIV prevention). Here, we describe formulation and preclinical development of a new multipurpose prevention technology product based on a long-acting injectable aqueous suspension formulation combining micronized medroxyprogesterone acetate (the progestin used in the long-acting injectable contraceptive product Depo-Provera®) and a rilpivirine nanosuspension for HIV prevention. Through the application of an extensive range of analytical methods, we have demonstrated that the resulting combination suspension formulation had a bimodal particle distribution, was stable, was sterilised by gamma irradiation, and provided sustained systemic and vaginal exposure of both drugs over at least one month following intramuscular injection in macaques. Further formulation development will be needed to sustain drug concentrations in the systemic/vaginal compartments over longer time periods, and to consider options for use of alternate antiretroviral drugs.

Med Check: Zuranolone for Depression, Uzedy for Schizophrenia, and More

Back to table of contents Previous article Next article Med CheckFull AccessMed Check: Zuranolone for Depression, Uzedy for Schizophrenia, and MoreTerri D’ArrigoTerri D’ArrigoSearch for more papers by this authorPublished Online:25 May 2023https://doi.org/10.1176/appi.pn.2023.06.6.1Zuranolone Found to Quickly Reduce Major Depression SymptomsAdults with major depressive disorder may experience mood improvements within days of taking zuranolone (50 mg/day), a study published in May in The American Journal of Psychiatry (AJP) suggests. Zuranolone is an oral, once-daily neuroactive steroid that acts on GABA-A receptors.The phase 3 trial included patients who were between the ages of 18 and 64 years, had received a diagnosis of major depressive disorder, had been experiencing symptoms of depression for a least four weeks, and had a Hamilton Depression Rating Scale (HAM-D) score of at least 24 at screening and before they started taking the assigned study medication.The researchers randomized 534 participants to take either 14 days of treatment with zuranolone 50 mg/day or placebo in the evening. The researchers evaluated the participants 10 times over the course of the 42-day trial using such assessments as the HAM-D, the Columbia–Suicide Severity Rating Scale, the Clinical Global Impressions severity score, and more.Compared with patients who took placebo, those who took zuranolone demonstrated a statistically significant improvement in depressive symptoms at day 15. “Numerically greater improvements in depressive symptoms for zuranolone versus placebo were observed by day 3 (least squares mean change from baseline HAM-D score, −9.8 vs. −6.8), which were sustained at all visits throughout the treatment and follow-up periods of the study,” the researchers wrote.FDA Approves Uzedy for Treating SchizophreniaIn April the U.S. Food and Drug Administration (FDA) approved Uzedy (risperidone extended-release injectable suspension) for the treatment of schizophrenia in adults, Teva and MedinCell announced. Uzedy is a long-acting subcutaneous antipsychotic that may be given in one- or two-month dosing intervals.In the phase 3 RISE trial, 544 patients aged 13 to 65 years with schizophrenia were randomized to receive a subcutaneous injection of Uzedy (either once per month or once every two months) or placebo. Those who received Uzedy once per month or once every two months had a reduction of 80.0% and 62.5% in the risk to relapse compared with those who received placebo, respectively. Results were similar in the phase 3 SHINE trial, which examined the long-term safety of the drug for up to 56 weeks in 336 patients aged 13 to 65 years with schizophrenia.A companion survey of participants in the SHINE trial found that 89% of patients and 92% of health professionals rated administration of Uzedy as easy when asked how easy or difficult it was to receive or administer the medication in its current form. Further, 70% of patients reported that Uzedy provided a better injection experience than their previous long-acting injectables (LAIs).Abilify Asimtufii Approved for Schizophrenia, Bipolar I TreatmentAbilify Asimtufii (aripiprazole extended release injectable suspension) has been approved by the FDA for the treatment of schizophrenia in adults and as a monotherapy treatment of bipolar I disorder in adults, Otsuka and Lundbeck announced in April. Abilify Asimtufii is a long-acting subcutaneous atypical antipsychotic that may be given every two months.The approval was based on safety and efficacy data from trials of Abilify Maintena, which is for once monthly dosing, and on the results of a phase 1-2 study. In the phase 1-2 study, 266 adults with schizophrenia or bipolar I disorder were randomly assigned to receive either Abilify Asimtufii 960 mg every 56 days, for a total of four injections or Abilify Maintena 400 mg administered every 28 days for a total of eight injections. Treatment with Abilify Asimtufii resulted in similar aripiprazole plasma concentrations and efficacy to Abilify Maintena. ■ ISSUES NewArchived

Cabotegravir Extended-Release Injectable Suspension: A Review in HIV-1 Pre-Exposure Prophylaxis.

Cabotegravir extended-release (ER) injectable suspension (Apretude™) is the first long-acting injectable option to be approved for HIV-1 pre-exposure prophylaxis (PrEP). As an HIV-1 integrase strand transfer inhibitor, cabotegravir ER injectable suspension prevents DNA integration and inhibits HIV-1 replication. Its slow absorption and long elimination half-life permit infrequent dosing (1month apart for two consecutive months, and every 2months thereafter). Cabotegravir ER injectable suspension is indicated in the USA for PrEP to reduce the risk of sexually acquired HIV-1 infection in at-risk adults and adolescents weighing ≥ 35 kg who have a negative HIV-1 test prior to initiation. In clinical trials, cabotegravir ER injectable suspension had superior efficacy to oral daily emtricitabine/tenofovir disoproxil fumarate (DF) in preventing acquisition of HIV-1 in at-risk transgender women (TGW), cisgender men who have sex with men (MSM), and cisgender women. The drug was generally well tolerated, although further long-term data are needed to fully determine its safety. With its convenient, less-frequent dosing schedule and its long-acting formulation enabling intramuscular administration, cabotegravir ER injectable suspension represents a novel and efficacious alternative to daily oral PrEP.

Risperidone for Extended-Release Injectable Suspension (Perseris)


 CADTH reimbursement reviews are comprehensive assessments of the clinical effectiveness and cost-effectiveness, as well as patient and clinician perspectives, of a drug or drug class.
 The assessments inform non-binding recommendations that help guide the reimbursement decisions of Canada's federal, provincial, and territorial governments, with the exception of Quebec.
 This review assesses risperidone for extended-release injectable suspension (Perseris), powder for suspension, 90 mg or 120 mg subcutaneous injection.
 Indication: Treatment of schizophrenia in adults.

A Noninterventional Cohort Study Assessing Time to All-Cause Treatment Discontinuation After Initiation of Aripiprazole Once Monthly or Daily Oral Atypical Antipsychotic Treatment in Patients With Recent-Onset Schizophrenia.

Introduction: Aripiprazole once-monthly 400 mg (extended-release injectable suspension) is effective in long-term maintenance treatment of schizophrenia based on clinical studies. As study results may not reflect clinical practice, we compared treatment persistence with aripiprazole once-monthly 400 mg versus daily oral atypical antipsychotics in a naturalistic setting.Methods: This was an observational, noninterventional study of patients (aged 18-35 years) with recent-onset schizophrenia (< 5 years post diagnosis) who initiated maintenance treatment with aripiprazole once-monthly 400 mg or any daily oral atypical antipsychotic during a schizophrenia-related hospitalization or within 3 months post hospital discharge (timeframe: July 13, 2017-July 31, 2019). Data were from patient files/obtained during routine visits. Patients were followed for ≤ 12 months or until all-cause treatment discontinuation (including lost to follow-up), whichever came first. Data were analyzed using a sample constructed with inverse probability of treatment weighting (IPTW).Results: Among 357 patients (aripiprazole once-monthly 400 mg: 215, oral atypical antipsychotics: 142), all-cause treatment discontinuation occurred in 87 (41%) of aripiprazole once-monthly 400 mg, 68 (48%) of oral atypical antipsychotic patients over 52 weeks. In the IPTW sample, time to all-cause discontinuation was significantly different between both groups in favor of aripiprazole once-monthly 400 mg (hazard ratio = 1.46; 95% CI, 1.05-2.03; P = .023). Generalizability of results to the overall population with schizophrenia was limited due to incomplete overlap of patient characteristics between cohorts. The primary reason for treatment discontinuation in both groups was voluntary discontinuation by subject (aripiprazole once-monthly 400 mg: 11%; oral atypical antipsychotics: 8%).Conclusions: In a naturalistic setting, younger patients with recent-onset schizophrenia treated with aripiprazole once-monthly 400 mg after hospitalization tended to discontinue treatment later than patients treated with daily oral atypical antipsychotics.Trial Registration: ClinicalTrials.gov identifier: NCT03130465.

Dynamic weight-bearing test during jumping: A sensitive outcome measure of chronic osteoarthritis pain in rats

Pain due to osteoarthritis (OA) often occurs during locomotion in the vertical direction when joints are subjected to high mechanical load, e.g. during standing up from a chair or using stairs. To investigate joint pain in OA rat models, dynamic weight-bearing or gait analysis is traditionally conducted during horizontal walking on a flat surface. However, in chronic models of OA, which are of particular translational relevance for the disease, differences in the readouts between OA and control rats are often weak and of high variability leading to an insufficient assay window for drug profiling. To measure pain-related symptoms more sensitively, we conducted a dynamic weight-bearing test in the moment of a strong voluntary mechanical load. For that, we permanently housed rats in a four-story rat colony cage (RCC) and determined hind paw forces during voluntary jumping from one level to the next. This outcome measure was named jump incapacitance. After inducing OA by destabilizing the medial meniscus (DMM), we found that during jumps the average ipsilateral over contralateral hind paw forces were significantly reduced compared with healthy controls (jump incapacitance) from early- (day 7) to late-stage disease (day 90). An intra-articular injection of Zilretta (triamcinolone acetonide extended-release injectable suspension) attenuated OA-induced jump incapacitance after 8 days compared with DMM rats receiving vehicle (p = 0.069). In contrast, a CatWalk test for gait disturbance failed to detect any significant alterations in the chronic course of the DMM model. In conclusion, the dynamic weight-bearing test during jumping represents a novel method to characterize joint pain symptoms even in a slowly progressive OA rat model. It is sensitive, observer independent, relates to clinically relevant endpoints and demonstrates backtranslation of a drug that is approved for the treatment of OA knee pain.

Evaluation of Opioid Overdose Reports in Patients Treated with Extended-Release Naltrexone: Postmarketing Data from 2006 to 2018.

IntroductionAfter treatment with naltrexone extended-release injectable suspension (XR-NTX), a µ-opioid receptor antagonist, opioid tolerance is reduced from pretreatment baseline. Patients may be vulnerable to opioid overdose if they attempt to override the blockade during treatment, at the end of a dosing interval, after missing a dose, or after discontinuing treatment.ObjectiveWe analyzed postmarketing data to characterize reporting rates of opioid overdose during treatment with and after discontinuation of XR-NTX.MethodsPostmarketing adverse event reports within the XR-NTX safety database, received 2006–2018, for patients treated with XR-NTX for any indication were reviewed for opioid overdose cases. Assessable cases were categorized by timing of the event from the last dose of XR-NTX (latency): ≤28 days (on treatment), 29–56 days, and >56 days from last dose of XR-NTX. Within each latency group, cases were further classified as serious and, of those, cases that had a fatal outcome.ResultsDuring the 12-year period, an estimated 495,602 patients received XR-NTX. Opioid overdose was reported in 161 cases; of these, 66 contained sufficient information to determine latency. Reporting rates of opioid overdose per 10,000 patients treated were similar among latency groups: 0.54 for ≤28 days (0.24 fatal), 0.34 for 29–56 days (0.16 fatal), and 0.44 for >56 days (0.40 fatal) from the last dose of XR-NTX.ConclusionsOver the 12-year period, the reporting rates of opioid overdose were similar during treatment with or after discontinuation of XR-NTX and <10/10,000 patients exposed. Our findings are limited by the nature of spontaneously reported safety data.Electronic supplementary materialThe online version of this article (10.1007/s40264-020-01020-4) contains supplementary material, which is available to authorized users.

Efficacy of semi-annual therapy of an extended-release injectable moxidectin suspension and oral doxycycline in Dirofilaria immitis naturally infected dogs

BackgroundDirofilaria immitis is a life-threatening nematode spreading globally. Arsenical treatment is currently recommended for removal of adult worms. However, arsenical treatment is not available in some countries, and there are dogs that cannot tolerate the rapid kill of adult worms; therefore, alternative adulticide slow-kill treatments are needed. Criticisms against the use of these alternative protocols include the potential for allowing disease to progress and for the development of ML-resistant worms.MethodsThe efficacy of a protocol that includes semi-annual doses (i.e. every 6 months) of commercially available extended-release injectable moxidectin suspension (ProHeart® SR-12) with 30-day oral administration of doxycycline was studied in 20 dogs with naturally occurring D. immitis infections. Each dog received treatment with ProHeart® SR-12 (0.5 mg moxidectin/kg) by subcutaneous injection and oral doxycycline (10 mg/kg/bid × 30 days) every 6 months until two consecutive negative antigen test results were obtained. Pulmonary and cardiac evaluations were performed by radiographic and echocardiographic parameters. Physical examinations, complete blood counts, clinical chemistry profiles, microfilariae and antigen tests were performed periodically.ResultsAt enrollment, all dogs were positive for D. immitis antigen and 18 were microfilaremic. On day 30, microfilaremia counts decreased, and all dogs became amicrofilaremic by day 150. On day 180, 11 dogs were antigen-negative, and 7 more became negative by day 360. The two remaining antigen-positive dogs converted to negative by day 540 or 810. All antigen tests performed 180 days after the first negative test were negative. There was no decline in cardiac performance of the dogs throughout the study. Overall, pulmonary clinical conditions, presence of worms by echocardiography, and enlargement of caudal and main pulmonary arteries improved after treatment. Physical examinations, complete blood count results, and clinical chemistry profiles were within normal reference values. Respiratory conditions were improved, no damage to the heart was observed, and the treatment protocol was well tolerated by the animals.ConclusionsThis alternative adulticide treatment was efficacious and well tolerated in naturally infected dogs. The injectable formulation provides the advantage of having veterinarians able to administer, monitor, and assess the efficacy and condition of the dog throughout the treatment and post-treatment periods.

Safety of an extended-release injectable moxidectin suspension formulation (ProHeart\xae 12) in dogs

BackgroundThe safety of ProHeart® 12 (PH 12; extended-release injectable suspension; 10% moxidectin in glyceryl tristearate microspheres) was evaluated in four studies using Beagle dogs and one study using ivermectin-sensitive Collies. The recommended dose is 0.5 mg/kg subcutaneously once yearly.MethodsStudy 1: safety margin was evaluated as 3 treatments of PH 12 (0× (control); 1× (recommended dose); 3× (3 times recommended dose) and 5× (5 times recommended dose) in 12 months via clinical observations, body weights, food consumption, injection site observations, physical examinations, moxidectin tissue assay, pharmacokinetics, and clinical and anatomic pathology. Study 2: safety in breeding-age males was demonstrated by semen testing at 14-day intervals from Day 7 to Day 91 post-treatment (0× or 3×). Study 3: reproductive safety in females was demonstrated by monitoring dams and litters following treatments (0× or 3×) administered during breeding, gestation, or lactation. Study 4: safety in dogs surgically implanted with adult heartworms was evaluated by clinical and laboratory monitoring following treatment with 0× or 3× administered 61 days post-implantation. Study 5: safety in ivermectin-sensitive dogs (120 µg/kg SC) was by clinical monitoring for 1 week after administering 1×, 3× or 5×.ResultsStudy 1: slight swelling clinically detectable at some 3× and 5× injection sites was characterized microscopically as granulomatous inflammation, like tissue responses to medical implants, interpreted as non-adverse. Pharmacokinetics were dose-proportional and there was little or no systemic accumulation. Residual moxidectin mean (range) at 1× injection sites after 1 year was 16.0% (0.045–37.6%) of the administered mass. Studies 2 and 3: no effects were identified in reproductive indices (females) or semen quality characteristics (males). Study 4: PH 12 produced marked reductions in circulating microfilariae and lower numbers of adult heartworms, but no adverse clinical signs were identified. Study 5: there were no abnormal clinical signs at 1×, 3× or 5× overdoses of PH 12 in ivermectin-sensitive dogs.ConclusionsPH 12 has a > 5× safety margin in both normal and ivermectin-sensitive dogs, has no effects on canine reproduction, and is well tolerated in heartworm-positive dogs. The only treatment-related finding was non-adverse, granulomatous inflammation at the injection site.

PMS41 - Cost Effectiveness Analysis of Intra-Articular Triamcinolone Acetonide Extended-Release Injectable Suspension (TA-ER) Versus Triamcinolone Acetonide Crystalline Suspension For Symptomatic Knee Osteoarthritis

To assess the cost-effectiveness of a single intra-articular (IA) injection of the recently-approved triamcinolone acetonide extended-release injectable suspension (TA-ER, formerly known as FX006) compared with conventional, commonly-used triamcinolone crystalline suspension (TAcs), in patients with symptomatic knee osteoarthritis (OA). We used a 3-state Markov model (TreeAge Software Inc., USA) to compare TA-ER (Flexion Therapeutics Inc., USA) with TAcs over 12 weeks. Analyses utilized patient-level data from three trials (NCT01487161, NCT02116972, NCT02357459). Participants with Kellgren-Lawrence Grade 2-3 knee OA and baseline Average Daily Pain-intensity scores of ≥5 to ≤9 were randomized to receive TA-ER 32 mg or TAcs 40 mg. Health Utilities Index Mark 3 (HUI-3) scores and Outcome Measures in Rheumatology (OMERACT)-OA Research Society International (OARSI)-defined “Strict” responder rates from previous pooled analyses were used to define utility scores and transition probabilities within the Markov model, respectively. Utility gained throughout the study was defined for responders versus non-responders and measured by area under the utility curve, expressed as quality-adjusted life years (QALYs). Costs included drug cost, physician assessment and injection fees, and conventional care. One-way sensitivity analysis used ±15% for continued response rates and QALYs gained per responder; all others were varied ±20%. Probabilistic sensitivity analyses and Monte Carlo simulations were also performed. The average utility gain for patients treated with TA-ER was 0.0281 QALYs over 12 weeks; cost/QALY was $4,570 and $1,515 for TA-ER and TAcs, respectively. The incremental cost-effectiveness ratio (ICER) of TA-ER was $19,883/QALY gained, sensitive to QALYs gained per responder and response rates in either TA-ER or TAcs groups. In Monte Carlo simulations, when willingness-to-pay threshold was set at $50,000/QALY, TA-ER was a cost-effective strategy in 63% of simulations. Compared with TAcs over a 3-month period, the $19,883/QALY ICER of TA-ER remained within the $50,000/QALY willingness-to-pay threshold to adopt a new treatment.

Triamcinolone acetonide extended-release injectable suspension (TA-ER) provides clinically relevant improvements in pain and function of knee osteoarthritis: a pooled analysis of 3 randomized clinical trials employing composite assessments

Triamcinolone acetonide extended-release injectable suspension (TA-ER) provides clinically relevant improvements in pain and function of knee osteoarthritis: a pooled analysis of 3 randomized clinical trials employing composite assessments

Triamcinolone acetonide extended-release injectable suspension (TA-ER) is associated with reduced blood glucose elevation vs. standard triamcinolone in type 2 diabetes mellitus patients with knee osteoarthritis: a randomized, blinded, parallel-group study

Triamcinolone acetonide extended-release injectable suspension (TA-ER) is associated with reduced blood glucose elevation vs. standard triamcinolone in type 2 diabetes mellitus patients with knee osteoarthritis: a randomized, blinded, parallel-group study

Assessment of the safety of repeat administration of triamcinolone acetonide extended-release injectable suspension in patients with knee osteoarthritis: trial design, methods and preliminary data

Assessment of the safety of repeat administration of triamcinolone acetonide extended-release injectable suspension in patients with knee osteoarthritis: trial design, methods and preliminary data

Review of Case Narratives from Fatal Overdoses Associated with Injectable Naltrexone for Opioid Dependence.

An extended-release injectable naltrexone suspension (Vivitrol®) was approved in USA in 2010 for the prevention of relapse to opioid dependence. Concerns, raised at the time of approval, about rebound overdose risk following the last dose, have not been adequately studied. We sought to determine the time period of concern for fatal overdose associated with Vivitrol. We performed a retrospective case review of Vivitrol spontaneous reports (October 2010-March 2016) in the US Food and Drug Administration Adverse Event Reporting System via the Freedom of Information Act. Case narratives were manually reviewed to identify overdose deaths amongst current and former patients, extracting information on the time from discontinuation, followed by causality assessment. Narratives on 263 deaths and overdose-related outcomes were obtained. One hundred and forty-five death reports were assessed for causality. Among these reports, cause of death was unknown in 46%, while 52 fatal overdoses met the case definition. Of 52 overdoses, time between the last dose and death was known for 28; 22 (84.6%) occurred within 2months of the last Vivitrol injection [median 46days (interquartile range 29.5-82)]. The sponsor's causality assessment in 75% of fatal overdoses repeated verbatim text that placed responsibility on underlying opioid dependence and precluded a link between medication and overdose or ignored rebound risk following treatment discontinuation. Vivitrol adverse event reports suggest the need to investigate twomonths following the last medicine injection as a period of particular concern for overdose. A registry study would best quantify risk. Providers should report suspected post-discontinuation overdoses to government authorities.

Aripiprazole Lauroxil Long-Acting Injectable: The Latest Addition to Second-Generation Long-Acting Agents.

Antipsychotics have long been the mainstay for the treatment of schizophrenia and other psychotic disorders. Long-acting injectables (LAI) of antipsychotics-provided once every two weeks to once every three months-promise to reduce the incidence of nonadherence. ARISTADA(™) (aripiprazole lauroxil; ALLAI) extended-release injectable suspension was approved by the U.S. Food and Drug Administration in October 2015 for the treatment of schizophrenia, and is the newest entrant in the LAI market. ALLAI is available as a single-use, pre-filled syringe, can be started in three different dosages, and also has the option of every six-week dosing. Treatment with oral aripiprazole is recommended for the first twenty-one days after the first ALLAI injection, which is a potential disadvantage. Adverse effects include sensitivity to extrapyramidal symptoms, especially akathisia, which is well documented in other aripiprazole preparations. There is no available data comparing ALLAI to other antipsychotics, and more head-to-head trials comparing different LAI formulations are needed. Based on the available data, ALLAI is an effective and safe option for treatment of schizophrenia. Further studies and post-marketing data will provide better understanding of this formulation.

Safety and Tolerability of Pharmacological Treatment of Alcohol Dependence: Comprehensive Review of Evidence.

Alcohol use disorders (AUD) cause significant morbidity and mortality worldwide, but pharmacological treatments for them are underused, despite evidence of efficacy. Acamprosate, naltrexone, nalmefene and disulfiram are all approved in one or more region for the treatment of AUD. Baclofen currently has a temporary indication in France. Safety considerations for using psychopharmacological treatments in this patient group include the impact of concurrent alcohol consumption at high levels; multiple physical comorbidities that may interfere with pharmacological effects, distribution and metabolism; and concomitant medication for the treatment of comorbid physical and psychiatric conditions. The five drugs, including an extended-release injectable suspension of naltrexone, have different safety profiles that need to be balanced with the treatment objective (initiation or continuation of abstinence, or reduction of drinking), individual patient preferences and comorbid conditions. Appropriate treatment will be based on the unique risk-benefit profile in each case.

Qualitative study of patients with dual pathology in treatment with aripiprazole extended-release injectable suspension

IntroductionStudies describe patients with dual pathology as subjects with worse clinical evolution and worse therapeutic response. These subjects have high percentages of worse therapeutic compliance and low adherence to psychopharmacological treatment. The conventional antipsychotics can induce dysphoria and worse craving and drug use. The long duration-injectable antipsychotics could serve as a good therapeutic alternative because they combine efficacy and tolerability.ObjectivesWe analyzed subjects treated with aripiprazole injectable to demonstrate its effectiveness on symptomatology, the reduction of craving and consumption of substances.Materials and methodsWe studied subjects with dual disorders at a Center for Attention to drug addicts treated with aripiprazole extended-release injectable. All of them met criteria for the diagnosis of disorders for cannabis and cocaine use. All of them had been previously treated with oral antipsychotics and/or injectable of long duration. Evolution of craving and consumption were evaluated through clinical interviews and urine analysis.ResultsCannabis was the main substance for all the patients. Three of them also often abused of cocaine. All of them were taking other treatments previously. The main causes of the change were: side effects and/or poor compliance. Only one patient discontinued follow-up. The rest of them showed good therapeutic adherence and better tolerability with aripiprazole injectable. The monthly dose was 400 mg.ConclusionsAripiprazole extended-release injectable is a good choice for dual disorders. A good therapeutic adherence involves not only a psychopathological improvement but also respect to craving and consumption, which makes aripiprazole injectable a suitable therapeutic option.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Alcohol and dual disorder. Paliperidone palmitate effectiveness

IntroductionAlcohol use is a common behavior in most people in our society. A first episode of alcoholism can be fully recovered through specialized treatment and other protective factors and need not become a relapse later.ObjectivesWhether there are differences in alcohol use after 1, 3 and 6 months after the administration of paliperidone palmitate extended-release injectable suspension in a sample of patients.Material and methodsThis is a descriptive study that analyzed the differences observed with respect to alcohol use after administration of paliperidone palmitate in a sample of 98 patients attending in a Mental Health Centre, in the Unit for drug dependency to present pathology dual.ResultsThe percentage of alcohol use at baseline is 56.1% of the total sample.One month after treatment with paliperidone palmitate the percentage of use is reduced to 31.6%. At 3 months of treatment the reduction is more significant assuming only the 6.1% of the total sample. Finally after 6 months of treatment the percentage of patients maintaining alcohol use is 4.1%, which represents a 52% reduction compared to the initial rate of use.ConclusionsThe data reflect a 92% reduction in alcohol use after 6 months of the administration of paliperidone palmitate.We can say that paliperidone palmitate is effective in reducing alcohol use in patients with dual diagnosis.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Tolerability and side effects of an extended-release injectable suspension of aripripazole in a series of inpatients in a dual diagnosis unit

IntroductionThe integrated care in dual diagnosis units involves selecting pharmacological treatment strategies for both substance use disorder and the non-addictive psychiatric disorder. It is recommended to choose drugs with a favorable balance between efficacy/tolerability, an adequate side effects profile and the minimal drug interactions.Objectives and aimsTo evaluate the tolerability and side effects after first administration-first dose of an extended-release injectable suspension of aripiprazole in a group of patients admitted to an acute dual diagnosis unit.MethodsThe study included a series of patients admitted in our unit from May to August 2015 that received the first dose of the aripiprazole preparation (400 mg). Evaluations included different scales for side effects (SAS, ESRS, UKU) and the clinical global impression scale (CGI).ResultsA total of 9 patients were included and evaluated (all men, mean age: 39-years-old). Diagnoses were: bipolar disorder (5/9), schizophrenia (2/9), schizoaffective disorder (1/9) and delusional disorder (1/9) with concomitant substance use disorder (6 cannabis, 2 alcohol, 1 cocaine). All of them without outpatient control and treatment at admission. The results of the clinical scales conclude that none of them had significant side effects, including extrapyramidal, with an improvement in the ICG scale.ConclusionTolerability of extended-release injectable suspension of aripiprazole was good in all cases. In the future, new cases should be included to extend the sample and to evaluate other aspects such as the craving for substances.Disclosure of interestThe authors have not supplied their declaration of competing interest.