Graduate students, as highly intelligent individuals, are more likely to experience mania during their studies than the general population. They are affected by learning pressure, environmental factors, and other factors and manifested as high spirits and irritability. Art therapy, as a relatively effective treatment method, is often used for psychological intervention and treatment. Therefore, this study innovatively constructs music courses from the perspective of ideological and political education to alleviate graduate students’ mania.

Fifty graduate students with mania from a certain university were selected as the research subjects and randomly divided into Group A and Group B. Group A used traditional treatment methods, while Group B added innovative music courses to the traditional treatment methods for combined treatment. After the experiment, the data were processed and analyzed using SPSS 20.0.

After the combination of results and intervention treatment, the overall compliance rate of student patients reached 98%, significantly higher than 60% in Group A; In the quality of life score, the social function score of Group B was 65.95 ± 4.20, the mental health score was 64.54 ± 4.89, and the psychological function score was 67.39 ± 5.14, all of which were higher than those of Group A.

From the perspective of ideological and political education in the curriculum, the innovative construction of music courses has an effective alleviating effect on graduate students’ mania.

Guangxi academic degree and postgraduate education reform project (No. JGY2021162).

A double-blind, randomized, active-controlled, parallel-group, noninferiority trial (NCT03345342) demonstrated that paliperidone palmitate once-every-6-months (PP6M) was noninferior to paliperidone palmitate once-every-3-months (PP3M) in preventing relapse in clinically stable adults with schizophrenia. This post hoc analysis assessed efficacy and safety following transition to PP6M from paliperidone once-monthly (PP1M) versus PP3M.

Adults with schizophrenia who were clinically stable on moderate/high doses of PP1M or PP3M were randomly assigned 1:2 to dorsogluteal PP3M or PP6M treatment for 12 months. The primary efficacy measure was time to relapse during the 12-month DB phase. Secondary endpoints included change from DB baseline to endpoint in Positive and Negative Syndrome Scale (PANSS) total and subscale scores, Clinical Global Impression-Severity (CGI-S) scale score, and Personal and Social Performance (PSP) scale score. Safety was assessed by treatment-emergent adverse events (TEAEs), vital signs, and clinical laboratory tests.

Of 702 patients in the study, 231 transitioned from PP1M to PP6M and 247 transitioned from PP3M to PP6M. Low relapse rates for PP6M were observed regardless of transition pathway (PP1M/PP6M: 7.8%; PP3M/PP6M: 7.3%). Changes from DB baseline to endpoint in PANSS total, PSP, and CGI-S scores were similar between transition groups. In the DB phase, ≥1 TEAE was observed in 61.0% and 63.2% of patients in the PP1M/PP6M and PP3M/PP6M, groups, respectively.

Adults with schizophrenia who transitioned to PP6M from either PP1M or PP3M experienced similarly low relapse rates. Additionally, symptom and functionality scores supported the primary analysis and, along with TEAE incidences, were comparable between transition groups.

Objectives for this survey are to determine similarities or differences in treatment goals reported by psychiatrists, patients with schizophrenia (SCZ) and caregivers in the US, as well as whether goals differed by patients currently on an oral antipsychotic (OAP) or long-acting injectable (LAI), and whether goals differed by age.

This was a real-world, cross-sectional survey of US psychiatrists, patients =18 years old diagnosed with SCZ, and caregivers. Data was collected using the Disease Specific Programme (DSP) methodology. Psychiatrists (n=120) completed detailed record forms for next 8 outpatients and 2 inpatients matching inclusion criteria. The same patients and their caregivers, if present, were invited by their psychiatrist to voluntarily complete a separate survey.

Responses on treatment goals were collected from psychiatrists for all patients included in the analysis (n=1161), patients (n= 542) and caregivers (n=130). Among 3 top goals, psychiatrists, patients and caregivers concurred that “decrease in disease symptoms” is most important (63%, 64%, 68% respectively). For psychiatrists and caregivers, second was “decrease in hospitalization for relapse” (41%, and 38% respectively), whereas for patients, it was “thinking clearly” (47%). Of the 3 least important goals, psychiatrists, patients and caregivers agreed with “sexual problems” (59%, 43%, 44%, respectively) and “weight gain” (38%, 44%, 38%, respectively).

When asked which goals were met by current medication, patients responded “decrease in disease symptoms” (68%) and “thinking clearly” (39%). However, caregivers responded “thinking clearly” (30%) was not met by current medication. Caregivers most important goals, “decrease in disease symptom” (70%) and “decrease in hospitalization for relapse” (41%), were met. Additional analyses of patients on OAPs and LAIs, did not show differences in goals. However, “decrease in disease symptoms” was numerically more important for patients on LAIs vs OAPs according to psychiatrists (68% vs 62%) and caregivers (77% vs 70% respectively). Caregivers responded “decrease in hospitalization for relapse” was met for 63% patients currently on an LAI and 35% OAP. No major differences in treatment goals were observed by patient age (18–35 vs 36–65 vs >65 years).

There is consensus among US psychiatrists, patients and caregivers on the most important treatment goal “decrease in disease symptoms”, regardless of patients’ current medication or age. For patients, “thinking more clearly” was second, compared with “decrease in hospitalization due to relapse”, for psychiatrists and caregivers. All agreed that least important treatment goals, related to AEs, were “weight gain” and “sexual problems”. More caregivers agreed “decrease in hospitalization for relapse” was met by patients on LAIs vs OAPs. These findings may help with discussions between psychiatrists, patients and caregivers.

Lundbeck LLC and Otsuka Pharmaceutical Development & Commercialization, Inc.

Learning aversion symptoms have become increasingly common among college students, who may lose interest in their studies, lack motivation, and even experience avoidance and aversion to school life. These emotions and behaviors not only affect their academic performance but may also cause harm to their long-term development and mental health. As a psychotherapy that focuses on the present and cultivates self-awareness, and acceptance, mindfulness therapy has shown positive therapeutic effects on various mental health problems. Combining cross-cultural human-computer interaction and collaborative translation teaching may provide a novel approach to treating college students’ learning aversion.

The study randomly divided 46 college students with learning aversion into experimental and control groups. The control group received routine treatment; The experimental group conducted cross-cultural human-computer interaction and collaborative translation teaching in combination with mindfulness therapy for treatment. The study used the self-made Academic Negative Emotion Scale to evaluate the academic aversion of college students.

In the measurement before the experiment, all students showed severe aversion to learning, but the difference between the two groups was not significant (P>0.05); After the experiment, the level of student aversion to learning in the experimental group was significantly improved and significantly lower than that in the control group (P<0.05).

Cross-cultural human-machine interaction collaborative translation teaching and mindfulness therapy can alleviate the degree of college students learning aversion and assist their regular learning and life.

At present, the social economy is in a period of fast-paced change in China, with various modes of production and life evolving and emerging. The transfer of agricultural land is the transformation of the utilization mode of the main factors of production in rural areas, and it is one of the contents of the social and economic reform in rural areas. In 2021, the area of rural land transfer is up to 3.7×1011 m2 in China, an increase of 4.3% over the previous year. 1,239 counties (cities, districts) and 18,731 townships have established agricultural land management rights transfer centers to provide services such as policy consultation, information release, and contract signing for both sides of the transfer. Farmers are the subjects of agricultural land management and transfer. Their behaviors are affected by their psychology to some extent. In the long-term, dynamic, and gradual process of agricultural land transfer, it is particularly important to respect farmers’ wishes, pay attention to farmers’ psychology, and guide farmers’ behavior. However, only a few written contracts were signed. Most are verbal agreements of spontaneous or collective land transfers. The verbal agreements auto-execute to some extent within certain limits. The goals of farmers in farmland transfer are diversified, and their cognition, willingness and psychological identity affect the performance of the contract and the effect of transfer.

The psychological contract of agricultural land transfer can be defined as the transferor and transferee of agricultural land transfer. Through a certain psychological suggestion mode, through the subjective cognition and understanding of the rights and obligations of both parties, rather than the direct explicit expression, a contract relationship of rights and obligations is formed. The party awarding contract and the contractor are the subjects of agricultural land transfer. Therefore, the subjects of the psychological contract of agricultural land transfer include farmers, village collectives and enterprises, all of whom have equal status, forming their own psychological contracts. The forming process of the psychological contract of agricultural land transfer includes four steps. Step one is cognition and judgment. Both parties to the transfer are aware of and judge their own rights and obligations based on external environmental information and their own circumstances. Step two is psychological expectations. Before information is transmitted, both sides of the transmission transform cognition and judgment into psychological expectations. The third step is to convey psychological expectations. Both sides of transfer transmit psychological expectations by means of direct patterns, such as oral form and written form, and implicit ways, such as perception and comprehension. Step four is the formation of the psychological contract. Both sides of transfer reciprocally admit information of psychological expectations transmitted in implicit ways, forming psychological contracts. If they can’t come to an agreement on psychological contracts, a new four-step cycle is entered.

The forming of the psychological contract of agricultural land transfer is shown in Figure 1. First, farmers’ behavior background, such as the experiences of land lease and transfer, the targets of land transfer and education, has an effect on the building of psychological contracts and its type. On the one hand, the farmers who have the experience of land transfer and get high benefits from it are much more motivated than those who don’t have that experience or ever have dissension while transferring. On the other hand, the targets of transfer and the education level of farmers affect the type of psychological contracts. Second, Farmers’ subjective norms, mainly reflected in the difference in folk customs, will form various communication modes and take different measures to deal with breaching contracts while transferring. Third, farmers’ behavior cognition reflects in their comprehension of the capability of executing contracts, including bargaining power, decision-making level and managing modes of the rent. The ability of behavior cognition and control of farmers has a positive influence on their behavior intention and happened.

According to the above results, in order to promote the reposeful transfer and orderly development of agricultural land, the following suggestions are proposed: The first is to improve the agricultural land transfer policy system, establish and improve the institutional environment for agricultural land transfer, create conditions for the establishment of farmers’ behavioral psychological contracts in the process of agricultural land transfers, and guide farmers to establish relationship psychological contracts. The second is to improve the market system, properly cultivate and develop agricultural land transfer intermediaries, reduce transaction costs, and reduce the probability of farmers’ psychological contracts being broken. The third is to guide farmers to establish a positive agricultural land transfer psychology based on their resource endowments such as labor force quality and cultural quality, and encourage farmers to make agricultural land transfer decisions such as subcontracting, leasing, reselling, and interchanging.Figure 1.

Psychological contracts of agricultural land transfer forming

Trichotillomania and skin picking disorder have been characterized as body-focused repetitive behavior (BFRB) disorders (i.e., repetitive self-grooming behaviors that involve biting, pulling, picking, or scraping one’s own hair, skin, lips, cheeks, or nails). Trichotillomania and skin picking disorder have also historically been classified, by some, as types of compulsive self-injury as they involve repetitive hair pulling and skin picking, respectively. The question of the relationship of these disorders to more conventional forms of self-injury such as cutting or self-burning remains incompletely investigated. The objective of this study was to examine the relationship of these two disorders with non-suicidal self-injury (NSSI).

Adults with trichotillomania (n = 93) and skin picking (n = 105) or both (n = 82) were recruited from the general population using advertisements and online support groups and completed an online survey. Participants completed self-report instruments to characterize clinical profiles and associated characteristics. In addition, each participant completed a mental health history questionnaire.

Of the 280 adults with BFRB disorders, 141 (50.1%) reported a history of self-injury independent of hair pulling and skin picking. Participants with a history of self-injury reported significantly worse pulling and picking symptoms (p < .001) and were significantly more likely to have co-occurring alcohol problems (p < .001), borderline personality disorder (p < .001), buying disorder (p < .001), gambling disorder (p < .001), compulsive sex behavior (p < 001), and binge eating disorder (p = .041).

NSSI appears common in trichotillomania and skin picking disorder and may be part of a larger constellation of behaviors associated with impulse control or reward-related dysfunction.

In prior studies, the dual M1/M4 preferring muscarinic receptor agonist xanomeline demonstrated antipsychotic activity in people with schizophrenia and Alzheimer’s disease, but its further clinical development was limited primarily by gastrointestinal side effects. KarXT combines xanomeline and the peripherally restricted muscarinic receptor antagonist trospium chloride. KarXT is designed to preserve xanomeline’s beneficial central nervous system effects while mitigating adverse events (AEs) due to peripheral muscarinic receptor activation. The efficacy and safety of KarXT in schizophrenia was demonstrated in the 5-week, randomized, double-blind, placebo-controlled EMERGENT-1 (NCT03697252), EMERGENT-2 (NCT04659161), and EMERGENT-3 (NCT04738123) trials.

The EMERGENT trials enrolled people with a recent worsening of positive symptoms warranting hospitalization, Positive and Negative Syndrome Scale total score ≥80, and Clinical Global Impression–Severity score ≥4. Eligible participants were randomized 1:1 to KarXT or placebo. KarXT dosing (xanomeline/trospium) started at 50 mg/20 mg twice daily (BID) and increased to a maximum of 125 mg/30 mg BID. Safety was assessed by monitoring for spontaneous AEs after administration of the first dose of trial drug until the time of discharge on day 35. Data from the EMERGENT trials were pooled, and all safety analyses were conducted in the safety population, defined as all participants who received ≥1 dose of trial drug.

A total of 683 participants (KarXT, n=340; placebo, n=343) were included in the pooled safety analyses. Across the EMERGENT trials, 51.8% of people in the KarXT group compared with 29.4% in the placebo group reported ≥1 treatment-related AE. The most common treatment-relatedAEs occurring in ≥5% of participants receiving KarXT and at a rate at least twice that observed in the placebo group were nausea (17.1% vs 3.2%), constipation (15.0% vs 5.2%), dyspepsia (11.5% vs 2.3%), vomiting (10.9% vs 0.9%), and dry mouth (5.0% vs 1.5%). The most common treatment-related AEs in the KarXT group were all mild or moderate in severity.

In pooled analyses from the EMERGENT trials, KarXT was generally well tolerated in people with schizophrenia experiencing acute psychosis. These findings, together with the efficacy results showing a clinically meaningful reduction in the symptoms of schizophrenia, support the potential of KarXT to be the first in a new class of antipsychotic medications based on muscarinic receptor agonism and a well-tolerated alternative to currently available antipsychotics.

Karuna Therapeutics

The opioid epidemic in the United States is getting worse: in 2020 opioid overdose deaths hit an all-time high of 92,183. This underscored the need for more effective and readily available treatments for patients with opioid use disorder (OUD). Prescription digital therapeutics (PDTs) are FDA-authorized treatments delivered via mobile devices (eg, smartphones). A real-world pilot study was conducted in an outpatient addiction treatment program to evaluate patient engagement and use of a PDT for patients with OUD. The objective was to assess the ability of the PDT to improve engagement and care for patients receiving buprenorphine medication for opioid use disorder (MOUD).

Patients with OUD treated at an ambulatory addiction treatment clinic were invited to participate in the pilot. The reSET-O PDT is comprised of 31 core therapy lessons plus 36 supplementary lessons, plus contingency management rewards. Patients were asked to complete at least 4 lessons per week, for 12-weeks. Engagement and use data were collected via the PDT and rates of emergency room data were obtained from patient medical records. Data were compared to a similar group of 158 OUD patients treated at the same clinic who did not use the PDT. Abstinence data were obtained from deidentified medical records.

Pilot participants (N = 40) completed a median of 24 lessons: 73.2% completed at least 8 lessons and 42.5% completed all 31 core lessons. Pilot participants had significantly higher rates of abstinence from opioids in the 30 days prior to discharge from the program than the comparison group: 77.5% vs 51.9% (P < .01). Clinician-reported treatment retention for pilot participants vs the comparison group was 100% vs 70.9% 30 days after treatment initiation (P < .01), 87.5% vs 55.1% at 90 days post-initiation (P < .01), and 45.0% vs 38.6% at 180 days post-initiation (P = .46). Emergency room visits within 90 days of discharge from the addiction program were significantly reduced in pilot participants compared to the comparison group (17.3% vs 31.7%, P < .01).

These results demonstrate substantial engagement with a PDT in a real-world population of patients with OUD being treated with buprenorphine. Abstinence and retention outcomes were high compared to patients not using the PDT. These results demonstrate the potential value of PDTs to improve outcomes among patients with OUD, a population for which a significant need for improved treatments exists.

Trinity Health Innovation and Pear Therapeutics Inc.

Anxiety disorder is one of the common mental health problems in college students, which hurts their study, work, and life. Comprehensive psychological crisis intervention is a complete psychological treatment method expected to be essential in treating anxiety disorders in college students.

One hundred college students with anxiety disorder were selected as research subjects and randomly divided into two groups. The experimental group received comprehensive psychological crisis intervention treatment and comprehensive intervention measures such as psychological assistance, cognitive behavioral therapy, and intimate relationship training. The control group received traditional psychotherapy, including counseling and medication. The Self-rating Anxiety Scale (SAS), Self-rating Depression Scale (SDS), and other assessment tools were used to carry out psychological measurements of the two groups of patients before, after, and at the follow-up point, respectively. The collected information was statistically analyzed by SPSS23.0 software.

After the comprehensive psychological crisis intervention treatment, the anxiety and depression levels of the experimental group were significantly reduced (P<0.001), and life satisfaction was significantly increased (P<0.001). Compared with the control group, the experimental group showed obvious advantages in curative effect.

Comprehensive psychological crisis intervention has shown remarkable efficacy in college students with anxiety disorders, can effectively reduce anxiety and depression, and improves the life satisfaction of patients. This approach may become an essential option for treating anxiety disorders in college students.

2021 Humanities and Social Sciences Research Project for Basic Research Business Expenses of Provincial Undergraduate Universities in Heilongjiang Province. No. 2021- kyywf-0384.

Meningitis causes inflammation of the meninges and when bacteria are not the cause may be considered aseptic. Drug-induced aseptic meningitis (DIAM) can arise from the use of certain medications. The pathophysiology of DIAM is not well understood. Within the antiepileptic medication class, only lamotrigine, carbamazepine, and levetiracetam have been associated with DIAM via documented cases. Common presentation of DIAM involves fever, headache, meningismus, and mental status changes (abnormal consciousness and focal neurological deficits). Other clinical features may include neck stiffness, photophobia, nausea, vomiting, abdominal pain, bone pain, hypotension, edema (facial and optic nerve), rash, and seizures. Case reports of DIAM with varying or limited symptomology exist. Therefore, the presentation alone will not allow for a DIAM diagnosis, prompting further analysis and diagnostic exclusion.

A middle-aged male presented with a 48-hour history of confusion, disorientation, unresponsiveness, and hypersomnolence. Past medical history included hypertension, hyperlipidemia, type-2 diabetes, and seizures. Home medication included chlorthalidone, levetiracetam, lisinopril, metformin, potassium chloride, rosuvastatin with no medication allergies reported. Upon admission, the patient denied fever, headache, nausea, neck pain, vomiting, and rash. Somnolence, dysarthria, and obtundation were noted during the physical evaluation. Hospital medications included home medications along with enoxaparin, correctional dose insulin lispro, and IV lactated ringers. Vitals and labs were unremarkable. On hospital day (HD) 1 the MRI scan was unremarkable, ruling out a demyelinating process. Serology tests (ie, ANA and dsANA) were negative. Neurology was consulted, and a lumbar puncture was performed. On HD-2 AEIM was suspected, prompting levetiracetam discontinuation and lacosamide initiation (50 mg by mouth twice daily). The CSF analysis was notable for pleocytosis (lymphocytic predominance at 96%), elevated protein (100 mg/dL), and slightly elevated glucose (79 mg/dL). The CSF VDRL was negative, ruling out neurosyphilis. Bacterial meningitis was ruled out based on the CSF analysis (WBC 144 × 103 and glucose) and the lack of bacterial growth on gram stain. Inasmuch, antibiotic therapy was not initiated. Empiric acyclovir 1000 mg IV every 8 hours was initiated as viral meningitis had not been eliminated, due to the lack of viral meningeal PCR testing. By HD-3, the CSF culture resulted without growth and the patient was alert and oriented. By HD-4 the patient was discharged, having received 6 doses of IV acyclovir, with 7 more days of oral therapy.

In 2018, McDonald et al documented the first case of probable levetiracetam-related antiepileptic induced meningitis (AEIM). The mainstay of treatment is discontinuing the offending agent. Resolution of symptoms is typically 2 to 3 days after drug discontinuation as seen in this patient case report. Symptomatic resolution within days of stopping the suspected offending drug has been observed in all reported cases of AEIM where 1 to 2 weeks is generally seen with viral meningitis. Applying the Naranjo Scale yields a score of 4, which indicates possible levetiracetam-induced meningitis in this adult patient. Providers should be cognizant when prescribing antiepileptics to assess and monitor for aseptic meningitis that may appear with atypical symptoms.

No funding

Ekbom’s delusion as a prelude to Cotard’s syndrome, has not heretofore been described.

Case study: A 45-year-old woman with a past diagnosis of bipolar disorder with psychotic features was admitted, having been up all night conversing with spirits, proclaiming that she had made a deal with Satan. Convinced that her grandmother was possessed by the devil, she smashed her grandmother’s head with a two-by-four. Results: Mental Status Examination: self conversing with her eyes darting around the room. Poor hygiene. Behavior: guarded and withdrawn. Oriented x2. Speech: hyperverbal. Insight and judgment: poor. Mood: hostile, aggressive, and angry. Thought process disorganized, incongruent, and tangentiality. She was convinced she was infested with little black bugs crawling around her insides which had been placed there by the devil. After two days of olanzapine she reported the bugs were no longer present, but rather that she herself was dead and that her organs were decomposing, which persisted through the remainder of the hospitalization.

Neuroimaging abnormalities in Ekbom’s syndrome involve the striatum, basal ganglia (putamen and caudate nucleus), insular and cingulate cortices, cortex (prefrontal, right parietal, and temporal lobes), right lingual and orbitofrontal gyri, and thalamus. In Cotard’s syndrome, abnormalities have been identified in the striatum, frontal and temporal lobes, and right-sided and bilateral hemispheres. An overlap between the delusions exists in the striatum, inferior parietal, and temporal lobes. A single lesion in the nondominant inferior parietal lobe may cause both syndromes, due to its substantial interconnection with the temporo-limbic areas. Since the parietal lobe is also involved in somatosensory processing, peradventure distorted sensory perception with associated sensation of formication may have been the nidus for the delusional infestation as well as a nidus for the perception of thanatos habitus. Such misperception may have then been amplified into a delusion because of a hyperconnection between the parietal lobe and the limbic system. This may represent a variant of the two-factor hypothesis of delusions whereby a distorted sensory perception is then misrepresented in a delusion. Dysfunction of the right hemisphere, which normally acts to censor the left, allows the delusion to manifest. A single lesion of the inferior parietal lobule may be sufficient for both sensory distortions and loss of inhibition of delusional interpretation of distorted sensation by the frontal lobe, yclept the sensorialist hypothesis.

In those with monothematic delusions, the search for transient fluctuation in delusional states may be revealing.

No Funding

Medication nonadherence is a public health concern and can impact clinical trial data quality. Traditional compliance collection (pill counts, diaries) can be unreliable in central nervous system trials. As such, strategies such as adherence technologies may play a key role in trial outcomes. AiCure, a computer vision-assisted dosing mobile application (app), collects dosing data and connects patients to sites for dosing support. Phone-based computer vision algorithms confirm dosing and transfer videos for artificial intelligence and human review. Boehringer Ingelheim is partnering with AiCure on pilot trials using AiCure adherence data to improve patient retention and clinical trial data quality. Here we report initial findings.

This pilot used data from two Phase II trials on the efficacy and safety of BI 409306 in people with schizophrenia (NCT03351244) or Attenuated Psychosis Syndrome (NCT03230097). The AiCure mobile app alerted participants to dosing protocols. The dose event was visually confirmed, providing sites a real-time view of adherence and allowing for targeted outreach and intervention. Adherence data from the first 2 weeks generated quantitative, machine-learning models to predict the individual adherence over the trial. Predictive modeling explored different monitoring periods (7-, 10-, and 14-day) and adherence cutoff points (0.8, 0.7, 0.6).

Initial AiCure assessment identified 43% of participants in NCT03351244 as ≤80% compliant (definition of compliance >80% compliant). Variance in adherence rates between electronic case report forms (eCRF; 78%) and AiCure (26%) data was also observed in the highly compliant/adherent group in NCT03230097. Using the first 2 weeks of adherence data (both studies combined), a participant’s adherence predicted their average adherence for the remainder of the trial. Observation of a participant’s adherence for the latest 4 weeks predicted the probability of premature dropout from the trial. There were further correlations of lower predicted adherence with actual disposition-based dropouts.

The early adherence predictive model (0.6 adherence cutoff) identified 22%, 20%, and 19% of patients for trial NCT03351244 (total n=235) as high-risk patients (low-adherence prediction) across 7-, 10-, and 14-day monitoring periods, respectively. Of those high-risk patients, 81%, 90%, and 96%, respectively, were truly nonadherent based on actual adherence data. The 14-day monitoring period model provided the lowest false omission rate, indicative of a better performing model.

AiCure data provided insights into patient behavior and adherence patterns which would not be available via CRF. Predictive models developed with AiCure adherence data can identify and predict future poor adherers. This creates opportunities to plan interventions and mitigation strategies to improve patient adherence during trials, thereby providing test drugs the best opportunity at proving efficacy.

Boehringer Ingelheim International GmbH (NCT03351244/1289-0049 and NCT03230097/1289-0032)

Slow release is a fundamental feature of long-acting injectable (LAI) antipsychotics. This property allows continuous drug exposure between dosing intervals. However, there can be a significant delay between giving the first LAI dose and achievement of efficacious plasma concentrations. This time period requires additional pharmacologic intervention. Until now, this delay was addressed with one of two strategies: 1) continuing with supplemental oral antipsychotic, or 2) giving more LAI up front (e.g. loading dose). A third strategy has now been developed to reduce the time needed for oral supplementation when starting the LAI aripiprazole lauroxil (AL) from 21days to 1day. A nano-crystalline milled dispersion of AL (ALNCD; brand name ARISTADA INITIO™) was formulated by reducing the AL particle diameter from micron-size particles to nanometer- sized particles. ALNCD has faster dissolution and a shorter half-life than AL and is designed to be used as a single injection along with a single oral aripiprazole dose of 30mg as a 1-day alternative to the 21days of oral aripiprazole supplementation. Here we provide an overview of the new 1-day initiation regimen for starting AL treatment, and demonstrate the relative contributions of each of its components.

A blinded, randomized, phase 1, pharmacokinetic (PK), and safety study compared the 1-day initiation regimen with the 21-day oral aripiprazole regimen. A combination of observed data, and population pharmacokinetic model–based simulations were used to plot plasma aripiprazole concentrations of single doses of ALNCD, 30mg oral aripiprazole, and AL, individually, and all three combined.

The PK profiles of the 1-day and 21-day initiation regimens (both in conjunction with either 441mg or 882mg doses of AL) were comparable, with therapeutically relevant aripiprazole levels achieved within 4days of treatment initiation. The safety profile of the 1-day initiation regimen was similar to the 21-day initiation regimen, and consistent with that of AL. Aripiprazole concentration–time profiles demonstrated that each component delivered aripiprazole to the systemic circulation at different time periods, with the 30mg dose of oral aripiprazole predominant in the first week, followed by ALNCD, and then AL.

The 1-day initiation regimen is well-tolerated and a suitable alternative to 21days of oral aripiprazole supplementation for starting AL. Each component of the 1-day initiation regimen, together with AL, is necessary to provide continuous coverage from treatment initiation until the next regularly scheduled AL injection.

Funding Acknowledgements: This study was funded by Alkermes Inc.