Mitigating Involuntary Psychiatric Admissions and Enhancing Well-Being via Long-Acting Injectables: A Six-Month Contrast of Two Cognitively Impaired Community Subcohorts

1. Introduction

The clinical management of patients presenting with comorbid psychotic disorders and intellectual or cognitive impairments remains one of the most formidable challenges in contemporary community psychiatry. Patients diagnosed with schizophrenia spectrum disorders (ICD-10: F20) or unspecified nonorganic psychoses (ICD-10: F29) frequently exhibit severe cognitive deficits. These deficits can manifest either as primary intellectual disabilities or as secondary cognitive decline progressively driven by the neurodestructive nature of active psychosis, chronic institutionalization, and comorbid substance use disorders. This specific patient subpopulation experiences disproportionate functional impairment, diminished quality of life (QoL), and severely compromised capacity for treatment adherence.

Oral antipsychotic regimens, while pharmacologically efficacious, heavily rely on consistent daily patient compliance—a requirement that is often unrealizable for individuals suffering from baseline cognitive or intellectual impairments. Poor adherence invariably triggers clinical exacerbations, leading to frequent psychiatric relapses, high rates of voluntary and involuntary hospitalizations via prosecutor orders, and a destructive cycle of revolving-door admissions. Furthermore, psychotic patients with intellectual disabilities frequently lack robust social support networks or live in isolation, which exponentially multiplies the risk of treatment discontinuation and subsequent behavioral crises.

Long-Acting Injectable (LAI) antipsychotics, comprising both first-generation formulations (e.g., Haloperidol decanoate) and modern second-generation agents (e.g., Aripiprazole once-monthly, Paliperidone palmitate once- or three-monthly, and novel Risperidone formulations), have revolutionized maintenance therapy in severe mental illness. By eliminating the necessity for daily oral intake, LAis offer stable pharmacokinetic profiles, guarantee objective adherence tracking, and significantly lower the statistical risk of relapse compared to oral alternatives. While the clinical utility of LAIs in the general schizophrenia population is extensively documented, localized real-world data evaluating their long-term impact specifically on community-dwelling psychotic individuals with documented comorbid intellectual or cognitive deficits remain scarce.

To bridge this literature gap, the present study—embedded within our long-standing “DNAng” research project—aims to evaluate the clinical and social outcomes of active LAI pharmacological maintenance therapy over a six-month observation window. Specifically, we investigate the influence of baseline demographic, clinical, and environmental parameters on longitudinal outcomes across two highly distinct community-dwelling subcohorts: i) individuals with primary intellectual disabilities who have successfully avoided historical psychiatric hospitalizations, and ii) individuals with prominent psychosis-induced cognitive decline and active substance comorbidities who possess a severe history of psychiatric admissions. By examining changes in hospitalization rates, clinical severity (via the CGI-S scale), and subjective quality of life (via the WHOQOL-BREF), this study seeks to elucidate the specialized role of LAIs in stabilizing cognitively vulnerable psychiatric patients within community settings.

2. Materials and Methods

2.1. Study Design and Patient Selection

This study adheres to the methodological framework of our long-standing “DNAng” research project, which evaluates psychiatric outcomes across two distinct settings: the community and correctional facilities. Participant enrollment and data collection spanned from June 2023 to September 2024. For the present study, from an initial broader sample of 98 patients, individuals with intellectual or cognitive impairment were selected and stratified across the community-dwelling patient environment exclusively, resulting in a targeted sample of 41 community-dwelling individuals.

The exact inclusion criteria for this targeted subpopulation required:

• A verified ICD-10 diagnosis of a psychotic disorder (F20–F29).
• A documented comorbid intellectual or cognitive impairment.
• Continuous maintenance treatment with a long-acting injectable (LAI) antipsychotic for a minimum threshold of six months.
• For the first subcohort: patients who have never been incarcerated in a correctional facility, currently reside in the community, and have no historical record of psychiatric hospitalization prior to or during the baseline evaluation.
• For the second subcohort: patients who have never been incarcerated in a correctional facility, currently reside in the community, and have a documented history of at least one psychiatric hospitalization prior to the initiation of LAI antipsychotic therapy.

In the present study, we investigated the clinical effects of various active LAI pharmacological agents within these community-dwelling subgroups. This analysis specifically examined the influence of various clinical and demographic parameters on long-term clinical outcomes, as well as the relative influence of: (a) primary intellectual disability, or (b) secondary cognitive decline driven by active psychosis, chronic alcohol use, and/or psychotropic substance use, and/or (c) the social support network and environmental baseline parameters, on the rate of psychiatric clinical admissions, involuntary placements, and psychiatric rehospitalizations prior to and following the initiation of LAI antipsychotic therapy.

To ensure diagnostic standardization, all clinical diagnoses (ICD-10 psychotic disorders, substance- and alcohol-use disorders), personality typologies (Cluster B and Cluster C), and cognitive-severity profiles were established via retrospective medical-record classification based on structured consensus evaluations from the treating multidisciplinary clinical teams. The baseline sociodemographic and clinical distribution of this subpopulation is comprehensively detailed in Table 1.

2.2. Subgroup Stratification and Baseline Cohort Characteristics

The initial community-dwelling sample derived from the project consisted of 68 patients (mean age: 40.66 ± 13.91 years; 70.59% male, n = 48). Within this baseline group, 35.29% (n = 24) possessed a diagnosis of paranoid schizophrenia (F20.0), 7.35% (n = 5) had a history of traumatic brain injury (TBI), 82.35% (n = 56) exhibited a Cluster C personality typology, and 41.18% (n = 28) presented with comorbid active substance use. From this initial population, the targeted sample of 41 patients with cognitive impairments was isolated and divided into two distinct subcohorts:

Subgroup 1: Non-Hospitalized Community Cohort (n = 22).

Patients within this subgroup exhibited primary intellectual disability or secondary cognitive decline, presented with a primary diagnosis of F20 or F31.0/F29 according to ICD-10 criteria, resided within community settings, and had no historical record of psychiatric clinic hospitalizations or correctional facility incarceration. All 22 individuals were maintained on LAI antipsychotic therapy for at least six months. The demographic breakdown comprised 12 males (54.55%) and 10 females (45.45%).

An ICD-10 diagnosis of paranoid schizophrenia (F20.0) was present in 5 patients (22.73% of this subcohort), including 4 females and 1 male. None of the F20.0 patients had a historical record of traumatic brain injury (TBI). Four of these patients (80%) presented with an anxious/fearful Cluster C personality profile, and none reported history of illicit substance use; a single female patient with borderline intelligence and a Cluster C profile reported historical alcohol misuse. Socially, 3 of these female patients resided with their parents, and 1 resided with her spouse while engaging in part-time employment. The single male patient (53 years old) presented with an erratic Cluster B personality profile, primary mild intellectual disability, and cohabited with his spouse. One female patient with a Cluster C profile and total substance abstinence exhibited secondary moderate cognitive decline driven by active psychosis. Cumulatively, 2 of the 5 patients (40%) with an F20.0 diagnosis maintained part-time employment.

An ICD-10 diagnosis within the F31.0/F29 spectrum was documented in the remaining 17 patients (77.27% of this subcohort), consisting of 11 males and 6 females. Traumatic brain injury (TBI) was present in 3 male patients. Cognitive profiling showed 3 patients with mild primary intellectual disability, 5 with moderate primary intellectual disability, and 5 with severe primary intellectual disability. A Cluster C personality profile was noted in 14 patients, while 3 presented with a Cluster B profile. Comorbid substance use was isolated: 1 male patient engaged in cannabis use and 3 male patients engaged in alcohol abuse, while all female patients reported absolute substance and alcohol abstinence. Socially, 1 male and 1 female patient lived with their respective spouses, 1 female patient resided in a specialized care facility, and the remaining 14 individuals (10 males, 4 females) lived with their parents.

Subgroup 2: Hospitalized Community Cohort (n = 19).

Patients within this subgroup presented with intellectual disability or cognitive impairment, a primary diagnosis of F20 or F31.0/F29, resided in the community, and possessed a confirmed history of at least one prior psychiatric hospitalization, with zero historical record of correctional incarceration. All 19 individuals were maintained on LAI therapy for at least six months. The demographic breakdown consisted of 16 males (84.21%) and 3 females (15.79%).

An ICD-10 diagnosis of paranoid schizophrenia (F20.0) was present in 13 patients (68.42% of this subcohort), comprising 10 males and 3 females. Within this clinical subgroup, 1 patient had a history of TBI. A Cluster B personality typology predominated, being present in 12 patients, while 1 patient exhibited a Cluster C profile. Cognitive stratification showed 3 patients with borderline intellectual functioning, 1 with secondary cognitive decline due to TBI, 7 with mild psychosis-induced cognitive decline, and 2 with moderate psychosis-induced cognitive decline. Comorbid substance use disorders were highly prevalent: 4 patients reported alcohol abuse/dependence, 4 reported use of other psychotropic substances, 2 reported cocaine use, and 4 reported active cannabis use. Socially, 1 patient lived with a spouse, 5 lived with their parents, and 7 lived entirely alone. Regarding vocation, 2 patients maintained full-time employment, while 11 were permanently disabled due to psychosis. Hospitalization histories indicated that 2 patients had prior voluntary admissions, while 11 patients had a history of involuntary admissions via prosecutor orders, with individual admission counts ranging between a minimum of 2 and a maximum of 6.

An ICD-10 diagnosis within the F31.0/F29 spectrum was established in 6 patients, all of whom were male (100.00%). None possessed a history of TBI. Four patients exhibited a Cluster B personality typology, and 2 presented with a Cluster C profile. Cognitive assessment indicated 1 patient with borderline primary intelligence, 3 with primary mild intellectual disability, 1 with mild secondary psychosis-induced cognitive decline, and 1 with severe secondary psychosis-induced cognitive decline. Comorbidities showed 3 patients with alcohol abuse/dependence, 1 with cocaine use, 3 with cannabis use, and 1 with other psychotropic substances. Socially, 3 resided with their spouses and 3 lived with their parents. Occupationally, 2 were unfit for work due to psychosis, 2 were engaged in part-time employment, and 2 were unfit for work due to medical reasons independent of psychosis. Admission histories indicated 1 patient with prior voluntary admissions and 5 patients with involuntary admissions via prosecutor orders, with admission counts ranging between a minimum of 1 and a maximum of 3.

2.3. Outcome Measures

Clinical severity was systematically assessed using the Clinical Global Impression-Severity (CGI-S) scale. Patients’ Quality of Life (QoL) was evaluated utilizing the single-item Global Quality of Life measure derived from the World Health Organization Quality of Life Brief Version (WHOQOL-BREF). This specific single item captures the patient’s comprehensive subjective perception of their overall quality of life and is originally scored on a standardized 1–5 Likert scale. For statistical harmonization and analysis, these scores were subsequently linearly transformed to a 0–4 scale. Standardized domain-specific subscores of the WHOQOL-BREF were not administered.

To evaluate therapeutic efficacy, longitudinal statistical comparisons were performed between the pre-treatment (baseline) and post-treatment evaluation windows. The baseline hospitalization-counting period and the post-treatment clinical observation period were fixed at exactly equal durations of six months for each individual participant. This rigorous timeframe windowing ensured a mathematically symmetric, matched-pairs pre-post design.

2.4. Statistical Analysis

Categorical and nominal variables were summarized using frequency distribution tables and percentages. Continuous variables and ordinal data (comprising the CGI-S and transformed Global QoL scores) were expressed as means and standard deviations (SD). Baseline between-group differences regarding sociodemographic parameters and clinical history traits (excluding age) were evaluated using the Chi-square (χ²) test. The non-parametric Mann-Whitney U test was employed to assess between-group differences for continuous or non-normally distributed baseline parameters (Table 1).

Within-group longitudinal shifts from baseline (pre-treatment) to the six-month post-treatment follow-up were evaluated using the Wilcoxon signed-rank test for paired samples. Furthermore, longitudinal analysis of hospitalization rates within the community cohort was restricted exclusively to the specific paired subset of patients for whom complete post-treatment medical records were available (paired n = 19). For these 19 individuals, post-treatment hospitalization rates were compared directly against their specific baseline values to ensure a mathematically robust, intra-subject paired comparison.

To determine the magnitude of the treatment effect between the evaluation periods, Cliff’s delta (δ) effect size, appropriate for matched-pairs ordinal observations, was calculated. To account for Type I error inflation resulting from multiple exploratory subgroup analyses, we established a family of planned comparisons consisting of four main clinical domains: hospitalization rates, CGI-S scores, QoL parameters, and diagnostic subgroup traits. Statistical significance was set a priori at α = 0.05. All statistical analyses were conducted using standardized computing software.

3. Results

3.1. Baseline Demographic and Clinical Comparisons Between Subgroups

A series of Chi-square (χ²) tests revealed statistically significant baseline differences between the non-hospitalized (n = 22) and previously hospitalized (n = 19) community-dwelling subgroups across multiple clinical and sociodemographic domains:

ICD-10 Diagnostic Distribution: (p = 0.0087).

Cognitive Profile Stratification (Intellectual Disability vs. Psychosis-Induced Decline): (p = 0.0060).

Comorbid Cannabis Use: (p = 0.0273)

Marital and Living Status: (p = 0.0113)

Occupational and Employment Status: (p = 0.0238)

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The Non-Hospitalized Profile (n = 22):

In the cohort with no history of psychiatric admission, the predominant ICD-10 diagnosis was within the F31.0/F29 spectrum. This sample was primarily characterized by primary intellectual disability rather than secondary decline. Behaviorally, the vast majority exhibited lifelong abstinence from psychotropic substances, particularly cannabis. Socially, these individuals resided in highly supportive environments, living almost exclusively with their parents or, in select cases, with a spouse/partner. Their functional inability to work was primarily attributed to their baseline intellectual disability, compounded secondarily by their psychotic illness.

• The Previously Hospitalized Profile (n = 19):

Conversely, in the cohort where all patients had a history of at least one psychiatric hospitalization, paranoid schizophrenia (F20.0) was the predominant diagnosis. The cognitive profile of this group was characterized by secondary cognitive impairment induced by the psychotic process itself. Furthermore, dual-diagnosis patterns were highly prevalent, with a majority reporting hazardous alcohol consumption and psychotropic substance use, alongside a distinct subpopulation actively using cannabis. Socially, a significant proportion of these patients lived entirely alone, lacking the structured supportive environment observed in the first group. Finally, their vocational impairment and inability to work were driven predominantly by the clinical severity of the psychosis.

3.2. Longitudinal Impact on Hospitalization Rates

• First Subgroup (n = 22):

In the first, non-hospitalized community-dwelling subcohort, no longitudinal changes were observed regarding psychiatric admissions. These patients had historical baseline values of zero admissions prior to the initiation of long-acting injectable (LAI) antipsychotic therapy, and complete abstinence from hospitalizations (0.00%) was maintained throughout the minimum six-month follow-up evaluation period.

• Second Subgroup (n = 19):

In sharp contrast, patients in the second subcohort—all of whom presented with a history of at least one prior psychiatric admission—demonstrated a drastic, statistically significant reduction in hospitalization rates following at least six months of continuous LAI antipsychotic therapy. Specifically, the mean number of total admissions decreased from a baseline pre-treatment value of 2.10 ± 1.28 to a post-treatment value of 0.05 ± 0.22 (Wilcoxon p = 0.0002), demonstrating an exceptionally robust treatment effect size (Cliff’s delta δ = 0.98, indicating a large effect).

3.3. Gender-Stratified Breakdown of Voluntary vs. Involuntary Admissions (Second Subgroup, n = 19)

To further isolate the clinical utility of LAI therapy, hospitalizations within the second subgroup were stratified by admission type (voluntary vs. involuntary via prosecutor orders) and gender:

Male Patients (n = 16):

• Voluntary Admissions: The absolute baseline count of voluntary admissions was 3. Following LAI therapy, the mean rate decreased from a baseline of 0.25 ± 0.56 to a post-treatment mean of 0.00 ± 0.00 (absolute count = 0). This longitudinal decrease did not reach statistical significance (Wilcoxon p = 0.10).
• Involuntary Admissions: The absolute baseline count of involuntary prosecutor-ordered admissions was 13. Following at least six months of LAI therapy, the mean rate of involuntary hospitalizations decreased drastically from 1.81 ± 1.55 to 0.06 ± 0.24 (absolute post-treatment count = 1). This marked reduction was highly statistically significant (Wilcoxon p = 0.002).

Female Patients (n = 3):

• Voluntary Admissions: The absolute baseline count of voluntary admissions was 0 (mean = 0.00 ± 0.00) and remained at zero (mean = 0.00 ± 0.00; absolute count = 0) during the post-treatment observation window.
• Involuntary Admissions: The absolute baseline count of involuntary prosecutor-ordered admissions was 3. Following LAI therapy, the mean rate decreased from 2.33 ± 0.47 to 0.00 ± 0.00 (absolute post-treatment count = 0). Due to the small sample size of the female cohort (n = 3), no null hypothesis significance testing could be statistically executed (Table 4).

3.4. Clinical Severity (CGI-S) and Quality of Life (WHOQOL-BREF) Outcomes

• First Subgroup (n = 22):

A highly pronounced, statistically significant improvement in clinical status and functional severity was observed after at least six months of continuous LAI therapy. The mean Clinical Global Impression-Severity (CGI-S) score decreased from 5.77 ± 0.86 at baseline (indicating severe illness) to 3.09 ± 0.92 at follow-up (indicating mild illness), demonstrating an exceptionally robust treatment effect size (Wilcoxon p < 0.001; Cliff’s delta δ = 0.97). Concurrently, subjective quality of life improved dramatically. The transformed single-item WHOQOL-BREF Global QoL score increased from a baseline mean of 0.59 ± 0.50 to 3.13 ± 0.83 at the six-month endpoint, capturing a major positive shift in patient perception (Wilcoxon p < 0.001; Cliff’s delta δ = -1.00, representing a maximum large effect size).

• Second Subgroup (n = 19):

Similarly, the previously hospitalized subcohort demonstrated highly significant improvements in global clinical functionality. The baseline CGI-S mean score shifted from 5.89 ± 0.80 down to 3.78 ± 1.08 post-treatment (Wilcoxon p = 0.0003), yielding a strong therapeutic effect size (Cliff’s delta δ = 0.87, large effect). Subjective quality of life parameters mirrored this positive clinical trajectory, with transformed WHOQOL-BREF Global QoL scores rising significantly from a baseline mean of 0.52 ± 0.51 to a post-treatment mean of 3.05 ± 0.84 (Wilcoxon p = 0.0001; Cliff’s delta δ = -1.00, large effect) (Table 3).

3.5. Distribution of Long-Acting Injectable (LAI) Antipsychotic Agents

The distribution of active pharmacological long-acting injectable agents varied across the two distinct community-dwelling subcohorts:

• First Subgroup (n = 22):

In the cohort of patients with no history of psychiatric hospitalization, second-generation atypical antipsychotics predominated. Aripiprazole once-monthly (400 mg) was administered to the vast majority of participants (19 patients, 86.36%). Paliperidone palmitate once-monthly (Xeplion, 150 mg) was utilized in 2 patients (9.09%), while the first-generation typical antipsychotic Haloperidol decanoate (Aloperidin Decanoas, 450 mg/month) was prescribed to a single patient (4.55%).

• Second Subgroup (n = 19):

In the previously hospitalized cohort, prescription patterns demonstrated broader pharmacological diversity. Aripiprazole once-monthly (Abilify Maintena 400 mg) remained the most frequent choice, administered to 11 patients (57.89%). Haloperidol decanoate (Aloperidin Decanoas) was utilized in 4 patients (21.05%). A long-acting three-monthly formulation of Paliperidone palmitate (Trevicta, 525 mg) was administered to 2 patients (10.53%). Finally, risperidone formulations were used in the remaining participants: 1 patient (5.27%) received risperidone long-acting injection once-monthly (Okedi) and 1 patient (5.27%) was maintained on a bi-weekly risperidone formulation (Risperdal Consta) (Table 2).

4. Discussion

The present real-world study demonstrates the profound clinical efficacy and psychosocial benefits of Long-Acting Injectable (LAI) antipsychotics in a highly vulnerable, yet under-researched subpopulation: community-dwelling psychiatric patients with comorbid intellectual or cognitive impairments. Our longitudinal analysis reveals that the continuous use of LAI formulations for at least six months significantly reduces psychiatric severity (CGI-S) and dramatically elevates subjective Quality of Life (QoL) across both investigated cohorts, while almost entirely eliminating active psychiatric hospitalizations.

A striking finding of this study is the baseline bifurcation of our sample into two distinct clinical profiles with contrasting hospitalization histories. In the non-hospitalized cohort (n = 22), patients were predominantly diagnosed within the F31.0/F29 spectrum and exhibited primary intellectual disabilities. Despite presenting with high baseline clinical severity (CGI-S: 5.77 ± 0.86), these individuals historically maintained zero hospitalizations. Our statistical analysis highlights that this success is deeply rooted in a protective socioeconomic matrix: 77.27% lived with their parents within a structured, highly supportive household, and 95.45% maintained lifelong abstinence from cannabis and other illicit psychotropic substances.

By contrast, the previously hospitalized cohort (n = 19) was characterized by a high prevalence of paranoid schizophrenia (F20.0) and secondary cognitive decline directly driven by the neuroprogressive nature of the psychosis. This cohort demonstrated a fragile social framework, with 36.84% of patients living entirely alone, alongside severe dual-diagnosis patterns, including high rates of comorbid alcohol (36.84%) and cannabis abuse (36.84%). For these unstable individuals, oral medication failure and subsequent cognitive deficits generated an aggressive “revolving-door” dynamic, resulting in a high baseline admission rate (mean: 2.10 ± 1.28).

Following the initiation of LAI therapy, the previously hospitalized cohort experienced a dramatic reduction in total hospitalizations, dropping to a post-treatment mean of 0.05 ± 0.22 (p = 0.0002; δ = 0.98). When dissecting this parameter by gender and admission modality, the clinical impact becomes even more profound. In male patients (n = 16), involuntary hospitalizations initiated via prosecutor orders collapsed from a baseline count of 13 down to just 1 single admission at the six-month follow-up (p = 0.002). In the female population (n = 3), involuntary admissions dropped from 3 to absolute zero.

This drastic mitigation of involuntary prosecutor-ordered admissions carries immense clinical, human, and economic implications. Involuntary psychiatric admissions are inherently traumatic, often damaging the therapeutic alliance, aggravating patient-family friction, and exacerbating cognitive regression. Furthermore, acute psychiatric inpatient stays place an extraordinary financial burden on public healthcare systems. By stabilizing these cognitively impaired individuals via a guaranteed pharmacological safety net—predominantly utilizing second-generation atypical LAIs like Aripiprazole once-monthly (86.36% in the first cohort, 57.89% in the second cohort) [9]—LAIs effectively break the destructive cycle of acute behavioral decompensation and involuntary containment.

Concurrently, the absolute synchronization of maximum treatment effect sizes regarding subjective Quality of Life (δ = -1.00 in both groups) and substantial reductions in clinical global severity confirms that the utility of LAIs extends far beyond mere symptomatic control. When medication compliance is removed from the daily cognitive burden of a patient with intellectual deficits, and when family caregivers are relieved from the constant stress of monitoring oral intake, global functionality and subjective well-being improve synergistically.

Limitations

Several limitations must be acknowledged in the interpretation of these findings. First, the sample size (N = 41) is relatively small, reflecting the highly specialized nature of this targeted subpopulation, which restricted our capacity to perform advanced multivariate analyses or execute significance tests on the small female subcohort (n = 3). Second, the retrospective nature of baseline data collection relies heavily on historical medical records, introducing potential reporting biases regarding substance use or exact hospitalization counts. Third, the fixed six-month observation window, while mathematically symmetric and ideal for capturing immediate post-treatment stabilization, is relatively brief; a longer longitudinal follow-up (e.g., 12 to 24 months) would be beneficial to evaluate the permanent sustainability of these clinical improvements.

5. Conclusions

In conclusion, maintenance therapy with Long-Acting Injectable (LAI) antipsychotics serves as a vital clinical tool for stabilizing community-dwelling psychotic patients complicated by comorbid intellectual disabilities or cognitive decline. For stable patients anchored within highly supportive family environments, LAIs successfully preserve their non-hospitalized status while maximizing functional improvement. Crucially, for unstable, socially isolated patients suffering from dual diagnoses, LAIs dramatically reduce clinical severity, optimize quality of life, and virtually eliminate traumatic, costly involuntary psychiatric hospitalizations via prosecutor orders. These real-world findings strongly advocate for the early, systematized integration of second-generation LAIs in the community management of cognitively vulnerable psychiatric populations.