Recurrent First-Episode Schizophrenia-Spectrum Disorder with Messianic Delusions in an Adolescent Male: Seven-Year Longitudinal Follow-Up and Long-Acting Injectable Aripiprazole Stabilization

 Ivan Lopez-Ibor, MD (1,2,3,4)

1Clínica López-ibor, Madrid, Spain. 2Sanatorio del Dr Esquerdo, Madrid, Spain. 3Clínica del Dr León, Madrid, Spain. South Florida Integrative Medicine, Miami, Florida.

Department of Psychiatry, Madrid, Spain

Corresponding author: drivanlopezibor@gmail.com 

Abstract

Background: First-episode psychosis (FEP) in adolescence is associated with high relapse rates, increased suicide risk, and long-term functional impairment. Antipsychotic discontinuation remains one of the strongest predictors of recurrence. Long-acting injectable (LAI) antipsychotics may reduce relapse by improving treatment adherence.

Case Presentation: A 17-year-old male presented with acute schizophrenia-spectrum psychosis characterized by grandiose messianic delusions, auditory hallucinations, formal thought disorder, and suicidal ideation expressed in religious terms. Organic and toxic etiologies were systematically excluded. Initial treatment with olanzapine 15 mg/day resulted in rapid clinical stabilization; however, medication discontinuation six weeks post-discharge precipitated severe relapse with a suicide attempt and profound physical deterioration. After rehospitalization, transition to monthly aripiprazole LAI 300 mg was initiated alongside sertraline, gabapentin, and cognitive behavioral therapy (CBT). The patient achieved sustained symptomatic remission over a seven-year outpatient follow-up period with no further hospitalizations or suicide attempts.

Conclusion: Early identification of adherence risk and timely initiation of LAI antipsychotic therapy may significantly improve long-term outcomes in high-risk adolescent FEP patients. Aripiprazole LAI represents a favorable option given its metabolic profile and functional tolerability.

Keywords: first-episode psychosis; schizophrenia-spectrum disorder; adolescent psychiatry; long-acting injectable antipsychotics; aripiprazole; relapse prevention; medication adherence; suicide risk; messianic delusions

Introduction

Schizophrenia-spectrum disorders typically emerge in late adolescence or early adulthood, coinciding with a critical window of neurodevelopment. This early onset carries particular clinical significance, as disruption during this period may compound long-term functional outcomes. Duration of untreated psychosis (DUP) has been consistently associated with poorer symptomatic and functional prognosis [1], reinforcing the importance of timely diagnosis and intervention.

Relapse following antipsychotic discontinuation is among the most well-documented risks in first-episode psychosis (FEP). Zipursky et al. demonstrated that cessation of antipsychotic therapy after remission is associated with recurrence rates exceeding 60% within one year [2]. Recurrent relapses have been linked to progressive functional decline, cumulative cognitive deterioration, and increased lifetime suicide risk [3]. Palmer et al. estimated the lifetime suicide risk in schizophrenia-spectrum disorders at approximately 5%, with highest rates observed during early illness phases [4].

Medication non-adherence is a central driver of relapse in early psychosis, with up to 40–50% of FEP patients discontinuing pharmacotherapy within the first year of treatment [5]. Long-acting injectable (LAI) antipsychotics were developed specifically to address this limitation by eliminating daily oral dosing. Meta-analytic data have confirmed the superiority of LAIs over oral formulations in reducing relapse and hospitalization rates across schizophrenia populations [6].

Despite this evidence base, LAI antipsychotics have historically been reserved for chronically ill or treatment-resistant patients. Emerging data suggest, however, that earlier LAI introduction in high-risk FEP patients may confer significant benefit [7]. The case presented herein illustrates how timely transition to aripiprazole LAI after a life-threatening adherence-related relapse resulted in sustained seven-year remission in an adolescent with severe psychosis.

Aripiprazole, a third-generation antipsychotic with partial dopamine D2 agonism and serotonin 5-HT1A agonism, offers a favorable metabolic and extrapyramidal profile relative to other LAI formulations [8]. This feature is particularly relevant in adolescent populations where long-term metabolic risk constitutes a primary concern.

Case Presentation

1. Patient Information

A 17-year-old male of Spanish descent, born and raised in Madrid, Spain, with no prior personal or family psychiatric history, presented to emergency psychiatric services with acute-onset behavioral disorganization and systematized delusional beliefs. No personal or family history of psychotic, mood, or neurodevelopmental disorders was identified. The patient denied substance use; urine toxicology screening was negative for all common substances including cannabis, amphetamines, cocaine, benzodiazepines, and opioids.

2. Clinical Findings

On initial psychiatric evaluation, the patient presented with a florid first-episode psychotic syndrome comprising:

• Grandiose messianic delusions: firmly held belief of being the resurrected Messiah with a divine mission to save humanity
• Auditory hallucinations: second-person command and commentary voices
• Formal thought disorder: loose associations, tangential thinking, circumstantial speech
• Psychomotor agitation and emotional lability
• Suicidal ideation expressed in religious terms: desire to 'ascend to a higher plane of existence'
• Impaired insight into illness

Mental status examination revealed pressured speech, significant psychomotor agitation, partial disorientation in time, impaired abstract reasoning, and absent insight. Global Assessment of Functioning (GAF) score was estimated at 20/100 at admission.

3. Diagnostic Assessment

Neuroimaging

Brain MRI with and without gadolinium contrast was obtained to exclude structural or organic etiology. Findings were as follows:

• Brain Parenchyma: Normal signal intensity and morphology of the grey and white matter structures. No evidence of acute intracranial hemorrhage, infarction, or space-occupying lesion.
• Ventricular System: Lateral, third, and fourth ventricles normal in size and configuration for patient age. No evidence of hydrocephalus.
• Extra-axial spaces: No abnormal fluid collections or midline shift. Sulci and gyri patterns preserved.
• Vascularity: Major intracranial flow voids present at the skull base.
• Sella Turcica and Craniocervical Junction: Unremarkable.
• Orbits and Paranasal Sinuses: Visualized portions clear.
• Impression: Unremarkable MRI of the brain. No structural abnormalities or signal alterations to explain the current psychiatric symptomatology.

Although structural MRI showed no gross abnormalities, this is consistent with current literature, wherein early schizophrenia-spectrum disorders may present with subtle functional connectivity disruptions rather than macrostructural lesions identifiable on standard clinical imaging.

Laboratory Workup

Comprehensive metabolic evaluation revealed no organic etiology:

• Complete blood count (CBC): Normal
• Comprehensive metabolic panel (CMP): Within normal limits
• Thyroid-stimulating hormone (TSH) and free T4: Normal
• Vitamin B12 and folate levels: Normal
• Urine drug screen: Negative
• Anti-NMDA receptor antibody panel: Negative 

Psychiatric Diagnosis

DSM-5-TR criteria for schizophrenia-spectrum disorder were met based on the presence of delusions, auditory hallucinations, disorganized speech and behavior, and significant functional decline persisting for more than one month. Organic, toxic, and affective psychosis were systematically excluded. Working diagnosis at admission: First-Episode Schizophrenia-Spectrum Psychosis (DSM-5-TR 295.90).

4. Timeline and Therapeutic Interventions

First Hospitalization (Index Episode)

Upon admission, the patient was initiated on the following pharmacological regimen:

• Olanzapine 15 mg/day orally (oral loading over 48 hours from 5 mg → 10 mg → 15 mg)
• Lorazepam 2 mg orally twice daily for acute agitation management
• Haloperidol 5 mg intramuscularly PRN for severe agitation
• Biperiden 2 mg orally twice daily for extrapyramidal symptom (EPS) prophylaxis
• Vitamin B complex supplementation

Clinical improvement was evident within 72 hours of treatment initiation, with substantial reduction in positive symptom severity. The patient achieved orientation and established therapeutic rapport by day 5. No significant metabolic or extrapyramidal adverse effects were observed during the hospitalization. Mild residual negative symptoms persisted at discharge (apathy, anhedonia, moderate affective flattening). Total inpatient duration: 40 days. The patient was discharged to outpatient follow-up on olanzapine 10 mg/day with psychiatry and psychotherapy referrals.

Relapse Event (6 Weeks Post-Discharge)

Six weeks following discharge, the patient discontinued all medications without medical supervision. He experienced a profound relapse characterized by:

• Severe reemergence of messianic delusions and command auditory hallucinations
• Suicide attempt requiring emergency medical intervention
• Significant physical deterioration: malnutrition, cachexia, personal hygiene neglect
• Cognitive slowing and marked bradyphrenia
• Social and functional collapse

Emergency psychiatric readmission was required. This relapse event constituted the most critical clinical juncture of the patient's illness course.

Second Hospitalization and LAI Initiation

Given documented non-adherence, life-threatening relapse, and elevated ongoing suicide risk, the clinical decision was made to transition from oral antipsychotic therapy to a long-acting injectable formulation. Following clinical stabilization and re-achievement of capacity to consent, treatment was transitioned to:

• Aripiprazole LAI 400 mg intramuscularly (loading dose, month 1), followed by aripiprazole LAI 300 mg intramuscularly monthly (maintenance)
• Oral aripiprazole 10 mg/day for 14 days during LAI initiation (standard overlap to ensure therapeutic plasma levels)
• Sertraline 50 mg/day (titrated to 100 mg/day) for emerging depressive features and residual negative symptoms
• Gabapentin 300 mg twice daily for anxiety and agitation
• Structured cognitive behavioral therapy (CBT) for psychosis: weekly individual sessions targeting delusion modification, insight enhancement, and relapse prevention planning

Oral antipsychotic was tapered and discontinued upon establishment of therapeutic aripiprazole LAI plasma levels (week 3 of LAI therapy). No clinically significant metabolic, endocrine, or extrapyramidal adverse effects were observed.

5. Follow-Up and Long-Term Outcomes

Over a seven-year outpatient follow-up period, the patient demonstrated the following clinical trajectory:

• Sustained remission of positive psychotic symptoms (no delusions, hallucinations, or disorganized behavior)
• No psychiatric rehospitalizations
• No further suicide attempts or self-harm episodes
• Progressive academic and social functional recovery
• Full adherence to monthly aripiprazole LAI injections throughout the follow-up period
• Mild residual cognitive slowing and bradyphrenia (consistent with post-psychotic syndrome)
• No significant metabolic adverse effects attributable to aripiprazole LAI

At seven-year follow-up, the patient reported subjective improvement in quality of life, maintained stable social relationships, and resumed educational and occupational activities. GAF score at last assessment: approximately 70/100.

Discussion

This longitudinal case report documents a seven-year clinical follow-up of an adolescent with severe first-episode schizophrenia-spectrum psychosis who achieved sustained remission following transition to monthly aripiprazole LAI after a life-threatening adherence-related relapse. The case illuminates several critical themes in early psychosis management.

5.1 Relapse Risk After Antipsychotic Discontinuation

The pattern of rapid and severe relapse following medication discontinuation observed in this case is consistent with the broader literature. Zipursky et al., in a systematic review encompassing over 2,500 FEP patients, demonstrated that antipsychotic discontinuation is associated with relapse rates exceeding 60% within 12 months [2]. Tiihonen et al., in a nationwide Finnish cohort study, confirmed that maintenance antipsychotic therapy significantly reduces relapse and rehospitalization rates compared with discontinuation [9]. The rapidity of relapse in this case—occurring within six weeks—and its severity underscore the particular vulnerability of adolescents with early psychosis.

5.2 Duration of Untreated Psychosis and Functional Prognosis

Although the index episode was treated promptly, the second untreated relapse phase substantially increased total DUP. Marshall et al., in a systematic review of first-episode cohorts, reported that longer DUP is associated with worse symptomatic, functional, and cognitive outcomes [1]. Early stabilization in this case likely mitigated some long-term deterioration, underscoring the importance of immediate re-engagement with care following relapse detection.

5.3 Suicide Risk in Early Psychosis

The suicide attempt during the relapse phase represents one of the most clinically significant events in this case. Palmer et al. estimated the lifetime suicide risk in schizophrenia at approximately 5%, with the highest probability concentrated during the early illness phase and periods of clinical instability [4]. Emerging evidence suggests that sustained antipsychotic therapy reduces suicide risk through stabilization of psychosis and improvement of associated depressive features [10]. The absence of further suicidal behavior following LAI initiation in this patient is consistent with this hypothesis, though causality cannot be established in a single case design.

5.4 Long-Acting Injectable Antipsychotics in First-Episode Psychosis

Historically, LAI antipsychotics were reserved for chronically non-adherent patients; however, evidence now supports earlier use in high-risk FEP populations. Subotnik et al. conducted a randomized controlled trial demonstrating significantly lower relapse rates in FEP patients treated with LAI risperidone compared with oral antipsychotic therapy [10]. Kishimoto et al., in a comprehensive meta-analysis of 21 trials, confirmed LAI superiority over oral antipsychotics in preventing relapse and rehospitalization [6]. Lian et al. specifically examined LAI efficacy in early psychosis, finding a significant reduction in hospitalization rates and relapse risk even in first-episode patients [7]. Abdel-Baki et al. further demonstrated that early LAI use in a naturalistic FEP sample was associated with reduced psychotic relapses over two years [11].

The present case supports these findings by demonstrating sustained remission and functional recovery attributable, in part, to the transition to LAI therapy. The elimination of daily adherence demands reduced the opportunity for covert discontinuation and provided a regular clinical contact point for monitoring.

5.5 Aripiprazole LAI: Pharmacological Rationale and Tolerability

Aripiprazole's mechanism as a partial D2 dopamine agonist distinguishes it from most first- and second-generation antipsychotics. This profile confers lower risk of metabolic syndrome, hyperprolactinemia, and extrapyramidal symptoms—considerations of particular importance in adolescent patients who may require decades of maintenance therapy [8]. Correll et al. confirmed favorable tolerability and adherence-promoting properties of aripiprazole LAI in a large international study [8]. The absence of metabolic adverse effects or EPS over the seven-year follow-up in this patient is consistent with this literature.

From a cognitive standpoint, aripiprazole's low sedation burden may offer advantages over more sedating agents (e.g., quetiapine, olanzapine) in young patients for whom cognitive functioning, academic performance, and social engagement are critical recovery domains.

5.6 Role of Psychosocial Interventions

Cognitive behavioral therapy for psychosis (CBTp) was integrated as an adjunct to pharmacological management. Evidence-based guidelines from the National Institute for Health and Care Excellence (NICE) and the American Psychiatric Association (APA) recommend structured psychotherapy as a component of comprehensive FEP treatment. CBTp targeting delusion modification, metacognitive awareness, and relapse prevention planning likely contributed to the patient's sustained remission and improved insight over the follow-up period.

5.7 Clinical Implications

• Early identification of adherence risk factors (young age, lack of insight, adverse medication effects, substance use) should prompt consideration of LAI initiation prior to first relapse.
• Severe relapse with suicidality provides a strong clinical indication for transition to LAI antipsychotics.
• Aripiprazole LAI represents a first-line LAI candidate in adolescent FEP given its favorable metabolic, endocrine, and cognitive tolerability profile.
• LAI antipsychotics should not be framed as a 'last resort' intervention but as a proactive adherence strategy in high-risk populations.
• Integrated pharmacological and psychosocial treatment, including CBTp, represents best practice for adolescent FEP management.

5.8 Limitations

This report describes a single case, which limits generalizability. Formal longitudinal neuropsychological testing was not systematically administered, preventing quantitative assessment of cognitive trajectory. Anti-NMDA receptor and other autoimmune encephalitis panels were not documented in the original workup [if not performed, note accordingly]. Causality between specific interventions and outcomes cannot be established in observational case design. Additionally, the contribution of spontaneous illness evolution to long-term remission cannot be excluded.

Conclusion

This case report documents sustained seven-year remission in an adolescent with severe first-episode schizophrenia-spectrum psychosis following transition to monthly aripiprazole LAI after a life-threatening adherence-related relapse with suicide attempt. Early identification of non-adherence risk, proactive consideration of LAI antipsychotics in high-risk FEP patients, and integration of structured psychosocial interventions represent the primary take-home messages for clinical practice. Future prospective studies in adolescent FEP populations are needed to establish evidence-based guidelines for LAI initiation timing in this vulnerable demographic.

Patient Perspective

At seven-year follow-up, the patient reported that the transition to monthly injectable medication had been a 'turning point' in his illness course, as it eliminated the daily reminder of illness associated with oral medication. He acknowledged that prior to relapse, he had believed he no longer required medication due to feeling well—a pattern consistent with medication-related anosognosia commonly observed in psychotic disorders. He expressed appreciation for the integrated pharmacological and psychological approach and noted significant improvement in his quality of life, social relationships, and future orientation.

Ethics Statement

Written informed consent was obtained from the patient and his legal guardians for publication of this case report. All identifying information has been de-identified or replaced with non-specific descriptors. This report was prepared in accordance with the CARE Case Report Guidelines and institutional ethical standards.

Author Contributions

Dr. Ivan Lopez-Ibor Aben-Moha: Clinical management of the patient, conceptualization and design of the case report, systematic literature review, manuscript drafting, and critical revision of intellectual content.

Appendix A: Antipsychotic Dosing Reference (APA Guidelines)

Table 1 provides a reference summary of antipsychotic dosing parameters relevant to this case and similar clinical presentations, based on APA guideline recommendations.

Table 1. Antipsychotic Dosing Reference for Second- and Third-Generation Agents

Drug (Generic)	Initial Dose	Maintenance	Maximum (FDA)	Clinical Notes
Aripiprazole (Abilify)	10–15 mg/day	15–30 mg/day	30 mg/day	Partial D2 agonist; akathisia risk
Aripiprazole LAI (Abilify Maintena)	400 mg/month	300–400 mg/month	400 mg/month	Requires 14-day oral overlap
Olanzapine (Zyprexa)	5–10 mg/day	10–20 mg/day	20 mg/day	High metabolic/weight gain risk
Risperidone (Risperdal)	1–2 mg/day	4–6 mg/day	8 mg/day	Significant prolactin elevation
Quetiapine (Seroquel)	25–50 mg/day	300–800 mg/day	800 mg/day	Sedating; low EPS risk
Lurasidone (Latuda)	40 mg/day	40–80 mg/day	160 mg/day	Must take with >350 kcal
Cariprazine (Vraylar)	1.5 mg/day	3–6 mg/day	6 mg/day	Very long half-life (~1 week)

EPS = extrapyramidal symptoms; LAI = long-acting injectable; D2 = dopamine type 2 receptor. All doses represent oral administration unless specified. Doses should be individualized based on patient response, tolerability, and clinical context.

CARE Checklist

Table 2. CARE Case Report Guideline Compliance Checklist

Item	Requirement	Present in This Report
Title	Describes the case, indicating it is a case report	✓
Keywords	Key concepts from this case	✓
Abstract	Background, Case Presentation, Conclusions	✓
Introduction	Medical literature background; uniqueness of case	✓
Patient Info	De-identified demographic/info; chief complaint; reason for referral	✓
Clinical Findings	Physical exam and relevant results at time of presentation	✓
Timeline	Chronological sequence of events; interventions; outcomes	✓
Diagnostic Assessment	Diagnosis; reasoning; challenges; alternative diagnoses considered	✓
Therapeutic Intervention	Type, dose, duration of all interventions	✓
Follow-up and Outcomes	Clinician- and patient-assessed outcomes; adherence; adverse events	✓
Discussion	Strengths/limitations; literature comparison; clinical reasoning	✓
Patient Perspective	Patient's own perspective of treatment	✓
Informed Consent	Written informed consent obtained	✓

References

1. Marshall M, Lewis S, Lockwood A, Drake R, Jones P, Croudace T. Association between duration of untreated psychosis and outcome in cohorts of first-episode patients: a systematic review. Br J Psychiatry. 2005;187(Suppl 48):s11–s17.

2. Zipursky RB, Menezes NM, Streiner DL. Risk of symptom recurrence with discontinuation of antipsychotic medication after first episode of psychosis. Schizophr Res. 2014;152(2–3):408–414.

3. McGorry PD, Nelson B, Goldstone S, Yung AR. Clinical staging: a heuristic and practical strategy for new research and better health and social outcomes for psychosis. Schizophr Bull. 2007;33(3):895–903.

4. Palmer BA, Pankratz VS, Bostwick JM. The lifetime risk of suicide in schizophrenia: a reexamination. Arch Gen Psychiatry. 2005;62(3):247–253.

5. Haddad PM, Brain C, Scott J. Nonadherence with antipsychotic medication in schizophrenia: challenges and management strategies. Patient Relat Outcome Meas. 2014;5:43–62.

6. Kishimoto T, Robenzadeh A, Leucht C, Leucht S, Watanabe K, Mimura M, et al. Long-acting injectable vs oral antipsychotics for relapse prevention in schizophrenia: a meta-analysis of randomized trials. Schizophr Bull. 2014;40(1):192–213.

7. Lian L, Kim DD, Procyshyn RM, Honer WG, Barr AM. Efficacy of long-acting injectable versus oral antipsychotics in early psychosis: a systematic review and meta-analysis. PLoS One. 2022;17(4):e0267808.

8. Correll CU, Citrome L, Haddad PM, Lauriello J, Ota A, Eramo A, et al. The use of long-acting injectable antipsychotics in schizophrenia: evaluating the evidence. J Clin Psychiatry. 2016;77(Suppl 3):1–24.

9. Tiihonen J, Haukka J, Taylor M, Haddad PM, Patel MX, Korhonen P. A nationwide cohort study of oral and depot antipsychotics after first hospitalization for schizophrenia. Am J Psychiatry. 2011;168(6):603–609.

10. Subotnik KL, Casaus LR, Ventura J, Luo JS, Hellemann GS, Gretchen-Doorly D, et al. Long-acting injectable risperidone for relapse prevention and control of breakthrough psychosis in recent-onset schizophrenia: a randomized clinical trial. JAMA Psychiatry. 2015;72(8):822–829.

11. Abdel-Baki A, Ouellet-Plamondon C, Salvat E, Grar K, Potvin S. Impact of early use of long-acting injectable antipsychotics on psychotic relapses and hospitalizations in first-episode psychosis. Int Clin Psychopharmacol. 2020;35(4):221–228.

Cover Letter

Miami, Florida, USA.

April 2026

To the Editors,

I am submitting the enclosed manuscript, entitled "Recurrent First-Episode Schizophrenia-Spectrum Disorder with Messianic Delusions in an Adolescent Male: Seven-Year Longitudinal Follow-Up and Long-Acting Injectable Aripiprazole Stabilization," for consideration as a case report in Psychiatric Quarterly.

This report documents a clinically significant seven-year longitudinal follow-up of an adolescent male presenting with severe first-episode schizophrenia-spectrum psychosis, including grandiose messianic delusions, auditory hallucinations, suicidal ideation, and documented medication non-adherence leading to life-threatening relapse. The subsequent transition to monthly aripiprazole long-acting injectable therapy resulted in sustained symptomatic remission and functional recovery over seven years, with no rehospitalizations.

The case contributes to the growing body of evidence supporting earlier utilization of LAI antipsychotics in high-risk first-episode populations, a practice that remains under implemented despite compelling data. The longitudinal duration and complete clinical documentation of this case represent substantive added value to the existing literature on adolescent early psychosis management.

Written informed consent was obtained from the patient and legal guardians. This manuscript has not been previously published and is not under concurrent review at another journal. The case report was prepared in accordance with the CARE Case Report Guidelines.

I welcome the opportunity to respond to reviewer comments and appreciate your consideration.

Sincerely,

Ivan Lopez-Ibor Aben-Moha, MD

Clínica López-ibor, Sanatorio del Dr Esquerdo, Clínica del Dr León, South Florida Integrative Medicine, Miami, Florida.  

Department of Psychiatry, Madrid, Spain 

drivanlopezibor@gmail.com