The Role of Lurasidone in Early-Onset Schizophrenia and Obsessive-Compulsive Disorder: A Case Report^*

Abstract

The comorbidity of schizophrenia and obsessive-compulsive disorder (OCD) has been demonstrated to result in more severe symptoms and a worse prognosis for patients, as well as a more challenging treatment process for clinicians. Lurasidone is a second-generation atypical antipsychotic approved for the treatment of schizophrenia. This case report aims to share the use and treatment process of lurasidone in a 28-year-old male patient with a history of OCD and schizophrenia since childhood. The patient has had multiple hospitalizations and suicide attempts and has received ECT (electroconvulsive therapy) and TMS (transcranial magnetic stimulation) treatment on numerous occasions. The patient has been resistant to various drug treatments, including clozapine. Following the administration of lurasidone at a dosage of 80 mg/day and above, the patient exhibited a regression in their psychotic symptoms, depressive and obsessive complaints, and demonstrated a substantial enhancement in social and cognitive functioning. No adverse effects related to lurasidone were reported. These findings suggest that lurasidone may be a safe treatment option for schizophrenia and comorbid disorders. Its receptor profile suggests many advantageous features in terms of both treatment and side effect tolerability, and it provides a significant improvement in functionality.

Main Points

• The coexistence of schizophrenia and OCD can be challenging for both the patient and the clinician.

• Lurasidone may be effective in reducing psychotic, depressive, and obsessive symptoms, especially at doses above 80 mg/day.

• Lurasidone may improve social and cognitive function, especially at doses above 80 mg/day.

• Lurasidone may be well tolerated by patients because of its receptor profile.

• The use of lurasidone should be considered as an alternative strategy in the treatment of schizophrenia and OCD.

Introduction

Schizophrenia is a chronic psychiatric disorder that has a profound impact on society, with high rates of cognitive and social dysfunction, reduced personal and community functioning, and high rates of disability. The treatment of schizophrenia involves many steps, such as controlling severe symptoms, preventing relapses and frequent hospitalizations, and improving adaptive skills to reintegrate the patient into society. The comorbidity of schizophrenia and OCD can lead to poorer insight, more severe positive, negative and depressive symptoms, higher cognitive deficits, more suicide attempts, and a worse prognosis for patients.¹ Lurasidone is an atypical antipsychotic enhanced for the treatment of schizophrenia. Studies have reported the efficacy of lurasidone in various aspects of schizophrenia and found that it provides significant improvements in positive, negative, and cognitive symptoms. Lurasidone can improve agitation and shows greater efficacy at higher doses.^2,3 It also appears to have antidepressant effects due to its affinity for 5-HT7, 5-HT2A, and 5-HT1A receptors. The receptor-binding profile of lurasidone is thought to be less associated with side effects such as anticholinergic effects, lipid abnormalities, hyperglycemia, and weight gain. Lurasidone has no major metabolic or cardiovascular effects (QT interval) and does not alter the metabolism of other drugs, with good efficacy and tolerability.^4,5 In this case report, the authors aimed to share the use and treatment process of lurasidone in the association of early- onset chronic schizophrenia and OCD, which can be a challenging profile for clinicians.

Case Presentation

A 28-year-old male patient was admitted to the child psychiatry clinic with visual hallucinations, insomnia, anger problems, obsessive-compulsive disorder (OCD), and suspiciousness that began at the age of 11 after his father left home and has been followed up in adult psychiatry since 2016 with a diagnosis of “obsessive-compulsive disorder and schizophrenia.” It was learned that the patient had been hospitalized on average twice a year since then, had attempted suicide several times, had received ECT and TMS several times, and had taken many medications, including clozapine, without benefit. The patient’s aunt was found to have OCD. Mental status examination revealed that his appearance was compatible with his age, self-care was reduced, communication was limited, and the amount of speech was reduced. His mood was depressed and anxious and his ability to evaluate, judge and abstract reality was impaired. There were auditory (hearing commanding voices) and visual (a girl) hallucinations, reference and persecutory delusions in thought content, suspicion, fear of making a mistake (not being sure of anything he does) and religious obsessions (cursing God), compulsions to check, to get family members to approve what he does, to constantly say “Bismillah” and pray, and suicidal thoughts in the patient’s examination. It was learned that the patient had poor functionality and could not work in a regular job during the trial. It was learned that he had attempted suicide with multiple drug ingestions and auditory hallucinations 1 week before admission and had been in intensive care for a few days. Lurasidone 80 mg/day was added to the existing treatment of aripiprazole 30 mg/day, escitalopram 20 mg/day, and paliperidone 150 mg/3 months. PANSS (Positive and Negative Syndrome Scale), MADRS (Montgomery-Asberg Depression Rating Scale), CGI (Clinical Global Impression Scafle), and Y-BOCS (Yale-Brown Obsessive Compulsive Scale) scales were administered to the patient on the day of admission and at the 4th, 8th, and 12th weeks. Scale scores of the patient on the day of admission and during the follow-up period are given in Table 1. At the 1-month follow-up, lurasidone was increased to 160 mg/day in the patient whose partial OCD symptoms, social isolation and low functionality persisted but whose positive symptoms and depressive symptoms regressed. At the follow-up visit the following month, the patient was reported to have no complaints except sleep disturbance, to have said to his mother for the first time “I am very well”, to have improved his self-care, to have changed his surname of the father who had abandoned him and acquired a new surname at the fourth month visit, to have started working as a cleaner at the district governor’s office at the fifth month visit, and to have found a girlfriend. No lurasidone-related side effects such as EPS, sedation, weight gain, etc. were observed.

Table 1.

Changes in Positive and Negative Syndrome Scale, Montgomery-Asberg Depression Rating Scale, and Clinical Global Impression Scale, and Yale-Brown Obsessive Compulsive Scale Scores during the Follow-up Period

Scales	Application Day	Follow-up 4th week	Follow-up 8th week	Follow-up 16th week
MADRS	48 (Severe Depression)	19 (Mild Depression)	4 (No Depression)	2 (No Depression)
PANNS: Positive Symptoms Subscale	28	11	9	7
PANNS: Negative Symptoms Subscale	35	19	11	8
YBOCS	27 (Severe)	16 (Moderate)	6 (None)	6 (None)
CGI: Severity of Illness	Severely ill	Moderately ill	Mildly ill	Borderline Mentally ill
CGI: Improvement	–	Minimally improved	Much improved	Much improved
CGI: Side effect severity	–	Do not interfere with the patient’s functioning	None	None

CGI, Clinical Global Impression Scale; MADRS, Montgomery-Asberg Depression Rating Scale; PANSS, Positive and Negative Syndrome Scale; Y-BOCS, Yale-Brown Obsessive Compulsive Scale.

Discussion

It is noteworthy that the patient’s psychotic symptoms, as well as their depressive and obsessive complaints, regressed after lurasidone treatment, and a significant increase in social and cognitive functioning was observed. In line with these observations, numerous contemporary studies have demonstrated the efficacy and tolerability of lurasidone in the management of early-onset schizophrenia and schizophrenia accompanied by predominant depressive symptoms.^4,6,7 The findings of these studies indicate that the therapeutic effects of lurasidone manifest at a dosage of 80 mg/day, with a dosage of 160 mg/day resulting in a more rapid regression of symptoms and enhancement in functionality. Notably, these studies did not report any adverse effects related to lurasidone. In a subsequent study involving 60 patients diagnosed with schizophrenia, it was observed that after 3 months of treatment with lurasidone at an average dose of 74 mg/day, there was an enhancement in quality of life and functionality scores, along with a reduction in disease symptoms. Notably, no adverse effects that would hinder the continuation of drug treatment were reported.⁸ In a separate study, lurasidone was found to be safe and effective in a group of European patients diagnosed with schizophrenia when administered at doses ranging from 40 mg/day to 160 mg/day, with minimal impact on metabolic parameters reported.⁹ A meta-analysis involving 2456 schizophrenia patients showed that there was no change in PANSS (Positive and Negative Syndrome Scale), MADRS (Montgomery-Asberg Depression Rating Scale), and CGI (Clinical Global Impression Scale) scores with 40 mg/day lurasidone. However, the study noted a significant shift in these scales when 80 mg/day, 120 mg/day, and 160 mg/day of lurasidone were administered.¹⁰ In 2 studies on lurasidone doses, it was reported that increasing the lurasidone dose from 40 mg/day to 80 mg/day may be more effective and well-tolerated in patients diagnosed with schizophrenia.^11,12 The findings of all these studies are compatible with the treatment process of the case under consideration. In the patient who demonstrated a satisfactory tolerance to 80 mg/day lurasidone, the dosage was increased to 160 mg/day as recommended in the literature, thereby achieving a more expeditious and efficacious outcome.

To the best of the authors’ knowledge, there is no study in the English literature on the use of lurasidone in the association of schizophrenia and OCD, but in a case report with OCD and anorexia nervosa, it was reported that a decrease in OCD symptoms was observed with lurasidone.¹³ In this case, a significant reduction in obsessive and depressive complaints is a noteworthy finding. It is known that lurasidone has an affinity for 5-HT7, 5-HT2A, and 5-HT1A receptors.⁴ In this case, it was hypothesized that lurasidone reduced depressive, obsessive-compulsive, and negative symptoms due to its affinity for 5-HT2A and 5-HT1A receptors. Concurrently, lurasidone was hypothesized to contribute to the improvement in the patient’s cognitive and negative symptoms by affecting glutamatergic activation through 5-HT7 receptor antagonism. The efficacy of lurasidone has been reported to increase at high doses⁴ and in this case, it was hypothesized that the initial dose of 80 mg/day and the subsequent increase to the maximum dose of 160 mg/day at the end of the first month may be a contributing factor to the rapid improvement in symptoms.

Consequently, the efficacy and safety of lurasidone treatment in the association of schizophrenia with OCD and depression may be a promising avenue for future studies. Lurasidone’s potential as a safe treatment option for schizophrenia and comorbid disorders is further supported by its receptor profile, which offers numerous advantages in terms of treatment and side effect tolerability, along with tangible improvements in functioning.

Funding Statement

The authors declared that this study has received no financial support.

Data Availability Statement:

The data that support the findings of this study are available on request from the corresponding author.