Perspectives of Clinical Researchers on Engagement With Digital Mental Health Interventions: Qualitative Interview Study.

Multiple sclerosis (MS) is characterized by acute or subacute onset of neurological symptoms, which frequently include muscle weakness, gait disturbance, sensory impairment, and visual impairment. MS presents with a variety of clinical symptoms, including extrapyramidal symptoms, intention tremors, bladder–rectum dysfunction, and seizures, which occur multiple times and undergo repeated exacerbations and remissions []. MS is also associated with a variety of psychiatric symptoms, including depressed mood, fatigue, suicidal ideation, and cognitive decline []. Two to three percent of patients exhibit psychotic symptoms characterized by persecutory delusions and auditory hallucinations, such as hearing one's name being called, and may exhibit symptoms similar to schizophrenia []. MS most commonly occurs at approximately 30 years [], which is close to that at which schizophrenia occurs, in the late teens and 30s. Therefore, it is important to consider MS in the differential diagnosis of schizophrenia. When psychiatric symptoms are prominent in the early stages of MS and neurological symptoms are not prominent, or when imaging examinations do not reveal typical abnormal findings in the cerebral white matter, it can be difficult to distinguish between MS and schizophrenia. Additionally, MS occurring during the course of schizophrenia may modify psychiatric symptoms and affect the development of treatment resistance. Here, we discuss a case in which MS was accidentally discovered during the long‐term of treatment‐resistant schizophrenia (TRS). The patient was a woman in her 50s, born in Japan as the first of two siblings, with no family history of schizophrenia or MS. She had high academic achievement and entered a university in an urban area. Thirty‐one years before presentation (X‐31), shortly after enrollment, she developed persecutory delusions and a persistent sense of being watched, and withdrew from university. In X‐28 she attended a local psychiatric clinic and was diagnosed with atypical psychosis but discontinued follow‐up without medication. Although hallucinations and delusions subsequently diminished and her symptoms were relatively stable for periods, she became socially withdrawn. She engaged intermittently in short‐term employment; however, episodic exacerbations of psychotic symptoms led to frequent job discontinuation, preventing sustained employment, and eventually becoming socially isolated at home (Figure ). In X‐15 she re‐presented with hallucinations and delusions, was diagnosed with schizophrenia, and was hospitalized. Haloperidol was started, and lithium was added to manage mood instability and agitation, with transient improvement. The initial benefit of haloperidol was not sustained, and subsequent deterioration became more pronounced as medication non‐adherence emerged. Even during outpatient treatment, the patient did not sustain independent functioning. Family members accompanied her during all outpatient visits and provided continuous support in daily life. Home‐based occupational therapy was introduced to promote social functioning; however, no meaningful functional recovery was achieved. In X‐10 she developed left peripheral facial nerve palsy; brain MRI at that time showed no intracranial lesions (Figure ), and symptoms remitted after steroid therapy. According to both the patient and her family, no acute or transient neurological symptoms or prior neurological care episodes were noted prior to this episode; therefore, it was considered the first recognized neurological manifestation. Thereafter, psychiatric instability increased. Adherence was assessed based on documented medication refusal in clinical records, supervised administration during hospitalization, injection records for long‐acting injectable (LAI) paliperidone, and collateral information from family members. She refused medications (stating “I only want to take the medicine that I developed”), manifested delusions of poisoning, frequently contacted police, and exhibited food refusal. Haloperidol (up to 6.25 mg/day) was switched to zotepine (up to 450 mg/day) with only partial benefit. During hospitalization at another hospital, adherence to zotepine was ensured by supervised administration. Lithium was later replaced with valproic acid, which was also prescribed for mood instability and agitation but without clinical benefit. In X‐4 involuntary tongue and neck movements led to a neurology consultation and diagnosis of drug‐induced cervical dystonia. Medication non‐adherence worsened; paliperidone long‐acting injection (up to 150 mg intramuscularly every 4 weeks) was added alongside zotepine. During inpatient care, paliperidone LAI was administered according to schedule without missed doses. Olanzapine (up to 7.5 mg/day) was subsequently administered during supervised inpatient treatment; however, no significant improvement in the psychotic symptoms was observed. Taken together, the overall clinical course met TRS cri