Clozapine Use in 22q11.2 Deletion Syndrome: A Systematic Review of the Literature.

BACKGROUND: 22q11.2 deletion syndrome confers significant risk for the development of schizophrenia. While current recommendations regarding the management of psychotic symptoms in affected individuals are generally in keeping with treatment guidelines for general schizophrenia populations, evidence for the use of clozapine has come from case reports and retrospective observational data. As no reviews on the topic currently exist, a systematic review of clozapine use in 22q11.2 deletion syndrome was completed. METHODS: In November 2023, a literature search was completed using both PubMed and Scopus to identify English-language articles that reported the use of clozapine in humans with 22q11.2 deletion syndrome. RESULTS: Twenty-six articles describing 57 individuals were deemed eligible for inclusion. Most individuals had a diagnosis of treatment-resistant schizophrenia. Where reported, the mean or median dose of clozapine was relatively low, and the majority of individuals exhibited a good response (approximately 65.5% across individual case reports/series). While seizures were unsurprisingly the most commonly reported serious adverse effect, the majority of individuals were able to remain on (or be restarted on) clozapine by having their dose decreased and/or by adding an anticonvulsant (most commonly valproate). CONCLUSIONS: This review reaffirms that individuals with 22q11.2 deletion syndrome may benefit from clozapine therapy even at a low dose, assuming they meet criteria for treatment-resistant schizophrenia and provided no contraindications exist. However, given the increased incidence of seizures in 22q11.2 deletion syndrome, the use of prophylactic anticonvulsant therapy should be considered, and hypoparathyroidism/hypocalcemia screened for and corrected before the initiation of clozapine. It is also recommended that clozapine blood levels be monitored.

Maternal 15q11.2-q13.1 duplication syndrome-associated psychosis and mania: a new case and review of the literature.

Maternal 15q11.2-q13.1 duplication syndrome is associated with a variety of developmental and neuropsychiatric abnormalities. Although schizophrenia-like presentations have been reported, details pertaining to the nature of the corresponding psychotic symptoms and their response to treatment have only been described in a few cases, and no reviews summarizing the literature currently exist. As such, we describe a new case of 15q11.2-q13.1 duplication syndrome-associated schizoaffective disorder and also performed a systematic review of the literature. Our patient's presentation is somewhat unique as she experienced visual hallucinations in the absence of auditory hallucinations. This is also the first report to describe full symptomatic remission in response to relatively low-dose atypical antipsychotic therapy.

Response to Treatment in 3q29 Deletion Syndrome-Associated Psychosis: A Mini-Review.

3q29 deletion syndrome is characterized by various developmental abnormalities, medical issues, and neuropsychiatric symptoms, including psychosis. Although this syndrome may confer the greatest risk for schizophrenia of any copy number variation, response to antipsychotic medication has infrequently been described in the literature, and no reviews on the topic currently exist. As such, the purpose of this article was to review treatment response in 3q29 deletion syndrome-associated psychosis. A review of the literature was completed in December 2022 for English language articles that described treatment response to antipsychotic medications in affected individuals with schizophrenia-like presentations. Five articles that collectively described eight individuals were included. Four individuals had a poor treatment response to non-clozapine antipsychotic medications, three had a partial response, and one individual's response to treatment was not described, despite having taken psychotropic medications of some kind. Additionally, three individuals received clozapine; one of whom partially responded, while two exhibited a good response. Treatment response did not clearly differ according to developmental history. 3q29 deletion syndrome may be associated with treatment-resistant psychotic symptoms. As such, clozapine therapy should be considered in such individuals, provided they meet criteria for treatment-resistant schizophrenia and no contraindications exist. However, this mini-review also highlights the need for more published case reports/series before more specific treatment recommendations can be made.

The Co-occurrence of Gastrointestinal Symptoms and Psychosis: Diagnostic Considerations.

Gastrointestinal issues are common in schizophrenia and may also co-occur with psychotic symptoms in a variety of other clinical contexts. Although their concurrent development may be coincidental, such presentations may also be attributable to a variety of underlying psychiatric, medical, and neurologic conditions. As patients may first present to mental health services, it is important that both psychiatrists and primary care physicians involved in the care of psychiatric populations have a familiarity with the differential diagnosis of co-occurring gastrointestinal and psychotic symptoms. This narrative review describes the numerous clinical scenarios in which gastrointestinal and psychotic symptoms commonly co-occur and highlights the practical implications thereof.

Clinically Relevant Anti-Neuronal Cell Surface Antibodies in Schizophrenia Spectrum Disorders.

Schizophrenia is a phenotypically heterogeneous and poorly understood disorder. While its etiology is likely multifactorial, immune system dysfunction has increasingly been implicated in its development. As hallucinations and delusions occur frequently and prominently in autoimmune encephalitis (AE), numerous studies have sought to determine whether a small subset of individuals diagnosed with schizophrenia possess anti-neuronal antibodies implicated in AE. Exploring this possibility is of clinical relevance, as identifying individuals with AE who have been misdiagnosed as having a primary psychotic disorder may allow for the implementation of appropriate immune-related therapies as early as possible in the course of the illness, in order to optimize outcomes, reduce illness chronicity, and minimize adverse events. This qualitative review serves to provide an overview of the existing literature on this topic, as well as to update previously published reviews. Although there is some evidence to suggest that in rare cases AE may be misdiagnosed as a primary psychotic disorder, particularly early in the course of the illness, numerous methodological differences between studies likely account for the highly variable findings, and interpretation of the results is particularly limited by a paucity of cerebrospinal fluid data. Moreover, the prevalence of misdiagnosis in chronic and treatment-resistant populations remains understudied. This is particularly problematic, as treatment resistance may represent an enriched population with respect to the presence of anti-neuronal antibodies, and given that such patients have few evidence-based treatment options available to them beyond clozapine.