Cholinesterase Inhibitors for Delusions and Hallucinations in Alzheimer Disease and Parkinson Disease: Questionably Significant Benefits.

Delusions and hallucinations are common in Alzheimer disease (AD) and Parkinson disease (PD), especially in the later stages of illness. Antipsychotic drugs are effective in treating these psychotic symptoms but are associated with an increased risk of serious adverse events, including mortality. There is therefore a need to explore other treatment approaches. In this context, a recent individual patient data meta-analysis of 17 randomized controlled trials (RCTs) conducted in AD (12 RCTs) and PD (5 RCTs) found that the cholinesterase inhibitor (ChEI) drugs donepezil, rivastigmine, and galantamine attenuated the severity of both delusions and hallucinations in both AD and PD. Most of these trials were 24 weeks in duration. The effect sizes, expressed as standardized mean differences (SMDs), were, however, small, lying in the -0.08 to -0.14 range. These values are so small as to be perhaps clinically insignificant. When analyses were restricted to data from patients who actually had delusions and hallucinations at baseline, all effect sizes became larger, lying in the -0.13 to -0.39 range; however, after correcting for multiple hypothesis testing, only the finding for delusions in PD remained statistically significant. The meta-analysis did not provide information on what the best doses were, how long it took for improvement to become evident, and what proportion of patients showed remission from psychotic symptoms. Whereas the signal identified in this meta-analysis merits examination in appropriately designed RCTs, the findings of the meta-analysis may not much change current treatment strategies because patients with dementia would probably anyway receive a ChEI. Therefore, if psychotic symptoms persist for 24 weeks despite optimally dosed ChEI treatment, and if behavioral and psychosocial interventions do not help, clinicians may need to consider the potential benefits vs risks of other drugs, such as atypical antipsychotics and pimavanserin, in a shared decision-making process.

ECT for Cotard syndrome in a 13-year-old.

This is a case report about a 13-year-old girl who presented with depression, severely reduced daily functioning, and eventually nihilistic delusions about being dead. The condition was interpreted as a presentation of Cotard syndrome as part of early-onset schizophrenia. Treatment with an antidepressant and multiple antipsychotic medications was not effective. The patient was then treated with ECT, resulting in subjective and measurable positive effects.

Residual or re-emergent impaired insight into delusions following remission is unrelated to later relapse during a randomized clinical trial of continuation pharmacotherapy for psychotic depression - The STOP-PD II Study.

BACKGROUND: Impaired insight into delusions is associated with a lower probability of remission of psychotic depression, independent of illness severity. The relationship between participant characteristics and impaired insight into delusions in remitted psychotic depression, and whether impaired insight is associated with risk of relapse of psychotic depression during continuation pharmacotherapy were examined. METHODS: Data were analyzed from 126 participants in the STOP-PD II study who experienced sustained remission of psychotic depression during 8-week stabilization treatment with sertraline plus olanzapine and were then randomized to 36 weeks of continuation treatment with sertraline plus either olanzapine or placebo. Insight into delusions was assessed with the Resolution of Delusions Scale (RODS). Linear regression analyses examined the associations between participant characteristics and insight into delusions. Cox proportional-hazards models examined whether i) change in RODS during stabilization treatment; or ii) RODS at the end of stabilization treatment predicted risk of relapse during 36 weeks of continuation treatment. RESULTS: Severity of psychosis before initiation of treatment was the only participant characteristic associated with the change in insight during stabilization treatment. Neither change in insight during stabilization treatment nor insight at the end of stabilization treatment was associated with risk of relapse. LIMITATIONS: Insufficient statistical power and the lack of variability in RODS scores at the time of randomization may have contributed to the absence of a relationship between RODS and risk of relapse. CONCLUSION: Residual or reemergent insight impairment following acute treatment does not preclude patients from sustaining remission of psychotic depression in a randomized placebo-controlled trial.

Treatment of Major Depression with Psychotic Features and Cotard's Syndrome after COVID-19 Infection in a Previously Healthy Patient: A Case Report.

BACKGROUND: COVID-19 pandemic is related to anxiety, depression, and psychotic symptoms either directly due to invasion or inflammation caused by the virus or indirectly due to related psychosocial stress: fear of infection, social isolation, and financial burden. CASE PRESENTATION: We present a 28-year-old female case of post-COVID major depression with psychotic features and Cotard's syndrome with no previous psychiatric history. Her complaints initially described the sadness of mood with early morning worsening, diminished interest in almost all activities, anhedonia, increased anxiety, ideas of worthlessness, hopelessness, guilt, decreased sleep, and appetite. Then, she developed severe depression with psychotic features such as delusions of persecution, poverty, and nihilism. Nihilistic delusions included a description of everything coming to an end. She thought that her organs were no more working. Later, she negated her existence and started believing that she was dead. The patient recovered after a combination of sertraline and olanzapine treatment. CONCLUSION: This case of a COVID-19 patient with psychotic depression and Cotard's delusion highlights the importance of evaluating mental health status and may contribute to our understanding of the potential risk of central nervous system impairment by SARS-CoV-2 infection.

Delusional Jealousy: How Can Treatment be Improved? A Case Report.

INTRODUCTION: Although delusional jealousy accounts for merely 10% of delusional disorders, it is associated to risk of serious violence and suicide. With this clinical case, we intend to explore the difficulties in the pharmacological approach of delusional jealousy disorder and to summarise the most recent findings in the treatment of this condition. METHODS: Case report. CASE PRESENTATION: A 76-year-old man involuntarily admitted to a psychiatric ward due to threats of physical aggression to his wife in the context of irreducible ideas of her infidelity. Initially, we observed an improvement of symptomatology with risperidone and its long-acting injectable formulation, but the emergence of hypotensive side effects required the off-label use of paliperidone palmitate 50 mg/ml. CONCLUSIONS: Few studies, mainly case reports, look at the specific treatment of delusional jealousy. Given the negative consequences for patients and for their spouses, better scientific evidence to treat this condition is needed.

Acute Onset Psychosis With Mystical Delusions in a Young Male Patient Following Discontinuation of Corticosteroid Therapy: A Case Report.

Corticosteroid-based drugs are widely used in the general population to treat several acute and chronic inflammatory conditions. However, the therapeutic efficacy of these drugs is often accompanied by severe psychiatric adverse effects through a yet unknown mechanism. To further complicate this situation, therapeutic strategies to counteract psychotic symptoms associated with these agents have yet to be devised. We report a case of a young white male Jehovah's Witness admitted to the psychiatry ward of the Maggiore della Carità Hospital, Novara, Italy. At admission, the patient presented with psychomotor agitation, auditory hallucinations, and thought disturbances, resulting in the working diagnosis of a manic episode with psychotic features. During the 16 days of his hospital admission, the patient was treated with antipsychotic medications (aripiprazole and haloperidol) and with benzodiazepines (lorazepam), and he achieved a complete remission of all psychotic symptoms. While his psychiatric history was negative, his medical records revealed a recent discharge from the infectious disease ward with a diagnosis of infectious mononucleosis treated with intravenous betamethasone. Thus, at discharge, a diagnosis of steroid-induced psychosis was made. In conclusion, our findings are suggestive of a potential role played by corticosteroids in the development of psychotic symptoms, for which routine screening protocols and therapeutic guidelines are still lacking.

Hallucinations and delusions associated with Parkinson's disease psychosis: safety of current treatments and future directions.

INTRODUCTION: Over half of Parkinson's disease (PD) patients develop psychotic symptoms, and PD psychosis (PDP) is associated with significant distress to patients, caregiver burden, and impairs quality of life. Pharmacological therapy is limited to atypical antipsychotics. AREAS COVERED: This review will summarize efficacy but will focus on the safety of antipsychotics for treating PDP, and in particular the off-target safety issues including cognitive impairment, sleep disturbance, cardiovascular effects, and motor function. EXPERT OPINION: Pimavanserin is the only medication approved in the US for treating PDP, however clozapine is also considered efficacious. Despite lack of substantial evidence for efficacy, quetiapine is commonly used to treat PDP. Despite the effectiveness of pimavanserin and clozapine for treating PDP, a need exists for additional pharmacological agents that are effective for PDP while providing an acceptable safety and tolerability profile. Medications to treat PDP should avoid worsening motor function, and also minimize sleep disturbances, cognitive impairment, cardiovascular effects, and other non-motor safety concerns. A neutral effect or reduction in mortality risk associated with PD and PDP would be ideal, and low rate of discontinuation due to AEs is desirable. Lastly, medications that can be used safely in combination with other pharmacological agents is essential.

A Young Japanese Patient with Spinocerebellar Ataxia Type 3 Presenting Depressive State with Cenesthopathy and Delusion: a Case Report.

Depressive state is a common complication of spinocerebellar ataxia type 3 (SCA3). To the best of our knowledge, cases of SCA3 presenting with cenesthopathy have not been described. Here, we present a case of a severe depressive state with cenesthopathy and delusion in a young Japanese man with SCA3. A 43-year-old Japanese man with SCA3 developed a severe depressive state with associated cenesthopathy and delusion. He was treated with escitalopram (10 mg/day) and olanzapine (2.5 mg/day). Computed tomography showed atrophy of the cerebellum, bilateral superior cerebellar peduncle, and tegmentum of the pons. Single-photon emission computed tomography demonstrated reduced blood flow in the cerebellum, vermis, and brainstem. After 8 weeks, his depressive state and delusion improved; however, his cenesthopathy persisted. We encountered a case of a severe depressive state with cenesthopathy and delusion in a young Japanese man with SCA3. This case supports previous studies that the cerebellum could have a role beyond motor functions.

Treatment of tardive dyskinesia: a review and update for dermatologists managing delusions of parasitosis.

INTRODUCTION: This article introduces to the dermatology provider two medications for the treatment of tardive dyskinesia (TD), which were the first medications approved by the US FDA specifically for the treatment of TD. In addition to describing these two new medications, this article will also provide a focused review of the pathogenesis of TD, as well as non-FDA-approved treatments, which have been tried prior to the advent of these medications. METHODS: A PubMed search was conducted and articles were reviewed by the senior authors and included if they were relevant for dermatologists regarding etiology, symptoms, risk, and treatment of TD. RESULTS: One of the most widely accepted explanations of TD involves the concept of 'dopamine receptor hypersensitivity state.' There are several other less well substantiated proposed pathogenic pathways of TD. The clinical manifestation is characterized by involuntary movements. Prevention includes switching to a 2nd generation agent or using the lowest dose possible for the shortest amount of time. Two new FDA-approved medications for TD are also discussed and reviewed. CONCLUSION: TD now has FDA-approved medications for treatment. Now, there is even more reason for the dermatologist to have increased confidence when treating delusions of parasitosis (DOP) with antipsychotic agents.

Everything is connected: Inference and attractors in delusions.

Delusions are, by popular definition, false beliefs that are held with certainty and resistant to contradictory evidence. They seem at odds with the notion that the brain at least approximates Bayesian inference. This is especially the case in schizophrenia, a disorder thought to relate to decreased - rather than increased - certainty in the brain's model of the world. We use an active inference Markov decision process model (a Bayes-optimal decision-making agent) to perform a simple task involving social and non-social inferences. We show that even moderate changes in some model parameters - decreasing confidence in sensory input and increasing confidence in states implied by its own (especially habitual) actions - can lead to delusions as defined above. Incorporating affect in the model increases delusions, specifically in the social domain. The model also reproduces some classic psychological effects, including choice-induced preference change, and an optimism bias in inferences about oneself. A key observation is that no change in a single parameter is both necessary and sufficient for delusions; rather, delusions arise due to conditional dependencies that create 'basins of attraction' which trap Bayesian beliefs. Simulating the effects of antidopaminergic antipsychotics - by reducing the model's confidence in its actions - demonstrates that the model can escape from these attractors, through this synthetic pharmacotherapy.

New-onset psychosis due to COVID-19.

This is a case report of a middle-aged man with no psychiatric history who presented with severe anxiety and psychotic symptoms from COVID-19. Following his discharge from intensive care unit, he was unable to sleep, was increasingly agitated and was observed hitting his head off the walls, causing haematomas. He remained highly anxious and developed paranoid delusions and auditory and tactile hallucinations, needing admission to a psychiatric ward. Treatment with antipsychotic medication gradually improved his symptoms in a few weeks. This case report highlights the new onset of psychosis due to COVID-19 infection. It demonstrates the importance of early identification and treatment of neuropsychiatric complications within an acute hospital setting. Furthermore, there is a need for research in this area to help in the prevention and treatment of such psychiatric complications due to COVID-19.

Brief psychotic disorder with delusion content related to the COVID-19 outbreak.

The COVID-19 outbreak has affected millions of people globally and it also has a huge psychological impact. The objective of this case report is to outline the possible effect of the COVID-19 pandemic to the content of delusions in patients with psychosis. Α 34-year-old male with no history of mental disorder, involuntarily hospitalized due to agitation and aggression towards others, experienced grandiose delusions, referential delusions and delusions of passivity. The content of all his delusions was related to the COVID-19 pandemic. His symptoms were not proven to be caused by any physical condition or substance use disorder. He was prescribed olanzapine 10mg bd and lorazepam 2,5mg td and demonstrated significant improvement with a complete subsidence of his symptoms within a week. He was discharged after a total of 13 days with an ICD-10 diagnosis of brief psychotic disorder. At his 6 months follow-up, he reported no psychiatric symptoms. Existing literature indicates a strong relationship between life experiences and the content of delusions. This case report highlights how the stressful life event of the COVID-19 outbreak affected the content of our patient's delusions.

Course and symptom and functional correlates of passivity symptoms in schizophrenia: an 18-year multi-follow-up longitudinal study.

BACKGROUND: Change in the experience of oneself may lay the groundwork for the development of additional hallucinations and delusions in individuals with schizophrenia. However, to date, the course and symptom and functioning correlates of passivity symptoms (cf. thought insertion, thought withdrawal) have not been measured consistently over long periods of time. Information on the course and correlates of passivity symptoms is essential for developing models of their contribution to schizophrenic illness. METHOD: Eighty-two individuals diagnosed with schizophrenia or schizoaffective disorder were recruited at an index hospitalization and reassessed at three or more follow-ups over the following 18 years. RESULTS: The results indicate that a small group of participants report passivity symptoms at all follow-ups, many reported passivity symptoms at some follow-ups, and the majority of individuals never reported passivity symptoms. The prevalence of passivity symptoms was similar to that for delusions of reference and persecutory delusions. Notably, when individuals did experience passivity symptoms, they also had a greater number of additional psychotic symptoms than individuals without passivity symptoms. Further, the presence of passivity symptoms was associated with work impairment at some assessments. CONCLUSIONS: Passivity symptoms present episodically, at a similar rate as delusions of reference and persecutory delusions, and when present, they are associated with having a higher number of additional psychotic symptoms, as well as having some impact on work functioning. These results suggest that passivity symptoms may increase vulnerability to additional psychotic symptoms and greater work impairment.

Brief Psychotic Disorder During the National Lockdown in Italy: An Emerging Clinical Phenomenon of the COVID-19 Pandemic.

The impact of the COVID-19 pandemic on psychosis remains to be established. Here we report 6 cases (3 male and 3 female) of first-episode psychosis (FEP) admitted to our hospital in the second month of national lockdown. All patients underwent routine laboratory tests and a standardized assessment of psychopathology. Hospitalization was required due to the severity of behavioral abnormalities in the context of a full-blown psychosis (the Brief Psychiatric Rating Scale [BPRS] = 75.8 ± 14.6). Blood tests, toxicological urine screening, and brain imaging were unremarkable, with the exception of a mild cortical atrophy in the eldest patient (male, 73 years). All patients were negative for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) throughout their stay, but 3 presented the somatic delusion of being infected. Of note, all 6 cases had religious/spiritual delusions and hallucinatory contents. Despite a generally advanced age (53.3 ± 15.6), all patients had a negative psychiatric history. Rapid discharge (length of stay = 13.8 ± 6.9) with remission of symptoms (BPRS = 27.5 ± 3.1) and satisfactory insight were possible after relatively low-dose antipsychotic treatment (Olanzapine-equivalents = 10.1 ± 5.1 mg). Brief psychotic disorder/acute and transient psychotic disorder diagnoses were confirmed during follow-up visits in all 6 cases. The youngest patient (female, 23 years) also satisfied the available criteria for brief limited intermittent psychotic symptoms. Although research on larger populations is necessary, our preliminary observation suggests that intense psychosocial stress associated with a novel, potentially fatal disease and national lockdown restrictions might be a trigger for FEP.