Management of Psychiatric Conditions in Patients With Comorbid Postural Orthostatic Tachycardia Syndrome: A Literature Review and Case Vignette.

Importance: Disorders of the autonomic nervous system are relatively common and have a significant impact on quality of life, offer very subtle diagnostic clues, and often mimic other disease processes, including certain psychiatric disorders. Pharmacologic treatment for psychiatric conditions in this group of patients can also be complicated by the pathophysiology of the various syndromes. Postural orthostatic tachycardia syndrome (POTS) is the final common pathway of a heterogenous group of underlying disorders that display similar characteristics.Observations: The current literature regarding the association between POTS and psychiatric conditions was reviewed. The literature showed an increased prevalence of mild/moderate depression and sleep disturbance in this population. Also, when psychiatric disorders occur in patients with POTS, clinicians may face challenges with regard to selecting appropriate psychopharmacologic interventions.Conclusions and Relevance: This review provides an evidence-based approach to treating common psychiatric conditions in those who suffer from POTS, with a particular emphasis on side effects that may worsen the associated symptoms. A list of the classes of psychopharmacologic treatment with a focus on adverse effects on heart rate and blood pressure is included, as is a case vignette of a patient with complex comorbid psychiatric conditions. It is of significant value to highlight the complexities associated with POTS; to raise awareness of the disorder, particularly in the context of psychiatric comorbidities; and to disseminate evidence-based information to aid clinicians in making informed medication choices with their patients.

Olanzapine long-acting injection, discontinuation rates and reasons for discontinuation: 10 years' experience at a UK high-secure hospital.

Background: Olanzapine pamoate has been shown to be an effective second-generation long-acting injection. Its popularity has possibly been adversely affected by the rare incidence of post-injection syndrome (PIS) and the associated requirement to monitor for 3 h after each injection. Objective: This study aimed to collect and present data on the use of olanzapine long-acting injection (OLAI) over a 10-year period in a high-security forensic hospital in South East England. Design: This was a non-interventional retrospective study collecting information from anonymised electronic patient and prescription records. As per hospital Trust guidelines, patient consent to access of hospital records was presumed unless explicitly withdrawn. Method: All patients prescribed OLAI between the years 2009 and 2019 were identified. Data collected included date that OLAI was started, stopped, dose range, side effects and concomitant medication. Results: Of 88 patients who were started OLAI, 45 (51%) continued at month 24. At 60 months, 22 of 70 (31%) patients for whom data were available continued with OLAI. Over 60% of continuers were on higher than recommended doses. Of almost 5000 injections administered, there was 1 episode of PIS. Conclusion: OLAI is an effective treatment for schizophrenia and schizoaffective disorder, especially when used in patients have been able to tolerate the drug and were stabilised on it for 24 months. In over half the patients who continued OLAI, the doses were higher than that recommended by the manufacturer. The incidence of PIS in this study was very low in comparison with other studies. Registration code: 2049.

Brugada syndrome: should we be screening patients before prescribing psychotropic medication?

Brugada syndrome (BrS) presents with a characteristic electrocardiogram (ECG) and is associated with sudden cardiac death. Until now, prolongation of QTc interval and its association with Torsade de Pointe and possible fatal arrhythmia have been the focus of routine baseline ECGs before prescribing psychotropic medication. A semi-systematic literature review was conducted using PubMed. The terms 'Brugada', 'Brugada Syndrome' AND 'psychotropic' 'antipsychotic' 'antidepressant' 'mood stabilisers' 'clozapine' 'Tricyclic Antidepressants' 'Lithium' were searched. From a search that delivered over 200 articles, 82 articles were included. Those that included details around causative medication, doses of medication and where clear timeline on drug cause were included. Where clarification was needed, the manufacturer of the medication was contacted directly. Psychotropic medication can be associated with BrS, Brugada phenocopy or unmasking of BrS, in overdose or in normal doses. Our results include a table summarising a number of psychotropic overdoses that led to BrS unmasking. Routine screening for BrS in patients before prescribing psychotropic medication is a natural extension of the baseline ECG currently routinely done to rule out QTc prolongation. Psychiatrists need to invest in ensuring better skills in interpreting ECGs and work closer with cardiologists in interpreting ECGs.

Mental state deterioration after switching from brand-name to generic olanzapine in an adolescent with bipolar affective disorder, autism and intellectual disability: a case study.

BACKGROUND: The appropriateness of use of generic instead of brand-name medication remains unresolved and controversial in several areas of medicine. Some evidence suggestive of variations in bioavailability and clinical effectiveness between different formulations make policy decisions occasionally difficult. The use of generic olanzapine is a widely acceptable practice on the basis of quality, safety and efficacy data and has been adopted in several countries. CASE PRESENTATION: The case of a 14 year old boy with bipolar affective disorder, autism and intellectual disability who had brand-name to generic olanzapine switch associated with rapid deterioration of his mental state is described. This clinical change was not related to any physical illness or other medication adjustment and resolved as rapidly when generic olanzapine was switched back to the brand-name formulation. CONCLUSIONS: Caution should be exercised when policy for switching from brand-name to generic psychotropic medications are made, especially when using medications off label, in extremes of age and in those patients with co-morbid complicating factors such as intellectual disability.

Comparative effectiveness of atypical antipsychotics in schizophrenia: what have real-world trials taught us?

Real-world, effectiveness studies add an important new dimension to the evaluation of the benefits of individual antipsychotics. Efficacy studies have already shown the unique effectiveness of clozapine, and suggested improved outcomes for olanzapine compared with some atypical antipsychotics and a reduced tendency to produce acute and chronic movement disorders for atypical compared with typical drugs. Recent effectiveness studies largely confirm these prior observations. The CATIE (Clinical Antipsychotic Trials of Intervention Effectiveness), CUtLASS (Cost Utility of the Latest Antipsychotic Drugs in Schizophrenia Study) and SOHO (Schizophrenia Outpatient Health Outcomes) programmes confirmed the superiority of clozapine over other antipsychotics; CATIE and SOHO also confirmed olanzapine as probably the second most effective antipsychotic. Effectiveness studies have confirmed the high incidence of adverse metabolic effects with clozapine, olanzapine and (with less certainty) quetiapine but the ZODIAC (Ziprasidone Observational Study of Cardiac Outcomes) study found no excess cardiovascular events or deaths for olanzapine compared with ziprasidone. Prior observations on reduced frequency of movement disorders for second-generation versus first-generation antipsychotics were also largely (but not uniformly) supported. Overall, recent real-world studies have done much to confirm prior observations from efficacy-based randomized, controlled trials.

Acetylcholinesterase Inhibitors (AChEI's) for the treatment of visual hallucinations in schizophrenia: a case report.

BACKGROUND: Visual hallucinations are commonly seen in various neurological and psychiatric disorders including schizophrenia. Current models of visual processing and studies in diseases including Parkinsons Disease and Lewy Body Dementia propose that Acetylcholine (Ach) plays a pivotal role in our ability to accurately interpret visual stimuli. Depletion of Ach is thought to be associated with visual hallucination generation. AchEI's have been used in the targeted treatment of visual hallucinations in dementia and Parkinson's Disease patients. In Schizophrenia, it is thought that a similar Ach depletion leads to visual hallucinations and may provide a target for drug treatment CASE PRESENTATION: We present a case of a patient with Schizophrenia presenting with treatment resistant and significantly distressing visual hallucinations. After optimising treatment for schizophrenia we used Rivastigmine, an AchEI, as an adjunct to treat her symptoms successfully. CONCLUSIONS: This case is the first to illustrate this novel use of an AchEI in the targeted treatment of visual hallucinations in a patient with Schizophrenia. Targeted therapy of this kind can be considered in challenging cases although more evidence is required in this field.

Acetylcholinesterase Inhibitors (AChEI's) for the treatment of visual hallucinations in schizophrenia: a review of the literature.

BACKGROUND: Visual hallucinations occur in various neurological diseases, but are most prominent in Lewy body dementia, Parkinson's disease and schizophrenia. The lifetime prevalence of visual hallucinations in patients with schizophrenia is much more common than conventionally thought and ranges from 24% to 72%. Cortical acetylcholine (ACh) depletion has been associated with visual hallucinations; the level of depletion being related directly to the severity of the symptoms. Current understanding of neurobiological visual processing and research in diseases with reduced cholinergic function, suggests that AChEI's may prove beneficial in treating visual hallucinations. This offers the potential for targeted drug therapy of clinically symptomatic visual hallucinations in patients with schizophrenia using acetylcholinesterase inhibition. METHODS: A systematic review was carried out investigating the evidence for the effects of AChEI's in treating visual hallucinations in Schizophrenia. RESULTS: No evidence was found relating to the specific role of AChEI's in treating visual hallucinations in this patient group. DISCUSSION: Given the use of AChEI's in targeted, symptom specific treatment in other neuropsychiatric disorders, it is surprising to find no related literature in schizophrenia patients. The use of AChEI's in schizophrenia has investigated effects on cognition primarily with non cognitive effects measured more broadly. CONCLUSIONS: We would suggest that more focused research into the effects of AChEI's on positive symptoms of schizophrenia, specifically visual hallucinations, is needed.

Delirium and its treatment.

Delirium occurs at rates ranging from 10% to 30% of all hospital admissions. It is a negative prognostic indicator, often leading to longer hospital stays and higher mortality. The aetiology of delirium is multifactorial and many causes have been suggested. The stress-diathesis model, which posits an interaction between the underlying vulnerability and the nature of the precipitating factor, is useful in understanding delirium. Preventing delirium is the most effective strategy for reducing its frequency and complications. Environmental strategies are valuable but are often underutilized, while remedial treatment is usually aimed at specific symptoms of delirium. Antipsychotics are the mainstay of pharmacological treatment and have been shown to be effective in treating symptoms of both hyperactive and hypoactive delirium, as well as generally improving cognition. Haloperidol is considered to be first-line treatment as it can be administered via many routes, has fewer active metabolites, limited anticholinergic effects and has a lower propensity for sedative or hypotensive effects compared with many other antipsychotics. Potential benefits of atypical compared with typical antipsychotics include the lower propensity to cause over-sedation and movement disorder. Of the second-generation antipsychotics investigated in delirium, most data support the use of risperidone and olanzapine. Other drugs (e.g. aripiprazole, quetiapine, donepezil and flumazenil) have been evaluated but data are limited. Benzodiazepines are the drugs of choice (in addition to antipsychotics) for delirium that is not controlled with an antipsychotic (and can be used alone for the treatment of alcohol and sedative hypnotic withdrawal-related delirium). Lorazepam is the benzodiazepine of choice as it has a rapid onset and shorter duration of action, a low risk of accumulation, no major active metabolites and its bioavailability is more predictable when it is administered both orally and intramuscularly.