Anticipatory anxiety of seizures: What is the best treatment?

Anxiety disorders affect roughly 25% of people with epilepsy (PWE), and are associated with a strong impairment of quality of life and a poorer stabilization of epilepsy. Anticipatory anxiety of seizure (AAS), defined by the persistent worry or fear to have another seizure, is highly frequent and associated with avoidant behavior. Unfortunately, AAS is often overlooked and untreated. Here, we present the case of a 35-year-old patient suffering from AAS secondary to focal epilepsy. We aimed to provide practical guidelines and tools for the screening and treatment of anxiety disorders in PWE. Regarding psychotropic medication, Sertraline or Citalopram might be good options for first-line treatment of AAS, since they are efficient against anxiety and well-tolerated in epilepsy.

Withdrawal syndrome after antipsychotics discontinuation: an analysis of the WHO database of spontaneous reports (Vigibase) between 2000 and 2022.

RATIONALE: Withdrawal syndrome (WDS) has been described after discontinuation of antipsychotics. WDS could be the consequence of an over-activation of the dopaminergic pathway. Antipsychotics with a higher affinity for dopamine D2 receptors could be associated with a higher risk of WDS. This study aims to address this statement and evaluate the risk difference for withdrawal syndrome between antipsychotics based on pharmacovigilance data. METHODS: We collected individual reports registered in Vigibase® between 01/01/2000 and 31/12/2022 of patients treated with antipsychotics and who had presented WDS. A disproportionality analysis was performed to evaluate the risk of reporting WDS with each antipsychotic compared to all other antipsychotics. We performed a correlation analysis to assess the correlation between the risk of reporting WDS for each antipsychotic in relation with their pKi for D2 and 5HT2A receptors. RESULTS: The most frequent psychiatric withdrawal symptoms after antipsychotic discontinuation were insomnia, anxiety and depression. Tremor, headache and dizziness were among the most frequently reported neurologic withdrawal symptoms. Tiotixene had the highest risk of reporting WDS (ROR 7.08; 95%CI 3.49 - 14.35) followed by pimozide (ROR 4.35; 95%CI 1.93 - 9.77), quetiapine (ROR 4.24; 95%CI 3.87 - 4.64), thioridazine (ROR 4.17; 95%CI 2.50-6.98) and ziprasidone (ROR 2.98; 95%CI 2.41-3.67). We found a poor correlation between D2/5HT2A binding affinity and the risk of reporting withdrawal syndrome (R2 = 0,094). CONCLUSION: Our results suggest that there might be a risk difference for WDS between antipsychotics. Tiotixene, pimozide and quetiapine were associated with a higher risk of reporting a WDS whereas this risk was lower with chlorpromazine, clozapine and fluphenazine. We could not address the issue of withdrawal psychosis, withdrawal dyskinesia, rebound psychosis or supersensitivity psychosis due to the lack of specific WHO medDRA coded terms to identify potential cases.

French Society for Biological Psychiatry and Neuropsychopharmacology (AFPBN) guidelines for the management of patients with partially responsive depression and treatment-resistant depression: Update 2024.

INTRODUCTION: The purpose of this update is to add newly approved nomenclatures and treatments as well as treatments yet to be approved in major depressive disorder, thus expanding the discussions on the integration of resistance factors into the clinical approach. METHODS: Unlike the first consensus guidelines based on the RAND/UCLA Appropriateness Method, the French Association for Biological Psychiatry and Neuropsychopharmacology (AFPBN) developed an update of these guidelines for the management of partially responsive depression (PRD) and treatment-resistant depression (TRD). The expert guidelines combine scientific evidence and expert clinicians' opinions to produce recommendations for PRD and TRD. RESULTS: The recommendations addressed three areas judged as essential for updating the previous 2019 AFPBN guidelines for the management of patients with TRD: (1) the identification of risk factors associated with TRD, (2) the therapeutic management of patients with PRD and TRD, and (3) the indications, the modalities of use and the monitoring of recent glutamate receptor modulating agents (esketamine and ketamine). CONCLUSION: These consensus-based guidelines make it possible to build bridges between the available empirical literature and clinical practice, with a highlight on the 'real world' of the clinical practice, supported by a pragmatic approach centred on the experience of specialised prescribers in TRD.

Management strategies for antidepressant-related sexual dysfunction.

Antidepressant-related sexual dysfunction is one of the most frequently met adverse effects for individuals suffering from major depressive disorder. When primary prevention by non-pharmacological measures fails, empirical coping strategies might be proposed. In this article, we present a brief overview of pharmacological strategies for antidepressant-related sexual dysfunction, considering antidepressants and conceivable corrective medications. We suggest dividing these strategies into three groups: (1) tapering (dose reduction, therapeutic window or short-term treatment interruption); (2) maintenance (focusing on spontaneous remission); (3) optimizing treatment (substitution for another antidepressant or addition of treatments to correct sexual side effects). Whichever strategy is selected, we encourage the clinician to propose the most adequate therapeutic option for the patient, while considering the efficacy and overall tolerance of the current antidepressant strategy, the affected phase of sexuality and patient preferences and gender. This summary is limited to antidepressant treatments and correctors marketed in France and aimed at a clinician reading to help manage patients suffering from antidepressant-induced sexual dysfunction.

Potential efficacy of dopaminergic antidepressants in treatment resistant anergic-anhedonic depression results of the chronic anergic-anhedonic depression open trial - CADOT.

Introduction: Among treatment-resistant depression (TRD), we identified anergic-anhedonic clinical presentations (TRAD) as putatively responsive to pro-dopaminergic strategies. Based on the literature, non-selective monoamine oxidase inhibitors (MAOI) and dopamine D2 receptor agonists (D2RAG) were sequentially introduced, frequently under the coverage of a mood stabilizer. This two-step therapeutic strategy will be referred to as the Dopaminergic Antidepressant Therapy Algorithm (DATA). We describe the short and long-term outcomes of TRAD managed according to DATA guidelines. Method: Out of 52 outpatients with TRAD treated with DATA in a single expert center, 48 were included in the analysis [severity - QIDS (Quick Inventory of Depressive Symptomatology) = 16 ± 3; episode duration = 4.1 ± 2.7 years; Thase and Rush resistance stage = 2.9 ± 0.6; functioning - GAF (Global Assessment of Functioning) = 41 ± 8]. These were followed-up for a median (1st - 3rd quartile) of 4 (1-9) months before being prescribed the first dopaminergic treatment and remitters were followed up 21 (11-33) months after remission. Results: At the end of DATA step 1, 25 patients were in remission (QIDS <6; 52% [38-66%]). After DATA step 2, 37 patients were in remission (77% [65-89%]) to whom 5 patients with a QIDS score = 6 could be added (88% [78-97%]). Many of these patients felt subjectively remitted (GAF = 74 ± 10). There was a significant benefit to combining MAOI with D2RAG which was maintained for at least 18 months in 30 patients (79% [62-95%]). Conclusion: These results support TRAD sensitivity to pro-dopaminergic interventions. However, some clinical heterogeneities remain in our sample and suggest some improvement in the description of dopamine-sensitive form(s).

[Pimavanserin and trazodone combination in behavioral disorders in severe dementia with Lewy bodies]. / Association pimavansérine et trazodone dans les troubles du comportementde la maladie à corps de Lewy sévère.

INTRODUCTION: Dementia with Lewy bodies (DLB) is characterized by neurocognitive disorders associated with core clinical features including hallucinations. There is currently no cure but a combination of symptomatic treatments: clozapine is commonly used in DLB-related psychosis. Pimavanserin is a serotonin 5HT-2A receptor inverse agonist that has recently been shown to reduce psychosis related to dementia. Trazodone is a serotonin reuptake inhibitor and a 5-HT2 receptor antagonist: it is effective in the treatment of the frontal syndrome and is commonly used in frontotemporal degeneration. PATIENTS AND METHODS: We describe three patients with DLB, hospitalized in the cognitive-behavioral unit of the University Hospitals of Strasbourg, who presented with major visual hallucinations, delusion, and an orbitofrontal syndrome including disinhibition, agitation, and irritability. The 3 patients were intolerant of low-dose Clozapine (neutropenia for one, somnolence for the other and Pisa syndrome and falls for the last one). We evaluated the Neuropsychiatric Inventory (NPI) before and after the introduction of both treatments. RESULTS: Given their psychotic and frontal symptoms, we used Pimavanserin and Trazodone simultaneously. After 4 to 6 weeks of treatment, a marked improvement was observed in all 3 patients, with a decrease of the NPI scores from a mean of 88 to 38. DISCUSSION AND CONCLUSION: To our knowledge, there is no previously described combination of these two treatments in DLB. A clinical trial combining these two molecules against pervasive behavioral disorders in DLB would be interesting in view of these preliminary results.

Suicidality and psychotic episodes after starting aripiprazole: two case reports.

Switching antipsychotic medication must be done carefully to ensure patient safety and a successful response. Here, we present two major psychotic decompensations that occurred following a switch to aripiprazole in two patients with schizophrenia. Mr. X was treated with paliperidone and experienced residual anxiety. Thus, a switch to aripiprazole was planned with risperidone and a gradual decrease in paliperidone. Initially, an increase in aripiprazole resulted in remission of his residual symptoms. However, two weeks later, he presented an anxiety relapse with persecutory ideas which required hospitalization. Mr. Y, who was treated for many years with risperidone, presented with a treatment resistant psychotic episode. A switch to aripiprazole enhanced his clinical condition. Despite the initial improvement, soon after discharge from the hospital, the patient presented psychotic symptoms requiring home intervention. Ultimately, the patient in the midst of a delusional recrudescence, had killed himself when the health care team arrived. A strong dopamine antagonist may lead to the development of dopaminergic upregulation. The addition of a partial agonist to these hypersensitive neurotransmitter pathways could explain these episodes. We agree with previous reports and recommend careful management when switching from strong dopamine antagonists to aripiprazole.

Clinical Pharmacy in Psychiatry: Towards Promoting Clinical Expertise in Psychopharmacology.

Although clinical pharmacy is a discipline that emerged in the 1960s, the question of precisely how pharmacists can play a role in therapeutic optimization remains unanswered. In the field of mental health, psychiatric pharmacists are increasingly involved in medication reconciliation and therapeutic patient education (or psychoeducation) to improve medication management and enhance medication adherence, respectively. However, psychiatric pharmacists must now assume a growing role in team-based models of care and engage in shared expertise in psychopharmacology in order to truly invest in therapeutic optimization of psychotropics. The increased skills in psychopharmacology and expertise in psychotherapeutic drug monitoring can contribute to future strengthening of the partnership between psychiatrists and psychiatric pharmacists. We propose a narrative review of the literature in order to show the relevance of a clinical pharmacist specializing in psychiatry. With this in mind, herein we will address: (i) briefly, the areas considered the basis of the deployment of clinical pharmacy in mental health, with medication reconciliation, therapeutic education of the patient, as well as the growing involvement of clinical pharmacists in the multidisciplinary reflection on pharmacotherapeutic decisions; (ii) in more depth, we present data concerning the use of therapeutic drug monitoring and shared expertise in psychopharmacology between psychiatric pharmacists and psychiatrists. These last two points are currently in full development in France through the deployment of Resource and Expertise Centers in PsychoPharmacology (CREPP in French).

Antihistamine and cationic amphiphilic drugs, old molecules as new tools against the COVID-19?

Several studies have reported that certain psychoactive drugs could have a protective effect against SARS-CoV-2. Herein, we propose that antihistamines (anti-H1) and cationic amphiphilic drugs (CAD), specifically, have the capacity to disrupt virus entry and replication. In addition, several of these molecules have limited side effects and as such could be promising prophylactic candidates against SARS-CoV-2 infection.

Anticipatory anxiety of epileptic seizures: An overlooked dimension linked to trauma history.

OBJECTIVE: Fear of having a seizure called anticipatory anxiety of epileptic seizure (AAS), constitutes a daily life burden but has been rarely studied. Our aim was to assess the prevalence and the determining factors of AAS in patients with drug-resistant focal epilepsy, a dimension that has not been thoroughly investigated before. METHODS: We conducted an observational, prospective study enrolling patients with drug-resistant focal epilepsy. The psychiatric assessment aimed to evaluate psychiatric comorbidities, trauma history, and quality of life using hetero-evaluation and self-assessment tools. Dimensions of anxiety specifically related to epilepsy (peri-and-inter-ictal) were explored as exhaustively as possible. RESULTS: AAS was found in 53 % of the 87 patients. We compared the two groups of patients: with or without AAS. Patients with AAS had a significantly shorter duration of epilepsy (p = 0.04). There was no difference between groups with respect to psychiatric disorders, except for cannabis dependence, more frequent in patients with AAS (p = 0.02). Compared to patients without AAS, those with AAS presented more subjective ictal anxiety (p = 0.0003) and postictal anxiety (p = 0.02), were more likely to avoid outdoor social situations due to seizure fear (p = 0.001), and had a poorer quality of life (QOLIE emotional well-being; p = 0.03). Additionally, they had experienced more traumatic events in their lifetime (p = 0.005) and reported more frequently a feeling of being unsafe during their seizures (p = 0.00002). SIGNIFICANCE: AAS is a specific dimension of anxiety, possibly linked to trauma history. AAS is strongly linked to subjective ictal anxiety but not to the objective severity of seizures or frequency.

Benefit of long-acting paliperidone in Huntington's disease: a case report.

Through this brief report, we described our clinical considerations about the treatment of motor fluctuations and psychiatric comorbidities in Huntington's disease, for example, aggressiveness and obsessive-compulsive disorders. Indeed, as classical treatment, for example, olanzapine and risperidone, were inefficient to improve motor disorders in our patient, we postulated that motor fluctuations could be influenced by the pharmacokinetic profile of oral risperidone. So, in line with recent practice in schizophrenia, we proposed empirically paliperidone 1-month long-acting injections hypothesized to improve motor fluctuations, treatment so far reserved to Huntington's disease patients who are noncompliant to oral risperidone. Improvement was soon observed concerning motor fluctuations, but also aggressiveness, supporting our initial hypothesis.

Enhancing the role played by clinical pharmacists in psychiatric settings to better integrate clinical psychopharmacology into the decision-making process.

The importance of clinical psychopharmacological knowledge for modern psychiatric care is both well-established and underdeveloped. Although psychiatric pharmacists are identified as experts in psychopharmacotherapy based on pharmacists' overall expertise in pharmacotherapy, in real-life health settings, such is not necessarily the case. As a matter of fact, (1) pharmacists' real expertise in pharmacotherapy is mainly seen as useful to patients (as part of therapeutic education), (2) pharmacists' practice methods are usually circumscribed to the framework of quality processes (e.g. comprehensive medication management) which are not particularly useful to clinicians who have a greater need for pharmacotherapeutic skills, (3) the difficulties in terms of collaboration between pharmacists and physicians are well-known. We describe here the implementation of an alternative system of pharmacotherapy counselling inspired by case by cases in which the remote expertise of pharmacists in psychopharmacology guided prescribers towards the implementation of recommendations from the literature. This shared decision-making process integrates both the clinical elements provided by the psychiatrist and the pharmacotherapeutic information provided by the clinical psychopharmacist, to promote evidence-based medicine (algorithmic data in recommendations) and tailor-made solutions (drug-drug and drug-disease interactions) for patients. In our experience, the success of such an initiative is likely to promote the development of clinical psychopharmacology in psychiatric settings. Importantly, within this framework, the pharmacovigilance unit and psychopharmacologist are useful resources to guide the decision-making process of the pharmacist-psychiatrist duo.

Towards a pharmacochemical hypothesis of the prophylaxis of SARS-CoV-2 by psychoactive substances.

An increasing body of evidence suggests a protective effect of some psychoactive substances against SARS-CoV-2 (Severe Acute Respiratory Syndrome coronavirus type 2). Recent findings suggest that patients with psychiatric disorders are less affected by SARS-CoV-2 than their caregivers, which may seem surprising given some of the frequent risk factors for an unfavorable course of the disease (e.g., obesity, diabetes, cardiovascular and pulmonary diseases). We propose here a mixed pharmacoepidemiological and pharmacochemical hypothesis to explain these findings. A number of psychotropic drugs exhibit activities against coronaviruses (Middle East Respiratory Syndrome coronavirus (MERS-CoV), the Severe Acute Respiratory Syndrome coronavirus (SARS-CoV-1) and the Infectious Bronchitis Virus (IBV)) and have been put forward as potentially anti-SARS-CoV-2. These treatments include numerous mee-too drugs (chemically and pharmacologically linked to those which have demonstrated anti-SARS-CoV-2 efficacy) which are frequently prescribed in psychiatric settings. Taken alone or in polypharmacy, these drugs could have a prophylactic anti-SARS-CoV-2 effect, explaining the unexpectedly low proportion of patients with psychiatric disorders and COVID-19. Associated factors such as nicotine can also be considered in the context of a broad chemoprophylactic hypothesis in patients with psychiatric disorders taking different psychoactive substances.

COVID-19: urgency for distancing from domestic violence.

BACKGROUND: Although COVID-19 is a major worldwide health threat, there is another global public health emergency that is becoming a growing challenge. Domestic violence is a public health and human rights issue that primarily affects women and children worldwide. Several countries have reported a significant increase in domestic violence cases since the COVID-19-induced lockdowns and physical distancing measures were implemented. The COVID-19 health crisis is exacerbating another pre-existing public health problem by increasing the severity and frequency of domestic violence, thus demonstrating the need to adopt significant and long-term measures. OBJECTIVE: Therefore, it is urgently necessary to promote and increase actions and policies to guarantee the safety and dignity of all victims of domestic violence worldwide. METHODS: This paper describes preventive measures and action plans to combat violence against women and children during the COVID-19 pandemic. CONCLUSION: The prevention of domestic violence must indeed be every government's priority and every citizen's responsibility.

Antecedentes: Aunque el COVID-19 es una amenaza mayor de la salud a nivel mundial, existe otra emergencia de salud pública global la cual está llegando a ser un desafío creciente. La violencia doméstica es un problema de salud pública y de derechos humanos que afecta primordialmente a mujeres y niños en todo el mundo. Varios países han reportado un aumento significativo en los casos de violencia domestica desde que se implementaron los confinamientos inducidos por COVID-19 y las medidas de distanciamiento físico. La crisis de salud del COVID-19 está exacerbando otro problema de salud pública preexistente al aumentar la gravedad y frecuencia de la violencia doméstica, lo cual demuestra la necesidad de adoptar medidas significativas y a largo plazo.Objetivo: Por lo tanto, es urgentemente necesario promover y aumentar las acciones y políticas para garantizar la seguridad y la dignidad de todas las víctimas de violencia doméstica en todo el mundo.Método: Este artículo describe medidas preventivas y planes de acción para combatir la violencia en contra de mujeres y niños durante la pandemia de COVID-19.Conclusiones: La prevención de la violencia doméstica debe ser, de hecho, la prioridad de todos los gobiernos y la responsabilidad de todos los ciudadanos.

Reconsidering Rigidity in the Diagnosis of Neuroleptic Malignant Syndrome: A Case Report.

Neuroleptic malignant syndrome (NMS) is a rare but potentially fatal syndrome classically encountered in patients receiving typical antipsychotic agents. However, many physicians have also reported the occurrence of NMS with atypical antipsychotics, notably with atypical presentations. In this report, we present a case in which a patient's antipsychotic regimen during a psychotic episode (which involved both typical and atypical antipsychotics) subsequently led to NMS. During his stay, the patient developed an altered level of consciousness, elevation of creatine phosphokinase, hemodynamic instability, and a fever. However, the patient did not have signs of rigidity, the cardinal sign of this syndrome. The authors concluded that patients could develop NMS without rigidity while receiving an antipsychotic. Given this presentation, the authors suggest that clinicians have a high level of suspicion for NMS to avoid misdiagnosis and subsequent adverse consequences. Hence, clinicians must be vigilant about atypical presentations of NMS without rigidity.