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.

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.

The anticholinergic impregnation scale: Towards the elaboration of a scale adapted to prescriptions in French psychiatric settings.

PURPOSE: Some drugs have anticholinergic activity and can cause peripheral or central side effects. Several scales exist to evaluate the potential anticholinergic effect of prescribed drugs but: (i) they are validated in the elderly and mainly assess the cognitive side effect of treatments; (ii) they do not concern some of the drugs frequently used in clinical psychiatry in France. The aim of our study is to develop a new scale, the anticholinergic impregnation scale (AIS), with drugs used in France and based on an assessment of the drugs used against peripheral anticholinergic adverse effects. METHODS: We assigned a score, ranging from 1 to 3, to a list of 128 drugs with a consensus approach obtained via literature data and expert opinions. We collected data from 7278 prescriptions in 34 French psychiatric facilities: age, sex, atropinic drugs, laxatives and treatments of xerophthalmia and xerostomia, in order to evaluate the association between AIS score and the prescription of drugs aiming to reduce peripheral anticholinergic side effects. RESULTS: The most frequently prescribed drugs were cyamemazine (n=1429; 20%) and tropatepine (n=1403; 19%), two drugs marketed almost exclusively in France and with a score of 3. The frequency of patients with a high AIS score, greater than 5, was significantly higher in patients who received laxatives and treatments of xerostomia. AIS score represents the first validated solution to evaluate anticholinergic load in psychiatry settings in France. CONCLUSION: The anticholinergic problem remains underevaluated in mental health settings. In order to rule out the confounding factor of mental disease, assessment of peripheral side effects can be considered more objective than the evaluation of cognitive function in psychiatric patients. Building scales appropriate for each state also appear essential to obtain an useful and effective tool in clinical practice.

[Assessing and making safe the medicine use pathway in paediatrics]. / Évaluation et sécurisation du circuit du médicament en pédiatrie.

Based on an assessment of adverse events in a follow-up care and rehabilitation unit in paediatrics, audits were carried out of the medicine use pathway. The evaluation grid taken from this study today serves as a basis for the audits carried out on the medicine use pathway on a national level.

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.

[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.

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).

[Snoezelen and animal-assisted therapy in dementia patients]. / Snoezelen et zoothérapie chez les patients déments.

A number of non medication-based methods of nursing care for geriatric patients have been developed over recent decades to treat non cognitive symptoms associated with dementia. Among these, Snoezelen rooms for multisensory behavioural therapy and animal-assisted therapy emerge as innovative strategies which could potentially complement other more frequently developed methods such as physical activity.

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.

Assessment of psychotropic-like properties of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in rats and human subjects.

In a previous clinical study, a probiotic formulation (PF) consisting of Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 (PF) decreased stress-induced gastrointestinal discomfort. Emerging evidence of a role for gut microbiota on central nervous system functions therefore suggests that oral intake of probiotics may have beneficial consequences on mood and psychological distress. The aim of the present study was to investigate the anxiolytic-like activity of PF in rats, and its possible effects on anxiety, depression, stress and coping strategies in healthy human volunteers. In the preclinical study, rats were daily administered PF for 2 weeks and subsequently tested in the conditioned defensive burying test, a screening model for anti-anxiety agents. In the clinical trial, volunteers participated in a double-blind, placebo-controlled, randomised parallel group study with PF administered for 30 d and assessed with the Hopkins Symptom Checklist (HSCL-90), the Hospital Anxiety and Depression Scale (HADS), the Perceived Stress Scale, the Coping Checklist (CCL) and 24 h urinary free cortisol (UFC). Daily subchronic administration of PF significantly reduced anxiety-like behaviour in rats (P < 0·05) and alleviated psychological distress in volunteers, as measured particularly by the HSCL-90 scale (global severity index, P < 0·05; somatisation, P < 0·05; depression, P < 0·05; and anger-hostility, P < 0·05), the HADS (HADS global score, P < 0·05; and HADS-anxiety, P < 0·06), and by the CCL (problem solving, P < 0·05) and the UFC level (P < 0·05). L. helveticus R0052 and B. longum R0175 taken in combination display anxiolytic-like activity in rats and beneficial psychological effects in healthy human volunteers.

Enhanced physician adherence to antibiotic use guidelines through increased availability of guidelines at the time of drug ordering in hospital setting.

PURPOSE: Some studies have shown that making practice guidelines accessible to physicians when they are making clinical decisions could improve prescribing practices. The aim of the study was to assess the benefit of impact on physician adherence of the intervention that consisted of embedding previously paper-based antibiotic guidelines in the computerized physician drug order entry system of a teaching hospital in order to make these guidelines available to physician at the time of antibiotic ordering. Before the intervention, these guidelines were available in booklet form in all the wards of the hospital. METHODS: Adherence to guidelines was evaluated in 471 consecutive antibiotic orders for pneumonia, 104 just before and 367 just after the intervention. The evaluation criteria were: the choice of the antibiotic relative to the context of acquisition of pneumonia, the daily dose, the planned duration of treatment. Evaluation of antibiotic orders was performed at the initiation of antibiotic treatment. RESULTS: The intervention was followed by a significant decrease in the proportion of antibiotic orders containing at least one criterion of non-conformity to the guidelines, respectively, 33% after vs. 51% (p<0.001) before the intervention. Proportion of non-conform orders decreased in the post- vs. pre-intervention period for the daily dosage of antibiotics, respectively, 12.2% vs. 26.9% (p<0.001), for the planned duration of treatment, respectively, 7.3% vs. 18.3% (p<0.001), whereas for the choice of antibiotics relative to the context of acquisition of pneumonia, the improvement failed to reach statistical significance, respectively, 18.2% vs. 25% (p=0.12). CONCLUSION: In this study, the increased availability of antibiotic guidelines at the time of drug ordering, combined with a periodical reinforcement educational round, was associated with an enhanced physician adherence to these guidelines.

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.

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).