Structural and functional changes associated with functional/dissociative seizures: A review of the literature.

INTRODUCTION: The term 'functional/dissociative seizures (FDS)' refers to a paroxysmal, transient clinical manifestation that may include motor, sensory, vegetative, psychological and cognitive signs, similar to the manifestations observed in epileptic seizures. In recent years, there has been an increase of literature in the field of brain imaging research on functional neurological disorders and, more specifically, on FDS. However, most of the studies have been carried out on limited samples. We propose an update of this review work by performing a systematic review of studies performed since 2017 in the field of neuroimaging in patients with FDS. METHODS: We conducted a systematic review of the literature using the PRISMA methodology and reproduced most of the methodological elements of the latest systematic literature review. RESULTS: Our work over the last five years has identified 14 articles. It is still difficult to isolate a distinct structure or network specifically involved in the mechanism of FDS. However, certain structures are recurrently involved in imaging studies, notably the amygdala, the orbitofrontal cortex, and the anterior cingulate cortex. CONCLUSION: The contribution of neuroimaging may allow a more precise explanation of the disorder for patients, avoiding the stigma frequently associated with this diagnosis. as with other 'conversion' phenomena which have traditionally been considered only as 'medically unexplained'. In the longer term and beyond a better understanding of the physiopathology of the disorder, the challenge of this neuroimaging work would be to identify specific imaging biomarkers for a diagnosis of FDS.

Adherence to clinical practice guidelines for using electroconvulsive therapy in elderly depressive patients.

OBJECTIVES: Electroconvulsive therapy (ECT) is one of the most effective treatments in mood disorders, mainly in major depressive episode (MDE) in the context of either unipolar (MDD) or bipolar disorder (BD). However, ECT remains a neglected and underused treatment. Older people are at high risk patients for the development of adverse drug reactions. In this context, we sought to determine the duration of MDEs and the number of lines of treatment before the initiation of ECT in patients aged 65 years or over according to the presence or absence of first-line indications for using ECT from international guidelines. METHODS: In this multicenter, retrospective study including patients aged 65 years or over with MDEs in MDD or BD who have been treated with ECT for MDEs, data on the duration of MDEs and the number of lines of treatment received before ECT were collected. The reasons for using ECT, specifically first-line indications (suicidality, urgency, presence of catatonic and psychotic features, previous ECT response, patient preference) were recorded. Statistical comparisons between groups used standard statistical tests. RESULTS: We identified 335 patients. The mean duration of MDEs before ECT was about 9 months. It was significantly shorter in BD than in MDD- about 7 and 10 months, respectively. The co-occurrence of chronic medical disease increased the duration before ECT in the MDD group. The presence of first-line indications for using ECT from guidelines did not reduce the duration of MDEs before ECT, except where there was a previous response to ECT. The first-line indications reduced the number of lines of treatment before starting ECT. CONCLUSION: Even if ECT seems to be a key treatment in the elderly population due to its efficacity and safety for MDEs, the delay before this treatment is still too long.

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.

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.

Drug-induced depressive symptoms: An update through the WHO pharmacovigilance database.

BACKGROUND: Depression is a highly incident condition and some drugs have been described as inducing or worsening depression. However, literature on this topic is rare and possibly outdated. METHODS: We performed disproportionality analyses using VigiBase®, the largest pharmacovigilance database worldwide to identify drugs associated with depression. Then we excluded drugs already known as depressogenic according to American Summary of Product Characteristics (SPC). We then reviewed drug mechanism of action, scientific literature and European SPC for each drug identified to assess a level of plausibility. We measured Reporting Odds Ratio (ROR) statistically significant and superior to 1, suggesting a significant association between a drug and the reporting of depressive symptoms. RESULTS: Out of the 5237 drugs extracted on VigiBase®, we have retained 89 new drugs associated with depression. More than half of drugs of interest are from nervous system. Opicapone (ROR: 20.66 95 %CI: 15.62-27.33), and gadoversetamide (ROR 18.62, 95 %CI 9.63-35.95) were the drugs with the highest ROR. Among the 89 drugs, 38 were considered already described such as suvorexant or ivacaftor, 20 likely associated such as anti-migraines drugs or new antipsychotic drugs and 31 potentially associated. LIMITATIONS: Pharmacovigilance studies have many inherent limitations, such as under-reporting bias, notoriety effect and protopathic bias. These results are not intended to establish a causal link, only a statistical association. CONCLUSION: We found a strong statistical signal and pharmacological plausibility for 58 new depressogenic drugs. This update list of suspected drugs may prove useful for doctors faced with potential cases of drug-induced depression or to stay aware in case. Other studies are needed to confirm the list.

Psychosis with use of amphetamine drugs, methylphenidate and atomoxetine in adolescent and adults.

BACKGROUND: Use of psychostimulants and relative drugs has increased worldwide in treatment of attention-deficit hyperactivity disorder (ADHD) in adolescents and adults. Recent studies suggest a potential association between use of psychostimulants and psychotic symptoms. The risk may not be the same between different psychostimulants. OBJECTIVE: To assess whether amphetamine or atomoxetine use is associated with a higher risk of reporting symptoms of psychosis than methylphenidate use in adolescents and adults, particularly in patients with ADHD. METHODS: Using VigiBase, the WHO's pharmacovigilance database, disproportionality of psychotic symptoms reporting was assessed among adverse drug reactions related to methylphenidate, atomoxetine and amphetamines, from January 2004 to December 2018, in patients aged 13-25 years. The association between psychotic symptoms and psychostimulants was estimated through the calculation of reporting OR (ROR). FINDINGS: Among 13 863 reports with at least one drug of interest, we found 221 cases of psychosis with methylphenidate use, 115 with atomoxetine use and 169 with a prescription of an amphetamine drug. Compared with methylphenidate use, amphetamine use was associated with an increased risk of reporting psychotic symptoms (ROR 1.61 (95% CI 1.26 to 2.06)]. When we restricted the analysis to ADHD indication, we found a close estimate (ROR 1.94 (95% CI 1.43 to 2.64)). No association was found for atomoxetine. CONCLUSION: Our study suggests that amphetamine use is associated with a higher reporting of psychotic symptoms, compared with methylphenidate use. CLINICAL IMPLICATIONS: The prescription of psychostimulants should consider this potential adverse effect when assessing the benefit-risk balance.

Older adults in psychedelic-assisted therapy trials: A systematic review.

BACKGROUND: Growing clinical interest in psychedelic-assisted therapies has led to a second wave of research involving psilocybin, lysergic acid diethylamide (LSD), 3,4-methylenedioxymethamphetamine (MDMA) and other substances. Data suggests that these compounds have the potential to treat mental health conditions that are especially prevalent in older adults such as depression, anxiety, existential distress, and posttraumatic stress disorder. AIMS: The goal of this study was to quantify the prevalence of older adults enrolled in psychedelic clinical trials and explore safety data in this population. METHODS: A systematic review was conducted following the 2020 PRISMA guidelines. Search criteria included all trials published in English using psychedelic substances to treat psychiatric conditions, including addiction as well as existential distress related to serious illness. Articles were identified from literature searches on PubMed, EBSCO, and EMBASE. RESULTS: 4376 manuscripts were identified, of which 505 qualified for further review, with 36 eventually meeting eligibility criteria. Of the 1400 patients enrolled in the 36 studies, only 19 were identified as 65 or older, representing less than 1.4% of all trial participants. For 10 of these 19 older adults, detailed safety data was obtained. No serious adverse events (AEs) occurred in any older adults and only transient mild-to-moderate AEs related to anxiety, gastrointestinal upset, and hypertension were reported during the psychedelic dosing sessions. CONCLUSIONS: While existing data in older adults is limited, it suggests that psychedelic-assisted psychotherapy can be safe and well tolerated in older adults. Therefore, psychedelic-assisted psychotherapy should be more rigorously investigated for the treatment of psychiatric conditions in this population.

Efficacy of traumatic memory reactivation with or without propranolol in PTSD with high dissociative experiences.

Background: Post-traumatic stress disorder (PTSD) with dissociative symptoms is now a full-fledged subtype of this disorder. The dissociative subtype is associated with a greater number of psychiatric comorbidities. To date, the impact of dissociation on the efficacy of PTSD treatment remains unclear.Objective: The aim of this study was to compare the efficacy of a traumatic memory reactivation procedure with the administration of propranolol or a placebo once a week for six consecutive weeks in reducing PTSD and MDE symptoms between PTSD subjects with or without high dissociative symptoms.Method: For that, we conducted a randomized clinical trial in 66 adults diagnosed with longstanding PTSD and measured the SCID PTSD module, the PTSD Checklist (PCL-S), Beck's Depression Inventory-II (BDI-II), and the Dissociative Experiences Scale (DES).Results: Patients with and without high dissociative experience had significant improvement in their PCL-S scores over the 6 treatment sessions, and PCL-S scores continued to decline in all patients during the post-treatment period. However, there was no correlation between the presence/absence of high dissociative experiences and no specific effect of propranolol treatment. We found exactly the same results for MDE symptoms. Interestingly, patients with high dissociative experiences before treatment exhibited very significant improvement in their DES scores after the 6 treatment sessions, and patients maintained this improvement 3 months post-treatment.Conclusions: The traumatic memory reactivation procedure is an effective way to treat dissociative symptoms in patients with PTSD, and improvement of these dissociative symptoms was associated with a decrease in both PTSD and depression severity.

Traumatic memory reactivation procedure is an effective way to treat dissociative symptoms in patients with PTSD.The improvement of these dissociative symptoms was associated to a decrease of both PTSD and depression severity.Dissociative symptoms do not seem to mitigate the efficacy of traumatic memory reactivation during the treatment of PTSD.