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OBJECTIVE: In 2019, a regional survey of potentially inappropriate prescriptions (PIP) of psychotropic drugs in elderly psychiatric inpatients was carried out highlighting their inappropriate use in this population. The aim of this study was to assess the clinical relevance - defined as the provision of an appropriate and necessary treatment, chosen from other alternatives as being the most likely to produce the expected results for a given patient - of these prescriptions considered inappropriate according to current established criteria. MATERIAL AND METHOD: Patients aged over 75, or 64 to 75 and polypathological with at least one PIP of psychotropic drugs or drugs with a high anticholinergic burden, identified by an audit grid established on the basis of STOPP/STARTv2 criteria and the Laroche list on the prescription at 48h of hospitalization, were included. The weighing of the inappropriateness nature of the prescription (resistance to treatment, period of crisis, comorbidities ) was established by a pharmacist-psychiatrist pair on the entire computerized record of the current episode. The clinical relevance of the PIP and the overall prescription was rated as 0 (irrelevant), 1 (partially relevant) or 2 (relevant). RESULTS: Thirty-four patients were included. One hundred and twenty-five PIP of psychotropic drugs were noted: 50.4% concerned benzodiazepines and non-benzodiazepines anxiolytics (BZD/Z), 25.6% neuroleptics (NL), 12% antidepressants (ATD) and 12% drugs with a high anticholinergic burden. On one hand, 49.2% of PIP of BZD/Z, 50% of PIP of NL and 20% of PIP of ATD were considered irrelevant. On the other hand, 49.2% of PIP of BZD/Z, 31.3% of PIP of NL and 13.3% of PIP of ATD were considered partially relevant. Furthermore, 1.6% of PIP of BZD/Z, 18.8% of PIP of NL and 66.7% of PIP of ATD were considered relevant. For PIPs of drugs with a high anticholinergic burden, 80% were deemed irrelevant, 13.3% partially relevant and 6.7% relevant. In all, of the 34 drug prescriptions studied, three (8.8%) were considered irrelevant, 11 (32.4%) partially relevant and 20 (58.8%) clinically relevant. CONCLUSION: This study highlighted the clinical relevance of more than half the prescriptions considered inappropriate according to current PPI criteria in the elderly. It underlines the interest of a new PPI detection tool for elderly patients with psychiatric disorders.
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Different types of resistance to passive movement, i.e. hypertonia, were described in schizophrenia spectrum disorders (SSD) long before the introduction of antipsychotics. While these have been rediscovered in antipsychotic-naïve patients and their non-affected relatives, the existence of intrinsic hypertonia vs drug-induced parkinsonism (DIP) in treated SSD remains controversial. This integrative review seeks to develop a commonly accepted framework to specify the putative clinical phenomena, highlight conflicting issues and discuss ways to challenge each hypothesis and model through adversarial collaboration. The authors agreed on a common framework inspired from systems neuroscience. Specification of DIP, locomotor paratonia (LMP) and psychomotor paratonia (PMP) identified points of disagreement. Some viewed parkinsonian rigidity to be sufficient for diagnosing DIP, while others viewed DIP as a syndrome that should include bradykinesia. Sensitivity of DIP to anticholinergic drugs and the nature of LPM and PMP were the most debated issues. It was agreed that treated SSD should be investigated first. Clinical features of the phenomena at issue could be confirmed by torque, EMG and joint angle measures that could help in challenging the selectivity of DIP to anticholinergics. LMP was modeled as the release of the reticular formation from the control of the supplementary motor area (SMA), which could be challenged by the tonic vibration reflex or acoustic startle. PMP was modeled as the release of primary motor cortex from the control of the SMA and may be informed by subclinical echopraxia. If these challenges are not met, this would put new constraints on the models and have clinical and therapeutic implications.
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Antipsicóticos , Doença de Parkinson Secundária , Transtornos Psicóticos , Esquizofrenia , Humanos , Esquizofrenia/complicações , Esquizofrenia/tratamento farmacológico , Antipsicóticos/uso terapêutico , Hipertonia Muscular/etiologia , Hipertonia Muscular/tratamento farmacológico , Transtornos Psicóticos/tratamento farmacológicoRESUMO
Identifying and validating a biomarker with high specificity in early-stage dementia with Lewy bodies (DLB) using a feasible method is crucial to enhance the current suboptimal diagnostic procedure. Previous research revealed abnormalities, including hypoperfusion in the right anterior insular cortex at group level, in prodromal DLB. Exploring hypoperfusion of the right anterior insula, at an individual-level and assessing its relevance as a potential imaging biomarker in early DLB, has, to our knowledge, not been investigated. Our preliminary study aims to assess the feasibility of the technique and to provide a methodological framework for further investigation. We assessed the feasibility and accuracy of the hypoperfusion of the right anterior insula per arterial spin labelling magnetic resonance imaging (ASL-MRI) as a diagnostic biomarker in early DLB and provided rough estimates of its sensitivity and specificity. Defining the region of interest based on previous research, we established the biomarker as the hypoperfusion of the right anterior insula. Discriminative and analytical performances were assessed in comparison to a control group of treatment-resistant depression patients. Bayesian diagnostic reasoning was employed to assess the biomarker diagnostic usability in early DLB in two scenarios: healthy elderly controls and mild cognitive impairment. Additionally, we updated probabilities by integrating data from the Mayo-clinic cognitive fluctuations scale and real-time quaking-induced conversion (RT-QuIC) α-synuclein data. Lastly, a whole-brain perfusion analysis of DLB patients was conducted to identify further brain regions with discriminative abilities. We successfully replicated the right anterior insular hypoperfusion (RAI-Hypo) in all DLB patients at the individual level. The overall sensitivity of the biomarker was 96%, and the specificity was 92%. Bayesian testing revealed the biomarker's highest performance in early-stage DLB with cognitive fluctuations, showcasing a diagnostic potential associated with a high precision and moderate accuracy. In a cognitively non-impaired population, the RAI-Hypo showed a limited usability and lacked in selectivity to qualify as a screening tool. The exploratory whole-brain analysis revealed perfect discriminative capacities in the bilateral anterior insulae and the left inferior parietal lobule. Further studies are needed to confirm our preliminary results. If performance is maintained in subsequent studies and is compared to a more suitable control population, the proposed biomarker may be eventually sufficient to discriminate early-stage DLB from non-DLB.
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Adverse drug reactions (ADRs) are a major public health issue, especially when it comes to the elderly. Potentially inappropriate prescribing (PIP) are one of the causes of ADRs in older people. A PIP can be defined as a prescription for which the benefit/risk ratio is unfavourable compared to other therapeutic alternatives. Psychotropic drugs are the second highest risk class for ADRs in the elderly. In order to reduce the prevalence of PIP, prescription assistance tools have been created. An inventory of PIP of psychotropic drugs in older patients hospitalized in psychiatry units was carried out in a French regional setting in 2019. A criteria grid was established based on 2 tools: STOPP/START criteria and Laroche's list adapted to French practice. This grid targeted each class of psychotropic drugs, drugs with a high anticholinergic burden and non-recommended combinations of psychotropic drugs. Three hundred forty-seven patients were included. A high prevalence of PPI was found for each class of psychotropic drugs. The highest prevalence of PPI was found among benzodiazepines (90.3%): long-term prescription, long half-life drugs, respiratory insufficiency or cognitive impairment condition. 56.5% of the subjects had a not-recommended combination of psychotropic drugs (prescription of drugs of the same pharmacotherapeutic class), 26% had a PIP of antipsychotics: prescription for insomnia, use of phenothiazine, 11.8% of drugs with anticholinergic properties and 7.4% of antidepressants: especially prescription of tricyclic drugs. These results obtained on a large population underline the interest of considering the specificities of prescriptions in the elderly. It shows both the interest and the limits of the current criteria defining the PIP in the context of a hospitalization in psychiatry for an acute disorder in elderly subjects.
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Antipsicóticos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Idoso , Humanos , Psicotrópicos/efeitos adversos , França , Proteínas Adaptadoras de Transdução de Sinal , Antagonistas ColinérgicosRESUMO
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).
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In the first half of the 20th century, well before the antipsychotic era, paratonia, Gegenhalten and psychomotor hypertonia were described as new forms of hypertonia intrinsic to particular psychoses and catatonic disorders. A series of astute clinical observations and experiments supported their independence from rigidity seen in Parkinson's disease. After World War II, motor disorders went out of fashion in psychiatry, with drug-induced parkinsonism becoming the prevailing explanation for all involuntary resistance to passive motion. With the 'forgetting' of paratonia and Gegenhalten, parkinsonism became the prevailing reading grid, such that the rediscovery of hypertonia in antipsychotic-naive patients at the turn of the 21st century is currently referred to as "spontaneous parkinsonism", implicitly suggesting intrinsic and drug-induced forms to be the same. Classical descriptive psychopathology gives a more nuanced view in suggesting two non-parkinsonian hypertonias: (i) locomotor hypertonia corresponds to Ernest Dupré's paratonia and Karl Kleist's reactive Gegenhalten; it is a dys-relaxation phenomenon that often needs to be activated. (ii) Psychomotor hypertonia is experienced as an admixture of assistance and resistance that partially overlaps with Kleist's spontaneous Gegenhalten, but was convincingly isolated by Henri Claude and Henri Baruk thanks to electromyogram recordings; psychomotor hypertonia is underpinned by "anticipatory contractions" of cortical origin, occurrence of which in phase or antiphase with the movement accounted for facilitation or opposition to passive motions. This century-old knowledge is not only of historical interest. Some results have recently been replicated in dementia and as now known to involve specific premotor systems.