People with coronavirus disease (COVID-19) might have several risk factors for delirium, which could in turn notably worsen the prognosis. Although pharmacological approaches for delirium are debated, haloperidol and other first-generation antipsychotics are frequently employed, particularly for hyperactive presentations. However, the use of these conventional treatments could be limited in people with COVID-19, due to the underlying medical condition and the risk of drug–drug interactions with anti-COVID treatments. On these premises, we carried out a rapid review in order to identify possible alternative medications for this particular population. By searching PubMed and the Cochrane Library, we selected the most updated systematic reviews of randomised trials on the pharmacological treatment of delirium in both intensive and non-intensive care settings, and on the treatment of agitation related to acute psychosis or dementia. We identified medications performing significantly better than placebo or haloperidol as the reference treatment in each population considered, and assessed the strength of association according to validated criteria. In addition, we collected data on other relevant clinical elements (i.e. common adverse events, drug-drug interactions with COVID-19 medications, daily doses) and regulatory elements (i.e. therapeutic indications, contra-indications, available formulations). A total of 10 systematic reviews were included. Overall, relatively few medications showed benefits over placebo in the four selected populations. As compared with placebo, significant benefits emerged for quetiapine and dexmedetomidine in intensive care unit (ICU) settings, and for none of the medications in non-ICU settings. Considering also data from indirect populations (agitation related to acute psychosis or dementia), aripiprazole, quetiapine and risperidone showed a potential benefit in two or three different populations. Despite limitations related to the rapid review methodology and the use of data from indirect populations, the evidence retrieved can pragmatically support treatment choices of frontline practitioners involved in the COVID-19 outbreak, and indicate future research directions for the treatment of delirium in particularly vulnerable populations.
BACKGROUND:: Treatment options for clozapine resistance are diverse whereas, in contrast, the evidence for augmentation or combination strategies is sparse.
AIMS:: We aimed to extract levels of evidence from available data and extrapolate recommendations for clinical practice.
METHODS:: We conducted a systematic literature search in the PubMed/MEDLINE database and in the Cochrane database. Included meta-analyses were assessed using Scottish Intercollegiate Guidelines Network criteria, with symptom improvement as the endpoint, in order to develop a recommendation grade for each clinical strategy identified.
RESULTS:: Our search identified 21 meta-analyses of clozapine combination or augmentation strategies. No strategies met Grade A criteria. Strategies meeting Grade B included combinations with first- or second-generation antipsychotics, augmentation with electroconvulsive therapy for persistent positive symptoms, and combination with certain antidepressants (fluoxetine, duloxetine, citalopram) for persistent negative symptoms. Augmentation strategies with mood-stabilisers, anticonvulsants, glutamatergics, repetitive transcranial magnetic stimulation, transcranial direct current stimulation or cognitive behavioural therapy met Grades C-D criteria only.
CONCLUSION:: More high-quality clinical trials are needed to evaluate the efficacy of add-on treatments for symptom improvement in patients with clozapine resistance. Applying definitions of clozapine resistance would improve the reporting of future clinical trials. Augmentation with second-generation antipsychotics and first-generation antipsychotics can be beneficial, but the supporting evidence is from low-quality studies. Electroconvulsive therapy may be effective for clozapine-resistant positive symptoms.
[Correction Notice: An Erratum for this article was reported in Vol 71(2) of <i>Nordic Journal of Psychiatry</i> (see record [rid]2017-02956-013[/rid]). In the original article, there were some errors. On page 236, 2nd column, lines 5-6, regarding review question 8: the correct effect size for positive symptoms is 0.18 (95% CI 0.06-0.30) and for negative symptoms 0.13 (95% CI (-0.01)-0.27). Thus, the endorsement for CBT currently has to be limited to persisting positive symptoms. There were also errors in supplementary Table 8. The errors in supplementary Table 8 have been corrected in the online version.] Background and aim: The Danish Health and Medicines Authority assembled a group of experts to develop a national clinical guideline for patients with schizophrenia and complex mental health needs. Within this context, ten explicit review questions were formulated, covering several identified key issues. METHODS: Systematic literature searches were performed stepwise for each review question to identify relevant guidelines, systematic reviews/meta-analyses, and randomized controlled trials. The quality of the body of evidence for each review question was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. Clinical recommendations were developed on the basis of the evidence, assessment of the risk-benefit ratio, and perceived patient preferences. RESULTS: Based on the identified evidence, a guideline development group (GDG) recommended that the following interventions should be offered routinely: antipsychotic maintenance therapy, family intervention and assertive community treatment. The following interventions should be considered: long-acting injectable antipsychotics, neurocognitive training, social cognitive training, cognitive behavioural therapy for persistent positive and/or negative symptoms, and the combination of cognitive behavioural therapy and motivational interviewing for cannabis and/or central stimulant abuse. SSRI or SNRI add-on treatment for persistent negative symptoms should be used only cautiously. Where no evidence was available, the GDG agreed on a good practice recommendation. CONCLUSIONS: The implementation of this guideline in daily clinical practice can facilitate good treatment outcomes within the population of patients with schizophrenia and complex mental health needs. The guideline does not cover all available interventions and should be used in conjunction with other relevant guidelines. (PsycInfo Database Record (c) 2021 APA, all rights reserved)
Clozapine constitutes the treatment of choice in patients with schizophrenia with persisting symptoms despite antipsychotics at adequate dose and treatment duration. However, an important proportion does not respond to optimal doses of clozapine, so the addition of a second antipsychotic might increase clinical response. Searching in Epistemonikos database, which is maintained by screening multiple databases, we identified 17 systematic reviews comprising 62 studies addressing the question of this article, including 26 randomized trials. We combined the evidence using meta-analysis and generated a summary of findings following the GRADE approach. We concluded adding a second antipsychotic to clozapine in patients with refractory schizophrenia probably leads to little or no difference in clinical response, and increases adverse effects.
الأهداف: دراستنا كان هدفين: أ) لتحديد منهجية كل المراجعات المنهجية الحالية من الأدوية العشبية الصينية (CHM) التي نشرت في مكتبة كوشران، ب) لتقييم جودة المنهجية من الاستعراضات وشملت.
منهجية / PRINCIPAL الموجودات: نحن إجراء بحث منهجي في قاعدة معطيات كوكرين للمراجعات المنهجية (CDSR، العدد 5، 2010) لتحديد كل المراجعات من آلية تبادل المعلومات. وكان ما مجموعه 58 تقييما مؤهلة للحصول على دراستنا. وكان واحد وعشرين من الاستعراضات وشملت واحدة على الأقل الطب الصيني التقليدي (TCM) ممارس باعتباره شريكا لها. 7 مراجعات لم تتضمن أي دراسة الابتدائية، واستعراض ما تبقى (ن = 51) اشتمل على وسيطة من 9 دراسات والمشاركين 936. وجرى تقييم مشاركة 50٪ من الاستعراضات ومستكملة إلى قبل عام 2008. وكانت الأسئلة الموجهة من قبل 39 مراجعة واسعة النطاق، والذي 9 استعراض الدراسات المختلطة مع الأدوية العشبية المختلفة. لOQAQ، كان متوسط درجة الجودة الشاملة (البند 10) 5.05 (95٪ CI؛ 4،58-5،52). تستخدم 16٪ من الدراسات الأولية التي شملت كل المراجعات تقييم الجودة المنهجية للدراسات الأولية، والكافي جيل تسلسل و 7٪ المستخدمة كافية إخفاء التخصيص. من استعراضات فارغا 51، تم الإبلاغ عن 23 تقييما بأنها غير حاسمة، في حين أن 27 وخلص أنه قد تكون هناك فائدة من آلية تبادل المعلومات، والذي كان محدودا من جانب نوعية رديئة أو كمية كافية من الدراسات المشمولة. وذكرت 58 استعراض تفتيش وسيطة من 7 قواعد البيانات الإلكترونية، في حين أن 10 تقييما لم البحث في أي قاعدة بيانات الصينية.
الاستنتاجات: حددت الدراسة لدينا الآن CDSR وشملت أعدادا كبيرة من الاستعراضات وآلية تبادل المعلومات، وبعض المجالات التي يمكن تحسينها، مثل ما يقرب من نصف استعراض شمل لم يكن لديهم بمشاركة ممارسين الطب الصينى التقليدى، وكانت لا ترقى إلى التاريخ وفقا لمعايير كوكرين، بعض الاستعراضات تجميع نتائج مختلف الأدوية العشبية وتجاهلت البحث في قواعد البيانات الصينية.
People with coronavirus disease (COVID-19) might have several risk factors for delirium, which could in turn notably worsen the prognosis. Although pharmacological approaches for delirium are debated, haloperidol and other first-generation antipsychotics are frequently employed, particularly for hyperactive presentations. However, the use of these conventional treatments could be limited in people with COVID-19, due to the underlying medical condition and the risk of drug–drug interactions with anti-COVID treatments. On these premises, we carried out a rapid review in order to identify possible alternative medications for this particular population. By searching PubMed and the Cochrane Library, we selected the most updated systematic reviews of randomised trials on the pharmacological treatment of delirium in both intensive and non-intensive care settings, and on the treatment of agitation related to acute psychosis or dementia. We identified medications performing significantly better than placebo or haloperidol as the reference treatment in each population considered, and assessed the strength of association according to validated criteria. In addition, we collected data on other relevant clinical elements (i.e. common adverse events, drug-drug interactions with COVID-19 medications, daily doses) and regulatory elements (i.e. therapeutic indications, contra-indications, available formulations). A total of 10 systematic reviews were included. Overall, relatively few medications showed benefits over placebo in the four selected populations. As compared with placebo, significant benefits emerged for quetiapine and dexmedetomidine in intensive care unit (ICU) settings, and for none of the medications in non-ICU settings. Considering also data from indirect populations (agitation related to acute psychosis or dementia), aripiprazole, quetiapine and risperidone showed a potential benefit in two or three different populations. Despite limitations related to the rapid review methodology and the use of data from indirect populations, the evidence retrieved can pragmatically support treatment choices of frontline practitioners involved in the COVID-19 outbreak, and indicate future research directions for the treatment of delirium in particularly vulnerable populations.
