The report of the joint WPA/CINP workgroup on the use and usefulness of antipsychotic medication in the treatment of schizophrenia.

This is a report of a joint World Psychiatric Association/International College of Neuropsychopharmacology (WPA/CINP) workgroup concerning the risk/benefit ratio of antipsychotics in the treatment of schizophrenia. It utilized a selective but, within topic, comprehensive review of the literature, taking into consideration all the recently discussed arguments on the matter and avoiding taking sides when the results in the literature were equivocal. The workgroup's conclusions suggested that antipsychotics are efficacious both during the acute and the maintenance phase, and that the current data do not support the existence of a supersensitivity rebound psychosis. Long-term treated patients have better overall outcome and lower mortality than those not taking antipsychotics. Longer duration of untreated psychosis and relapses are modestly related to worse outcome. Loss of brain volume is evident already at first episode and concerns loss of neuropil volume rather than cell loss. Progression of volume loss probably happens in a subgroup of patients with worse prognosis. In humans, antipsychotic treatment neither causes nor worsens volume loss, while there are some data in favor for a protective effect. Schizophrenia manifests 2 to 3 times higher mortality vs the general population, and treatment with antipsychotics includes a number of dangers, including tardive dyskinesia and metabolic syndrome; however, antipsychotic treatment is related to lower mortality, including cardiovascular mortality. In conclusion, the literature strongly supports the use of antipsychotics both during the acute and the maintenance phase without suggesting that it is wise to discontinue antipsychotics after a certain period of time. Antipsychotic treatment improves long-term outcomes and lowers overall and specific-cause mortality.

Correction to: The impact on functioning of second-generation antipsychotic medication side effects for patients with schizophrenia: a worldwide, cross-sectional, web-based survey.

[This corrects the article DOI: 10.1186/s12991-020-00292-5.].

The impact on functioning of second-generation antipsychotic medication side effects for patients with schizophrenia: a worldwide, cross-sectional, web-based survey.

BACKGROUND: It is well established that the different antipsychotics used for schizophrenia symptoms differ substantially in their side effects. However, relatively little is known about the impact of these side effects on functioning from the patient's perspective. We aimed to understand how key side effects of second-generation antipsychotics impact the functioning and quality of life (QoL) of patients with schizophrenia. METHODS: This is a cross-sectional, web-based survey of patient-reported side effect burden of antipsychotic drugs in adults with schizophrenia. The survey was deployed in the United States, Canada, Australia, Spain, Italy, Norway, and Denmark. It included sociodemographic and clinical questions, the Quality of Life Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q-SF), and the Glasgow Antipsychotic Side-Effect Scale (GASS). Eight pre-defined key side effects classified as activating ("Shaky hands or arms," "Restlessness," and "Difficulty sleeping"), sedating ("Sleepy during the day", "Feeling drugged or like a zombie," and "Feeling dizzy/Fainted") or other side effects ("Problems enjoying sex" and "Gaining weight"), and additional questions related to impacts on function and quality of life were asked. RESULTS: In total, 435 participants (mean age: 38 years, 53.8% female) were included. The total Q-LES-Q-SF score indicated overall medium satisfaction with their quality of life (score of 44.3; possible range 14-70). The most prevalent side effects were "Sleepy during the day" (83.2%), "Difficulty sleeping" (74.7%), "Dry mouth" (63.9%), "Problems enjoying sex" (53.4%) and "Gaining weight" (52.4%). Women reported the side effects of "Sleepy during the day", "Problems enjoying sex" and "Gaining weight" more frequently than men. Key side effects impacted physical, social, occupational and psychological aspects of functioning. Patients with key side effects often felt frustrated by their experiences. Total Q-LES-Q-SF score showed a significant inverse correlation with the score of pre-defined groups of side effects indicating worse QoL in association with more severe key side effects in these patients. CONCLUSION: Stable patients with schizophrenia taking second-generation antipsychotics live with many side effects, including activating and sedating side effects, sexual side effects, and weight gain. Presence of these side effects is associated with substantial impacts across all aspects of daily functioning and lower quality of life and satisfaction.

Malaria radical cure opportunity assessment in India: Discussing opportunities through stakeholder convening workshop and recommendation for improved access to malaria treatment.

India contributes to over 40% of the global Plasmodium vivax disease burden, and P. vivax contributes to approximately one-third of all malaria in India. Government of India has set goals to eliminate malaria by 2030. Doing so will require scaling up existing and new strategies, treatments and diagnostic tools. Access to appropriate diagnosis and treatment for P. vivax malaria is currently limited, and it is unclear how new tools will be rolled out. To support the government in its malaria elimination efforts, the current challenges associated with access to best clinical management of vivax malaria must be understood and mitigated to effectively deploy new tools and scale up existing solutions. The recent Food and Drug Administration (US-FDA) as well as Therapeutics Goods Administration (Australian TGA) approval of tafenoquine, developed by GSK GlaxoSmithKline and Medicines for Malaria Venture (MMV) as a new single-dose radical cure treatment for P. vivax malaria, and the commercial availability of new point-of-care glucose-6-phosphate dehydrogenase (G6PD) tests provide new opportunities to improve clinical management of vivax malaria in India. This report discusses the background, objectives, implementation strategies, and next steps that came out of the Stakeholder Workshop on Malaria Radical Cure in New Delhi, India on 4 February 2019. The focus was to understand the risks and opportunities associated with access to best clinical practices for managing vivax malaria in India. A key outcome was to propose a framework for articulating and segmenting important investment opportunities for improving access to best clinical practices for P. vivax radical cure in India.

Fractional-dose inactivated poliovirus vaccine, India.

In 2016, the World Health Organization (WHO) announced a global shortage of inactivated poliovirus vaccine that was expected to last until 2020 at least. In response, WHO's Strategic Advisory Group of Experts on Immunization recommended that countries consider a strategic shift to fractional-dose inactivated poliovirus vaccine, which involves a new dosing schedule (i.e. administered at 6 and 14 weeks of age) and has a different mode of delivery than full-dose inactivated poliovirus vaccine (i.e. intradermal rather than intramuscular). Introduction of fractional-dosing requires careful planning and management to ensure adequate vaccine supplies, to prevent wastage, to provide training for health workers, and to ensure accurate record-keeping. In early 2016, given the global vaccine shortage and a limited supply from domestic manufacturers, India's Expert Advisory Group on polio recommended the staggered introduction of fractional-dosing. India was the first country to introduce fractional-dose inactivated poliovirus vaccine into routine immunization, initially in eight states in 2016. Following a rapid assessment of its initial implementation, fractional-dosing was extended and, by June 2017, all Indian states were covered. Here we summarize India's experience with the introduction, discuss the challenges faced and the strategies used to address them, and report on the outcomes achieved. We also describe the lessons learnt, especially managing vaccine supplies and wastage, monitoring and supervision, and training needs. As the use of fractional-dose inactivated poliovirus vaccine is dose-sparing and reduces the cost of the immunization programme, it will remain an important part of India's long-term strategy for polio vaccination.

En 2016, l'Organisation mondiale de la Santé (OMS) a annoncé une pénurie mondiale du vaccin antipoliomyélitique inactivé, prévue pour durer jusqu'à 2020 au minimum. Face à cette situation, le Groupe stratégique consultatif d'experts sur la vaccination a recommandé aux pays d'envisager un changement de stratégie afin de privilégier l'utilisation du vaccin antipoliomyélitique inactivé en doses fractionnées, ce qui implique un nouveau calendrier de vaccination (administration du vaccin à l'âge de 6 et de 14 semaines) et un mode d'administration différent de celui du vaccin antipoliomyélitique inactivé en dose complète (par voie intradermique et non pas par voie intramusculaire). L'introduction d'une vaccination en doses fractionnées exige de la rigueur en matière de planification et de gestion, afin de garantir des stocks de vaccins suffisants, d'éviter les gaspillages, de former les agents de santé et d'assurer une tenue précise des dossiers médicaux. Début 2016, du fait de la pénurie mondiale du vaccin et d'un approvisionnement limité par les fabricants nationaux, le Groupe consultatif d'experts de l'Inde sur l'éradication de la poliomyélite a recommandé d'introduire progressivement les doses fractionnées. Si bien que l'Inde est le premier pays à avoir introduit le vaccin antipoliomyélitique inactivé en doses fractionnées dans le calendrier de vaccination systématique, d'abord dans huit États en 2016. Après une rapide évaluation de cette mise en œuvre initiale, l'utilisation des doses fractionnées s'est étendue, pour finalement être effective dans tous les États indiens en juin 2017. Dans cet article, nous récapitulons l'expérience de l'Inde à ce sujet, nous évoquons les défis rencontrés et les stratégies employées pour les surmonter ainsi que les résultats obtenus. Nous décrivons également les enseignements tirés de cette expérience, notamment en matière de gestion des stocks de vaccins, de prévention des gaspillages, de suivi et de supervision, mais aussi concernant les besoins en formation. Étant donné que l'utilisation de doses fractionnées du vaccin antipoliomyélitique inactivé permet d'économiser des doses vaccinales et de réduire le coût du programme de vaccination, cela restera un élément essentiel dans la stratégie à long terme de l'Inde en matière de vaccination contre la poliomyélite.

En 2016, la Organización Mundial de la Salud (OMS) anunció una escasez mundial de vacunas inactivadas del poliovirus que se esperaba que se prolongara al menos hasta 2020. En respuesta, el Grupo de asesoramiento estratégico de expertos en inmunización de la OMS recomendó que los países consideraran la posibilidad de un cambio estratégico hacia una vacuna inactivada del poliovirus de dosis fraccionada, que incluye un nuevo esquema de dosificación (es decir, administrada a las seis y a las catorce semanas de edad) y que tiene un modo de administración diferente al de la vacuna inactivada del poliovirus de dosis completa (es decir, intradérmica y no intramuscular). La introducción de la dosis fraccionada requiere una planificación y una gestión minuciosas para garantizar el suministro adecuado de las vacunas, evitar el despilfarro, formar a los trabajadores sanitarios y garantizar el mantenimiento de registros precisos. A principios de 2016, dada la escasez mundial de vacunas y el limitado suministro de los fabricantes nacionales, el Grupo de asesoramiento experto sobre la polio de la India recomendó la introducción escalonada de dosis fraccionadas. La India fue el primer país en introducir la vacuna inactivada del poliovirus de dosis fraccionada en la inmunización sistemática, inicialmente en ocho estados en 2016. Tras una rápida evaluación de la aplicación inicial, se amplió la dosificación fraccionada y, para junio de 2017, se cubrieron todos los estados de la India. En este documento se resume la experiencia de la India con la introducción, se examinan los problemas encontrados y las estrategias utilizadas para resolverlos y se informa sobre los resultados alcanzados. También se describen las lecciones aprendidas, especialmente en lo que se refiere a la gestión de los suministros de vacunas y el desperdicio, el seguimiento y la supervisión, y las necesidades de formación. Dado que el uso de la vacuna inactivada del poliovirus de dosis fraccionada ahorra dosis y reduce el coste del programa de inmunización, seguirá siendo una parte importante de la estrategia a largo plazo de la India para la vacunación contra la polio.

Self-Reported Training Adequacy, Experience, and Comfort Level in Performing Schizophrenia-Related Clinical Skills among Psychiatry Residents and Fellows.

OBJECTIVE: In the context of an educational program on schizophrenia for psychiatry trainees, this survey study analyzed associations between self-reported training adequacy, experience in providing patient care, and comfort level in performing schizophrenia-related clinical skills. The influence of the education on comfort level was also assessed for each skill. METHODS: Survey respondents were psychiatry residents and fellows who participated in a schizophrenia education program at an in-person workshop or through online videos recorded at the workshop. In a pre-program survey, participants reported their experience in providing schizophrenia patient care and rated their training adequacy and comfort level for performing seven clinical skills involved in diagnosing and treating schizophrenia. The post-program survey included items for reassessing comfort level in performing the skills. RESULTS: Across the seven clinical skills, the proportion of respondents (n = 79) who agreed or strongly agreed that their training was adequate ranged from 29 to 88 %. The proportion of high ratings for comfort level in skill performance ranged from 45 to 83 %. Comfort level was significantly associated with training adequacy for all seven clinical skills and with experience in providing patient care for four skills. For all skills, comfort level ratings were significantly higher after versus before the educational workshop. Commonly indicated needs for further training included education on new therapies, exposure to a broader range of patients, and opportunities for longitudinal patient management. CONCLUSIONS: Psychiatry trainees' self-reported, disease-specific training adequacy, experiences, and comfort level have unique applications for developing and evaluating graduate medical curriculum.

Acceptability of locally produced ready-to-use therapeutic foods in Ethiopia, Ghana, Pakistan and India.

Successful treatment of severe acute malnutrition has been achieved with ready-to-use therapeutic food (RUTF), but only 15% of children with severe acute malnutrition receive RUTF. The objective of this study was to determine whether new formulations of RUTF produced using locally available ingredients were acceptable to young children in Ethiopia, Ghana, Pakistan and India. The local RUTFs were formulated using a linear programming tool that allows for inclusion of only local ingredients and minimizes cost. The study consisted of 4 two-arm, crossover, site-randomized food acceptability trials to test the acceptability of an alternative RUTF formula compared with the standard peanut-based RUTF containing powdered milk. Fifty children with moderate wasting in each country were enrolled in the 2-week study. Acceptability was measured by overall consumption, likeability and adverse effects reported by caregivers. Two of the four RUTFs did not include peanut, and all four used alternative dairy proteins rather than milk. The ingredient cost of all of the RUTFs was about 60% of standard RUTF. In Ethiopia, Ghana and India, the local RUTF was tolerated well without increased reports of rash, diarrhoea or vomiting. Children consumed similar amounts of local RUTF and standard RUTF and preferred them similarly as well. In Pakistan, local RUTF was consumed in similar quantities, but mothers perceived that children did not enjoy it as much as standard RUTF. Our results support the further investigation of these local RUTFs in Ethiopia, Ghana and India in equivalency trials and suggest that local RUTFs may be of lower cost.

Report of the WPA section of pharmacopsychiatry on the relationship of antiepileptic drugs with suicidality in epilepsy.

INTRODUCTION: This report from the World Psychiatric Association Section on Pharmacopsychiatry examines the possible relationship of antiepileptic drugs with suicide-related clinical features and behaviors in patients with epilepsy. MATERIALS AND METHODS: A systematic review of the MEDLINE search returned 1039 papers, of which only 8 were considered relevant. A critical analysis of the Food and Drug Administration (FDA) report on the increase risk for patients under antiepileptics to manifest suicidality is also included in this report. RESULTS: The analysis of these studies revealed that the data are not supportive of the presence of a "class effect" on suicide-related behavior; on the contrary, there are some data suggesting such an effect concerning treatment with topiramate, lamotrigine, and levetiracetam for which further research is needed. DISCUSSION: For the majority of people with epilepsy, anticonvulsant treatment is necessary and its failure for any reason is expected to have deleterious consequences. Therefore, clinicians should inform patients and their families of this increased risk of suicidal ideation and behavior, but should not overemphasize the issue. Specific subgroups of patients with epilepsy might be at a higher risk, and deserve closer monitoring and follow-up. Future research with antiepileptics should specifically focus on depression and suicidal thoughts.

The schizophrenia syndrome, circa 2024: What we know and how that informs its nature.

With new data about different aspects of schizophrenia being continually generated, it becomes necessary to periodically revisit exactly what we know. Along with a need to review what we currently know about schizophrenia, there is an equal imperative to evaluate the construct itself. With these objectives, we undertook an iterative, multi-phase process involving fifty international experts in the field, with each step building on learnings from the prior one. This review assembles currently established findings about schizophrenia (construct, etiology, pathophysiology, clinical expression, treatment) and posits what they reveal about its nature. Schizophrenia is a heritable, complex, multi-dimensional syndrome with varying degrees of psychotic, negative, cognitive, mood, and motor manifestations. The illness exhibits a remitting and relapsing course, with varying degrees of recovery among affected individuals with most experiencing significant social and functional impairment. Genetic risk factors likely include thousands of common genetic variants that each have a small impact on an individual's risk and a plethora of rare gene variants that have a larger individual impact on risk. Their biological effects are concentrated in the brain and many of the same variants also increase the risk of other psychiatric disorders such as bipolar disorder, autism, and other neurodevelopmental conditions. Environmental risk factors include but are not limited to urban residence in childhood, migration, older paternal age at birth, cannabis use, childhood trauma, antenatal maternal infection, and perinatal hypoxia. Structural, functional, and neurochemical brain alterations implicate multiple regions and functional circuits. Dopamine D-2 receptor antagonists and partial agonists improve psychotic symptoms and reduce risk of relapse. Certain psychological and psychosocial interventions are beneficial. Early intervention can reduce treatment delay and improve outcomes. Schizophrenia is increasingly considered to be a heterogeneous syndrome and not a singular disease entity. There is no necessary or sufficient etiology, pathology, set of clinical features, or treatment that fully circumscribes this syndrome. A single, common pathophysiological pathway appears unlikely. The boundaries of schizophrenia remain fuzzy, suggesting the absence of a categorical fit and need to reconceptualize it as a broader, multi-dimensional and/or spectrum construct.

Improving psychotherapeutic medication prescribing in Florida: implementation of the Florida Medicaid Drug Therapy Management Program (MDTMP).

This paper describes a program that was established by Florida Medicaid to improve the quality of prescribing of psychotherapeutic medications. It relates the process used for defining quality medication treatment including the definitions of unusual psychotherapeutic medication indicators (UPMI). It details the results of analysis of FY 2007-2008 pharmacy claims data using these indicators that enabled the Program to identify practices and prescribers that required targeted interventions. The most frequently triggered UPMI for adults involved the use of 2 or more antipsychotics for greater than 60 days; high doses of psychotherapeutic medications was the indicator most frequently triggered for children closely followed by the use of 2 or more antipsychotics for more than 45 days. Prescriptions that triggered UPMI were concentrated in a small number of prescribers. These results led to the Program focusing on these high frequency practices and on the prescribers most associated with them. They also led to the implementation of new quality improvement initiatives like the implementation of a psychiatric telephone consultation line for pediatricians who are treating children with serious emotional disturbances who do not have access to child psychiatrists.

Efficacy of pharmacotherapy in bipolar disorder: a report by the WPA section on pharmacopsychiatry.

The current statement is a systematic review of the available data concerning the efficacy of medication treatment of bipolar disorder (BP). A systematic MEDLINE search was made concerning the treatment of BP (RCTs) with the names of treatment options as keywords. The search was updated on 10 March 2012. The literature suggests that lithium, first and second generation antipsychotics and valproate and carbamazepine are efficacious in the treatment of acute mania. Quetiapine and the olanzapine-fluoxetine combination are also efficacious for treating bipolar depression. Antidepressants should only be used in combination with an antimanic agent, because they can induce switching to mania/hypomania/mixed states/rapid cycling when utilized as monotherapy. Lithium, olanzapine, quetiapine and aripiprazole are efficacious during the maintenance phase. Lamotrigine is efficacious in the prevention of depression, and it remains to be clarified whether it is also efficacious for mania. There is some evidence on the efficacy of psychosocial interventions as an adjunctive treatment to medication. Electroconvulsive therapy is an option for refractory patients. In acute manic patients who are partial responders to lithium/valproate/carbamazepine, adding an antipsychotic is a reasonable choice. The combination with best data in acute bipolar depression is lithium plus lamotrigine. Patients stabilized on combination treatment might do worse if shifted to monotherapy during maintenance, and patients could benefit with add-on treatment with olanzapine, valproate, an antidepressant, or lamotrigine, depending on the index acute phase. A variety of treatment options for BP are available today, but still unmet needs are huge. Combination therapy may improve the treatment outcome but it also carries more side-effect burden. Further research is necessary as well as the development of better guidelines and algorithms for the step-by-step rational treatment.

Obsessive-compulsive symptoms in schizophrenia: implications for future psychiatric classifications.

Although obsessive-compulsive symptoms are not considered primary features, they are prevalent, independent of psychosis, and substantially modify clinical characteristics, course, treatment and prognosis of schizophrenia. The authors highlight the clinical significance of obsessive-compulsive symptoms in schizophrenia, provide diagnostic criteria for "schizo-obsessive" patients and address future directions for research.

Trends in adult antipsychotic polypharmacy: progress and challenges in Florida's Medicaid program.

We studied trends in antipsychotic polypharmacy over a 4 year period in order to see if a change occurred when a statewide quality improvement program aimed at reducing the practice was implemented. Antipsychotic polypharmacy prevalence rates were calculated for eight 6-month periods for enrollees with schizophrenia and schizoaffective disorder and for those with all other diagnoses. Prevalence increased from 1/2003 to 12/2004 and then declined for 4 successive 6 month periods beginning in the 1/2005-6/05 period when the program began. Piecewise linear regression results for both diagnostic groups confirmed that the change in the likelihood of antipsychotic polypharmacy during the four 6 month periods before program implementation were significantly different than during the four 6 month periods following implementation. While it is impossible to control for the effects of all variables in evaluating the impact of any system wide intervention the data suggest that the program did help to reduce the use of antipsychotic polypharmacy.

Aspiration Pneumonia Due to Migration of Fracture Tracheostomy Tube after 14 Years of Use.

Tracheostomy is a common life-saving surgical procedure, which has its own short- and long-term surgical complications. Occasionally, after being in place for several years, the tube may fracture, causing a foreign body reaction in the bronchus followed by life-threatening pneumonia. We report a rare case of a 29-year-old man with a known leukodystrophy disorder whose tracheostomy tube was never changed in 14 years. He presented with signs of sepsis and respiratory distress. The management and intraoperative findings, including recommendations for tracheostomy care, were described.

When you hear hoofbeats, think horses and zebras: The importance of a wide differential when it comes to frontotemporal lobar degeneration.

Frontotemporal lobar degeneration (Frontotemporal dementia in DSM 4/FTD) is a progressive brain disease which frequently presents with neuropsychiatric symptoms. Prevalence of FTD is low, however the prognosis is poor. Early identification of FTD may improve quality of life, minimize behavioral disturbances and help with end of life planning. Diagnosis of FTD is often a diagnostic challenge as it has wide differentials. Authors discuss three clinical cases with their initial clinical presentation, diagnostic complexity and subsequent management.

Schizophrenia, "just the facts" 4. Clinical features and conceptualization.

Although dementia praecox or schizophrenia has been considered a unique disease entity for the past century, its definitions and boundaries have continued to vary over this period. At any given time, the changing concept of schizophrenia has been influenced by available diagnostic tools and treatments, related conditions from which it most needs to be distinguished, extant knowledge and scientific paradigms. There is significant heterogeneity in the etiopathology, symptomatology, and course of schizophrenia. It is characterized by an admixture of positive, negative, cognitive, mood, and motor symptoms whose severity varies across patients and through the course of the illness. Positive symptoms usually first begin in adolescence or early adulthood, but are often preceded by varying degrees of negative and cognitive symptomatology. Schizophrenia tends to be a chronic and relapsing disorder with generally incomplete remissions, variable degrees of functional impairment and social disability, frequent comorbid substance abuse, and decreased longevity. Although schizophrenia may not represent a single disease with a unitary etiology or pathogenetic process, alternative approaches have thus far been unsuccessful in better defining this syndrome or its component entities. The symptomatologic, course, and etio-pathological heterogeneity can usefully be addressed by a dimensional approach to psychopathology, a clinical staging approach to illness course, and by elucidating endophenotypes and markers of illness progression, respectively. This will allow an approach to the deconstruction of schizophrenia into its multiple component parts and strategies to reconfigure these components in a more meaningful manner. Possible implications for DSM-V and ICD-11 definitions of schizophrenia are discussed.