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Abstract Background Attitudes towards antipsychotic medication play an important part in the treatment for schizophrenia and related disorders. We aimed measuring general practitioners' attitudes to antipsychotic drugs and their adverse side effects and comparing these with the attitudes of the general population. Methods Analysis and comparison of two representative samples, one comprising 100 General Practitioners (GPs), the other 791 individuals randomly selected from the general population. The setting was the German speaking cantons of Switzerland. Results General practitioners have significantly more positive attitudes towards anti-psychotic drugs than the general public. They reject widespread prejudices about the use of anti-psychotic medication significantly more than the general population. In particular the risk of dependency was assessed as 'low' by GP's (80%), in contrast to only 18% of the general population sample. In no instance did a majority of the GPs advise not tolerating any of the 10 possible adverse effects presented in this study. This is in marked contrast to the general population sample, where a majority recommended discontinuation for movement disorder (63%), strong tremor (59%), risk of dependency (55%) and feelings of unrest (54%). Conclusion As well as effective management of side-effects being a vital aspect of patient and carer education, prescribing doctors need to be aware that their mentally ill patients are likely to be confronted with extremely negative public attitudes towards antipsychotic medication and with strong pressures to stop taking their medication in the event of side-effects.

Objective: The Dutch law on youth care (the Youth Act) was implemented from 2015 onwards. One of the government's aims by implementing this new policy was de-medicalization of youths by separating youth mental healthcare from the rest of the healthcare system. A previous study conducted by our research group showed that prevalence rates of antipsychotic drug prescriptions stabilized among Dutch youth in the period 2005–2015, just before the introduction of the Youth Act. In our study, we aimed to describe antipsychotic drug use among Dutch children aged 0–19 years old before and after implementation of the Youth Act (2010–2019). Methods: We analyzed prescription data of 7405 youths aged 0–19 years using antipsychotic drugs between 2010 and 2019, derived from a large Dutch community pharmacy-based prescription database (IADB.nl). Results: Prevalence rates of antipsychotic drug use per thousand youths decreased significantly in youths aged 7–12 years old in 2019 compared to 2015 (7.9 vs 9.0 p < 0.05). By contrast, prevalence rates increased in adolescent females in 2019 compared to 2015 (11.8 vs 9.5 p < 0.05). Incidence rates increased significantly in adolescent youths in 2019 compared to 2015 (3.9 vs 3.0 p < 0.05), specifically among adolescent girls (4.2 per thousand in 2019 compared to 3.0 per thousand in 2015). Dosages in milligram declined for the most commonly prescribed antipsychotic drugs during the study period. The mean duration of antipsychotic drug use in the study period was 5.7 (95% CI 5.2–6.2) months. Conclusion: Despite the aim of the Youth Act to achieve de-medicalization of youths, no clear reduction was observed in prevalence rates of antipsychotic drugs or treatment duration in all subgroups. Prevalence rates even increased in adolescent females.

BackgroundIt is unknown why professionals' adherence to guideline recommendations on antipsychotic drug prescription in the intellectual disabilities care is insufficient. This study aimed to explore barriers and facilitators in the implementation and use of these recommendations.MethodsIn‐depth interviews with four intellectual disability physicians, two psychiatrists and five behavioural scientists were used to explore the implementation and use of guideline recommendations.ResultsBarriers in adhering to recommendations were lack of collaboration of different disciplines involved in the treatment of psychiatric and behavioural disorders and lack of enforcement of an appropriate monitoring of side‐ and treatment effects. When guideline recommendations were translated into organizational policies, clinicians were able to divide responsibilities and tasks, needed to appropriately implement guideline recommendations in daily clinical practice.ConclusionsTo facilitate the use of guideline recommendations, organizations should translate recommendations into organization‐specific policies, involving physicians and behavioural scientists in this process, while simultaneously creating more practical and technological support.

AbstractBackgroundResults of discontinuation of antipsychotics in people with intellectual disability are variable and may depend on staff factors.MethodWe attempted to taper off antipsychotics in 14 weeks after which participants were free to restart. We investigated the influence of support professionals' feelings towards challenging behaviour, their knowledge of psychotropic drugs and clinicians' judgements of participants' behavioural functioning on whether or not antipsychotics were completely discontinued after 16, 28 and 40 weeks.ResultsOf the 129 participants, 61% achieved discontinuation at 16 weeks; at 28 and 40 weeks, 46% and 40% were completely discontinued. Staff's feelings of Depression/Anger towards their client's behaviour, less knowledge about psychotropic medication and clinicians' judgements of behavioural worsening were negatively associated with achievement of discontinuation.ConclusionsTo enhance discontinuation off‐label drug use, staff's feelings should be explored, their knowledge of psychotropic drugs improved and reasons for clinicians' judgements of participants' behavioural worsening investigated.

The author discusses the issue of rising incidents of off-label prescribing of antipsychotic drugs to children and young people in Canada. He notes that antipsychotic drugs are increasingly being used to treat behavioral and mood disorders in children and youth and discusses the social, economic, cultural and political issues reflected in this trend. He talks about the challenges in educating the public about the danger of using antipsychotic drugs and ways of reducing off-label prescribing. ; Peer reviewed ; Final article published

Abstract Background Government policy encourages increasing involvement of patients in their long-term care. This paper describes the development and pilot evaluation of a 'Medication Review Tool' designed to assist people to participate more effectively in discussions about antipsychotic drug treatment. Methods The Medication Review Tool developed consisted of a form to help patients identify pros and cons of their current antipsychotic treatment and any desired changes. It was associated with a website containing information and links about antipsychotics. For the trial, participants diagnosed with psychotic disorders were recruited from community mental health services. Cluster randomisation was used to allocate health professionals (care co-ordinators) and their associated patients to use of the Medication Review Tool or usual care. All participants had a medical consultation scheduled, and those in the intervention group completed the Medication Review Tool, with the help of their health professional prior to this, and took the completed Form into the consultation. Two follow-up interviews were conducted up to three months after the consultation. The principal outcome was the Decision Self Efficacy Scale (DSES). Qualitative feedback was collected from patients in the intervention group. Results One hundred and thirty patients were screened, sixty patients were randomised, 51 completed the first follow-up assessment and 49 completed the second. Many patients were not randomised due to the timing of their consultation, and involvement of health professionals was inconsistent. There was no difference between the groups on the DSES (-4.16 95 % CI -9.81, 1.49), symptoms, side effects, antipsychotic doses or patient satisfaction. Scores on the Medication Adherence Questionnaire indicated an increase in participants' reported inclination to adherence in the intervention group (coefficient adjusted for baseline values -0.44; 95 % CI -0.76, -0.11), and there was a small increase in positive attitudes to antipsychotic medication (Drug Attitude Inventory, adjusted coefficient 1.65; 95 % CI -0.09, 3.40). Qualitative feedback indicated patients valued the Tool for identifying both positive and negative aspects of drug treatment. Conclusions The trial demonstrated the design was feasible, although challenges included service re-configurations and maintaining health professional involvement. Results may indicate a more intensive and sustained .

Background: Schizophrenia is a chronic serious mental disorder with prevalence close to 0.7%. Early symptoms of schizophrenia generally appear in late adolescence or the early twenties. The prognosis is usually worse in cases of early onset. The symptomatology of schizophrenia is complex and can vary a lot between individuals. The two main symptom dimensions are referred to as positive symptoms and negative symptoms. The most common positive symptoms are: hallucinations, particularly auditory hallucinations, delusions, disturbances of thought and persecutory ideation. The most common negative symptoms are: lack of social interest, loss of personal hygiene, reduced motivation, loss of insight and blunting of affect. Over 100 variants are now known in the genome that increase the risk of schizophrenia and the genetic pathogenesis is therefore very complex. Environmental risk factors are believed to play a role in the pathogenesis of schizophrenia, especially cannabis use in adolescence. The socioeconomic cost of schizophrenia is very high because the disease often causes disability among young sufferers. Patients with schizophrenia have a reduced life expectancy of 22.5-25 years. The main reasons are unhealthy lifestyle (most patients smoke, take little exercise, use alcohol or illicit substances and are on a poor diet), cardiovascular disease and suicide. About 20-30% of patients do not respond to conventional antipsychotic treatment and are said to have treatment-resistant schizophrenia (TRS). The only approved treatment that has proven to be efficacious in TRS and been shown to improve overall mortality as well as reduce suicide attempts and probably the odds of suicide is the antipsychotic clozapine. Despite this clozapine is often used rather late in the disease course, most probably due to many side effects and some rare adverse drug reactions (ADR) which can be life-threatening for a very small proportion of TRS patients. A much greater number of patients with TRS lose years of life because they commit suicide or die prematurely due to an unhealthy lifestyle than those who pass away as a result of these rare ADRs. Despite this the proportion of TRS patients with schizophrenia that have ever had clozapine prescribed is much less than the expected 20-30% in most countries. Fewer still remain on the treatment long term for various reasons. Clozapine is not available in a depot injectable preparation and that limits its effectiveness in the treatment of patients with lack of insight or who have difficulty in taking tablets daily. Objective: To study the use of clozapine in the treatment of schizophrenia in Iceland and to assess serious side effects of antipsychotics, focusing on clozapine. Assess neutropenia and the progression to agranulocytosis and compare the prevalence for patients on clozapine versus those that have never been on clozapine. Examine the proportion of patients who had developed diabetes or dyslipidemia and compare it to a standard Icelandic population. Finally, to contribute to Evidence-Based as well as Value-Based Practice and shared decision-making in the often challenging treatment and long term care of patients with TRS. Method: The study population consisted of patients who had participated in an ongoing joint research project of Landspitali University Hospital and deCODE genetics on psychotic disorders. Patients were recruited to the study between 1986-2014. A total of 611 patients with schizophrenia took part in the study. Patients' health records were searched electronically to identify patients who had used clozapine. The health records were then reviewed to confirm use of clozapine. Patients´ health records were searched electronically to seek information on side effects and ADRs as well as the blood test database at Landspitali. Statistical analyses were performed using STATA. Results: The use of clozapine in Iceland is described in paper I. Two hundred and one patients took clozapine at some point during the study. The mean age at the start of clozapine use was 37.8 years. Some 71.2% of patients who began treatment with clozapine remained on clozapine treatment 20 years later. It was estimated that 11.4% of patients with schizophrenia in Iceland were using clozapine and that 16% had ever tried clozapine treatment. Antipsychotic polypharmacy was common since two out of every three patients, 65.6%, also used other antipsychotics alongside treatment with clozapine. Paper II focuses on neutropenia and agranulocytosis in the course of treatment of TRS with clozapine versus other antipsychotics. After the first 18 weeks of clozapine treatment the median number of days between neutrophil measurements was 124 days. Neutropenia was observed in 34 patients out of 188 on clozapine and of those 24 developed mild neutropenia (granulocytes between 1500-1900/mm3). One year after the neutropenia 28 patients out of 34 were still on clozapine. No difference was observed in the proportion of patients who developed moderate to severe neutropenia (granulocytes in the range 0-1400/mm3) between patients on clozapine versus TRS patients who had never been on clozapine. In paper III it was presented that women on clozapine were 4.4 times more likely to have been diagnosed with type 2 diabetes (T2D) than women in the general population. Males on clozapine were 2.3 times more likely to have been diagnosed with T2D than males in the general population. Triglycerides were higher both among those with schizophrenia who had been on clozapine as well as among patients with schizophrenia who had never received clozapine compared to the general population. One case of ketoacidosis was identified in a patient with type 1 diabetes. Conclusions: More patients with TRS in Iceland and other countries should get the opportunity to be offered treatment with clozapine. A large proportion of neutropenia developing during clozapine treatment is probably not caused by clozapine. If clozapine treatment proves to be effective a decision to stop clozapine should only be taken following careful consideration of all possible options in cases of moderate neutropenia, because there are usually no other alternative treatment options available that offer comparable effectiveness available. Doctors must be well aware of the risk of metabolic syndrome during clozapine treatment, especially the high risk of T2D developing in women. ; Bakgrunnur: Geðklofi er langvinnur alvarlegur geðsjúkdómur með algengi nálægt 0,7%. Fyrstu einkenni geðklofa koma oftast fram seint á unglingsárum eða á þrítugsaldri, en þeim mun fyrr sem sjúkdómurinn kemur fram eru horfurnar að jafnaði verri. Einkennaróf geðklofa er margþætt og birtingarform veikindanna getur því verið talsvert mismunandi milli einstaklinga. Tvær helstu víddir sjúkdómsins eru svokölluð jákvæð einkenni og neikvæð einkenni (brottfallseinkenni). Algengustu jákvæðu einkennin eru: ofskynjanir og þá einkum ofheyrnir, ranghugmyndir, truflun á hugsun og aðsóknarkennd. Algengustu neikvæðu einkennin eru: félagsleg einangrun, skert persónuhirða, minni áhugahvöt, innsæisleysi og skert tilfinningaleg viðbrögð. Nú eru þekktir yfir 100 breytileikar í erfðamenginu sem auka líkur á geðklofa og samband erfða og svipgerðar því afar flókið. Talið er að umhverfisþættir komi auk þess við sögu í tilurð geðklofa, ekki síst regluleg notkun unglinga á kannabisefnum. Samfélagslegur kostnaður vegna geðklofa er hár þar sem sjúkdómurinn veldur mjög oft örorku ungs fólks. Sjúklingar með geðklofa lifa að meðaltali 22,5-25 árum skemur en aðrir. Helstu ástæður þess eru óheilbrigður lífstíll (flestir reykja, lítil hreyfing, óheilbrigt mataræði og notkun vímugjafa), hjarta og æðasjúkdómar og loks sjálfsvíg. Um 20-30% sjúklinga svara ekki hefðbundinni meðferð með geðrofslyfjum og eru þeir sagðir vera með meðferðarþráan geðklofa. Eina meðferðin sem hefur sannað sig sem gagnreynd meðferð hjá þeim hópi er geðrofslyfið clozapín, en oft er það notað frekar seint í sjúkdómsferlinu vegna margvíslega aukaverkana, sem sumar hverjar geta verið lífshættulegar. Mun fleiri sjúklingar með meðferðarþráan geðklofa falla þó fyrir eigin hendi en látast vegna þessara sjaldgæfu aukaverkana, en clozapín er það lyf sem helst minnkar líkur á sjálfsvígum og dregur úr dánartíðni í þessum hópi. Þrátt fyrir það eru margir læknar ragir við að bjóða sjúklingum meðferðina og hlutfall sjúklinga sem fær að reyna clozapín meðferð vegna meðferðarþrás geðklofa er hvarvetna mun lægra en 20-30%. Clozapín er ekki til sem forðalyf í sprautuformi. Það takmarkar notagildi þess í tilfellum þar sem sjúklingar hafa mjög skert innsæi eða ráða illa við að taka töflur daglega. Markmið: Að rannsaka notkun clozapíns hér á landi í meðferð geðklofa og alvarlegar aukaverkanir geðrofslyfja með áherslu á clozapín. Skoða kyrningafæð (neutropenia) og tengingu hennar við algjöra kyrningafæð (agranulocytosis) og bera saman tíðnina hjá sjúklingum á clozapín og þeim sem hafa aldrei farið á clozapín. Einnig á að kanna tíðni sykursýki og blóðfituröskunar og bera saman við almennt íslenskt þýði. Síðast en ekki síst að þróa frekar gagnreynda og gildismiðaða meðferð og sameiginlega ákvarðanatöku í langtíma meðferð meðferðarþrás geðklofa. Aðferð: Þýðið í rannsókninni samanstóð af sjúklingum sem hafa tekið þátt í geðrofsrannsókn LSH og Íslenskrar erfðagreiningar. Sjúklingum var safnað í rannsóknina á árunum 1986-2014. Samtals voru upplýsingar um 611 sjúklinga notaðar í rannsókninni. Til að finna sjúklinga sem höfðu notað geðrofslyfið clozapín var leitað að rafrænum skjölum í sjúkraskrá Landspítala sem bentu til clozapín notkunar. Þau skjöl voru lesin til að meta hvort hægt væri að staðfesta clozapín notkun. Til að finna upplýsingar um aukaverkanir var framkvæmd rafræn leit í sjúkraskrám auk þess sem aðgangur fékkst að blóðprufugagnagrunni Landspítala. Tölfræðiúrvinnsla var gerð í STATA. Niðurstöður: Í grein I er fjallað um notkun clozapíns á Íslandi. Tvöhundruð og einn sjúklingur hafði fengið meðferð með clozapíni. Meðalaldur við upphaf clozapíns notkunar reyndist 37,8 ár á tímabilinu. Um 71,2% sjúklinga sem hófu meðferð með clozapíni voru enn á clozapín meðferð 20 árum síðar. Við áætluðum að 11,4% sjúklinga með geðklofa á Íslandi væru að taka clozapín og 16% þeirra hefðu einhvern tíma reynt meðferð með lyfinu. Fjöllyfjanotkun geðrofslyfja var algeng samhliða clozapín meðferð þar sem tveir af hverjum þremur sjúklingum eða 65,6% notuðu önnur geðrofslyf samhliða meðferð með clozapíni. Grein II fjallar um kyrningafæð og algjöra kyrningafæð. Eftir fyrstu 18 vikurnar á clozapín meðferð þá var miðgildi milli mælinga á kyrningum 124 dagar. Kyrningafæð greindist hjá 34 sjúklingum af 188 á clozapín meðferð en oftast var um að ræða væga kyrningafæð (kyrningar milli 1500-1900/mm3 ) eða hjá 24 sjúklingum. Einu ári eftir kyrningarfæð voru 28 af 34 sjúklingum ennþá á clozapíni. Enginn munur kom fram á tíðni alvarlegrar kyrningafæðar (kyrningar á bilinu 0-1400/mm3 ) hjá sjúklingum á clozapíni og sjúklingum með geðklofa sem höfðu aldrei farið á clozapín meðferð. Í grein III kemur fram að konur sem hafa tekið clozapín voru 4,4 sinnum líklegri en konur í almennu þýði til að hafa greinst með sykursýki týpu 2. Karlar á clozapín meðferð voru 2,3 sinnum líklegri til að hafa greinst með sykursýki týpu 2 en karlar í almennu þýði. Þríglýseríð voru einnig hærri bæði hjá þeim sem höfðu tekið clozapín og hjá sjúklingum með geðklofa sem höfðu aldrei tekið clozapín samanborið við almennt þýði. Eitt tilfelli af ketónblóðsýringu greindist hjá sjúklingi með sykursýki af týpu 1. Ályktanir: Hærra hlutfall sjúklinga með meðferðarþráan geðklofa á Íslandi og í öðrum löndum ætti að eiga þess kost að reyna meðferð með clozapíni. Stór hluti af kyrningafæð sem kemur fram hjá sjúklingum á clozapín meðferð stafar líklega ekki af lyfinu. Því þarf að ígrunda vel ákvarðanir um að hætta clozapín meðferð einstaklinga með meðferðarþráan geðklofa á grundvelli miðlungs alvarlegrar kyrningafæðar hafi meðferð skilað góðum árangri og þar sem þá er almennt ekki önnur meðferð með sambærilega virkni í boði. Læknar þurfa að vera vel vakandi fyrir efnaskiptavillu af völdum clozapíns og þá sérstaklega sykursýki týpu 2 hjá konum. ; Landspitali, The National University Hospital European Union's Seventh Framework Programme for research, technological development and demonstration under grant agreement no. 279227 (CRESTAR).

Die Detektion von UAWs gewinnt zunehmend an klinischer, ökonomischer und damit auch politischer Relevanz. "Arzneimittelsicherheit in der Psychiatrie" ist ein langjährig etabliertes Pharmakovigilanzprogramm, welches Medikamente nach deren Marktzulassung in der Psychiatrie überwacht. Von 1993 bis 2012 wurden bei 213 Fällen Leberwerterhöhungen unter Antipsychotikatherapie als schwere UAW nach den Definitionen von AMSP erfasst. Von 1993 bis 2002 galten jene Fälle als schwer, wenn laborchemisch ALT, AST > 100 U/L und/oder γGT > 200 U/L nachzuweisen war. Ab 2003 werden jene Fälle als schwer defininiert, bei denen ALT, AST, γGT oder AP um mehr als das Fünffache des oberern Referenzwertes erhöht sind. Für die Analysen der Laborwerte wurden die Fälle aufgrund der Vergleichbarkeit erst ab 2003 herangezogen (n = 134). Am häufigsten war die ALT (n = 103; 76,9 %) um mehr als das Fünffache der oberen Norm erhöht. Insgesamt fanden sich unter den 213 Fällen mit Leberwerterhöhung 150 Patienten (70,4 %), bei denen das Antipsychotikum alleine für das Auftreten der UAW angeschuldigt wurde. Unter den Kombinationsanschuldigungen waren die Kombinationen mit Antidepressiva am häufigsten (n = 31; 49,2 %), gefolgt von den Antipsychotika (n = 25; 39,7 %), wobei im Speziellen am häufigsten Olanzapin und die Antidepressiva Mirtazapin und Venlafaxin mit jeweils 9 Fällen in Kombination angeschuldigt wurden. Unter den Antipsychotika wurden die atypischen Antipsychotika am häufigsten angeschuldigt (n = 170; 70,2 %). Trotz der zahlreichen Alleinanschuldigungen wurden in 80,3 % der Fälle mit Leberwerterhöhung die Antipsychotika in Komedikation verabreicht, was unter dem Aspekt der Polypharmazie als Toxizitätsverstärkung vermutet werden könnte. Schwere Leberwerterhöhungen nach den Kriterien von AMSP sind insgesamt eher seltene UAWs. Olanzapin (0,18 %), Clozapin (0,12 %) und Perazin (0,12 %) wiesen dabei die höchste ermittelte Inzidenz der Leberwerterhöhung auf. Aus Studien ist ersichtlich, dass Olanzapin und Clozapin zu einer starken Gewichtszunahme führen und so das metabolische Syndrom mit konsekutiver Leberschädigung verursachen können, was die hohe Inzidenz erklären könnte. 95 % der Fälle erholten sich von der Leberwerterhöhung, was im Zusammenhang mit dem Absetzen (n = 170; 79,8 %) oder der Reduktion (n = 33; 15,5 %) des Antipsychotikums gesehen werden kann. Bei der Betrachtung der Altersgruppen (0-30; 31-60; 61-90; 91-120 Jahre) konnte gezeigt werden, dass die Inzidenz bei der jüngsten Altersgruppe am höchsten war (0,15 %) und mit dem Alter stetig abnahm. Diese Beobachtung war vorwiegend beim männlichen Geschlecht vorzufinden, wohingegen bei Frauen die Häufigkeit über das Alter relativ konstant blieb. Männer waren auch signifikant jünger als Frauen. Die gewonnenen Ergebnisse schaffen ein adäquates Bild über die Häufigkeiten und die schwierige Vorhersehbarkeit und Klassifzierung von schweren Leberwerterhöhungen, zeigen jedoch gerade anhand der schwerwiegenden Verläufe, dass es wichtig ist, die Möglichkeit des Auftretens dieser UAW zu kennen, um so früh wie möglich therapeutisch eingreifen zu können; auch nach schon jahrelanger Therapie. ; In recent years, the detection of side effects of various medical treatments has gained more clinical, economic, and political relevance. "Arzneimittelsicherheit in der Psychiatrie" is a well-established pharmacovigilance program, which supervises psychotropic drugs after they have been put on the market. From 1993 until 2012 AMSP charted 213 cases of severe liver enzyme elevation as a result of the use of psychotropic drugs. From 1993 until 2002, AMSP defined liver enzyme elevations as a severe side effect if ALT or AST became higher than 100 U/L and/or yGT became higher than 200 U/L in an individual's blood tests. Since 2003 those cases have been categorized as a severe drug reaction if a liver enzyme elevation of ALT, AST or yGT increased to higher than five times the upper reference value. In order to increase comparability, only the laboratory values from 2003 until 2012 were analyzed (n=134). Most frequently ALT was elevated to more than five times its upper reference value (n=103; 76,9%). All in all, in 150 of 213 cases (70,4%) of severe liver enzyme elevation, only a single antipsychotic drug was present. In the cases where drug combinations were used and where a severe drug reaction occurred, the presence of antipsychotic and anti-depressive drugs were found to be the most common combination (n=31; 49,2%), following the combination of two or more antipsychotic drugs (n=25; 39,7%). Specifically, the combination of Olanzapine and Mirtazapine or Olanzapine and Venlafaxine (9 cases each) were found to be the most common. Among antipsychotic drugs, the atypical ones were found to be more frequently responsible for causing severe liver enzyme elevation (n=170; 70,2%). Despite the fact that most antipsychotic drugs were present alone, co-medication was found to be a very frequent characteristic in all cases (80,3%). This can be explained by the notion that polypharmacy causes higher toxicity. Severe liver enzyme elevations are still very rare events. Olanzapine (0,18%), Clozapine (0,12%) and Perazine (0,12%) created the highest rates of severe liver enzyme elevations. Clinical studies have shown that Olanzapine and Clozapine can cause weight gain and result in metabolic syndrome, which can lead to liver toxicity. 95% of the individuals who experienced severe liver enzyme elevations recovered completely, most likely due to stopping (n=170; 79,8%) or reducing (n=33; 15,5%) the antipsychotic medication. Taking a look at the different age groups (0-30; 31-60; 61-90; 91-120 years), the rate of elevation in the youngest group was the highest (0,15%). This rate decreased inversely as the age of the group increased. This inverse relationship between severe liver enzyme elevation and the age of the group was most clearly found in the male groups. Men suffering from severe liver enzyme elevations under antipsychotic treatment were found to be significantly younger than women suffering from severe liver enzyme elevations under antipsychotic treatment. These results offer an adequate depiction of the rate, challenging predictability, and classification of severe liver enzyme elevations. The fatality rate of this affliction makes clear the importance of ascertaining the possibility of sever liver enzyme elevations in an individual as early as possible. ; 2019-01-31 ; 2019-12-31

Noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonists can produce positive and negative symptomatology as well as impairment of cognitive function that closely resemble those present in schizophrenia. In rats, these drugs induce a behavioral syndrome (characterized by hyperlocomotion and stereotypies), an enhanced glutamatergic transmission in the medial prefrontal cortex, and damage to retrosplenial cortical neurons in adult rats, which was measured as the induction of the stress protein 72/73 kDa heat shock protein (Hsp72/73). In the present work we have examined the existence of possible differences among different antipsychotic drugs in their capacity to block immunolabeling of Hsp72/73 in the retrosplenial cortex of the rat induced by the potent NMDA receptor antagonist, MK-801. In addition, the effects of selective monoaminergic agents were also studied to delineate the particular receptors responsible for the actions of antipsychotic drugs. Pretreatment with clozapine, chlorpromazine, olanzapine, ziprasidone -and to a lesser extent haloperidol- reduced the formation of Hsp72/73 protein in the rat retrosplenial cortex after the administration of MK-801. In addition, antagonism at dopamine D2 (raclopride), 5-HT2A (M100907) and α1-adrenoceptors (prazosin) as well as agonism at 5-HT1A receptors (BAY x 3702) also diminished the MK-801-induced number of cells labeled with Hsp72/73. Each of these effects may contribute to antipsychotic action. The results suggest that the efficacy of atypical antipsychotic drugs in the clinic may result from a combined effect on 5-HT2A, 5-HT1A and α1-adrenergic receptors added to the classical dopamine D2 receptor antagonism. ; This work was supported by the Instituto de Salud Carlos III, Subdirección General de Evaluación y Fomento de la Investigación (FIS Grants PI070111 and PI1001103), Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM, and by the Innovative Medicine Initiative Joint Undertaking under grant agreement no. 115008, of which resources are composed of EFPIA in-kind contribution and financial contribution from the European Union's Seventh Framework Programme (FP7/2007-2013). Funding by the Generalitat de Catalunya (2009SGR220) and co-funding by the European Regional Development Fund (a way to build Europe) is also acknowledged ; Peer reviewed

Introduction: Atypical antipsychotic drugs, with superior tolerability and possibly superior efficacy, were expected to give schizophrenia patients better quality of life (QOL) than conventional treatment. Research findings are equivocal. Method: We evaluated QOL using three subjective measures – Drug Attitude Inventory (DAI); Sickness Impact Profile (SIP); Schizophrenia Quality of Life Scale (SQLS) – in 126 routinely seen patients whose treatment was stable for six months, regardless of co-morbidity, current clinical status and concomitant medications. Severity of disorder was assessed with the Global Assessment Schedule (GAS). Results: Fifty patients were on conventional treatment and 76 on atypical treatment. Atypical patients were more likely to be abusing substances ( p = 0.02) and living independently ( p = 0.00). Conventionally treated patients were older than atypically treated patients. Conventionally treated patients suffered schizophrenia almost twice as long as atypically treated patients. Atypically treated patients enjoyed substantially better quality of life than conventionally treated patients on all measures. The effects of confounding variables, i.e. age, duration, accommodation, co-morbid substance misuse and time spent in hospital, were evaluated with the General Linear Model. This confirmed the status of drug treatment as the primary predictor of all aspects of QOL. Conclusion: We conclude that quality of life is genuinely superior on atypical treatment even allowing for the confounding effects of differential prescribing habits: atypical treatment tends to be reserved for younger, less seriously ill patients. There is no scientific or clinical rationale to support this practice.

Background: Recent studies analysing the trends in antipsychotic (AP) prescriptions for children and adolescents have raised concerns regarding the influence of socioeconomic status. Previous findings have also shown variable prescription rates for first-generation (FG) and second-generation (SG) APs.Method: Our objectives were to assess the proportion of patients from low-income families receiving APs and the most commonly prescribed APs in France. We conducted a descriptive analysis of AP drugs dispensed during a 1-year period (July 1, 2013-June 30, 2014) in a northwestern region of France with 941,857 subjects less than 18 years old. All data were extracted from an exhaustive, individual and anonymous social security database. We obtained each subject's socioeconomic status (by identifying their affiliation with a specific social security program) and also collected sociodemographic data, drug type, prescribing and dispensing dates and amount, and prescriber type (e.g., hospital physician, general practitioner, psychiatrist, paediatrician).Results: There were two main novel findings. First, we found that the proportion of patients with AP prescriptions was nearly ten times higher in low-income families than in the general population: 35.9% of CMU-C patients compared to 3.7% in all of Pays de la Loire (X-2 = 7875.1, p < 0.001). Additionally, we found a higher rate of FGAP than SGAP prescriptions (65% vs. 57%).Conclusions: Our study suggests two types of AP misuse that could provide interesting targets for public healthcare interventions.First, our results strongly suggest an over-representation of patients from low-income families. Low-income families primarily resided in areas with low physician density and appeared to receive drugs to treat their conditions more frequently than other individuals. This increased prescription rate is a public health issue, potentially requiring political action. Second, the use of FGAPs did not adhere to the latest recommendations for drug use in this population, and this discrepancy should be addressed with informational campaigns targeted to medical practitioners.

Campaigns to scale up mental health services in low-income countries emphasise the need to improve access to psychotropic medication as part of effective treatment yet there is little acknowledgement of the limitations of psychotropic drugs as perceived by those who use them. This paper considers responses to treatment with antipsychotics by people with mental illness and their families in rural Ghana, drawing on an anthropological study of family experiences and help seeking for mental illness. Despite a perception among health workers that there was little popular awareness of biomedical treatment for mental disorders, psychiatric services had been used by almost all informants. However, in many cases antipsychotic treatment had been discontinued, even where it had been recognised to have beneficial effects such as controlling aggression or inducing sleep. Unpleasant side effects such as feelings of weakness and prolonged drowsiness conflicted with notions of health as strength and were seen to reduce the ability to work. The reduction of perceptual experiences such as visions was less valued than a return to social functioning. The failure of antipsychotics to achieve a permanent cure also cast doubt on their efficacy and strengthened suspicions of a spiritual illness which would resist medical treatment. These findings suggest that efforts to improve the treatment of mental disorders in low-income countries should take into account the limitations of antipsychotic drugs for those who use them and consider how local resources and concepts of recovery can be used to maximise treatment and support families.