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20-Year Nationwide Follow-Up Study on Discontinuation of Antipsychotic Treatment in First-Episode Schizophrenia.

https://arctichealth.org/en/permalink/ahliterature301781
Source
Am J Psychiatry. 2018 08 01; 175(8):765-773
Publication Type
Journal Article
Research Support, Non-U.S. Gov't
Date
08-01-2018
Author
Jari Tiihonen
Antti Tanskanen
Heidi Taipale
Author Affiliation
From the Department of Clinical Neuroscience, Karolinska Institutet, Stockholm; the Department of Forensic Psychiatry, University of Eastern Finland, and Niuvanniemi Hospital, Kuopio; the Impact Assessment Unit, National Institute for Health and Welfare, Helsinki; and the School of Pharmacy, University of Eastern Finland, Kuopio.
Source
Am J Psychiatry. 2018 08 01; 175(8):765-773
Date
08-01-2018
Language
English
Publication Type
Journal Article
Research Support, Non-U.S. Gov't
Keywords
Adult
Antipsychotic Agents - administration & dosage - therapeutic use
Female
Finland - epidemiology
Follow-Up Studies
Hospitalization - statistics & numerical data
Humans
Male
Middle Aged
Proportional Hazards Models
Recurrence
Registries
Risk factors
Schizophrenia - drug therapy
Withholding Treatment
Abstract
It is generally believed that after the first episode of schizophrenia, the risk of relapse decreases with time in patients who are stabilized. Many treatment guidelines recommend that after stabilization, antipsychotic treatment should be continued for 1-5 years, and longer exposure should be avoided if possible. However, there is no published evidence to substantiate this view. The authors used nationwide databases to investigate this issue.
Prospectively gathered nationwide register data were used to study the risk of treatment failure (psychiatric rehospitalization or death) after discontinuation of antipsychotic treatment. Multivariate Cox regression was used to assess outcomes among all patients hospitalized for the first time with a schizophrenia diagnosis in Finland during the period of 1996-2014 (N=8,719).
The lowest risk of rehospitalization or death was observed for patients who received antipsychotic treatment continuously (adjusted hazard ratio=1.00), followed by patients who discontinued antipsychotic use immediately after discharge from the first hospital treatment (hazard ratio=1.63, 95% CI=1.52-1.75), within 1 year (hazard ratio=1.88, 95% CI=1.57-2.24), within 1-2 years (hazard ratio=2.12, 95% CI=1.43-3.14), within 2-5 years (hazard ratio=3.26, 95% CI=2.07-5.13), and after 5 years (a median of 7.9 years) (hazard ratio=7.28, 95% CI=2.78-19.05). Risk of death was 174%-214% higher among nonusers and patients with early discontinuation of antipsychotics compared with patients who received antipsychotic treatment continuously for up to 16.4 years.
Whatever the underlying mechanisms, these results provide evidence that, contrary to general belief, the risk of treatment failure or relapse after discontinuation of antipsychotic use does not decrease as a function of time during the first 8 years of illness, and that long-term antipsychotic treatment is associated with increased survival.
Notes
CommentIn: Am J Psychiatry. 2018 Aug 1;175(8):712-713 PMID 30064241
CommentIn: Am J Psychiatry. 2018 Sep 1;175(9):908-909 PMID 30173547
CommentIn: Am J Psychiatry. 2018 Sep 1;175(9):909 PMID 30173555
CommentIn: Am J Psychiatry. 2018 Dec 1;175(12):1266-1267 PMID 30501413
CommentIn: Am J Psychiatry. 2018 Dec 1;175(12):1267 PMID 30501421
PubMed ID
29621900 View in PubMed
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Aberrant functioning of the putamen links delusions, antipsychotic drug dose, and compromised connectivity in first episode psychosis--Preliminary fMRI findings.

https://arctichealth.org/en/permalink/ahliterature270781
Source
Psychiatry Res. 2015 Aug 30;233(2):201-11
Publication Type
Article
Date
Aug-30-2015
Author
Tuukka T Raij
Teemu Mäntylä
Tuula Kieseppä
Jaana Suvisaari
Source
Psychiatry Res. 2015 Aug 30;233(2):201-11
Date
Aug-30-2015
Language
English
Publication Type
Article
Keywords
Adolescent
Adult
Antipsychotic Agents - administration & dosage - adverse effects
Case-Control Studies
Delusions - drug therapy - physiopathology
Female
Finland
Humans
Magnetic Resonance Imaging
Male
Nerve Net - drug effects - physiopathology
Psychiatric Status Rating Scales
Psychotic Disorders - drug therapy - physiopathology
Putamen - drug effects - physiopathology
Young Adult
Abstract
The dopamine theory proposes the relationship of delusions to aberrant signaling in striatal circuitries that can be normalized with dopamine D2 receptor-blocking drugs. Localization of such circuitries, as well as their upstream and downstream signaling, remains poorly known. We collected functional magnetic resonance images from first-episode psychosis patients and controls during an audiovisual movie. Final analyses included 20 patients and 20 controls; another sample of 10 patients and 10 controls was used to calculate a comparison signal-time course. We identified putamen circuitry in which the signal aberrance (poor correlation with the comparison signal time course) was predicted by the dopamine theory, being greater in patients than controls; correlating positively with delusion scores; and correlating negatively with antipsychotic-equivalent dosage. In Granger causality analysis, patients showed a compromised contribution of the cortical salience network to the putamen and compromised contribution of the putamen to the default mode network. Results were corrected for multiple comparisons at the cluster level with primary voxel-wise threshold p
PubMed ID
26184459 View in PubMed
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[Acute delusional psychosis and neuroleptic malignant syndrome after emigration of a Russian German patient].

https://arctichealth.org/en/permalink/ahliterature208497
Source
Psychiatr Prax. 1997 May;24(3):147-9
Publication Type
Article
Date
May-1997
Author
J. Podschus
J. Kirsch
R. van Heys
B. Winzer
Author Affiliation
Psychiatrische Klinik Intensiv- und Kriseninterventionsstation Freie Universität Berlin.
Source
Psychiatr Prax. 1997 May;24(3):147-9
Date
May-1997
Language
German
Publication Type
Article
Keywords
Adult
Antipsychotic Agents - administration & dosage - adverse effects
Delusions - diagnosis - drug therapy - psychology
Drug Therapy, Combination
Emigration and Immigration
Ethnic Groups - psychology
Germany
Haloperidol - administration & dosage - adverse effects
Humans
Male
Methotrimeprazine - administration & dosage - adverse effects
Neuroleptic Malignant Syndrome - diagnosis - drug therapy - psychology
Paranoid Disorders - diagnosis - drug therapy - psychology
Psychiatric Status Rating Scales
Psychotic Disorders - diagnosis - drug therapy - psychology
Siberia - ethnology
Abstract
Emigration is often followed by psychic disorders. The special issue of Germans from the GUS-States immigrating to Germany is presented. The modus of paranoid reaction is discussed along the biography and the criteria of ICD 10. The acute paranoid psychosis was complicated by a neuroleptic malignant syndrome.
PubMed ID
9273559 View in PubMed
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Adverse effects associated with high-dose olanzapine therapy in patients admitted to inpatient psychiatric care.

https://arctichealth.org/en/permalink/ahliterature105792
Source
Clin Toxicol (Phila). 2014 Jan;52(1):39-43
Publication Type
Article
Date
Jan-2014
Author
A B Petersen
S E Andersen
M. Christensen
H L Larsen
Author Affiliation
Department of Clinical Pharmacology, Bispebjerg Hospital , Copenhagen , Denmark.
Source
Clin Toxicol (Phila). 2014 Jan;52(1):39-43
Date
Jan-2014
Language
English
Publication Type
Article
Keywords
Adult
Antipsychotic Agents - administration & dosage - adverse effects - therapeutic use
Basal Ganglia Diseases - chemically induced - epidemiology
Benzodiazepines - administration & dosage - adverse effects - therapeutic use
Central Nervous System - drug effects
Denmark - epidemiology
Depression, Chemical
Drug Overdose - epidemiology - mortality
Electrocardiography - drug effects
Female
Hospitals, Psychiatric
Humans
Inpatients
Long QT Syndrome - chemically induced
Male
Neuroleptic Malignant Syndrome - physiopathology
Psychotic Disorders - complications - drug therapy
Retrospective Studies
Risk assessment
Abstract
In 2012, Danish psychiatrist raised concerns regarding the use of high-dose olanzapine in the treatment of patients. The present study was part of an audit carried out by the Mental Health Services of the Capitol Region of Denmark regarding this topic. Objective. To assess the potential risks associated with high-dose olanzapine treatment (> 40 mg daily) in inpatient psychiatric units.
The study was an observational case series based on review of patient charts. The main inclusion criterion was treatment with at least one daily dose > 40 mg olanzapine during the index admission in the period between 1st of January and 15th of March 2012. Six additional criteria were applied in order to target the subgroup of patients most likely to have experienced an adverse event due to treatment with olanzapine. The physician order entry system and the central patient register containing patient specific information about diagnoses and treatments were used for identification of study population.
The 91 patients included in the study received maximum daily doses of olanzapine ranging from 45 to 160 mg and in 25% of patients, the total antipsychotic load exceeded 2000 mg of chlorpromazine equivalents. Extrapyramidal symptoms and sedation were the most frequent adverse events with frequencies of 27% and 25%, respectively. Furthermore, other well-known adverse events such as weight gain (14%), hypotension (2%), neuroleptic malignant syndrome (2%) and corrected QT-interval (QTc) prolongation (1%) were also observed in some patients. Five patients died and in two of these cases, olanzapine was concluded to be a possible contributing cause of death.
Increased frequency of extrapyramidal symptoms and sedation as well as severe toxicity was observed in patients treated with up to 160 mg olanzapine per day. In order to prevent harmful outcomes, the clinicians should be ready to act appropriately if toxic effects of olanzapine occur. Treatment cessation should be immediate if serious adverse events such as neuroleptic malignant syndrome arise.
PubMed ID
24313745 View in PubMed
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Antidepressants and antipsychotics classified with torsades de pointes arrhythmia risk and mortality in older adults - a Swedish nationwide study.

https://arctichealth.org/en/permalink/ahliterature278475
Source
Br J Clin Pharmacol. 2016 Apr;81(4):773-83
Publication Type
Article
Date
Apr-2016
Author
Bengt Danielsson
Julius Collin
Gudrun Jonasdottir Bergman
Natalia Borg
Peter Salmi
Johan Fastbom
Source
Br J Clin Pharmacol. 2016 Apr;81(4):773-83
Date
Apr-2016
Language
English
Publication Type
Article
Keywords
Aged, 80 and over
Antidepressive Agents - administration & dosage - adverse effects - classification - therapeutic use
Antipsychotic Agents - administration & dosage - adverse effects - classification - therapeutic use
Drug Prescriptions - statistics & numerical data
Female
Humans
Logistic Models
Male
Mortality - trends
Multivariate Analysis
Registries
Risk
Sweden - epidemiology
Torsades de Pointes - chemically induced - mortality
Abstract
The aim of the study was to examine mortality risk associated with use of antidepressants and antipsychotics classified with torsades de pointes (TdP) risk in elderly.
A matched case-control register study was conducted in people 65 years and older dying outside hospital from 2008-2013 (n = 286,092) and matched controls (n = 1,430,460). The association between prescription of antidepressants and antipsychotics with various TdP risk according to CredibleMeds (www.crediblemeds.org) and all-cause mortality was studied by multivariate conditional logistic regression adjusted for comorbidity and several other confounders.
Use of antidepressants classified with known or possible TdP risk, was associated with higher adjusted risk for mortality (OR 1.53, 95% CI 1.51, 1.56 and OR 1.63, 95% CI 1.61, 1.67, respectively) compared with antidepressants classified with conditional TdP risk (OR 1.25, 95% CI 1.22, 1.28) or without TdP classification (OR 0.99, 95% CI 0.94, 1.05). Antipsychotics classified with known TdP risk were associated with higher risk (OR 4.57, 95% CI 4.37, 4.78) than antipsychotics with possible risk (OR 2.58, 95% CI 2.52, 2.64) or without TdP classification (OR 2.14, 95% CI 2.03, 2.65). The following risk ranking was observed for commonly used antidepressants: mirtazapine > citalopram > sertraline > amitriptyline and for antipsychotics: haloperidol > risperidone >olanzapine > quetiapine.
The CredibleMeds system predicted drug-associated risk for mortality in the elderly at the risk class level. Among antipsychotics, haloperidol, and among antidepressants, mirtazapine and citalopram, were associated with the highest risks. The results suggest that the TdP risk with antidepressants and antipsychotics should be taken into consideration when prescribing to the elderly.
Notes
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PubMed ID
26574175 View in PubMed
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Antipsychotic doses among community-dwelling persons with Alzheimer disease in Finland.

https://arctichealth.org/en/permalink/ahliterature266764
Source
J Clin Psychopharmacol. 2014 Aug;34(4):435-40
Publication Type
Article
Date
Aug-2014
Author
Heidi Taipale
Marjaana Koponen
Antti Tanskanen
Anna-Maija Tolppanen
Jari Tiihonen
Sirpa Hartikainen
Source
J Clin Psychopharmacol. 2014 Aug;34(4):435-40
Date
Aug-2014
Language
English
Publication Type
Article
Keywords
Aged, 80 and over
Alzheimer Disease - drug therapy - epidemiology - psychology
Antipsychotic Agents - administration & dosage
Cohort Studies
Dose-Response Relationship, Drug
Female
Finland - epidemiology
Follow-Up Studies
Humans
Male
Residence Characteristics
Abstract
Use of antipsychotics for treatment of behavioral and psychological symptoms of dementia is frequent among persons with Alzheimer disease (AD). Doses used in long-term therapy have not been previously reported. We describe antipsychotic doses used among community-dwelling persons with AD and investigate factors associated with high-dose use. The MEDALZ-2005 (Medication use and Alzheimer disease) cohort is a nationwide sample including all persons with clinically diagnosed AD at the end of year 2005 in Finland (n = 28,093). Data including prescriptions, comorbidities, and hospital discharge diagnoses were collected from nationwide registers. Antipsychotic doses in monotherapy were investigated during 2006 to 2009. Among 8920 antipsychotic users, 4% (n = 336) used antipsychotics with high dose. Typical antipsychotics were more often used with high dose than atypical antipsychotics. High-dose use was associated with younger age (
PubMed ID
24875073 View in PubMed
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Antipsychotic dosing patterns for schizophrenia in three treatment settings.

https://arctichealth.org/en/permalink/ahliterature196219
Source
Psychiatr Serv. 2001 Jan;52(1):96-8
Publication Type
Article
Date
Jan-2001
Author
G. Remington
C M Shammi
R. Sethna
R. Lawrence
Author Affiliation
Department of Psychiatry, University of Toronto, Ontario, Canada. gary_remington@camh.net
Source
Psychiatr Serv. 2001 Jan;52(1):96-8
Date
Jan-2001
Language
English
Publication Type
Article
Keywords
Adult
Antipsychotic Agents - administration & dosage
Canada
Chlorpromazine - administration & dosage
Dosage Forms
Drug Utilization - statistics & numerical data
Drug Utilization Review
Female
Guideline Adherence
Hospitals, Community - statistics & numerical data
Hospitals, County - statistics & numerical data
Hospitals, Teaching - statistics & numerical data
Humans
Inpatients - statistics & numerical data
Male
Outpatients - statistics & numerical data
Practice Guidelines as Topic
Retrospective Studies
Schizophrenia - drug therapy
Therapeutic Equivalency
Abstract
Daily dosages of antipsychotic medications were evaluated to determine whether current guidelines advocating lower dosing are being followed. A chart review of 163 outpatients with schizophrenia was undertaken in three outpatient hospital settings-a general community hospital, a provincial hospital, and an academic teaching hospital. The daily dosage in chlorpromazine equivalents was significantly higher in the provincial hospital (773.8 mg) than in the community hospital (355 mg) or the academic hospital (424.8 mg). A greater proportion of patients at the provincial hospital received conventional antipsychotics than novel antipsychotics or depot antipsychotics, and a greater proportion received more than one antipsychotic.
PubMed ID
11141536 View in PubMed
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Antipsychotic Drugs and Risk of Hip Fracture in People Aged 60 and Older in Norway.

https://arctichealth.org/en/permalink/ahliterature284004
Source
J Am Geriatr Soc. 2016 Jun;64(6):1203-9
Publication Type
Article
Date
Jun-2016
Author
Marit S Bakken
Jan Schjøtt
Anders Engeland
Lars B Engesaeter
Sabine Ruths
Source
J Am Geriatr Soc. 2016 Jun;64(6):1203-9
Date
Jun-2016
Language
English
Publication Type
Article
Keywords
Aged
Antipsychotic Agents - administration & dosage
Female
Hip Fractures - epidemiology
Humans
Incidence
Male
Middle Aged
Norway - epidemiology
Registries
Risk factors
Abstract
To examine associations between exposure to various subgroups of antipsychotic drugs and risk of hip fracture in older adults.
Nationwide cohort study.
Norway, 2005-2010.
Everyone living in Norway born before 1945 (N = 906,422).
Information was obtained on all prescriptions of antipsychotic drugs dispensed from 2004 to 2010 (Norwegian Prescription Database) and data on all primary hip fractures from 2005 to 2010 (Norwegian Hip Fracture Registry). Incidence rates of hip fracture during person-time exposed and unexposed to antipsychotic drugs were compared by calculating the standardized incidence ratio (SIR).
Thirty-nine thousand nine hundred thirty-eight (4.4%) participants experienced a primary hip fracture. Greater risk of hip fracture was associated with exposure to any antipsychotic (SIR = 2.1, 95% confidence interval (CI) = 1.9-2.1), first-generation antipsychotics (SIR = 2.0, 95% CI = 1.8-2.2), second-generation antipsychotics (SIR = 2.2, 95% CI = 1.9-2.4), prolactin-sparing antipsychotics (SIR = 2.4, 95% CI = 1.8-3.1) and prolactin-elevating antipsychotics (SIR = 2.0, 95% CI = 1.9-2.2).
In people aged 60 and older in Norway, those who took an antipsychotic drug had twice the risk of sustaining a hip fracture during exposure than during nonexposure. Although confounding by indication, comorbidity, or other drugs used cannot be excluded, this association is relevant for clinical practice because hip fracture and antipsychotic drug use are prevalent in vulnerable older individuals. Clinical studies examining mechanisms or causality of the observed association between antipsychotic drug use and excess risk of hip fracture are needed.
PubMed ID
27321599 View in PubMed
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Antipsychotic drug treatment in the prodromal phase of schizophrenia.

https://arctichealth.org/en/permalink/ahliterature189535
Source
Am J Psychiatry. 2002 Jul;159(7):1230-2
Publication Type
Article
Date
Jul-2002
Author
Tyrone D Cannon
Matti O Huttunen
Minna Dahlström
Ilkka Larmo
Pirkko Räsänen
Alo Juriloo
Author Affiliation
Department of Psychology, University of California-Los Angeles, 1285 Franz Hall, Los Angeles, CA 90095, USA. cannon@psych.ucla.edu
Source
Am J Psychiatry. 2002 Jul;159(7):1230-2
Date
Jul-2002
Language
English
Publication Type
Article
Keywords
Adolescent
Adult
Antipsychotic Agents - administration & dosage - therapeutic use
Drug Administration Schedule
Family
Female
Finland - epidemiology
Humans
Male
Neuropsychological Tests
Psychiatric Status Rating Scales
Risperidone - administration & dosage - therapeutic use
Schizophrenia - drug therapy - epidemiology
Schizophrenic Psychology
Severity of Illness Index
Treatment Outcome
Verbal Learning
Abstract
The safety and tolerability of short-term treatment with a low dose of risperidone was evaluated in adolescents with prodromal symptoms and a family history of schizophrenia.
Four prodromal high-risk adolescents and six first-episode patients with schizophrenia were treated with average doses of 1.0 and 1.8 mg/day of risperidone, respectively, in an 8- to 12-week open-label trial.
No significant treatment-related adverse events were noted. Severity of thought and behavior disturbance ratings declined by about 30%; performance on a test of verbal learning improved by about 100% during treatment in both prodromal and first-episode patients, changes that achieved statistical significance despite the small group sizes.
These findings are preliminary and should not be used to guide health care decisions at this time. Randomized controlled trials are needed to determine whether antipsychotic drug treatment of prodromal patients can delay or prevent onset or attenuate the clinical course of schizophrenia.
PubMed ID
12091205 View in PubMed
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126 records – page 1 of 13.