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  • 1.
    Jönsson, Anna K
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology. Natl Board Forens Med, Dept Forens Genet and Forens Chem, Linkoping, Sweden.
    Schill, Johan
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Jönköping, Sweden.
    Olsson, Hans
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Psychiatry. Region Jönköping, Sweden.
    Spigset, Olav
    St Olavs Univ Hosp, Norway; Norwegian Univ Sci and Technol, Norway.
    Hägg, Staffan
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology.
    Venous Thromboembolism During Treatment with Antipsychotics: A Review of Current Evidence2018In: CNS Drugs, ISSN 1172-7047, E-ISSN 1179-1934, Vol. 32, no 1, p. 47-64Article, review/survey (Refereed)
    Abstract [en]

    This article summarises the current evidence on the risk of venous thromboembolism (VTE) with the use of antipsychotics. An increasing number of observational studies indicate an elevated risk of VTE in antipsychotic drug users. Although the use of certain antipsychotics has been associated with VTE, current data can neither conclusively verify differences in occurrence rates of VTE between first- and second-generation antipsychotics or between individual compounds, nor identify which antipsychotic drugs have the lowest risk of VTE. The biological mechanisms involved in the pathogenesis of this adverse drug reaction are still to be clarified but hypotheses such as drug-induced sedation, obesity, increased levels of antiphospholipid antibodies, enhanced platelet aggregation, hyperhomocysteinaemia and hyperprolactinaemia have been suggested. Risk factors associated with the underlying psychiatric disorder may at least partly explain the increased risk. Physicians should be aware of this potentially serious and even sometimes fatal adverse drug reaction and should consider discontinuing or switching the antipsychotic treatment in patients experiencing a VTE. Even though supporting evidence is limited, prophylactic antithrombotic treatment should be considered in risk situations for VTE.

  • 2.
    Jönsson, Anna K.
    et al.
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Pharmacology.
    Spigset, Olav
    Department of Clinical Pharmacology, St. Olav University Hospital, Trondheim, Norway.
    Hägg, Staffan
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Pharmacology.
    Venous Thromboembolism in Recipients of Antipsychotics: Incidence, Mechanisms and Management2012In: CNS Drugs, ISSN 1172-7047, E-ISSN 1179-1934, Vol. 26, no 8, p. 649-662Article, review/survey (Refereed)
    Abstract [en]

    Since chlorpromazine was introduced to the market in the early 1950s, theuse of antipsychotic drugs has been associated with venous thromboembolism(VTE) in a number of reports. During the last decade the evidence hasbeen strengthened with large epidemiological studies. Whether all antipsychoticsincrease the risk for VTE or the risk is confined to certain drugs is stillunclear. The aim of this article is to present an updated critical reviewfocusing on the incidence, mechanisms and management of VTE in users ofantipsychotics. After searching the databases PubMed and Scopus for relevantarticles we identified 12 observational studies, all of which were publishedafter the year 2000. In most of these studies an elevated risk of VTE wasobserved for antipsychotic drugs, with the highest risk for clozapine, olanzapineand low-potency first-generation antipsychotics. The risk seems to becorrelated with dose. The elderly, who mainly use lower doses, do not showan increased risk of VTE to the same extent as younger subjects.The underlying biological mechanisms explaining the association betweenantipsychotic medication and VTE are to a large extent unknown. Severalhypotheses have been proposed, such as body weight gain, sedation, enhancedplatelet aggregation, increased levels of antiphospholipid antibodies,hyperprolactinaemia and hyperhomocysteinaemia. The risk of VTE in schizophreniaand other psychotic disorders may also be related to the underlyingdisease rather than the medication.Very limited evidence exists to guide how cases of VTE in subjects usingantipsychotics should be handled. An attempt to compile an algorithm wherethe patients’ individual risk of VTE is assessed and preventive clinical measuresare suggested has been published recently. Strong consideration shouldbe given to discontinuation of the offending antipsychotic drug in patientsexperiencing a VTE, and another antipsychotic drug with a presumably lowerrisk should be chosen if antipsychotic drug treatment is still indicated. It isessential that physicians and patients are aware that VTE may be an adversedrug reaction to the antipsychotic treatment so the condition is identifiedearly and treated appropriately.

  • 3.
    Nussbaumer, Barbara
    et al.
    Department for Evidence-based Medicine and Clinical Epidemiology, Danube University, Krems, Austria.
    Morgan, Laura C.
    Research Triangle Institute Int, NC 27709 USA.
    Reichenpfader, Ursula
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences. Department for Evidence-based Medicine and Clinical Epidemiology, Danube University, Krems, Austria.
    Greenblatt, Amy
    Research Triangle Institute Int, NC 27709 USA.
    Hansen, Richard A.
    Auburn University, AL 36849 USA.
    Van Noord, Megan
    Department for Evidence-based Medicine and Clinical Epidemiology, Danube University, Krems, Austria.
    Lux, Linda
    Research Triangle Institute Int, NC 27709 USA.
    Gaynes, Bradley N.
    University of N Carolina, NC 27599 USA.
    Gartlehner, Gerald
    Danube University of Krems, Austria; Research Triangle Institute Int, NC 27709 USA.
    Comparative Efficacy and Risk of Harms of Immediate- versus Extended-Release Second-Generation Antidepressants: A Systematic Review with Network Meta-Analysis2014In: CNS Drugs, ISSN 1172-7047, E-ISSN 1179-1934, Vol. 28, no 8, p. 699-712Article, review/survey (Refereed)
    Abstract [en]

    Major depressive disorder (MDD) has detrimental effects on an individuals personal life, leads to increased risk of comorbidities, and places an enormous economic burden on society. Several second-generation antidepressants are available as both immediate-release (IR) and extended-release formulations. The advantage of extended-release formulations may be the potentially improved adherence and a lower risk of adverse events. We conducted a systematic review to assess the comparative efficacy, risk of harms, and patients adherence of IR and extended-release antidepressants for the treatment of MDD. English-language abstracts were retrieved from PubMed, EMBASE, the Cochrane Library, PsycINFO, and International Pharmaceutical Abstracts from 1980 to October 2012, as well as from reference lists of pertinent review articles and grey literature searches. We included head-to-head randomized controlled trials (RCTs) of at least 6 weeks duration that compared an IR formulation with an extended-release formulation of the same antidepressant in adult patients with MDD. We also included placebo-controlled trials to conduct a network meta-analysis. To assess harms and adherence, in addition to RCTs, we searched for observational studies with a parts per thousand yen1,000 participants and a follow-up of a parts per thousand yen12 weeks. We dually reviewed abstracts and full texts and assessed quality ratings. Lacking head-to-head evidence for many comparisons of interest, we conducted network meta-analyses using Bayesian methods. Our outcome measure of choice was response on the Hamilton Depression Rating Scale. We located seven head-to-head trials and 94 placebo- and active-controlled trials for network meta-analysis. Overall, our analyses indicate that IR and extended-release formulations do not differ substantially with respect to efficacy and risk of harms. The evidence is mixed with respect to differences in adherence, indicating lower adherence for IR formulations. The lack of head-to-head comparisons for many drugs compromises our conclusions. Network meta-analyses have methodological limitations that need to be taken into consideration when interpreting findings. Available evidence currently shows no clear differences between the two formulations and therefore we cannot recommend a first choice. However, if adherence or compliance with one medication is an issue, then clinicians and patients should consider the alternative medication. If adherence or costs are a problem with one formulation, consideration of the other formulation to provide an adequate treatment trial is reasonable.

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