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      Compliance with the guidelines for laboratory monitoring of patients treated with lithium: A retrospective follow‐up study among ambulatory patients in the Netherlands

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          Abstract

          Objectives

          Laboratory monitoring of patients using lithium is important to prevent harm and to increase effectiveness. The aim of this study is to determine compliance with the guidelines for laboratory monitoring of patients treated with lithium overall and within subgroups.

          Methods

          Patients having at least one lithium dispensing for 6 months or longer between January 2010 and December 2015 were identified retrospectively using data from the Dutch PHARMO Database Network. Laboratory monitoring was defined as being compliant with the Dutch Multidisciplinary Clinical Guideline Bipolar Disorders when lithium serum levels, creatinine and thyroid‐stimulating hormone (TSH) had been measured at least every 6 months during lithium use.

          Results

          Data were analyzed from 1583 patients with a median duration of 7‐ to 6‐months period of lithium use. Results indicated that patients had been monitored over 6‐month period for lithium serum levels 65% of the time, for creatinine 73% of the time and for TSH 54% of the time. Just over one seventh (16%) of patients had been monitored in compliance with the guidelines for all three parameters during total follow‐up. Especially males, patients aged below 65 years, patients receiving prescriptions solely from general practitioners, prevalent users of lithium, patients without interacting co‐medication, and patients without other days with laboratory measurements had been monitored less frequently in compliance with the guidelines.

          Conclusions

          A considerable proportion of patients had not been monitored in accordance with the guidelines. Further research is needed to understand the reasons for noncompliance and to implement strategies with the ultimate goal of optimizing safety and effectiveness for patients treated with lithium.

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          Most cited references31

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          The use of lithium for the treatment of bipolar disorder: Recommendations from clinical practice guidelines.

          Lithium is an effective mood stabilizer that is used principally for the management of bipolar disorder (BD). Its administration is complex and often requires sophisticated management and assiduous monitoring. When considering the use of lithium therapy for bipolar disorder, clinicians are advised to refer to recommendations outlined in clinical practice guidelines (CPGs); but because of varying emphases placed by different international CPGs, recommendations addressing the practical use of lithium lack consistency.
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            Long-term lithium treatment in bipolar disorder: effects on glomerular filtration rate and other metabolic parameters

            Background Concerns about potential adverse effects of long-term exposure to lithium as a mood-stabilizing treatment notably include altered renal function. However, the incidence of severe renal dysfunction; rate of decline over time; effects of lithium dose, serum concentration, and duration of treatment; relative effects of lithium exposure vs. aging; and contributions of sex and other factors all remain unclear. Methods Accordingly, we acquired data from 12 collaborating international sites and 312 bipolar disorder patients (6142 person-years, 2669 assays) treated with lithium carbonate for 8–48 (mean 18) years and aged 20–89 (mean 56) years. We evaluated changes of estimated glomerular filtration rate (eGFR) as well as serum creatinine, urea–nitrogen, and glucose concentrations, white blood cell count, and body-mass index, and tested associations of eGFR with selected factors, using standard bivariate contrasts and regression modeling. Results Overall, 29.5% of subjects experienced at least one low value of eGFR (  55; risk of ≥2 low values was 18.1%; none experienced end-stage renal failure. eGFR declined by 0.71%/year of age and 0.92%/year of treatment, both by 19% more among women than men. Mean serum creatinine increased from 0.87 to 1.17 mg/dL, BUN from 23.7 to 33.1 mg/dL, glucose from 88 to 122 mg/dL, and BMI from 25.9 to 26.6 kg/m2. By multivariate regression, risk factors for declining eGFR ranked: longer lithium treatment, lower lithium dose, higher serum lithium concentration, older age, and medical comorbidity. Later low eGFR was also predicted by lower initial eGFR, and starting lithium at age ≥ 40 years. Limitations Control data for age-matched subjects not exposed to lithium were lacking. Conclusions Long-term lithium treatment was associated with gradual decline of renal functioning (eGFR) by about 30% more than that was associated with aging alone. Risk of subnormal eGFR was from 18.1% (≥2 low values) to 29.5% (≥1 low value), requiring about 30 years of exposure. Additional risk factors for low eGFR were higher serum lithium level, longer lithium treatment, lower initial eGFR, and medical comorbidity, as well as older age.
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              Clinical relevance of drug-drug interactions : a structured assessment procedure.

              Computerised drug interaction surveillance systems (CIS) may be helpful in detecting clinically significant drug interactions. Experience with CIS reveals that they often yield alerts with questionable clinical significance, fail to provide relevant information on risk factors for the adverse reaction of the interaction and fail to detect all significant drug interactions. These problems highlight the importance of transparency and selectivity in choosing the drug interactions to be included in CIS. In The Netherlands, the Working Group on Pharmacotherapy and Drug Information is responsible for maintenance of the CIS of the Royal Dutch Association for the Advancement of Pharmacy (KNMP). The Working Group developed an evidence-based procedure for structured assessment of drug-drug interactions and revised all drug interactions in the CIS accordingly. For every drug interaction four core parameters were assessed: (i) evidence on the interaction; (ii) clinical relevance of the potential adverse reaction resulting from the interaction; (iii) risk factors identifying patient, medication or disease characteristics for which the interaction is of special importance; and (iv) the incidence of the adverse reaction. On the basis of this assessment the drug-drug interactions for inclusion in the CIS were selected. After revision of the drug combinations in the KNMP-CIS, the Working Group judged 22% of the combinations to be not interacting and another 12% to be interacting but not requiring action. On the basis of this assessment the subset of drug combinations for which interaction alerts are generated and the information on management of a drug interaction alert for users of the CIS were adapted. When an alert is generated by the CIS, the user of the system is supplied with comprehensive information on the four core parameters, the mechanism of the interaction and critical information for management of the interaction for the individual patient. This structured procedure offers the possibility for transparent and reproducible assessment of the clinical relevance of drug interactions. A CIS selectively generating interaction alerts based on this assessment may help in realising the goal of good clinical practice and may offer a methodology to further increase drug safety.
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                Author and article information

                Contributors
                e.r.heerdink@uu.nl
                Journal
                Bipolar Disord
                Bipolar Disord
                10.1111/(ISSN)1399-5618
                BDI
                Bipolar Disorders
                John Wiley and Sons Inc. (Hoboken )
                1398-5647
                1399-5618
                02 January 2019
                August 2019
                : 21
                : 5 ( doiID: 10.1111/bdi.v21.5 )
                : 419-427
                Affiliations
                [ 1 ] Division of Pharmacoepidemiology and Clinical Pharmacology Utrecht Institute for Pharmaceutical Sciences, Utrecht University Utrecht The Netherlands
                [ 2 ] Brocacef Ziekenhuisfarmacie Maarssen The Netherlands
                [ 3 ] Clinical Pharmacy University Medical Center Utrecht Utrecht The Netherlands
                [ 4 ] Transparant Centre for Psychiatry Leiden The Netherlands
                [ 5 ] Department of Psychiatry Leiden University Medical Center Leiden The Netherlands
                [ 6 ] SCAL Medical Diagnostics Leiden The Netherlands
                [ 7 ] PHARMO Institute for Drug Outcomes Research Utrecht The Netherlands
                [ 8 ] Department of Epidemiology and Biostatistics VU University Medical Center Amsterdam Netherlands
                [ 9 ] Research Group Innovation of Pharmaceutical Care University of Applied Sciences Utrecht Utrecht The Netherlands
                Author notes
                [*] [* ] Correspondence

                Eibert R Heerdink, Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.

                Email: e.r.heerdink@ 123456uu.nl

                Author information
                https://orcid.org/0000-0002-5946-7209
                Article
                BDI12730
                10.1111/bdi.12730
                6767377
                30472760
                1672cdc6-6dc3-4738-a8d4-0431e31758ff
                © 2018 The Authors. Bipolar Disorders Published by John Wiley & Sons Ltd

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                Page count
                Figures: 3, Tables: 2, Pages: 9, Words: 5835
                Categories
                Original Article
                Research Articles
                Original Articles
                Custom metadata
                2.0
                bdi12730
                August 2019
                Converter:WILEY_ML3GV2_TO_NLMPMC version:5.6.9 mode:remove_FC converted:30.09.2019

                Neurology
                compliance,guideline,guideline compliance,lithium,monitoring
                Neurology
                compliance, guideline, guideline compliance, lithium, monitoring

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