https://doi.org/10.1177/0269881118780014 Journal of Psychopharmacology 1–6 © The Author(s) 2018 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0269881118780014 journals.sagepub.com/home/jop Introduction After more than half a century of regular use and extensive clini- cal research (Shorter, 2009), the prime role of lithium in the phar- macological treatment of bipolar disorder is well established. Lithium is effective in the prevention of affective episodes (Severus et al., 2014) and has a strongly documented suicide pre- ventive effect (Baldessarini et al., 2006; Lewitzka et al., 2015). It is a cornerstone in the guidelines for the treatment of bipolar dis- order in Sweden (Adler et al., 2014) as well as in the UK (Goodwin et al., 2016; National Institute for Health and Care Excellence, 2014) and the USA (Hirschfeld et al., 2010). Furthermore, lithium augmentation is a well-validated third-line treatment in the man- agement of patients with treatment-refractory depression (Cleare et al., 2015; Edwards et al., 2013). The main shortcomings of lithium are its narrow therapeutic window and organ toxicity for the thyroid and parathyroid glands and the kidneys. Other clinically significant side effects include tremor, weight gain, decreased emotional reactivity, diarrhoea and skin reactions (Bendz and Aurell, 2004). Nephrotoxicity is argua- bly the most important safety aspect of long-term lithium treat- ment. The effect on tubular structure and function can result in an impaired ability to concentrate urine and lithium-induced diabetes insipidus is the most common lithium renal side effect (Azab et al., 2015). The association between long-term lithium treatment and chronic impairment of the glomerular function is less common but of great clinical importance, as it may result in progressive loss of renal function and renal failure (Aiff et al., 2015; Azab et al., 2015). The early recognition of lithium nephrotoxicity has led to the development of safety guidelines, which require regular monitor- ing of serum lithium levels (S-Li) and dose adjustments to reach specified target levels when needed, as well as biochemical moni- toring of primarily renal, thyroid and parathyroid function. In Sweden, guidelines for long-term lithium treatment have been introduced since the early 1980s. Guidelines used in different clin- ics/regions in Sweden and the Swedish Psychiatric Association’s recommendations are generally congruent with those valid in the UK and the USA, with certain differences, mainly with regards to recommended target S-Li. The aims of the guidelines are to ensure Compliance with the safety guidelines for long-term lithium treatment in Sweden Mihaela Golic 1 , Harald Aiff 2 , Per-Ola Attman 3 , Bernd Ramsauer 4 , Staffan Schön 5 and Jan Svedlund 2 Abstract Background: Lithium has been used for more than 50 years and guidelines for treatment monitoring have been documented in Sweden since the beginning of the 1980s. Aims: The aim of this study was to describe compliance over time with the Swedish guidelines for long-term lithium treatment. Methods: The study material was obtained from Sahlgrenska University Hospital’s laboratory database. We analysed data (serum lithium and serum creatinine) of adult patients treated with lithium between 1981 and 2010, and determined compliance with guidelines and serum lithium levels over time. Results: Our study material included 2841 patients and 25,300 treatment-years. The compliance with guidelines’ recommendations regarding lithium and creatinine monitoring increased from 36% in 1981 to 68% in 2010. Women were on average 2% more compliant than men (p < 0.01). Most lithium samples (87–94%) were within recommended intervals throughout the study period. The average lithium level decreased from 0.70 mmol/L in 1981 to 0.58 mmol/L in 2001, and remained stable thereafter. Conclusions: Compliance with lithium monitoring guidelines improved slowly but steadily over time. It took three decades to reach a compliance rate of just below 70%. Gender differences were small, but with a significantly better compliance rate for women. Serum lithium was kept within the recommended target interval to a large extent, throughout the study period. Keywords Lithium, creatinine, guidelines, compliance, gender 1 Department of Psychiatry, Varberg Hospital, Varberg, Sweden 2 Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden 3 Department of Nephrology, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden 4 Department of Nephrology, Skaraborg Hospital, Skövde, Sweden 5 Swedish Renal Registry, Jönköping County Hospital, Jönköping, Sweden Corresponding author: Mihaela Golic, Department of Psychiatry, Varberg Hospital, Träslövsvägen 25B, Varberg, 432 43, Sweden. Email: mihaela.golic@gmail.com 780014JOP 0 0 10.1177/0269881118780014Journal of PsychopharmacologyGolic et al. research-article 2018 Original Article