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Background: Long-term lithium treatment decreases kidney function. However, it remains unclear whether stopping lithium improves kidney function.

Objectives: To study kidney function in patients who stopped and subsequently restarted lithium treatment.

Methods: Mirror-image design using data from the LiSIE retrospective cohort study. The mirror was set to when lithium was stopped with a 5-year pre- and post-mirror period. Adult patients with bipolar, schizoaffective disorder or unipolar depression, who had lithium ≥4.5 years in the pre-mirror period, were included. Creatinine measurements were available from 1997 to 2017. The main outcome was the difference in mean annual change of the estimated glomerular filtration rate (eGFR) adjusted for sex, hypertension and diabetes mellitus.

Results: A total of 168 participants (94 women, 74 men) were included. Mean annual eGFR change was −1.58 (−1.87 to −1.28) mL/min/1.73 m²/year before and −0.023 (−0.49 to +0.44) mL/min/1.73 m²/year after lithium discontinuation (p < 0.0001 for difference). The improvement was 0.77 (0.35–1.20) mL/min/173 m²/year in participants with eGFR >60 mL/min/1.73 m², and 3.03 (2.15–3.92) mL/min/1.73 m²/year for participants with eGFR <30 mL/min/1.73 m². The effect was persistent over the 5-year post-mirror study period. For participants restarting lithium, the mean annual eGFR change was −1.71 (−2.26 to −1.16) mL/min/1.73 m²/year, a setback compared to their lithium-free post-mirror period (p < 0.0001). We did not see any difference compared to the pre-mirror period (p = 0.51).

Conclusions: Stopping lithium slowed down mean eGFR decline. This effect was more pronounced in participants with lower eGFR at the time of lithium discontinuation. In participants who restarted lithium, the annual decline of eGFR reverted to pre-lithium discontinuation levels.

Objectives: Previous research has suggested antiviral properties for lithium, including potential effectiveness against COVID-19 in vitro. This study aimed to investigate the impact of lithium and other psychotropic drugs on the risks of mortality, hospitalization, and ICU admission due to COVID-19 among individuals with bipolar disorder. The primary objective was to assess whether lithium was beneficial in COVID-19-infection in a real-world population.

Methods: Retrospective register study using data from multiple Swedish patient registers, including 39,063 individuals in Sweden with bipolar disorder and prescribed mood stabilizers. Outcomes included COVID-19-associated death, hospitalization, and ICU admission between 11 March 2020 and 10 March 2021. Multivariate logistic regression adjusted for age, sex, and somatic comorbidities was conducted.

Results: Lithium were prescribed to 44.2 % of patients, either as mono- or combination therapy; other mood stabilizers were prescribed to 55.8 %. There were no significant associations between lithium and COVID-19-associated death, hospitalization, or ICU admission. Atypical antipsychotics were associated with increased odds ratios for COVID-19-associated death (OR 1.58 [95 % CI 1.01–2.47]), hospitalization (OR 1.80 [95 % CI 1.49–2.18]), and ICU admission (OR 2.25 [95 % CI 1.33–3.80]). Benzodiazepines were associated with a significant increase in COVID-19-associated death (OR 1.54 [95 % CI 1.01–2.35]) and hospitalization OR 1.26 [95 % CI 1.03–1.53]). In an ad hoc analysis, lithium monotherapy was, however, associated with reduced hospitalizations and ICU admissions.

Conclusions: Our findings weaken the hypothesis that lithium reduces the risk of severe events associated with COVID-19 infection in bipolar disorder.

Background: Reports at the beginning of the COVID-19 pandemic suggested differences in COVID-19-associated mortality between individuals with serious mental disorders (SMD) and the population at large.

Aim: To compare the pattern of COVID-19-associated mortality in individuals with and without SMD in Sweden over the two main pandemic years.

Methods: We compared the pattern of COVID-19-associated mortality in individuals with and without SMD in Sweden during 2020 and 2021. For SMD, we included psychotic disorder, bipolar disorder, and severe depression. The analysis was based on summary data from the Swedish Board of Health and Welfare covering the entire adult Swedish population.

Results: The overall relative risk (RR) for experiencing a COVID-19-associated death was 1.66 (CI 1.50–1.83; p < 0.001) for individuals with SMD versus individuals without SMD. The corresponding RRs were 3.25 (CI 2.84–3.71; p < 0.001) for individuals with psychotic disorder, 1.06 (CI 0.88–1.26; p = 0.54) for individuals with bipolar disorder, and 1.03 (CI 0.80–1.32; p = 0.80) for individuals with severe depression. Compared to their respective counterparts in the non-SMD group, in the psychotic disorder and severe depression group, the RR were higher in women than in men. In the bipolar disorder group, the RR was higher in men than in women. The RR of COVID-19-associated death was generally higher in younger individuals with SMD. Individuals with psychosis between 18 and 59 years had the highest RR of COVID-19-associated death with 7.25 (CI 4.54–11.59; p<0.001).

Conclusions: Individuals with SMD, and particularly those with psychotic disorders, had a higher risk of COVID-19-associated death than the general population. As this is a pattern also seen with other infections, people with SMD may be similarly vulnerable in future pandemics.

Background: The clinical relevance of lithium nephropathy is subject to debate. Kidney function decreases with age and comorbidities, and this decline might lead to attribution bias when erroneously ascribed to lithium. We aimed to investigate whether patients with bipolar or schizoaffective disorder had faster decline in estimated glomerular filtration rate (eGFR) compared with the general population, whether observed differences in the steepness of the decline were attributable to lithium, and whether such changes depended on the length of lithium exposure.

Methods: In this cross-sectional cohort study, we used clinical data from the Lithium–Study into Effects and Side-effects (LiSIE) retrospective cohort study, which included patients with bipolar disorder or schizoaffective disorder whose medical records were reviewed up to Dec 31, 2017, and the WHO Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA) study, covering a representative sample of the general population in northern Sweden aged 25–74 years. The primary outcome was the age-associated decline of creatinine-based eGFR, assessed using linear regression. We adjusted for sex and grouped for different lengths of lithium exposure (never or <1 year, 1–5 years, >5–10 years, and >10 years). For patients with moderate-to-severe kidney disease we identified the underlying nephropathy in the case records.

Findings: From LiSIE, we included 785 patients (498 [63%] female and 287 [37%] male), with a mean age of 49·8 years (SD 13·2; range 25–74). From MONICA, we included 1549 individuals (800 [52%] female and 749 [48%] male), with a mean age of 51·9 years (13·8; 25–74). No ethnicity data were collected. Adjusted for duration of lithium exposure, eGFR declined by 0·57 mL/min/1·73 m2/year (95% CI 0·50–0·63) in patients with bipolar disorder or schizoaffective disorder and by 0·57 mL/min/1·73 m2/year (0·53–0·61) in the reference population. Lithium added 0·54 mL/min/1·73 m2 (0·43–0·64) per year of treatment (p<0·0001). After more than 10 years on lithium, decline was significantly steeper than in all other groups including the reference population (p<0·0001). Lithium nephropathy was judged to be the commonest cause of moderate-to-severe chronic kidney disease, but comorbidities played a role. The effect of lithium on eGFR showed a high degree of inter-individual variation.

Interpretation: Steeper eGFR decline in patients with bipolar disorder or schizoaffective disorder can be attributed to lithium, but the trajectory of kidney function decline varies widely. Comorbidities affecting kidneys should be treated assertively as one possible means to affect the trajectory. In patients with a fast trajectory, a trade-off is required between continuing lithium to treat mental health problems and discontinuing lithium for the sake of renal health.

Funding: Norrbotten County Research and Learning Fund Sweden, Visare Norr (Northern County Councils Regional Federation Fund), Swedish Kidney Foundation (Njurfonden), Swedish Kidney Association (Njurförbundet), Norrbotten section.

Translation: For the Swedish translation of the Summary see Supplementary Materials section.

Background: Individuals with severe mental disorder (SMD) have a higher risk of somatic comorbidity and mortality than the rest of the population. We set up a population-based study to assess whether individuals with SMD had a higher risk of death associated with a COVID-19 infection (COVID-19 associated death) than individuals without SMD.

Methods: Exploratory analysis with a cross-sectional design in the framework of a population-based register study covering the entire Swedish population. The Swedish Board for Health and Welfare (Socialstyrelsen) provided anonymized tabulated summary data for further analysis. We compared numbers of COVID-19 associated death in individuals with SMD (cases) and without SMD (controls). We calculated the odds ratio (OR) for the whole sample and by age group and four comorbidities, namely diabetes, cardiovascular disease, hypertension, chronic lung disease.

Results: The sample comprised of 7,923,859 individuals, 103,999 with SMD and 7,819,860 controls. There were 130 (0.1%) COVID-19 associated deaths in the SMD group and 4,945 (0.06%) in the control group, corresponding to an OR of 1.98 (CI 1.66-2.35; p < 0.001). The odds were 4-fold for the age groups between 60 and 79 years and 1.5-fold for cardiovascular diseases. Individuals with SMD without any of the risk factors under study had 3-fold odds of COVID-19 associated death.

Conclusion: Our preliminary results identify individuals with SMD as a further group at increased risk of COVID-19 associated death. In regard to comorbidities, future studies should explore the potential confounding or mediation role in the relationship between SMD and COVID-19 associated deaths.

 Individuals with severe mental disorders (SMDs) such as psychotic disorders, bipolar disorders, and single manic episodes have increased mortality associated with COVID-19 infection. We set up a population-based study to examine whether individuals with SMD also had a higher risk of hospitalization and death from other infectious conditions. Anonymized and summarized data from multiple Swedish patient registers covering the entire Swedish population were supplied by the Swedish National Board of Health and Welfare. The frequencies of hospitalizations and deaths associated with influenza/pneumonia and sepsis in individuals with SMD were compared with the rest of the population during 2018–2019. Possible contributing comorbidities were also examined, of which diabetes, cardiovascular disease, chronic lung disease, and hypertension were chosen. A total of 7,780,727 individuals were included in the study; 97,034 (1.2%) cases with SMD and 7,683,693 (98.8%) controls. Individuals with SMD had increased risk of death associated with influenza/pneumonia (OR = 2.06, 95% CI [1.87–2.27]) and sepsis (OR = 1.61, 95% CI [1.38–1.89]). They also had an increased risk of hospitalization associated with influenza/pneumonia (OR = 2.12, 95% CI [2.03–2.20]) and sepsis (OR = 1.89, 95% CI [1.75–2.03]). Our results identify a need for further evaluation of whether these individuals should be included in prioritized risk groups for vaccination against infectious diseases other than COVID-19.

The prescription of thyroid hormone replacement therapy (THRT) has increased in the general population; the thyroid stimulating hormone (TSH) threshold to initiate THRT has decreased. It remains unclear whether a similar trend has occurred in patients with bipolar disorder (BD). In this work we explore patterns and trends of prescribing THRT in patients with BD or schizoaffective disorder (SZD) with an observational study and time‐trend analysis in the framework of the LiSIE (Lithium—Study into Effects and Side Effects) retrospective cohort study. In most patients, THRT was initiated for subclinical hypothyroidism. The median TSH at which THRT was started was 6.0 (IQR 4.0) mIU/L and the median free serum thyroxine (fT4) at which THRT was started was 11.8 (IQR 3.9) pmol/L. The median TSH concentration at the start of THRT decreased annually with 0.10 mIU/L (p = 0.047) and was higher in patients treated with lithium than in patients treated with other mood stabilisers (p = 0.02). In conclusion, THRT was typically initiated in the context of mild or absent alterations of thyroid function tests with a decreasing TSH threshold. As THRT is rarely reversed once initiated, clinicians need to weigh up potential benefits and risks when prescribing THRT for subclinical hypothyroidism in patients with BD or SZD.