Lifetime risk of severe kidney disease in lithium-treated patients: a retrospective study.

BACKGROUND: Lithium is an essential psychopharmaceutical, yet side effects and concerns about severe renal function impairment limit its usage. AIMS: Our objectives were to quantify the occurrence of chronic kidney disease stage 4 or higher (CKD4 +) within a lithium-treated population, using age- and time-specific cumulative incidence and age-specific lifetime risk as measures of disease occurrence. Additionally, we aimed to investigate the association between the duration of lithium treatment and the risk of CKD4 + . METHODS: We identified patients from the Sahlgrenska University Hospital's laboratory database. We conducted a retrospective cohort study employing cumulative incidence functions that account for competing deaths to estimate cumulative and lifetime risk of CKD4 + . A subdistribution hazards model was employed to explore baseline covariates. For measuring the association between the duration of lithium treatment and CKD4 + occurrence, we used a matched 1:4 case-control study design and logistic regression. RESULTS: Considering a 90-year lifetime horizon, the lifetime risk of CKD4 + for patients initiating lithium treatment between ages 55 and 74 ranged from 13.9% to 18.6%. In contrast, the oldest patient group, those starting lithium at 75 years or older, had a lower lifetime risk of 5.4%. The 10-year cumulative risk for patients starting lithium between ages 18 and 54 was minimal, ranging from 0% to 0.7%. Pre-treatment creatinine level was a predictive factor, with a hazard ratio of 4.6 (95% CI 2.75-7.68) for values within the upper third of the reference range compared to the lower third. Moreover, twenty or more years of lithium exposure showed a strong association with an increased risk of CKD4 + compared to 1-5 years of lithium use, with an odds ratio of 6.14 (95% CI 2.65-14.26). CONCLUSIONS: The risk of CKD4 + among lithium-treated patients exhibited significant age-related differences. Patients under 55 years old had negligible 10-year risk, while the lifetime risk for those aged 75 and older was limited. Duration of lithium treatment, especially exceeding 20 years, emerged as a significant risk factor. For individual risk assessment and prediction, consideration of age, pre-treatment creatinine levels, and the chosen time horizon for prediction is essential.

Patient Experience of Digitalized Follow-up of Antidepressant Treatment in Psychiatric Outpatient Care: Qualitative Analysis.

BACKGROUND: Nonadherence to pharmaceutical antidepressant treatment is common among patients with depression. Digitalized follow-up (ie, self-monitoring systems through mobile apps) has been suggested as an effective adjunct to conventional antidepressant treatment to increase medical adherence, improve symptoms of depression, and reduce health care resource use. OBJECTIVE: The aim of this study was to determine patients' experience of digitalized follow-up using a mobile app as an adjunct to treatment concurrent with a new prescription, a change of antidepressant, or a dose increase. METHODS: This was a qualitative, descriptive study. Patients at 2 psychiatric outpatient clinics were recruited at the time of changing antidepressant medication. After using a mobile app (either a commercial app or a public app) for 4-6 weeks with daily registrations of active data, such as medical intake and questions concerning general mental health status, individual semistructured interviews were conducted. Recorded data were transcribed and then analyzed using content analysis. RESULTS: In total, 13 patients completed the study. The mean age was 35 (range 20-67) years, 8 (61.5%) were female, and all reported high digital literacy. Overall, the emerging themes indicated that the patients found the digital app to be a valuable adjunct to antidepressant treatment but with potential for improvement. Both user adherence and medical adherence were positively affected by a daily reminder and the app's ease of use. User adherence was negatively affected by the severity of depression. The positive experience of visually presented data as graphs was a key finding, which was beneficial for self-awareness, the patient-physician relationship, and user adherence. Finally, the patients had mixed reactions to the app's content and requested tailored content. CONCLUSIONS: The patients identified several factors addressing both medical adherence and user adherence to a digital app when using it for digitalized follow-up concurrent with the critical time related to changes in antidepressant medication. The findings highlight the need for rigorous evidence-based empirical studies to generate sustainable research results.

The low risk for early renal damage during lithium treatment has not changed over time.

BACKGROUND: Modern lithium management guidelines were introduced to improve the renal prognosis of lithium patients. AIMS: To examine whether prospects for severe renal impairment (defined as chronic kidney disease at least stage 4 (CKD4)), in long-term lithium patients, have changed over time after the introduction of lithium monitoring guidelines. METHODS: The time to and hazard for CKD4 were compared between three patient cohorts who started long-term lithium in three consecutive decades: 1980s, 1990s and 2000s. The follow-up time was 10 years after completion of 1-year treatment. The data were collected from Sahlgrenska University Hospital's laboratory database. RESULTS: In all, 2169 patients were included: 623 in Cohort 1 (started lithium during 1980s), 874 in Cohort 2 (1990s) and 672 in Cohort 3 (2000s). Compliance with lithium monitoring guidelines improved, and mean serum lithium decreased, through the cohorts. In all, 22 patients developed CKD4 during follow-up. The time to CKD4 was the same in all three cohorts (overall: 10.96 years, 95% confidence interval: 10.94-11 years). Age and serum creatinine concentration at start were significant risk factors, while sex had no prognostic value. After adjusting for the significant covariates, there was no statistically significant difference in the hazard for CKD4 between the three cohorts. CONCLUSION: The risk for severe renal damage during the first decade of long-term lithium is low, but has not changed over time. Our data suggest that improved compliance with lithium guidelines is not reflected in less risk for severe renal damage.

Coma, Severe Hypotension, and Pinpoint Pupils After Olanzapine Intoxication in the Intensive Care Unit with Symptom Reversal After Administration of Flumazenil.

BACKGROUND Olanzapine is an antipsychotic drug and is used in critical care to treat delirium. There is no known antidote to olanzapine intoxication. Overdosing olanzapine can cause, tremor, bradykinesia, hypotension somnolence, coma, and miosis. CASE REPORT We present the case of a previously healthy 69-year-old man who after routine mitral valve surgery developed pneumonia and severe sepsis requiring several weeks on a ventilator in the Intensive Care Unit. He developed delirium and paranoia and was prescribed olanzapine. After 4 doses, he became hypotensive and nonresponsive and developed pinpoint pupils. The symptoms were reversed minutes after administration of flumazenil. The clinical picture in this case corresponds well with an olanzapine intoxication. No other drugs, such as benzodiazepines or opioids, had been administered that could explain the reaction. Olanzapine intoxication is known to present with hypotension, coma, and miosis. The doses given were normal starting doses for olanzapine in the outpatient setting but much higher than recommended doses in the intensive care setting. CONCLUSIONS This case illustrates a risk for severe adverse effects, even within normal prescription range, when olanzapine is used in the intensive care setting. Finally, it is intriguing that the symptoms were reversed after administration of flumazenil, a selective competitive antagonist of the GABA receptor. Olanzapine mainly effects dopamine, serotonin, a1-adrenergic, histamine, and muscarinic receptors, but a low affinity to GABA and benzodiazepine sites can perhaps explain the observed effect.

[The number of patients diagnosed with ADHD and the number of prescriptions for ADHD are increasing]. / Behandling av ADHD hos vuxna.

The core symptoms of ADHD (Attention Deficit Hyperactivity Disorder) are inattention, hyperactivity and impulsivity.  The multimodal treatment of ADHD consists of a combination of pharmacological treatment, psychoeducation, psychotherapy and occupational therapy interventions. The treatment needs to be individualized with clear and measurable goals. There are risks of not treating ADHD in the form of social exclusion and low functioning. The number of patients diagnosed with ADHD and the number of prescriptions for ADHD are increasing every year in Sweden but there are large regional differences.

Inter-rater reliability among psychiatrists when assessing depression according to the Montgomery-Åsberg Depression Rating Scale.

INTRODUCTION: Montgomery-Åsberg Depression Rating Scale (MADRS) is a validated tool for rating the depth of depression. The structured interview guide for the MADRS (SIGMA) is an interview guide that has been developed in order to increase the inter-rater reliability. Patients often meet more than one psychiatrists during their hospitalization for depression. A divergent rating of depression between psychiatrists could affect both the treatment and the outcome. This makes knowledge of the inter-rater reliability among psychiatrists important. AIM: The primary aim of this study was to measure the inter-rater reliability between psychiatrists when rating depression using the MADRS. METHODS: Ten in-patients, who were diagnosed with depression, were filmed while being interviewed using the SIGMA. The patients were after that instructed to rate themselves using the self-rating version of the MADRS. Ten psychiatrists rated the pre-recorded interviews according to the MADRS. The inter-rater reliability was measured using intra-class correlation (ICC). RESULTS: The mean ICC for the total MADRS score was 0.952 (95% CI 0.891-0.986; p<.001) and Cronbach's alpha 0.961. ICC values for each item ranged between 0.866 and 0.978 (p<.001). Cronbach's alpha ranged between 0.905 and 0.984. The ICC values, when comparing the psychiatrists rating to the patients rating, ranged between 0.307 and 0.809 (p<.001). CONCLUSION: All of the ICC values in the study, except when comparing the psychiatrists rating to the patients self-rating, were considered to be excellent. This study confirms the findings of reliability found in similar studies which involved fewer raters and not exclusively psychiatrists.

Starting lithium in patients with compromised renal function - is it wise?

BACKGROUND: Little is known of the risks involved for patients who, at the start of lithium treatment, already have compromised renal function. AIMS: To assess the risk of developing severe renal impairment (chronic kidney disease (CKD) 4-5) among those patients and to explore predictors for the progression. METHODS: A retrospective longitudinal cohort study using data from Sahlgrenska University Hospital's laboratory database 1981-2017. We compared the risk of developing CKD 4-5 in two patient cohorts: an exposed cohort of 83 patients who had high serum creatinine prior to start of lithium and a reference cohort of 83 patients with normal serum creatinine, matched by gender, duration of lithium treatment and age at the start of lithium treatment. The patients' medical charts were reviewed and the Swedish Renal Registry was used to identify patients with renal replacement therapy. RESULTS: There were no significant differences between the exposed and reference cohorts with respect to our matching criteria. Almost half the patients in the exposed cohort versus only 10% of the reference patients progressed to CKD 4-5 (HR 6.7, 95%CI 3.1-14.3, p < 0.001) during a mean observation time of more than 10 years. The progressors were older at the start of lithium treatment and were characterised by a higher burden of comorbid somatic diseases, in particular cardiovascular diseases. CONCLUSIONS: Compromised renal function prior to initiating lithium treatment increases the risk of developing severe renal impairment. Monitoring of renal function should include somatic comorbidity among older patients.

Cardiovascular comorbidity increases the risk for renal failure during prophylactic lithium treatment.

BACKGROUND: The development of lithium-associated kidney damage is still a matter of controversy. We have addressed this question by investigating the role of somatic comorbidity for developing kidney failure in lithium treated patients. METHODS: The study group comprised of 1741 adult patients with normal creatinine levels at the start of lithium treatment. Patients who developed severe renal failure (CKD stages 4-5, n = 109), were matched by sex, time on lithium and age at start of lithium, with 109 controls (CKD stages 1-2) that did not develop severe renal failure. RESULTS: Patients in CKD 4-5 did not differ significantly from controls (CKD 1-2) in sex (females/males were 76/33 in both groups), time on lithium (mean 9.8 years, SD 6.4; vs. 9.6, SD 6.2) or age at start of lithium (mean 61.6 years, SD 13.4; vs. 60.5 years, SD 12.3), respectively. However, comparisons between groups showed a significantly higher prevalence of somatic comorbidity (p < 0.001), especially cardiovascular diseases (p < 0.003), among patients in CKD 4-5. LIMITATIONS: Patients in our study group were relatively old and the findings are therefore not generalizable to patients starting lithium at an early age. The retrospective design, relying on available charts, did not allow to grade severity of comorbid conditions other than need for hospitalisation or chronic drug treatment. CONCLUSIONS: Our findings emphasize the role of somatic comorbidity for renal damage in lithium treated patients and especially the role of cardiovascular comorbidity. Monitoring of somatic comorbidity should be taken into account in treatment recommendations and safety routines in long-term prophylactic lithium treatment.

Compliance with the safety guidelines for long-term lithium treatment in Sweden.

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.

Effects of 10 to 30 years of lithium treatment on kidney function.

Long-term lithium treatment is associated with end-stage renal disease, but there is little evidence of a clinically significant reduction in renal function in most patients. We previously found that 1.5% of people who took lithium from the 1960s and 1970s developed end-stage renal disease; however, none of the patients who started after 1980 had end-stage renal disease. Here we aimed to study the prevalence and extent of kidney damage during the course of long-term lithium treatment since 1980. We retrieved serum lithium and creatinine levels from 4879 patients examined between 1 January 1981 and 31 December 2010. Only patients who started their lithium treatment during the study period and had at least 10 years of cumulative treatment were included. The study group comprised 630 adult patients (402 women and 228 men) with normal creatinine levels at the start of lithium treatment. There was a yearly increase in median serum creatinine levels already from the first year of treatment. About one-third of the patients who had taken lithium for 10-29 years had evidence of chronic renal failure but only 5% were in the severe or very severe category. The results indicate that a substantial proportion of adult patients who are treated with lithium for more than a decade develop signs of renal functional impairment, also when treated according to modern therapeutic principles. Our results emphasise that lithium treatment requires continuous monitoring of kidney function.

End-stage renal disease associated with prophylactic lithium treatment.

The primary aim of this study was to estimate the prevalence of lithium associated end-stage renal disease (ESRD) and to compare the relative risk of ESRD in lithium users versus non-lithium users. Second, the role of lithium in the pathogenesis of ESRD was evaluated. We used the Swedish Renal Registry to search for lithium-treated patients with ESRD among 2644 patients with chronic renal replacement therapy (RRT)-either dialysis or transplantation, within two defined geographical areas in Sweden with 2.8 million inhabitants. The prevalence date was December 31, 2010. We found 30 ESRD patients with a history of lithium treatment. ESRD with RRT was significantly more prevalent among lithium users than among non-lithium users (p<0.001). The prevalence of ESRD with RRT in the lithium user population was 15.0‰ (95% CI 9.7-20.3), and close to two percent of the RRT population were lithium users. The relative risk of ESRD with RRT in the lithium user population compared with the general population was 7.8 (95% CI 5.4-11.1). Out of those 30 patients, lithium use was classified, based on chart reviews, as being the sole (n=14) or main (n=10) cause of ESRD in 24 cases. Their mean age at the start of RRT was 66 years (46-82), their mean time on lithium 27 years (12-39), and 22 of them had been on lithium for 15 years or more. We conclude that lithium-associated ESRD is an uncommon but not rare complication of lithium treatment.

The impact of modern treatment principles may have eliminated lithium-induced renal failure.

We have previously shown that lithium can cause end-stage renal disease (ESRD): however, this serious side-effect of lithium in prophylactic treatment of mood disorders may reflect the treatment regime of the 1960s and 1970s. Today's modern treatment routines, intended to reduce or eliminate lithium-induced ESRD (Li-ESRD), were introduced in Sweden in the early 1980s. The aim of the present study was to test the hypothesis that these routines have eliminated the risk of Li-ESRD. We used the Swedish Renal Registry to identify patients on renal replacement therapy (RRT), treated with dialysis or renal transplantation, with suspected Li-ESRD in two regions of Sweden with altogether about three million inhabitants. We reviewed their medical records to verify the exposure to lithium treatment, the diagnosis of Li-ESRD and the date of starting the lithium treatment. We found 32 RRT patients in whom lithium treatment was the sole or main contributing cause of ESRD. The starting year of their lithium treatment was between 1965-1980 in all patients. No patient started lithium treatment later than 1980. Modern lithium treatment may have eliminated the risk of Li-ESRD. Our findings support the continued use of lithium as a safe drug for the long-term treatment of mood disorders.