Patterns and clinical outcomes of lithium treatment

Abstract

Patterns and consequences of lithium use’. In chapter 2.1 we studied lithium use patterns in out-patients within the last decade. In line with the increase in alternatives and the Dutch guidelines, we observed an increase in use of atypical antipsychotics and valproic acid and a decrease in use tricyclic antidepressants next to lithium. In chapter 2.2 we assessed the association between mood state and patient reported ADRs. The prevalence and the severity of ADRs increased with decreasing mood state into the depressive range (p?0.05). This association may complicate objective ADR assessment. In chapter 2.3, we investigated the risk of fractures in patients using lithium. Current use of lithium was associated with a decreased risk of fractures (adjusted odds ratio [OR] 0.75, 95% confidence interval [CI];0.64-0.88). Among past users an increased risk of fractures was observed (adjusted OR 1.35; 95% CI;1.01-1.79), increasing with time since discontinuation. ‘Determinants and treatment of potential lithium intoxications’ In chapter 3.1 we explored drug-drug interactions (NSAIDs, diuretics, renin-angiotensin inhibitors, theophyllin, antibiotics) as a determinant of elevated lithium serum levels. Cases were patients with an increase ?50% in lithium serum level resulting in a serum level ?1.3 mmol/l. Controls showed stable therapeutic lithium serum levels. Five (9.8%) controls and 15 (29.4%) of the 51 cases used potentially interacting co-medication; OR 3.83; (95% CI;1.28-11.48) and OR of 2.70 (95% CI;0.78-9.31) after adjustment for, irregularity in lithium dispensing pattern, change in lithium dosing, and age. Eight (15.7%) cases and zero controls started potentially interacting co-medication; OR of 20.13 (95% CI;1.13-359). Use of potentially interacting co-medication tends to be associated with elevated lithium serum levels. In chapter 3.2. we investigated the impact of environmental temperature on lithium serum levels, 41 102 lithium serum levels (3 054 patients) were linked to season and average daily temperature. A statistically significant but therapeutically irrelevant difference in mean lithium serum levels across seasons (p?0.001) and temperature categories (p?0.001) was found. Lithium intoxication is a very serious condition that arises easy due to its narrow therapeutic window and the large variation in clearance. In chapter 3.3 we investigated available practice guidelines for the treatment of lithium intoxication. We found profound variability in completeness and employability. ‘Nephrogenic complications of lithium’ In chapter 4.1 we investigated serotonergic antidepressants as a determinant of polyuria in patients using lithium. Twelve (26%) of the 46 patients with polyuria used serotonergic antidepressants compared to ten (14%) of the 70 patients without polyuria; OR 2.86; 95% CI 1.00-8.21, adjusted for age, gender, use of antiepileptics and thyreomimetics. In chapter 4.2 we investigated the kidney urine concentrating mechanism in patients using lithium. The kidney urinary cAMP, AQP-2 levels and urine osmolality were determined during water loading and following 1-desamino-8-D-arginine-vasopressin dDAVP administration. The partial correlation between urinary cAMP (mmol/l) and urine osmolality was 0.94 (p?0.001). No significant correlation was observed between urinary AQP-2 (mol/mol creatinine) and osmolality nor between urinary cAMP and AQP-2. In lithium-induced kidney urine concentrating deficit in man, the cAMP generation in response to dDAVP administration after water loading, is impaired