Patient reporting and severity of adverse drug reactions (ADRs) during long-term lithium treatment for bipolar disorder are affected by both serum lithium concentration and mood state, say Dutch researchers.

Compared with randomized controlled studies, the effectiveness of lithium treatment for bipolar disorders is lower in naturalistic follow-up, with nonadherence one of the major contributory factors. Previous studies have indicated that ADRs are a major reason for discontinuing treatment.

To determine the impact of mood state and lithium ADRs, Antoine Egberts, from Utrecht University, and colleagues conducted a 26-year follow-up study of 186 patients aged ?18 years treated at an outpatient lithium clinic between 1973 and 2000.

Information on the presence and severity of nine specific ADRs that frequently occur as a result of lithium treatment and can be identified by patients was gathered by a research nurse at each monthly scheduled visit. Serum lithium level and mood state were also assessed at each visit.

In all, 94.6% of patients had at least two ADR questionnaires completed during follow-up, giving a total of 8056 questionnaires. The median duration of patient follow-up was 5.7 years. At least one ADR was reported by all but two patients.

The serum lithium level at each interview was within the therapeutic range for 62.5% of patients, and mood state was rated as euthymic in 73.4% of cases. Adjusting for mood state, serum lithium level was significantly associated with the number of present ADRs, as well as with the average severity of all present ADRs.

Further adjustment for mood state, age at study inclusion, gender, and duration of lithium use confirmed that serum lithium was significantly associated with the number and severity of reported ADRs. Specifically, patients with a serum lithium level of 0.6 mmol/l, 0.9 mmol/l, and 1.2 mmol/l had an average number of ADRs of 3.3, 3.6, and 3.8, respectively.

When adjusting for serum lithium level, there was a significant association between mood state and the average number and severity of ADRs, with depressed mood, euthymic, and manic patients having an average of 2.0, 3.3, and 4.6 ADRs, respectively.

Interestingly, of the ADRs, tiredness and concentration deficits were most strongly linked to mood state, while polyuria and polydipsia were mostly strongly linked to serum lithium level.

The team writes in the journal Bipolar Disorders: “In conclusion, we found that both mood state and lithium serum level are independently associated with the prevalence and the severity of patient-reported ADRs in patients on lithium treatment.”

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