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• W2956393602 abstract "All international guidelines state lithium as a first-line maintenance treatment for bipolar disorder 1 but few give lithium primacy over other drugs 2. The paper by Hui 3 in the current issue of Acta Psychiatrica Scandinavica identified 6 predictors of good response to lithium in a meta-analysis of 71 studies including over 12,000 patients with bipolar disorder, while at the same time emphasizing that findings are heterogeneous and should be interpreted with cation due to potential biases and confounding. Until more strong and valid predictors emerge, this Editorial holds the position that lithium should be the drug of choice for maintenance treatment of bipolar disorder in general, that is, the single first-line treatment, as during the last decade the evidence for the maintenance effect and side-effects of lithium has increased substantially, as shortly summarized below. Lithium is the drug qualifying most to fulfill the term a mood stabilizer with a proved effect in mania, bipolar depression, and prevention of manic as well as depressive episodes 4. It is clinically meaningful when choosing a maintenance drug for bipolar disorder to give priority to drugs that have proven effects in all phases of bipolar disorder, so patients do not have to switch between drugs during different states of the illness (depression, mania, mixed episodes) or during different risk phases (risk for mania/mixed episodes or risk for depression). Two drugs, only, have proven effects in all these situations, lithium and quetiapine. Nevertheless, trials comparing the maintenance effects of quetiapine and lithium are enriched in favor of patients tolerating and/or responding to quetiapine in an acute episode. In such selected populations, lithium did as well as quetiapine compared with placebo 5, and in this way, the industry initiated randomized controlled trial (RCT) ironically strongly increase the evidence for lithium. Also specifically in people with first-episode mania, continuation treatment with lithium rather than quetiapine following initial combination therapy is superior in terms of mean levels of symptoms during a 1-year trial period, as found in an Australian study. In fact, the evidence base for the maintenance effect of lithium in bipolar disorder is far larger than for any other drug comprising 21 RCTs comparing lithium with other drugs or placebo 6. Data on maintenance treatment comprise four trials on valproate, three on lamotrigine, three on olanzapine, and quetiapine, respectively, and fewer for all other drugs 6. Based on the meta-analysis of these data, it was concluded that compared with other drugs lithium should be the first-line treatment when prescribing a relapse-prevention drug in patients with bipolar disorder, notwithstanding its tolerability profile 6. Findings from RCTs are supported by results from observational studies on the efficiency of lithium monotherapy in real-life circumstances as recently systematically reviewed 7. Eight out of nine identified studies including a total of <14 000 patient found that maintenance lithium monotherapy was associated with improved outcome compared with another mood stabilizer in monotherapy, including valproate, lamotrigine, olanzapine, quetiapine, unspecified anticonvulsants, carbamazepine/lamotrigine, unspecified atypical antipsychotics, and unspecified antipsychotics 7. Among side-effects to lithium giving most concerns are long-term renal and thyroid potential effects. Recent studies suggest that such outcomes are rare in modern settings and that the concerns have been overestimated being, at least partly, results of surveillance bias. Data from 6 large observational studies since 2010 suggest that the finding of decreased renal function associated with lithium treatment may, at least partly, be a result of surveillance bias, and further, data do not point toward an increased risk of end-stage chronic kidney disease associated with lithium treatment in modern settings 8. These findings show that it is possible to avoid end-stage kidney disease by initial and regular monitoring of serum creatinine every 3–6 months and aiming for a serum lithium level of 0.6–0.8 mmol per liter 9. Recent data similarly show that hypothyroidism is frequent in bipolar disorder regardless of treatment suggesting that at least part of prior findings of lithium-associated hypothyroidism may be a result of surveillance bias due to frequent thyroid testing in these patients 10. Among the important predictors of lithium response identified by Hui 3, shorter prelithium illness duration, number of episodes prior to lithium, and number of hospitalisations prior to lithium emphasize the importance of starting lithium early when the diagnosis of bipolar disorder is made 11. Notably, equally important findings from the study are the negative findings although these results may be a result of decreased statistical power. Bipolar disorder subtype, that is, bipolar disorder type I vs. type II, and alcohol and drug use did not separate response to lithium in 11 and three studies, respectively. In clinical practice, it is difficult to know which drug to prescribe for these patients. Although more data on the effect of lithium in bipolar II are needed, the negative finding in relation to subtype of bipolar disorder is in accordance with prior studies also suggesting maintenance effects of lithium in bipolar disorder type II 12. Clinicians may be reluctant to prescribe lithium for patients with bipolar disorder and alcohol and drug use due to the fear of disturbed adherence and the risk of lithium intoxication during periods with alcohol and drug consumption. On the other hand, treatment with lithium may decrease consumption due to mood stabilizing effects and the negative prediction in the Hui paper 3 may suggest that lithium may be used in this avenue of treatment. Findings from several studies suggest that treatment with lithium may protect against suicide, dementia, and cardiovascular disorders (references from the author). Major changes have occurred in prescription patterns for bipolar disorder during the recent decade. Use of lithium decreased, while the use of lamotrigine, quetiapine, and antidepressants increased in Scandinavia according to population-based studies 13, 14 and in the USA (see reference 13). A total of 34% are prescribed lithium in Denmark, 55% in Sweden 14, and 70% in the Netherlands 15, whereas a US national market scan during 2002–2003 (see reference 13) found that lithium was prescribed as the initial drug for 7.5% of patients only. These changes occurred during the recent decade during which the evidence base for maintenance treatment of lithium increased substantially as described above. To conclude, currently we have no strong valid predictors of lithium response in bipolar disorder and the use of lithium is decreasing. Lithium should be used substantially more corresponding to around 70% of patients with bipolar disorder as in the Netherlands. Lithium should be the drug of choice for maintenance therapy as the single first-line treatment, as also recommended by others 6, 16. LVK has within the preceding three years been a consultant for Lundbeck." @default.
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• W2956393602 date "2019-07-16" @default.
• W2956393602 modified "2023-10-14" @default.
• W2956393602 title "Lithium as the drug of choice for maintenance treatment in bipolar disorder" @default.
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• W2956393602 doi "https://doi.org/10.1111/acps.13070" @default.
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