Are serum lithium levels related to the polarity of recurrence in bipolar disorders?

Abstract

The primary objective is to test whether the polarity of recurrence (depressive vs manic or mixed), is related to lithium levels. A total of 86 euthymic bipolar patients (DSM-IV) on lithium monotherapy were prospectively followed up for 2.5 years with regular monitoring of both lithium levels and psychopathology. The last lithium level during the free interval that preceded worsening of affective symptoms was related to polarity of symptoms. To account for effects of major confounders, results were corroborated by multivariate analysis. An intervention for manic or mixed symptomatology was required in 27 patients, whereas 22 patients were treated for depressive symptoms. Average lithium levels preceding reappearance of manic or mixed symptomatology were lower than levels preceding reappearance of depressive symptoms (0.53+/-0.13 vs 0.66+/-0.21 mmol/l, P=0.01). This result was confirmed using logistic regression analyses with type of index episode, diagnostic subtype and residual manic and depressive symptoms as covariates. The results indicate that manic or mixed recurrences might rather occur at lower lithium levels, whereas the depressive pole prevails in the higher range. If substantiated by further studies, this finding might indicate that higher lithium levels are needed to prevent manic episodes than to prevent depressive episodes.

Clinical Expression of Bipolar Disorder Type I as a Function of Age and Polarity at Onset

“…Some adjustment of the serum concentrations of mood regulators may also be required, as a function of polarity patterns. Lithium concentrations in the lower part of the therapeutic range may be sufficient for the optimal prevention of depressive episodes, whereas higher lithium concentrations, within the therapeutic range, may be required for optimal protection against manic/mixed episodes [37][38][39] .…”

New Ways to Classify Bipolar Disorders: Going from Categorical Groups to Symptom Clusters or Dimensions

“…The serum levels of mood regulators may also require some adjustment according to the polarity patterns. Lithium levels at the lower range of the therapeutic range may be sufficient for the optimal prevention of depressive episodes, whereas higher lithium levels within this range may be required for optimal protection against manic/mixed episodes [11,12]. As some comorbidities may be associated with the polarity (onset and/or predominant), prevention strategies could be anticipated, particularly in terms of suicidal behaviour or substance misuse.…”

The World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for the Biological Treatment of Bipolar Disorders: Update 2012 on the long-term treatment of bipolar disorder

“…Lithium concentrations ≤0.6 mmol/L seemed to be ineffective preventing new manic episodes in RCTs , but may be still sufficient to prevent depression (Severus et al 2010). Higher lithium concentrations may not necessarily protect better against depression; a post-hoc analysis of the MAP study found that lithium concentrations preceding reappearance of depressive symptoms were significantly higher than those preceding new manic episodes (Severus et al 2009;Kleindienst et al 2007). Any need to discontinue lithium often poses a problem.…”