Lithium in the episode and suicide prophylaxis and in augmenting strategies in patients with unipolar depression

Abstract

BackgroundDepressive disorders are a leading cause of the global burden of disease and are associated with high recurrent often continuing morbidity and high excess mortality by suicide and cardiovascular disease. Whilst there are established, effective and cost-effective treatments for depression, their long-term management is often neglected: there is continuing controversy over the case of need for long-term treatment including lifelong treatment and safety issues.Objective and methodsIn this narrative review, we critically examine the evidence for the effectiveness and safety of lithium salts in the long-term management of unipolar depression. We refer to existing recent international guidelines as well as the scientific literature selectively and against the background of our longstanding experience with patients suffering from unipolar depression who are often under treated or inappropriately treated.Results and discussionAccording to many studies mostly dating back to the 1970/1980s, lithium is efficacious in the prophylaxis of unipolar depression particularly depression with melancholia and delusional depression and showing a clearly episodic course. Also the efficacy of lithium maintenance treatment following recovery by ECT has been clearly shown. Moreover, convincing evidence exists that lithium has added value and benefit for its unique anti-suicidal effects as well as reducing mortality by other causes. The anti-suicidal effect has been convincingly demonstrated in bipolar as well as in unipolar patients. Nevertheless its use in the management of patients with unipolar depression has not been properly recognized by a majority of textbooks and guidelines. Whilst it has been well considered as an effective treatment for depression that has not responded to antidepressants as an adjunct treatment, also called augmentation, it has been much less recommended for the prevention of recurrent episodes of unipolar depression. One of the reasons for this neglect is the blurring of the diagnosis “unipolar depression” by modern diagnostic tools. Lithium will hardly work in a patient with “unipolar depression spectrum disease”.ConclusionsWe conclude that lithium is an effective prophylactic treatment for carefully selected patients with unipolar depression and is safe when prescribed in recommended doses/plasma lithium levels and with regular, careful monitoring. We propose that lithium prophylaxis can be indicated in patients with unipolar depression and that the occurrence of 2 episodes of depression within 5 years is a practical criterion for starting lithium prophylaxis particularly in severe depression with psychotic features and high suicidal risk. Furthermore, an indication might be considered especially in unipolar patients in whom a bipolar background is suspected. In some cases, lithium prophylaxis may be recommended after a single episode of depression that is severe with high suicidal risk and continued life-long.

Lithium and Renal Impairment: A Review on a Still Hot Topic

“…Since then, research into lithium's effects has established lithium as an effective treatment for bipolar disorder, both acutely and in maintenance treatment [2]. Moreover, it has been found effective in unipolar depression [3], and an anti-suicidal effect independent from its moodstabilizing properties has been suggested [4,5]. Finally, recent data have indicated a possible role for lithium in preventing mild cognitive impairment and dementia [6].…”

Evaluation of clarity of presentation and applicability of monitoring instructions for patients using lithium in clinical practice guidelines for treatment of bipolar disorder

“…Lithium is used in the treatment and prevention of mood episodes in patients with bipolar disorder (BD), as well as in an augmenting strategy in patients with treatment‐resistant depression . Adequate monitoring of lithium treatment is essential in order to assess, at the level of the individual patient, the balance between efficacy and side effects, and to adjust the treatment if necessary .…”

Efficacy and Effectiveness of Lithium in the Long-Term Treatment of Bipolar Disorders: An Update 2018

“…In spite of this, given that lithium is the only drug with evidence of efficacy in the prevention of both manic and depressive episodes in nonenriched study designs [10], the authors of both meta-analyses and accompanying commentaries [11,12] concluded that lithium should remain the standard treatment in the longterm management of bipolar disorders [4,5]. The evidence for lithium's unique antisuicidal properties as well as lithium's ability to control for subsyndromal symptoms further strengthen this view [13][14][15][16][17].…”