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

Depressive 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.

In 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.

According 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".

We 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.