Is Lithium Still a First-Line Treatment in the Prophylaxis of Bipolar Mood Disorder? (1999)

ABSTRACT Lithium has been the treatment of choice for the prophylaxis of bipolar affective illness for the past 25 years. Recently, doubts have been expressed about its value for the prevention of affective illness, the acute treatment of mania, and as an adjunctive treatment for resistant depression. This paper reviews the evidence of the value of lithium for these indications, with emphasis on its prophylactic effect. Published material conclusively shows that lithium is effective in reducing further episodes of affective illness in patients with clear bipolar mood disorder with no other associated psychiatric condition and who are compliant with therapy. Lithium should only be prescribed as a prophylactic agent to patients who agree to take the drug long-term and who can be closely supervised during treatment. Keywords: Bipolar Mood Disorder; Discontinuation; Human; Lithium; Prevention INTRODUCTION Lithium was reintroduced into psychiatry 50 years ago and has been licensed for the treatment of affective disorder for the past 30 years. It remains the treatment of choice for the prophylaxis of bipolar affective disorder and is also widely used for the prevention of recurrent depression, as an adjunct to drug therapy for resistant depression and for the acute treatment of mania (Jefferson, 1998). It is also valuable for control of aggressive behaviour (Tyrer, 1994) and for certain medical disorders including cluster headache and neutropenia. Lithium is estimated to be used by one in every 1000 to 1300 people in the United Kingdom at any one time (McCreadie & Morrison, 1985). DOUBTS ABOUT CLINICAL UTILITY Despite its widespread use, the value of lithium has recently been questioned on stringent evidence-based criteria (Moncrieff, 1997). On review of the published data, Moncrieff finds insufficient evidence to suggest lithium is effective for three of its most commonly recommended uses: prophylaxis of bipolar disorder; treatment of acute mania; and augmentation of treatment in resistant depression. This paper has provoked advocates of lithium treatment into a vigorous defence of the value of this drug (Cookson, 1997; Baldessarini & Tondo, 1998a; Jefferson, 1998). Why should there still be continuing controversy about the value of lithium after 30 years of regular clinical use? It is instructive to examine Moncrieff's criticisms and relate them to the historical use of lithium. PROPHYLAXIS OF BIPOLAR DISORDER Moncrieff's main concerns about the studies that have been carried out to examine the effect of lithium for the prophylaxis of bipolar disorder are related to the fact that a number of these trials used a discontinuation design and numerous studies have now shown that patients with bipolar disorder who are stabilised with lithium are particularly prone to manic relapse on discontinuation of the drug (Mander & Loudon, 1988; Suppes et al., 1991). It has consistently been shown that if lithium treatment is not adequately monitored, the relapse rate is higher than when supervision is carried out in out-patient lithium clinics (Kehoe & Mander, 1992; Guscott & Taylor, 1994). Furthermore, Moncrieff is concerned that the research into the natural history of bipolar disorder raises further doubts about the impact of lithium. Unless it can be shown that administration of lithium reduces the frequency of affective episodes in patients with bipolar affective disorders who have not previously been treated with the drug, its value is clearly not established. Moncrieff is quite correct in pointing out that studies of patients receiving short-term prophylactic lithium, who subsequently reduce the dose or stop taking the drug can affect interpretation of the effectiveness of lithium. In a study examining 14 patients with bipolar disorder who were maintained effectively by lithium for some years, discontinuation of lithium in a double-blind cross-over design led to half of the patients becoming manic within two weeks (Mander & Loudon, 1988). …