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Lithium maintenance treatment of depression and mania in bipolar I and bipolar II disorders.

Tondo L, Baldessarini RJ, Hennen J, and Floris G (1998).

American Journal of Psychiatry 155:638-645.

Most of the literature concerning lithium in bipolar illness has focused on the immediate benefits of treatment, as well as on lithium’s ability to reduce the risk of suicide. Here, the authors found strong evidence that longer delays in initiating sustained treatment with lithium were associated with fewer reductions in morbidity during subsequent treatment. This suggests that patients with bipolar disorder who receive early treatment with lithium may have less long-term morbidity. The article also suggests that, although both subtypes showed marked improvement from lithium, patients with the bipolar II subtype might have the most lasting benefits.

This paper adds to a number of studies that have demonstrated the benefits of lithium maintenance treatment for bipolar patients. The authors wanted to clarify the benefits of lithium in patients with bipolar disorder in general, but more specifically compare its benefits in bipolar type I and bipolar type II disorders.

To do so, the authors studied the clinical research records of patients with DSM-IV diagnosed bipolar disorder (188 with type I and 129 with type II) to determine the frequency and duration of affective episodes and hospitalizations before (mean=8.38 years) and during (mean=6.35 years) maintenance treatment with lithium. The main difference between the subtypes of bipolar disorder, as defined by the DSM-IV, is the presence of mania in type I, and hypomania in type II. The authors point out that bipolar II syndrome is not merely a milder form of bipolar disorder, but is highly associated with morbidity, including suicide. In this study, bipolar II patients were more likely to be women, have a later age of onset (26.8 and 33.3 years for types I and II, respectively), be married and employed, and have a longer time before the onset of lithium treatment.

The authors found that lithium had a protective effect for both forms of bipolar disorder. The time from the end of an episode to the start of the next episode was longer when the patients were receiving lithium. For both subtypes, lithium was also associated with reductions in various measures of morbidity, such as having fewer episodes per year and spending less time ill. Lithium, however, conferred greater benefit to bipolar II patients, reducing both mania and depressive morbidity. Bipolar II patients also had a significantly greater reduction of episodes per year and spent less time ill. During treatment, bipolar II patients had almost 6-fold longer intervals between episodes and were twice as likely as type I patients to have no new episodes.

The authors also studied factors influencing successful lithium treatment and found that gender, family history, education, marital and employment status, age of onset, number of episodes or percentage of time ill, manic, or depressed before lithium treatment, and the presence of a rapid-cycling course before lithium treatment did not affect patients’ improvement. Duration of treatment and serum lithium concentrations were weakly related to improvement. However, the duration of illness before starting lithium maintenance was strongly negatively associated with clinical improvement—starting lithium maintenance earlier predicted greater improvement.

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