Morbidity in treated bipolar disorder: A one‐year prospective study using daily life chart ratings

Abstract

In this paper we describe the use of systematic retrospective and prospective life chart methodology and document the substantial morbidity experienced even in closely monitored and aggressively treated bipolar patients rated on a daily basis for 1 year. 35 BP I (n = 26) and BP II (n = 9) patients were recruited for an ongoing treatment study comparing the prophylactic effects of lithium or carbamazepine for 1 year with a crossover to the other drug in the second year, and a third year on the combination of the two. Adjuncts such as antidepressants and neuroleptics were allowed in each phase when clinically required. The results of the combined cohort for the first year are presented in this manuscript. All patients also had a retrospective life chart completed to map affective episodes based on the degree of functional incapacity (mild, moderate, severe). For prospective ratings patients were usually interviewed biweekly (but at a minimum of every 4 weeks), and daily ratings integrating degree of functional incapacity and self‐rated mood based on the Life Chart Method and Manual (the NIMH‐LCM) were obtained. In the first year of treatment 12 patients (34.3%) had to have their treatment phase (lithium or carbamazepine) discontinued far the fallowing reasons: jive were hospitalized, five had severe dysfunction without hospitalization, and two had treatment‐limiting side effects. Adjunctive treatment was required by 71.4%. The mean number of days ill for each level of severity for all the patients was as follows (in days): 66.1, mild depression; 31.1, moderate depression; 2.8, severe depression; and 28.7, mild mania; 5.4, moderate mania; 0.9, severe mania; or a mean of 40.2 d/year with moderate to severe illness‐related dysfunction. The duration of illness prior to study entry correlated with time depressed in the prospective year. These findings suggest that closely‐monitored bipolar patients followed with prospective daily ratings during treatment with a primary mood stabilizer (carbamazepine or lithium) experience a substantial degree of morbidity and the need far adjunctive antidepressants and neuroleptics. There was notable continuity between course of illness life charted in the retrospective year and that observed prospectively. Depression 2:95–104 (1994). ©1994 Wiley‐Liss, Inc.

Relationship of Mania Symptomatology to Maintenance Treatment Response with Divalproex, Lithium, or Placebo

“…Two recent maintenance studies have reported that lithium was not superior to placebo in delaying a new depressive episode, whereas lamotrigine was superior to placebo, with similar results in a combined analysis (Bowden et al, 2003a;Calabrese et al, 2003;Goodwin et al, 2004). An earlier maintenance study of lithium indicated an increased rate of depressive episodes in both rapid cycling and nonrapid cycling patients compared with placebo (Dunner et al, 1976), and a crossover study indicated little long-term benefit on depressive symptoms in bipolar disorder (Denicoff et al, 1994). However, a plausible mechanism for the worsening of depression, we observed in the initially euphoric manic patients treated with lithium is not selfevident.…”

The place of anticonvulsant therapy in bipolar illness

“…In one acute mania study (Post et al 1987) and several prophylaxis studies (Okuma et al 1973;Post et al 1983;Elphick 1985), a high percentage of response was observed in rapid-cycling patients. However, when rapidcycling patients were compared with non-rapid-cycling patients in the recent studies of Okuma (1993), andDenicoff et al (1994, andunpublished observations) in our group, both found a higher prophylactic response rate to carbamazepine in non-rapid cycling patients. Okuma's data are revealing in that the 53% response rate to carbamazepine in those patients with a history of rapid cycling (compared with 76% in those without) is still substantially higher than the 30% response rate observed for lithium in patients with a history of rapid cycling (compared with 64% in those without such a history).…”

“…Lithium response rates of 80% continue to be cited in many articles and text books, yet the largest controlled trial of lithium in acute mania showed only 50% improvement after three weeks in approximately 50% of the patients, in an intentto-treat analysis (Bowden et al 1994). Similarly, a substantial series of studies in many academic and clinical settings also reveals that some 50% of patients may show inadequate prophylactic response (Prien et al 1988;Gelenberg et al 1989;Maj et al 1989;Aagaard and Vestergaard 1990;Harrow et al 1990;O'Connell et al 1991;Vestergaard 1992;Denicoff et al 1994;Gitlin et al 1995). Moreover, under the rubric of "lithium therapy", lithium carbonate is often not the only drug used as it is frequently augmented by antidepressants and neuroleptics or benzodiazepines.…”

A review of the evidence for carbamazepine and oxcarbazepine in the treatment of bipolar disorder

“…50 % of patients (Bowden et al, 1994). Furthermore, many studies have suggested that a similar proportion of patients may have an inadequate prophylactic response to lithium, the most recent being Denicoff et al (1994) and Gitlin et al (1995). In addition, the side-effect profile of lithium makes compliance a significant problem.…”