Long-term outcome of lithium prophylaxis in patients initially classified as complete responders

Abstract

The long-term outcome of lithium prophylaxis was explored in 43 bipolar and 36 unipolar patients who had been classified as complete responders after the first 2 years of treatment. These patients were followed up prospectively for a further period of 5 years (treatment period II), during which their psychopathological state was assessed monthly or bimonthly. Forty-nine patients completed treatment period II, 2 died during this period, 7 did not attend the unit any more and could not be traced, and 21 definitively interrupted lithium treatment before the end of the period. In 18 cases the decision to stop lithium was taken by the patient. Twenty-five patients relapsed during the treatment period II. Four relapsers had three or more episodes concentrated during the last 2 years of treatment. These results suggest that the predictive value of an initial favourable response to lithium should not be overrated, and that the impact of the drug on the long-term course of major affective disorders in ordinary clinical conditions might be less dramatic than currently believed.

Maintenance Efficacy of Divalproex in the Prevention of Bipolar Depression

“…Furthermore, clinical variables such as episode sequence (Kokopolus et al, 1980;Maj et al, 1989), frequency of mood cycling (Dunner and Fieve, 1974;Bowden 1995;Denicoff et al, 1997), presence of mood-congruent or -incongruent psychotic features of the index episode (Greil et al, 1998;Tohen et al, 1992), comorbid conditions (especially anxiety disorders) (Greil et al, 1998;Feske et al, 2000), and family history (Grof et al, 1994) may provide further explanation of the differential response to lithium and divalproex. Some of these may need to be described in future studies as potential explanatory factors of treatment response.…”

A rapid and systematic review and economic evaluation of the clinical and cost-effectiveness of newer drugs for treatment of mania associated with bipolar affective disorder

“…Strategies for treatment often become more complex and a variety of combinations of mood stabilisers are often used, principally because resistance to monotherapy may increase with time. 71 Indeed, it has been suggested that the elderly reflect a largely resistant subgroup. 1 The use of adjunctive therapy raises the issue of safety and pharmacokinetic interactions, and long-term safety issues will need to be investigated in the elderly.…”

Beyond Lithium in the Treatment of Bipolar Illness

“…There is increasing recognition of the inadequacy of "lithium treatment" in bipolar illness, even with adjunctive antidepressants and neuroleptics (Maj et al 1989;Aagaard and Vestergaard 1990;O'Connell et al 1991;Vestergaard 1992;Gitlin et al 1995). Some bipolar patient subtypes are particularly prone to lithium nonresponsiveness; among these are patients with dysphoric mania and rapid cycling; a negative family history for bipolar illness in first-degree relatives; the episode sequence pattern of depression-mania-well interval (i.e., the D-M-I pattern as opposed to the M-D-I pattern); more than three episodes prior to the initiation of prophylaxis (Sarantidis and Waters 1981;O'Connell et al 1991;Denicoff et al 1997); a history of co-morbid substance abuse; and those patients with a history of head trauma or other such medical co-morbidities as multiple sclerosis, etc.…”

“…In addition, it is recognized that patients with initial excellent responses to lithium can begin to develop breakthrough episodes in subsequent extended years of follow-up (Maj et al 1989;Post et al 1992). In our series of 66 lithium-refractory patients, 23 (34.9%) seem to have developed their lithium-refractoriness over more prolonged periods of follow-up, in a pattern resembling tolerance.…”