A larger number of previous episodes of affective disorder was associated with poor antimanic response to lithium but not to divalproex. This differential treatment response did not result from current rapid cycling or mixed states.
Explanations for reduced response to lithium in subjects with many previous episodes include the following: 1) Lithium resistance may develop with repeated episodes (2). Reduced response to lithium prophylaxis has been reported in patients with many episodes and early onset (3) and in those with more than three previous manic episodes (11). 2) Multiple lithium discontinuations could result in refractoriness to lithium. Most patients, however, have similar responses before and after lithium is discontinued (12, 13). Furthermore, in this study, previous response to lithium predicted current response (4). 3) A group of patients may have frequent episodes that were always lithium resistant, representing an inherently unstable subtype of bipolar disorder. If this proves true, early identification of such patients will be valuable in establishing lifetime treatment strategies.
These results are related only to treatment of acute mania. Further studies are needed to determine whether these relationships extend to maintenance treatment.
Differential Effect of Number of Previous Episodes of Affective Disorder on Response to Lithium or Divalproex in Acute Mania
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