Would early response (in one week) to Lithium predict short term response in classic manic episode?:Jl Aff Dis:Jan 2013


Lithium is still the gold standard treatment for bipolar disorder, though prescription rates are declining, probably due to the availability of ‘easy to prescribe’ medications. Lithium is the medication of choice in those with Classic Mania ( euphoric mood), family history of BD and those with no psychiatric comorbidity. Lithium may not be the choice when 1. mixed state /dysphoric mania 2.rapid cycling 3. higher prevalence of depressive states 4.comorbid substance use 5.secondary to physical illness.

In depression, there is more interest in the idea that early response to antidepressants may predict better short/longterm benefit. Would early response (in one week)  to Lithium predict short term response in  classic manic episode in Bipolar Disorder?

Rodrigo Machado-Vieira et al (David A. Luckenbaugh, Marcio G. Soeiro-de-Souza ,Getulio Marca , Ioline D. Henter , Joao V. Busnello , Wagner F. Gattaz , Carlos A. Zarate Jr ) try to answer this question by doing  a post- hoc analysis of data from the lithium/placebo arm of a randomized, double-blind, placebo-controlled trial in BD-I (current manic episode) (Machado-Vieira et al., 2008).

Patients: Adults with BD1,more than 22 on YMRS (Young’s), medication free for 4 weeks prior to admission, having good physical health.Exclusion criteria: rapid cycling,mixed episodes, previous history of refractoriness to lithium, current comorbid substance abuse , current Axis I psychiatric disorder other than BD.

All patients were started on lithium 600 mg/d; after one week, the dose was increased to 900 mg/d. Thereafter, a flexible dose was used in response to plasma lithium levels (maintained at 0.6–1.2 mmol/L).


33% responded (50% decrease in symptoms)  in first week. another 39% showed 20% decrease in symptom score. 22% met remission (liberal criteria, score < 12) by end of week one.

By 4 weeks, 63% responded, another 17% had 20% improvement, 52% met liberal criteria for remission, 39% met strict remission (score < 7) criteria.

Of those patients showing early improvement at Week 1, 79% (26/33) had a 50% or better response by study endpoint. In contrast, for those who had not improved by the end of Week 1, only 23% (3/13) had a response at study endpoint. Remission also follows a similar pattern.

Conclusion: In classic euphoric manic episodes in adult BD1 with out comorbidity, early response to Lithium mono therapy  is predictive of short term response ( 4 weeks).  among those who showed no response by end of one week , 23% only responded at 4 weeks,

Limitations: post-hoc analysis.

Comment: Identifying those manic patients who would benefit from lithium is  important in clinical management. A close watch on response in the early phase of treatment would help in deciding treatment options.

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