Clinical Outcome of Valproate Maintenance Treatment
in Bipolar I Disorder at Srinagarind Hospital
Suchat Paholpak MD*,
Sirikul Jaikasemwong MD**, Ajchara Roumcharoenkiat MD*,
Patharee Paholpak MD*, Poonsri Rangseekajee MD*
Affiliation :
* Department of Psychiatry, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
** Khon Kaen Rajanagarindra Psychiatric Hospital, Khon Kaen, Thailand
Objective : To determine-in a clinical setting-the rate and time to recurrence of any mood episode during valproate maintenance
treatment for bipolar I disorder.
Material and Method: A retrospective cohort based on medical records of both in- and out-patient with bipolar I disorder
(DSM-IV-TR) seen at Srinagarind Hospital between January 1, 2009 and December 31, 2010 was done. A recurrence was
observed if the patient had fulfilled the remission criteria and valproate was the maintenance drug. Survival analysis and
Cox regression analysis were used to analyze the data.
Results : Eighty-five patients with 124 remitted mood episodes met the inclusion criteria. Of the 85 patients, the average
age was 41.417.1 years (range, 18-89); 49.4% were males; 48.2% married; 42.4% completed secondary school, 30.6%
completed a bachelor degree; 35.3% were unemployed, and 34.1% were government employees. Twenty remitted mood
episodes (16.1%) were in maintenance treatment with valproate only. The remaining 104 (83.9%) were in maintenance
treatment with valproate in combination with other agents. There were 50 recurrences from 36 patients during the two years
of study, the recurrence per a patient ranged from 1 to 3 times. The rate of recurrence was 21%/year or 2.2/100 person-
months (95% CI = 1.65-2.93). The average time to recurrence to any mood episode was 33 months (95% CI = 15.06-50.94).
With multivariable Cox regression, a statistically significant greater risk for a recurrence was associated with: (a) the
previous episode being hospitalized (adjusted hazard ratio = 5.88, 95% CI = 2.76-12.36, p<0.001); (b) blood valproate
concentration during maintenance treatment <50 μg/mL (adjusted hazard ratio = 3.07, 95% CI = 1.11-8.53, p = 0.03);
and (c) time duration (month) of valproate maintenance treatment (adjusted hazard ratio = 0.98, 95% CI = 0.96-0.99,
p = 0.001). With the adjusted hazard ratio 0.98, it could be interpreted in the other way that each additional month of taking
valproate was associated with a statistically significant protective factor that decreased the risk of recurrence by 2% from
the previous month.
Conclusion : In the authors’ clinical setting, valproate both singly and in combination with other psychotropic agents used
for maintenance treatment of bipolar I disorder yielded a recurrence rate of 21% per year or 2.2 per 100 person-months
and time to any mood episode recurrence of 33 months. The present result has importance for both clinical treatment
decision-making and patient economic status.
Keywords : Maintenance treatment, Bipolar I disorder, Valproate, Recurrent rate, Time to recurrence
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