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Clinical correlates associated with the long-term response of bipolar disorder patients to lithium, valproate or lamotrigine: A retrospective study.

ABSTRACT: BACKGROUND:Although mood stabilizers such as lithium (LIT), valproate (VAL), and lamotrigine (LMT) appear to be efficacious treatments for bipolar disorder (BD) in research settings, the long-term response to these mood stabilizers in clinical practice is highly variable among individuals. Thus, the present study examined the characteristics associated with good or insufficient responses to long-term treatment with LIT, VAL, or LMT for BD. METHODS:This study retrospectively analyzed the medical records of patients who visited an outpatient clinic with a diagnosis of BD I or II. Data from patients who were treated with one of three mood stabilizing medications (LIT, VAL, or LMT) for more than 6 months were selected, and the long-term treatment responses were evaluated using the Alda scale. For the purposes of this study, two response categories were formed: insufficient response (ISR), including non-response or poor response (Alda total score ? 6), and good response (GR; Alda total score ? 7). RESULTS:Of the 645 patients included in the present study, 172 were prescribed LIT, 320 were prescribed VAL, and 153 were prescribed LMT for at least 6 months. A binary logistic regression analysis revealed that a diagnosis of BD II (odds ratio [OR], 8.868; 95% confidence interval [CI], 1.123-70.046; p = 0.038), comorbid alcohol/substance use disorder (OR, 4.238; 95% CI, 1.154-15.566; p = 0.030), and a history of mixed episodes (OR, 4.363; 95% CI, 1.191-15.985; p = 0.026) were significant predictors of LIT-ISR. Additionally, a depressive-predominant polarity significantly predicted LMT-GR (OR, 8.586; 95% CI, 2.767-26.644; p < 0.001). CONCLUSION:The present findings demonstrated that patients with a diagnosis of BD II, a comorbid alcohol/substance problem, or a history of mixed episodes were not likely to respond to LIT treatment. Additionally, LMT might be a better treatment choice for patients with a depressive-predominant polarity.

SUBMITTER: Woo YS

PROVIDER: S-EPMC6953788 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND:When evaluating the long-term treatment response to mood stabilizers using the Alda scale, mood stabilizer combination therapy is typically considered a confounding factor, and patients receiving combination therapy are excluded from the analysis. However, this may result in bias if those under combination therapy are worse treatment responders. This study aims to explore whether the Alda scale is applicable to patients taking lithium and valproate combination therapy. We compared long-term treatment response in patients receiving monotherapy and combination therapy of the two drugs, and investigated clinical correlates of the responses to each drug. METHODS:The study subjects consisted of 102 patients with bipolar I (BD-I) or bipolar II (BD-II) disorder who had been undergoing maintenance treatment with lithium and/or valproate for more than 2 years at a single specialized bipolar disorder clinic. Long-term treatment response was measured using the Alda scale and compared among the lithium monotherapy group, the valproate monotherapy group, and the mood stabilizer combination group. Clinical correlates of long-term treatment response were evaluated in lithium users and valproate users separately. RESULTS:There were no significant differences in terms of baseline illness characteristics among groups. The combination group showed the worst treatment response for all the response measurements applied. This group also had the higher rate of 'poor responder' with a statistically significant difference compared to valproate group. Older age at onset and (hypo)manic episode at onset showed significant positive associations with total Alda score in lithium users, while comorbid anxiety disorders, obsessive-compulsive disorder and mixed episode showed significant negative associations in valproate users. CONCLUSIONS:The combination group had poorer long-term treatment response but did not show distinct clinical characteristics compared to the monotherapy groups. When exploring the long-term effects of mood stabilizers, excluding patients undergoing combination treatment could result in bias because they may represent a poor response group. The long-term treatment responses of lithium and valproate had different clinical correlates.

Project description:Concerns about potential adverse effects of long-term exposure to lithium as a mood-stabilizing treatment notably include altered renal function. However, the incidence of severe renal dysfunction; rate of decline over time; effects of lithium dose, serum concentration, and duration of treatment; relative effects of lithium exposure vs. aging; and contributions of sex and other factors all remain unclear.Accordingly, we acquired data from 12 collaborating international sites and 312 bipolar disorder patients (6142 person-years, 2669 assays) treated with lithium carbonate for 8-48 (mean 18) years and aged 20-89 (mean 56) years. We evaluated changes of estimated glomerular filtration rate (eGFR) as well as serum creatinine, urea-nitrogen, and glucose concentrations, white blood cell count, and body-mass index, and tested associations of eGFR with selected factors, using standard bivariate contrasts and regression modeling.Overall, 29.5% of subjects experienced at least one low value of eGFR (<60 mL/min/1.73 m2), most after ≥15 years of treatment and age > 55; risk of ≥2 low values was 18.1%; none experienced end-stage renal failure. eGFR declined by 0.71%/year of age and 0.92%/year of treatment, both by 19% more among women than men. Mean serum creatinine increased from 0.87 to 1.17 mg/dL, BUN from 23.7 to 33.1 mg/dL, glucose from 88 to 122 mg/dL, and BMI from 25.9 to 26.6 kg/m2. By multivariate regression, risk factors for declining eGFR ranked: longer lithium treatment, lower lithium dose, higher serum lithium concentration, older age, and medical comorbidity. Later low eGFR was also predicted by lower initial eGFR, and starting lithium at age ≥ 40 years.Control data for age-matched subjects not exposed to lithium were lacking.Long-term lithium treatment was associated with gradual decline of renal functioning (eGFR) by about 30% more than that was associated with aging alone. Risk of subnormal eGFR was from 18.1% (≥2 low values) to 29.5% (≥1 low value), requiring about 30 years of exposure. Additional risk factors for low eGFR were higher serum lithium level, longer lithium treatment, lower initial eGFR, and medical comorbidity, as well as older age.

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Clinical correlates associated with the long-term response of bipolar disorder patients to lithium, valproate or lamotrigine: A retrospective study.

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