A re-examination of antidepressant treatment-emergent mania in bipolar disorders: evidence of gender differences.

OBJECTIVE: To explore the prevalence and clinical profile of males and females who develop antidepressant treatment-emergent mania (ATEM). METHOD: From an original sample of 754 patients with BD, we identified ATEM+ cases (n = 75) and ATEM- controls (n = 135) that met stringent criteria. We specifically examined the combinations of clinical factors that best classified males and females as ATEM+ cases. RESULTS: Seventy-five individuals were classified as ATEM+; 87% of ATEM events occurred during antidepressant monotherapy. Regression analyses demonstrated that the presence of an alcohol and/or substance use disorder [Odds Ratio (OR) 6.37], a history of one or more suicide attempts (OR 4.19) and higher number of depressive episodes per year of illness (OR 1.71) correctly classified 73% of males. In contrast, 84% of females were correctly classified on the basis of a positive history of thyroid disorder (OR 3.23), a positive family history of BD I (OR 2.68) and depressive onset polarity (OR 2.01). CONCLUSION: Using stringent definitions of ATEM status to reduce the probability of inclusion of false-positive cases and false-negative controls, we identified for the first time that the risk profiles for the development of an ATEM differ significantly according to gender.

Association between thyroid autoimmunity and antidepressant treatment-emergent mania in pediatric mood disorders.

Risk factors associated with antidepressant treatment-emergent mania(ATEM) are poorly characterized in child and adolescent populations. To identify better biomarkers, we aimed to explore whether thyroid autoimmunity is associated with ATEM in pediatric mood disorders. We enrolled two groups of pediatric mood disorders, those with ATEM+ (n = 29) and those with ATEM- controls (n = 31). All diagnoses were made according to structured interviews by the clinicians. Autoimmune thyroiditis (anti-thyroid peroxidase antibodies [TPO-abs] and thyroid function (thyroid-stimulating hormone [TSH] and free thyroxin [FT4]) were assessed. Logistic regression was used to explore the relationship between TPO-abs seroprevalence and ATEM+ while controlling for covariates. Group comparisons showed that the patient with ATEM+ had significantly higher seroprevalence and titer of TPO-abs compared to ATEM- controls. In logistic regression analysis adjusting for age, gender, Tanner stage, body mass index, antipsychotic treatments, smoking status and family history of thyroid disorder, the seroprevalence of TPO-abs (>60 U/mL) was significantly associated with ATEM+ (OR = 3.67, 95% confidence interval [CI] = 1.2-11.1, p = 0.022). Our findings demonstrated that seroprevalence and titer of TPO-abs in pediatric mood disorders are associated with ATEM+ status. TPO-abs could potentially serve as a biomarker when assessing the risk of ATEM in the child and adolescent population.

Dosage-related nature of escitalopram treatment-emergent mania/hypomania: a case series.

OBJECTIVE: Several studies have documented that treatment with various antidepressant agents can result in mood switching during major depressive episodes. Escitalopram, one of the newer selective serotonin reuptake inhibitors (SSRIs), is considered preferable due to its relatively high efficacy and acceptability. Although a few cases of escitalopram treatment-emergent mania have been reported, it remains unknown whether this effect is dose-related. METHOD: In the present report, we discuss three cases of treatment-emergent mania/hypomania in patients receiving escitalopram for major depressive episodes. No patients had a family or personal history of bipolar disorder. RESULTS: In all three cases, manic or hypomanic symptoms emerged within 1 month right after the dosage of escitalopram was increased to 20 mg/day. Moreover, manic episodes subsided as the dosage of escitalopram was reduced. Mood switching was not observed after the cessation of escitalopram treatment. CONCLUSION: Our case series indicates that escitalopram may induce treatment-emergent mania/hypomania in a dose-related manner. Treatment at lower doses and with careful upward titration might be favorable in certain patients with bipolar depression and major depressive disorder in order to minimize the risk of mood switching.