Serotonin transporter polymorphism interacts with childhood adversity to predict aspects of impulsivity.

The serotonin transporter polymorphism has been linked--often in interaction with environmental adversity--to a variety of outcomes, including affective disorders. This polymorphism is widely viewed as relating to anxiety traits. A different view is that it relates instead to impulsivity (vs. control) in reacting to emotions. In a test of the latter view, 303 students were genotyped on this polymorphism and completed self-reports bearing on impulsive reactions to emotions (including both negative and positive emotions in separate measures), impulsive tendencies that do not stem from emotions, and childhood adversity. The impulsivity measures reflected three latent variables: pervasive influence of feelings, feelings (including positive feelings) triggering action, and failure to carry through on intentions (with no mention of emotion). Interactions between genotype and adversity emerged for both emotion-related aspects of impulsivity. Theoretical implications of the findings are discussed.

Lamotrigine plus quetiapine combination therapy in treatment-resistant bipolar depression.

BACKGROUND: Lamotrigine and quetiapine are commonly used in bipolar disorder, but there are no published systematic studies of their use in combination for treatment-resistant bipolar depression. METHODS: We studied 39 trials in outpatients (15 with bipolar I disorder, 22 with bipolar II disorder, and 1 with bipolar disorder not otherwise specified; 1 patient had 2 trials) with depression resistant to quetiapine or lamotrigine who were taking a mean of 1.7 other prescription psychotropic medications. Patients were given either open-label lamotrigine or quetiapine naturalistically, for up to 12 weeks of combination therapy. RESULTS: Lamotrigine (mean dose, 204.2 mg/d) plus quetiapine (mean dose, 188.5 mg/d) increased the euthymia rate (0.0% to 46.2%), decreased syndromal (79.5% to 30.8%) and subsyndromal (20.5% to 15.4%) depression rates, and improved Clinical Global Impression-Severity (mean change, -1.0) and Global Assessment of Functioning (mean change, +5.9) scores. Approximately one-fifth of patients discontinued therapy (20.5%) or required subsequent additional pharmacotherapy (20.5%). Only 10.3% discontinued due to adverse effects, and there was no significant change in mean body weight. CONCLUSIONS: The findings of this uncontrolled open pilot study must be viewed with caution. However, randomized, double-blind, placebo-controlled studies are warranted to confirm the possibility that combination therapy with lamotrigine and quetiapine is effective and well tolerated in patients with treatment-resistant bipolar depression.

Long-term effectiveness of quetiapine in bipolar disorder in a clinical setting.

OBJECTIVE: To assess quetiapine effectiveness in bipolar disorder (BD) patients in a clinical setting. METHODS: We naturalistically administered open quetiapine to outpatients assessed with the Systematic Treatment Enhancement Program for BD (STEP-BD) Affective Disorders Evaluation, and monitored longitudinally with the STEP-BD Clinical Monitoring Form. RESULTS: 96 patients (36 BD I, 50 BD II, 9 BD NOS, 1 Schizoaffective Bipolar Type, mean ± SD age 42.3 ± 13.8 years, 66.7% female) received quetiapine, combined with an average of 2.5 (in 66.7% of patients at least 2) other psychotropic medications and 0.9 non-psychotropic medications, started most often during depressive symptoms (53.1%) or euthymia (37.5%). Mean quetiapine duration and final dose were 385 days and 196 mg/day (50.0% of patients took ≤75 mg/day). Quetiapine was discontinued in 38.5% of trials, after on average 307 days, most often (in 19.8%) due to CNS adverse effects (primarily sedation). In 38.5% of trials quetiapine was continued on average 328 days with no subsequent psychotropic added. In 22.9% quetiapine was continued on average 613 days, but had subsequent psychotropic added after on average 113 days, most often for depressive symptoms. In 67 trials started at Stanford, quetiapine tended to primarily maintain euthymia and relieve depressive symptoms. In 29 trials started prior to Stanford, continuing quetiapine tended to primarily maintain euthymia and relieve mood elevation symptoms. Aside from sedation, quetiapine was generally well tolerated. CONCLUSIONS: In bipolar disorder outpatients quetiapine had a moderate (38.5%, with 385-day mean duration) discontinuation rate, and commonly did not require subsequent additional pharmacotherapy, suggesting effectiveness in a clinical setting.

Do positive emotions predict symptomatic change in bipolar disorder?

OBJECTIVES: Bipolar disorder is associated with positive emotion disturbance, though it is less clear which specific positive emotions are affected. METHODS: The present study examined differences among distinct positive emotions in recovered bipolar disorder (BD) patients (n = 55) and nonclinical controls (NC) (n = 32) and whether they prospectively predicted symptom severity in patients with BD. At baseline, participants completed self-report measures of several distinct trait positive emotions. Structured assessments of diagnosis and current mood symptoms were obtained for BD participants. At a six-month follow-up, a subset of BD participants' (n = 39) symptoms were reassessed. RESULTS: BD participants reported lower joy, compassion, love, awe, and contentment compared to NC participants. BD and NC participants did not differ in pride or amusement. For BD participants, after controlling for baseline symptom severity, joy and amusement predicted increased mania severity, and compassion predicted decreased mania severity at the six-month follow-up. Furthermore, amusement predicted increased depression severity and pride predicted decreased severity of depression. Awe, love, and contentment did not predict symptom severity. CONCLUSIONS: These results are consistent with a growing literature highlighting the importance of positive emotion in the course of bipolar disorder.

Effectiveness of lamotrigine in bipolar disorder in a clinical setting.

OBJECTIVE: To assess lamotrigine effectiveness in bipolar disorder (BD) patients in a clinical setting. METHOD: Open lamotrigine was naturalistically administered to outpatients at the Stanford University BD Clinic assessed with the Systematic Treatment Enhancement Program for BD (STEP-BD) Affective Disorders Evaluation, and monitored longitudinally with the STEP-BD Clinical Monitoring Form. RESULTS: One hundred and ninety-seven patients (64 BD I, 110 BD II, 21 BD NOS, 2 Schizoaffective Bipolar Type, mean+/-SD age 42.2+/-14.4 years, 62% female) had 200 trials of lamotrigine. Lamotrigine was combined with a mean of 2.1+/-1.5 other psychotropic medications, most often during euthymia or depressive symptoms. Mean lamotrigine duration was 434+/-444 days, and mean final dose was 236+/-132mg/day without valproate, and 169+/-137mg/day with valproate. Lamotrigine was discontinued in only 26.5% of trials at 255+/-242 days, most often due to inefficacy, and seldom due to adverse effects. In 31.5% of trials lamotrigine was continued 264+/-375 days with no subsequent psychotropic added. In 42.0% of trials lamotrigine was continued 674+/-479 days, but had subsequent psychotropic added at 146+/-150 days, most often for anxiety/insomnia and depressive symptoms. In 145 trials started at Stanford, lamotrigine primarily yielded relief of depressive symptoms or maintained euthymia. In 55 trials in which lamotrigine was started prior to Stanford, lamotrigine primarily maintained euthymia. Lamotrigine was generally well tolerated, with no serious rash, and only 3.5% discontinuing due to benign rash. CONCLUSION: In a cohort of bipolar disorder outpatients commonly with comorbid conditions, and most often receiving complex combination therapy, lamotrigine had a low (26.5%, with an overall mean duration of treatment of 434 days) discontinuation rate, suggesting effectiveness in BD in a clinical setting.