Psychiatric adverse events during treatment with brodalumab: Analysis of psoriasis clinical trials.

BACKGROUND: Individuals with psoriasis are at increased risk for psychiatric comorbidities, including suicidal ideation and behavior (SIB). OBJECTIVE: To distinguish between the underlying risk and potential for treatment-induced psychiatric adverse events in patients with psoriasis being treated with brodalumab, a fully human anti-interleukin 17 receptor A monoclonal antibody. METHODS: Data were evaluated from a placebo-controlled, phase 2 clinical trial; the open-label, long-term extension of the phase 2 clinical trial; and three phase 3, randomized, double-blind, controlled clinical trials (AMAGINE-1, AMAGINE-2, and AMAGINE-3) and their open-label, long-term extensions of patients with moderate-to-severe psoriasis. RESULTS: The analysis included 4464 patients with 9161.8 patient-years of brodalumab exposure. The follow-up time-adjusted incidence rates of SIB events were comparable between the brodalumab and ustekinumab groups throughout the 52-week controlled phases (0.20 vs 0.60 per 100 patient-years). In the brodalumab group, 4 completed suicides were reported, 1 of which was later adjudicated as indeterminate; all patients had underlying psychiatric disorders or stressors. LIMITATIONS: There was no comparator arm past week 52. Controlled study periods were not powered to detect differences in rare events such as suicide. CONCLUSIONS: Comparison with controls and the timing of events do not indicate a causal relationship between SIB and brodalumab treatment.

What Lies Beneath the Face Value of a BOX WARNING: A Deeper Look at Brodalumab.

Brodalumab, a fully human antibody of the interleukin-17 receptor, is highly effective in the treatment of moderate-to-severe plaque psoriasis. However, based on safety signals identified in clinical trials, brodalumab carries a boxed warning regarding possible risks of suicidal ideation and behavior (SIB). The validity of this link remains controversial, especially in the context of the psoriasis population as well as clinical trial data from other recently approved treatments. Herein, we critically examine the association between brodalumab and SIB. J Drugs Dermatol. 2018;17(8 Suppl):s29-34.

Comparison of antidepressant classes and the risk and time course of suicide attempts in adults: propensity matched, retrospective cohort study.

BACKGROUND: Placebo-controlled clinical trials have led to concern over possible increased risk of suicide-related events in some populations exposed to antidepressants. AIMS: To evaluate the risk of suicide attempts by antidepressant drug class and the presence or absence of depression. METHOD: A retrospective propensity-matched new-user cohort study was used to compare participants with incident depression classified by antidepressant treatment with each other and with the general population. RESULTS: Among the treated group, the suicide attempt rate peaked in the month prior to diagnosis then decreased steadily over the next 6 months. Among the pharmacologically untreated group, the highest rate was seen in the second month after diagnosis. Cohorts with depression had significantly higher suicide attempt risk than the general population, but the treated group did not differ significantly from the untreated group. CONCLUSIONS: Patients on antidepressants did not have significantly higher risk compared with untreated patients. No significant differences were observed for patients treated with individual serotonin-noradrenaline reuptake inhibitors (SNRIs) or selective serotonin reuptake inhibitors (SSRIs) or by class (SSRI v. SNRI cohorts).

Multimodal functional and structural neuroimaging investigation of major depressive disorder following treatment with duloxetine.

BACKGROUND: Longitudinal neuroimaging studies of major depressive disorder (MDD) have most commonly assessed the effects of antidepressants from the serotonin reuptake inhibitor class and usually reporting a single measure. Multimodal neuroimaging assessments were acquired from MDD patients during an acute depressive episode with serial measures during a 12-week treatment with the serotonin-norepinephrine reuptake inhibitor (SNRI) duloxetine. METHODS: Participants were medication-free MDD patients (n = 32; mean age 40.2 years) in an acute depressive episode and healthy controls matched for age, gender, and IQ (n = 25; mean age 38.8 years). MDD patients received treatment with duloxetine 60 mg daily for 12 weeks with an optional dose increase to 120 mg daily after 8 weeks. All participants had serial imaging at weeks 0, 1, 8, and 12 on a 3 Tesla magnetic resonance imaging (MRI) scanner. Neuroimaging tasks included emotional facial processing, negative attentional bias (emotional Stroop), resting state functional MRI and structural MRI. RESULTS: A significant group by time interaction was identified in the anterior default mode network in which MDD patients showed increased connectivity with treatment, while there were no significant changes in healthy participants. In the emotional Stroop task, increased posterior cingulate activation in MDD patients normalized following treatment. No significant group by time effects were observed for happy or sad facial processing, including in amygdala responsiveness, or in regional cerebral volumes. Reduced baseline resting state connectivity within the orbitofrontal component of the default mode network was predictive of clinical response. An early increase in hippocampal volume was predictive of clinical response. CONCLUSIONS: Baseline resting state functional connectivity was predictive of subsequent clinical response. Complementary effects of treatment were observed from the functional neuroimaging correlates of affective facial expressions, negative attentional bias, and resting state. No significant effects were observed in affective facial processing, while the interaction effect in negative attentional bias and individual group effects in resting state connectivity could be related to the SNRI class of antidepressant medication. The specificity of the observed effects to SNRI pharmacological treatments requires further investigation. TRIAL REGISTRATION: Registered at clinicaltrials.gov ( NCT01051466 ).

The relationship between change in apathy and changes in cognition and functional outcomes in currently non-depressed SSRI-treated patients with major depressive disorder.

AIMS: Apathy in the context of treated major depressive disorder (MDD) is a frequently observed phenomenon in clinical practice. This study aimed to assess the validity of the Rothschild Scale for Antidepressant Tachyphylaxis® (RSAT) and the Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ) for measuring apathy, and to assess the relationship between apathy and possible contributing factors, in patients with MDD and residual apathy in the absence of depressed mood. METHODS: The underlying structure and validity of the RSAT and CPFQ were assessed via factor analysis and correlation with the Apathy Evaluation Scale-Clinician rated version (AES-C) in 483 patients who had previously responded to treatment with a selective serotonin reuptake inhibitor. The relationship between apathy and contributing variables was investigated via structural equation modeling. Correlation and regression analyses were conducted to examine the relationship between the Sheehan Disability Scale (SDS) and the RSAT, CPFQ, and AES-C. RESULTS: The RSAT and CPFQ were validated with the AES-C with respect to energy and motivation. The latent variable "Energy and Interest", based on the energy, motivation, and interest items (RSAT and CPFQ), was a major contributing factor to apathy. Improvements in function (SDS) were significantly correlated with, and predicted by, improvements in apathy and cognitive and physical functioning (assessed by the RSAT, CPFQ, and AES-C). CONCLUSIONS: These analyses provide further information on apathy and its assessment in the context of treated MDD. A better understanding of apathy will aid further investigation of this phenomenon and, ultimately, determination of the most appropriate approach for its clinical management.

Comprehensive review of factors implicated in the heterogeneity of response in depression.

BACKGROUND: Heterogeneity in overall response and outcomes to pharmacological treatment has been reported in several depression studies but with few sources that integrate these results. The goal of this study was to review the literature and attempt to identify nongenetic factors potentially predictive of overall response to depression treatments. METHODS: A comprehensive review of the literature from the last 10 years was performed using three key databases (PubMed, EMBASE, and Cochrane). All relevant studies that met the inclusion criteria were selected and scored for their levels of evidence using the NICE scoring method. A subjective assessment of the strength of evidence for each factor was performed using predefined criteria. RESULTS: Our broad search yielded 76 articles relevant to treatment heterogeneity. Sociodemographic factors, disease characteristics, and comorbidities were the most heavily researched areas. Some of the factors associated with more favorable overall response include being married, other social support, and low levels of baseline depressive symptoms. Evidence relating to baseline disease severity as a factor predictive of antidepressant response was particularly convincing among the factors reviewed. The presence of comorbid anxiety and pain contributed to worse antidepressant treatment outcomes. CONCLUSIONS: Several factors either predictive of or associated with overall response to antidepressant treatment have been identified. Inclusion of factors predictive of response in the design of future trials may help tailor treatments to depression patients presenting to the average clinical practice, resulting in improved outcomes.

Assessment of depressive symptoms and functional outcomes in patients with major depressive disorder treated with duloxetine versus placebo: primary outcomes from two trials conducted under the same protocol.

OBJECTIVE: Return of functional ability is a central goal in the treatment of major depressive disorder. We conducted two trials with the same protocol that was designed to assess functioning after 8 Weeks of treatment with duloxetine. METHODS: The a priori primary outcome was improvement in the Hamilton Depression Rating Scale (HAMD) item 7 (work/activities). Secondary outcomes included improvement in depressive symptoms assessed by the HAMD Maier subscale, and improvement in functioning assessed by the Sheehan Disability Scale (SDS), and the Social Adaptation Self-evaluation Scale (SASS). Patients were randomly assigned to duloxetine 60 mg/day (Trial I, n = 257; Trial II, n = 261) or placebo (Trial I, n = 127; Trial II, n = 131). Changes from baseline were analyzed using a mixed-effects model repeated measures approach. RESULTS: At Week 8, duloxetine was superior to placebo in improving HAMD work/activities (p < 0.001) in Trial II, but not Trial I (p = 0.051), and Maier scores (p < 0.01) in both trials. At Week 12, duloxetine was superior to placebo on improving SASS scores in both trials, and the SDS in Trial II. CONCLUSION: Treatment with duloxetine was associated with significant improvement in depressive symptoms compared with placebo, but improvement in HAMD work/activities was inconsistent at 8 weeks.

Effectiveness of adjunctive antidepressant treatment for bipolar depression.

BACKGROUND: Episodes of depression are the most frequent cause of disability among patients with bipolar disorder. The effectiveness and safety of standard antidepressant agents for depressive episodes associated with bipolar disorder (bipolar depression) have not been well studied. Our study was designed to determine whether adjunctive antidepressant therapy reduces symptoms of bipolar depression without increasing the risk of mania. METHODS: In this double-blind, placebo-controlled study, we randomly assigned subjects with bipolar depression to receive up to 26 weeks of treatment with a mood stabilizer plus adjunctive antidepressant therapy or a mood stabilizer plus a matching placebo, under conditions generalizable to routine clinical care. A standardized clinical monitoring form adapted from the mood-disorder modules of the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, was used at all follow-up visits. The primary outcome was the percentage of subjects in each treatment group meeting the criterion for a durable recovery (8 consecutive weeks of euthymia). Secondary effectiveness outcomes and rates of treatment-emergent affective switch (a switch to mania or hypomania early in the course of treatment) were also examined. RESULTS: Forty-two of the 179 subjects (23.5%) receiving a mood stabilizer plus adjunctive antidepressant therapy had a durable recovery, as did 51 of the 187 subjects (27.3%) receiving a mood stabilizer plus a matching placebo (P=0.40). Modest nonsignificant trends favoring the group receiving a mood stabilizer plus placebo were observed across the secondary outcomes. Rates of treatment-emergent affective switch were similar in the two groups. CONCLUSIONS: The use of adjunctive, standard antidepressant medication, as compared with the use of mood stabilizers, was not associated with increased efficacy or with increased risk of treatment-emergent affective switch. Longer-term outcome studies are needed to fully assess the benefits and risks of antidepressant therapy for bipolar disorder. (ClinicalTrials.gov number, NCT00012558 [ClinicalTrials.gov].).

Linkage disequilibrium mapping of the chromosome 6q21-22.31 bipolar I disorder susceptibility locus.

We previously reported genome-wide significant evidence for linkage between chromosome 6q and bipolar I disorder (BPI) by performing a meta-analysis of original genotype data from 11 genome scan linkage studies. We now present follow-up linkage disequilibrium mapping of the linked region utilizing 3,047 single nucleotide polymorphism (SNP) markers in a case-control sample (N = 530 cases, 534 controls) and family-based sample (N = 256 nuclear families, 1,301 individuals). The strongest single SNP result (rs6938431, P = 6.72 x 10(-5)) was observed in the case-control sample, near the solute carrier family 22, member 16 gene (SLC22A16). In a replication study, we genotyped 151 SNPs in an independent sample (N = 622 cases, 1,181 controls) and observed further evidence of association between variants at SLC22A16 and BPI. Although consistent evidence of association with any single variant was not seen across samples, SNP-wise and gene-based test results in the three samples provided convergent evidence for association with SLC22A16, a carnitine transporter, implicating this gene as a novel candidate for BPI risk. Further studies in larger samples are warranted to clarify which, if any, genes in the 6q region confer risk for bipolar disorder.

Brain-derived neurotrophic factor association with amygdala response in major depressive disorder.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) has an essential role in synaptic plasticity and neurogenesis. BDNF mediates amygdala-dependent learning for both aversive and appetitive emotional memories. The expression of BDNF in limbic regions is posited to contribute the development of depression, and amygdala responsivity is a potential marker of depressive state. METHODS: The present study examined the relationship between platelet BDNF levels and amygdala volume and function in major depressive disorder (MDD). Participants were 23 MDD (mean age 38.9 years) and 23 healthy controls (mean age 38.8 years). All participants were recruited from the community. MDD participants were in a current depressive episode of moderate severity and medication-free. Amygdala responses were acquired during a functional MRI task of implicit emotional processing with sad facial expressions. RESULTS: Significant correlation was observed between platelet BDNF levels and left amygdala responses, but no significant correlations were found with right amygdala responses or with amygdala volumes. LIMITATIONS: Interactions with neuroprotective as well as neurotoxic metabolites in the kyneurenine pathway were not examined. CONCLUSIONS: Relationship between BDNF levels and amygdala responsivity to emotionally salient stimuli in MDD could reflect the importance of BDNF in amygdala-dependent learning with clinical implications for potential pathways for treatment.

Suicidal ideation and depressive symptoms among bipolar patients as predictors of the health and well-being of caregivers.

OBJECTIVES: Few studies have addressed the physical and mental health effects of caring for a family member with bipolar disorder. This study examined whether caregivers' health is associated with changes in suicidal ideation and depressive symptoms among bipolar patients observed over one year. METHODS: Patients (N = 500) participating in the Systematic Treatment Enhancement Program for Bipolar Disorder and their primary caregivers (N = 500, including 188 parental and 182 spousal caregivers) were evaluated for up to one year as part of a naturalistic observational study. Caregivers' perceptions of their own physical health were evaluated using the general health scale from the Medical Outcomes Study 36-item Short-Form Health Survey. Caregivers' depression was evaluated using the Center for Epidemiological Studies of Depression Scale. RESULTS: Caregivers of patients who had increasing suicidal ideation over time reported worsening health over time compared to caregivers of patients whose suicidal ideation decreased or stayed the same. Caregivers of patients who had more suicidal ideation and depressive symptoms reported more depressed mood over a one-year reporting period than caregivers of patients with less suicidal ideation or depression. The pattern of findings was consistent across parent caregivers and spousal caregivers. CONCLUSIONS: Caregivers, rightly concerned about patients becoming suicidal or depressed, may try to care for the patient at the expense of their own health and well-being. Treatments that focus on the health of caregivers must be developed and tested.

Association study of 21 circadian genes with bipolar I disorder, schizoaffective disorder, and schizophrenia.

OBJECTIVE: Published studies suggest associations between circadian gene polymorphisms and bipolar I disorder (BPI), as well as schizoaffective disorder (SZA) and schizophrenia (SZ). The results are plausible, based on prior studies of circadian abnormalities. As replications have not been attempted uniformly, we evaluated representative, common polymorphisms in all three disorders. METHODS: We assayed 276 publicly available 'tag' single nucleotide polymorphisms (SNPs) at 21 circadian genes among 523 patients with BPI, 527 patients with SZ/SZA, and 477 screened adult controls. Detected associations were evaluated in relation to two published genome-wide association studies (GWAS). RESULTS: Using gene-based tests, suggestive associations were noted between EGR3 and BPI (p = 0.017), and between NPAS2 and SZ/SZA (p = 0.034). Three SNPs were associated with both sets of disorders (NPAS2: rs13025524 and rs11123857; RORB: rs10491929; p < 0.05). None of the associations remained significant following corrections for multiple comparisons. Approximately 15% of the analyzed SNPs overlapped with an independent study that conducted GWAS for BPI; suggestive overlap between the GWAS analyses and ours was noted at ARNTL. CONCLUSIONS: Several suggestive, novel associations were detected with circadian genes and BPI and SZ/SZA, but the present analyses do not support associations with common polymorphisms that confer risk with odds ratios greater than 1.5. Additional analyses using adequately powered samples are warranted to further evaluate these results.

Effectiveness of a quantitative electroencephalographic biomarker for predicting differential response or remission with escitalopram and bupropion in major depressive disorder.

We examined the Antidepressant Treatment Response (ATR) index as a predictor of differential response and remission to escitalopram, bupropion, or a combination of the two medications, in subjects with major depressive disorder (MDD). Three hundred seventy-five subjects had a baseline quantitative electroencephalographic (QEEG) study preceding 1 week of treatment with escitalopram, 10 mg, after which a second QEEG was performed and the ATR index was calculated. Subjects then were randomized to continue escitalopram, switch to bupropion, or receive a combination of the two. Clinical response was assessed using the 17-item Hamilton Depression Rating Scale at 49 days of treatment. Accuracy of ATR in predicting response and remission was calculated. There were no significant differences between response and remission rates in the three treatment groups. A single ATR threshold was useful for predicting differential response to either escitalopram or bupropion monotherapy. Subjects with ATR values above the threshold were more than 2.4 times as likely to respond to escitalopram as those with low ATR values (68% vs. 28%). Subjects with ATR values below the threshold who were switched to bupropion treatment were 1.9 times as likely to respond to bupropion alone as those who remained on escitalopram treatment (53% vs. 28%). The ATR index did not provide a useful prediction of response to combination treatment. The ATR index may prove useful in predicting responsiveness to different antidepressant medications.

Comparative effectiveness of biomarkers and clinical indicators for predicting outcomes of SSRI treatment in Major Depressive Disorder: results of the BRITE-MD study.

Patients with Major Depressive Disorder (MDD) may not respond to antidepressants for 8 weeks or longer. A biomarker that predicted treatment effectiveness after only 1 week could be clinically useful. We examined a frontal quantitative electroencephalographic (QEEG) biomarker, the Antidepressant Treatment Response (ATR) index, as a predictor of response to escitalopram, and compared ATR with other putative predictors. Three hundred seventy-five subjects meeting DSM-IV criteria for MDD had a baseline QEEG study. After 1 week of treatment with escitalopram, 10 mg, a second QEEG was performed, and the ATR was calculated. Subjects then were randomly assigned to continue with escitalopram, 10 mg, or change to alternative treatments. Seventy-three evaluable subjects received escitalopram for a total of 49days. Response and remission rates were 52.1% and 38.4%, respectively. The ATR predicted both response and remission with 74% accuracy. Neither serum drug levels nor 5HTTLPR and 5HT2a genetic polymorphisms were significant predictors. Responders had larger decreases in Hamilton Depression Rating Scale (Ham-D(17)) scores at day 7 (P=0.005), but remitters did not. Clinician prediction based upon global impression of improvement at day 7 did not predict outcome. Logistic regression showed that the ATR and early Ham-D(17) changes were additive predictors of response, but the ATR was the only significant predictor of remission. Future studies should replicate these results prior to clinical use.

Psychosocial treatments for bipolar depression: a 1-year randomized trial from the Systematic Treatment Enhancement Program.

CONTEXT: Psychosocial interventions have been shown to enhance pharmacotherapy outcomes in bipolar disorder. OBJECTIVE: To examine the benefits of 4 disorder-specific psychotherapies in conjunction with pharmacotherapy on time to recovery and the likelihood of remaining well after an episode of bipolar depression. DESIGN: Randomized controlled trial. SETTING: Fifteen clinics affiliated with the Systematic Treatment Enhancement Program for Bipolar Disorder. Patients A total of 293 referred outpatients with bipolar I or II disorder and depression treated with protocol pharmacotherapy were randomly assigned to intensive psychotherapy (n = 163) or collaborative care (n = 130), a brief psychoeducational intervention. INTERVENTIONS: Intensive psychotherapy was given weekly and biweekly for up to 30 sessions in 9 months according to protocols for family-focused therapy, interpersonal and social rhythm therapy, and cognitive behavior therapy. Collaborative care consisted of 3 sessions in 6 weeks. MAIN OUTCOME MEASURES: Outcome assessments were performed by psychiatrists at each pharmacotherapy visit. Primary outcomes included time to recovery and the proportion of patients classified as well during each of 12 study months. RESULTS: All analyses were by intention to treat. Rates of attrition did not differ across the intensive psychotherapy (35.6%) and collaborative care (30.8%) conditions. Patients receiving intensive psychotherapy had significantly higher year-end recovery rates (64.4% vs 51.5%) and shorter times to recovery than patients in collaborative care (hazard ratio, 1.47; 95% confidence interval, 1.08-2.00; P = .01). Patients in intensive psychotherapy were 1.58 times (95% confidence interval, 1.17-2.13) more likely to be clinically well during any study month than those in collaborative care (P = .003). No statistically significant differences were observed in the outcomes of the 3 intensive psychotherapies. CONCLUSIONS: Intensive psychosocial treatment as an adjunct to pharmacotherapy was more beneficial than brief treatment in enhancing stabilization from bipolar depression. Future studies should compare the cost-effectiveness of models of psychotherapy for bipolar disorder. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00012558.

Prescription patterns of psychotropic medications in elderly compared with younger participants who achieved a "recovered" status in the systematic treatment enhancement program for bipolar disorder.

OBJECTIVES: This study compares prescription patterns between young adults and elderly with bipolar disorder who achieved a recovery status during the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). DESIGN: STEP-BD is a multicenter National Institute of Mental Health-funded project designed to evaluate the longitudinal outcome of patients with bipolar disorder. The STEP-BD study involved extensive assessment across multiple domains including demographic data, diagnosis, symptom severity, treatment, and clinical status. Patients achieved "recovered" status when they experienced eight consecutive weeks without significant symptoms. PARTICIPANTS: The authors analyzed data of all subjects who achieved a recovered status at least once in their participation. MEASUREMENTS: The authors compared treatment regimes and doses among young participants with middle age (N = 3,364), 20-59 years old, and older participants 60 and above (N = 246). RESULTS: Of the 3,615 STEP-BD participants who had a lifetime diagnosis of bipolar subtypes I or II, 67.6% (N = 2442) achieved a recovered status during their participation. A total of 78.5% (N = 193) of older patients recovered compared with 66.8% of the younger cohort. On average, participants who reached a recovered status took 2.05 medications with no difference between age groups. Lithium was prescribed to 37.8% of younger patients compared with only 29.5% of older participants. The mean dosages taken by younger and older patients differed significantly only for lithium, valproate, and risperidone with elderly individuals prescribed lower daily dosages. Significant reduction in lithium dosing was observed among individuals aged 50 and older and among individuals 60 and older for valproate. Although valproate was more often prescribed, 42.1% of recovered bipolar elder achieved recovery with lithium alone compared with only 21.3% of the younger cohort. CONCLUSION: This data shows recovery is achievable in the elderly though more than one medication is often needed regardless of age.

A single blind comparison of lithium and lamotrigine for the treatment of bipolar II depression.

BACKGROUND: Treatment studies are lacking for patients with bipolar II disorder (BDII). The objective of this study was to compare lamotrigine (LTG) and lithium (Li) monotherapy for the treatment of BDII depression. METHODS: Patients with BDII acute depression were randomized to open-label monotherapy with LTG or Li, and evaluated by trained raters blinded to treatment. Patients were titrated to 200 mg/day of LTG over 8 weeks or at least 900 mg/day of Li over 2 weeks (serum level 0.6-1.2 mEq/L), and seen biweekly for 16 weeks. The primary outcome variable was change in the Hamilton Depression Rating Scale 17-item (Ham-D(17)), evaluated using mixed effects random regression. RESULTS: Both groups showed significant improvement from baseline to endpoint on the Ham-D(17) (p<0.0001), with no between group differences (p=0.95). Seventy-two percent of the population was rapid cycling by DSM-IV criteria. No differences in response were noted between rapid cyclers and non-rapid cyclers. Early termination for any cause was 42%. The Li group reported significantly more side effects, although drop-out due to side effects did not differ between groups. LIMITATIONS: This study was limited by an open treatment design, a lack of placebo arm, and uneven treatment groups. CONCLUSIONS: Lamotrigine and lithium were effective monotherapy for BDII depression, with comparable response and remission rates. Naturalistic design and lack of placebo limit conclusions, though patient history indicated long standing depression unlikely to be alleviated by time. Patients who received Li reported more side effects, but this did not appear to impact drop-out rates.

Current issues: women and bipolar disorder.

While the treatment of bipolar disorder (BD) is typically complex, the treatment of women with bipolar disorder is even more challenging because clinicians must also individualize treatment based on the potential for pregnancy, drug interactions with oral contraceptives, and an increased risk of endocrine diseases that can either impact the course of illness or become manifest with some treatments. Women with BD should be checked for hypothyroidism, and if prescribed antidepressants, carefully watched for rapid cycling or a mood switch to mania, hypomania, or a mixed state. Several medications interact with oral contraceptives or increase the risk of developing polycystic ovary syndrome. Consideration of possible pregnancy is essential, and should be planned in advance whenever possible. Rates of recurrence have been shown to be equal in pregnant and nonpregnant women with BD. Risks of medication to the fetus at various points of development must be balanced against the risks of not treating, which is also detrimental to both fetus and mother. The postpartum period is a time of especially high risk; as many as 40% to 67% of women with BD report experiencing a postpartum mania or depression. The decision to breastfeed must also take into account the adverse impact of sleep deprivation in triggering mood episodes. In order to best address these issues, clinicians must be familiar with the data and collaborate with the patient to assess risks and benefits for the individual women and her family.

Other race effect on amygdala response during affective facial processing in major depression.

OBJECTIVE: The other race effect, also known as own race bias, refers to the enhanced ability to recognize faces belonging to one's own race relative to faces from another race. The other race effect is associated with increased amygdala response in healthy individuals. The amygdala is a key node in emotion processing which shows impaired functioning in depression and has been proposed to be a marker of depressive state. We investigated the impact of the other race effect on amygdala responses in depression. METHODS: Participants were 30 individuals with major depression (mean age 39.4 years) and 23 healthy individuals (mean age: 38.8 years) recruited from the community. Participants were Asian, Black/African American and Caucasian. During a functional MRI scan, participants viewed Caucasian faces which displayed a range of sad expressions. A region of interest analysis of left and right amygdala responses was performed. RESULTS: Increased bilateral amygdala responses were observed in response to the Caucasian face stimuli in participants who were Asian or Black/African American as compared to Caucasian participants in both healthy individuals and individuals with major depression. There was no significant group by race interaction effect. CONCLUSIONS: Increased amygdala responses associated with the other race effect were evident in both individuals with major depression and in healthy participants. Increased amygdala responses with the other race effect is a potential confound of the neural correlates of facial processing in healthy participants and in mental health disorders. The implications of the other race effect on impairments in interpersonal functioning in depression require further investigation.

Intensive psychosocial intervention enhances functioning in patients with bipolar depression: results from a 9-month randomized controlled trial.

OBJECTIVE: Psychosocial interventions are effective adjuncts to pharmacotherapy in delaying recurrences of bipolar disorder; however, to date their effects on life functioning have been given little attention. In a randomized trial, the authors examined the impact of intensive psychosocial treatment plus pharmacotherapy on the functional outcomes of patients with bipolar disorder over the 9 months following a depressive episode. METHOD: Participants were 152 depressed outpatients with bipolar I or bipolar II disorder in the multisite Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) study. All patients received pharmacotherapy. Eighty-four patients were randomly assigned to intensive psychosocial intervention (30 sessions over 9 months of interpersonal and social rhythm therapy, cognitive behavior therapy [CBT], or family-focused therapy), and 68 patients were randomly assigned to collaborative care (a 3-session psychoeducational treatment). Independent evaluators rated the four subscales of the Longitudinal Interval Follow-Up Evaluation-Range of Impaired Functioning Tool (LIFE-RIFT) (relationships, satisfaction with activities, work/role functioning, and recreational activities) through structured interviews given at baseline and every 3 months over a 9-month period. RESULTS: Patients in intensive psychotherapy had better total functioning, relationship functioning, and life satisfaction scores over 9 months than patients in collaborative care, even after pretreatment functioning and concurrent depression scores were covaried. No effects of psychosocial intervention were observed on work/role functioning or recreation scores during this 9-month period. CONCLUSIONS: Intensive psychosocial treatment enhances relationship functioning and life satisfaction among patients with bipolar disorder. Alternate interventions focused on the specific cognitive deficits of individuals with bipolar disorder may be necessary to enhance vocational functioning after a depressive episode.