Efficacy of cariprazine in patients with bipolar depression and higher or lower levels of baseline anxiety: a pooled post hoc analysis.

Post hoc analyses evaluated cariprazine, a dopamine D 3 -preferring D 3 /D 2 receptor partial agonist, in patients with bipolar I depression and high baseline anxiety. Data were pooled from two phase 3, randomized, double-blind, placebo-controlled studies in adults with bipolar I disorder and a major depressive episode (NCT02670538, NCT02670551). Cariprazine 1.5 and 3 mg/d were evaluated in patient subgroups with higher and lower baseline anxiety. In patients with higher baseline anxiety, significant differences for cariprazine 1.5 mg/d versus placebo were observed on change in Montgomery-Åsberg Rating Scale (MADRS) total score, Hamilton Anxiety Rating Scale (HAM-A) total score and subscale scores, and rates of MADRS remission ( P < 0.05 all); nonsignificant numerical improvements were observed for cariprazine 3 mg/d versus placebo. In patients with lower anxiety, differences versus placebo were significant for HAM-A (cariprazine 3 mg/d) and MADRS (cariprazine 1.5 and 3 mg/d) total score changes ( P < 0.05 all). Rates of treatment-emergent mania were low and similar for cariprazine and placebo. Cariprazine 1.5 mg/d had consistent effects on anxiety and depression symptoms in patients with bipolar I depression and higher baseline anxiety; tolerability was favorable. Given few proven treatments for this common comorbidity, these preliminary results are promising.

Adjunctive Cariprazine for the Treatment of Patients With Major Depressive Disorder: A Randomized, Double-Blind, Placebo-Controlled Phase 3 Study.

OBJECTIVE: The purpose of this study was to investigate the efficacy of cariprazine, a dopamine D3-preferring D3/D2 and serotonin 5-HT1A receptor partial agonist, as adjunctive therapy for patients with major depressive disorder and nonresponse to at least one antidepressant monotherapy. METHODS: In this double-blind placebo-controlled study, adults with major depressive disorder and inadequate response to antidepressants alone were randomized in a 1:1:1 ratio to placebo, cariprazine at 1.5 mg/day, or cariprazine at 3.0 mg/day. The primary outcome was change from baseline to week 6 in total score on the Montgomery-Åsberg Depression Rating Scale (MADRS). Least-squares mean differences were estimated in the modified intent-to-treat (mITT) population using a mixed-effects model for repeated measures with adjustment for multiple comparisons. RESULTS: The mITT population comprised 751 patients (placebo: N=249; cariprazine 1.5 mg/day: N=250; cariprazine 3.0 mg/day: N=252). At week 6, the mean reduction from baseline in MADRS total score was significantly greater with cariprazine 1.5 mg/day than with placebo (-14.1 vs. -11.5) but not with cariprazine 3.0 mg/day (-13.1). Significant differences between the cariprazine 1.5 mg/day and placebo groups were also observed at weeks 2 and 4. Meeting the MADRS response criteria was significantly more likely among patients receiving cariprazine 1.5 mg/day than placebo (44.0% vs. 34.9%); remission rates were not significantly different among groups. Common treatment-emergent adverse events (≥5% in either cariprazine group and twice the placebo rate) were akathisia and nausea. CONCLUSIONS: Adjunctive cariprazine at 1.5 mg/day demonstrated efficacy in reducing depressive symptoms in adults with major depressive disorder and inadequate response to antidepressants alone. Cariprazine was generally well tolerated, with a safety profile that was consistent with previous findings.

The effect of antidepressant treatment on HIV and depression outcomes: results from a randomized trial.

BACKGROUND: Depression is a major barrier to HIV treatment outcomes. OBJECTIVE: To test whether antidepressant management decision support integrated into HIV care improves antiretroviral adherence and depression morbidity. DESIGN: Pseudo-cluster randomized trial. SETTING: Four US infectious diseases clinics. PARTICIPANTS: HIV-infected adults with major depressive disorder. INTERVENTION: Measurement-based care (MBC) - depression care managers used systematic metrics to give HIV primary-care clinicians standardized antidepressant treatment recommendations. MEASUREMENTS: Primary - antiretroviral medication adherence (monthly unannounced telephone-based pill counts for 12 months). Primary time-point - 6 months. Secondary - depressive severity, depression remission, depression-free days, measured quarterly for 12 months. RESULTS: From 2010 to 2013, 149 participants were randomized to intervention and 155 to usual care. Participants were mostly men, Black, non-Hispanic, unemployed, and virally suppressed with high baseline self-reported antiretroviral adherence and depressive severity. Over follow-up, no differences between arms in antiretroviral adherence or other HIV outcomes were apparent. At 6 months, depressive severity was lower among intervention participants than usual care [mean difference -3.7, 95% confidence interval (CI) -5.6, -1.7], probability of depression remission was higher [risk difference 13%, 95% CI 1%, 25%), and suicidal ideation was lower (risk difference -18%, 95% CI -30%, -6%). By 12 months, the arms had comparable mental health outcomes. Intervention arm participants experienced an average of 29 (95% CI: 1-57) more depression-free days over 12 months. CONCLUSION: In the largest trial of its kind among HIV-infected adults, MBC did not improve HIV outcomes, possibly because of high baseline adherence, but achieved clinically significant depression improvements and increased depression-free days. MBC may be an effective, resource-efficient approach to reducing depression morbidity among HIV patients.

Treating depression within the HIV "medical home": a guided algorithm for antidepressant management by HIV clinicians.

People living with HIV/AIDS (PLWHA) suffer increased depression prevalence compared to the general population, which negatively impacts antiretroviral (ART) adherence and HIV-related outcomes leading to morbidity and mortality. Yet depression in this population often goes undiagnosed and untreated. The current project sought to design an evidence-based approach to integrate depression care in HIV clinics. The model chosen, measurement-based care (MBC), is based on existing guidelines and the largest randomized trial of depression treatment. MBC was adapted to clinical realities of HIV care for use in a randomized controlled effectiveness trial of depression management at three academic HIV clinics. The adaptation accounts for drug-drug interactions critical to ongoing ART effectiveness and can be delivered by a multidisciplinary team of nonmental health providers. A treatment algorithm was developed that enables clinically supervised, nonphysician depression care managers (DCMs) to track and monitor antidepressant tolerability and treatment response while supporting nonpsychiatric prescribers with antidepressant choice and dosing. Quality of care is ensured through weekly supervision of DCMs by psychiatrists. Key areas of flexibility that have been important in implementation have included flexibility in timing of assessments, accommodation of divergence between algorithm recommendations and provider decisions, and accommodation of delays in implementing treatment plans. This adaptation of the MBC model to HIV care has accounted for critical antidepressant-antiretroviral interactions and facilitated the provision of quality antidepressant management within the HIV medical home.

Feasibility of nurse-led antidepressant medication management of depression in an HIV clinic in Tanzania.

OBJECTIVE: Sub-Saharan Africa has the highest HIV prevalence worldwide and depression is highly prevalent among those infected. The negative impact of depression on HIV outcomes highlights the need to identify and treat it in this population. A model for doing this in lower-resourced settings involves task-shifting depression treatment to primary care; however, HIV-infected individuals are often treated in a parallel HIV specialty setting. We adapted a model of task-shifting, measurement-based care (MBC), for an HIV clinic setting and tested its feasibility in Tanzania. MBC involves measuring depressive symptoms at meaningful intervals and adjusting antidepressant medication treatment based on the measure of illness. METHOD: Twenty adults presenting for care at an outpatient HIV clinic in Tanzania were enrolled and followed by a nurse care manager who measured depressive symptoms at baseline and every 4 weeks for 12 weeks. An algorithm-based decision-support tool was utilized by the care manager to recommend individualized antidepressant medication doses to participants' HIV providers at each visit. RESULTS: Retention was high and fidelity of the care manager to the MBC protocol was exceptional. Follow through of antidepressant prescription dosing recommendations by the prescriber was low. Limited availability of antidepressants was also noted. Despite challenges, baseline depression scores decreased over the 12-week period. CONCLUSIONS: Overall, the model of algorithm-based nursing support of prescription decisions was feasible. Future studies should address implementation issues of medication supply and dosing. Further task-shifting to relatively more abundant and lower-skilled health workers, such as nurses' aides, warrants examination.

Correlates of HIV testing among abused women in South Africa.

Gender-based violence increases a woman's risk for HIV but little is known about her decision to get tested. We interviewed 97 women seeking abuse-related services from a nongovernmental organization (NGO) in Johannesburg, South Africa. Forty-six women (47%) had been tested for HIV. Caring for children (odds ratio [OR] = 0.27, 95% confidence interval [CI] = [0.07, 1.00]) and conversing with partner about HIV (OR = 0.13, 95% CI = [0.02, 0.85]) decreased odds of testing. Stronger risk-reduction intentions (OR = 1.27, 95% CI = [1.01, 1.60]) and seeking help from police (OR = 5.51, 95% CI = [1.18, 25.76]) increased odds of testing. Providing safe access to integrated services and testing may increase testing in this population. Infection with HIV is highly prevalent in South Africa where an estimated 16.2% of adults between the ages of 15 and 49 have the virus. The necessary first step to stemming the spread of HIV and receiving life-saving treatment is learning one's HIV serostatus through testing. Many factors may contribute to someone's risk of HIV infection and many barriers may prevent testing. One factor that does both is gender-based violence.