There are limited data to guide treatment continuation decisions for clinicians caring for patients with treatment resistant depression (TRD). Identifying the magnitude of early improvement (at Weeks 4 and 8) as a predictor of long-term outcomes for TRD can guide treatment continuation decisions.

To evaluate the probability of achieving response or remission by Week 32 in patients with TRD after 4 or 8 weeks of esketamine nasal spray (ESK-NS) treatment, flexibly dosed in combination with an ongoing selective serotonin/serotonin-norepinephrine reuptake inhibitor (SSRI/SNRI).

ESCAPE‑TRD was a randomised phase IIIb trial comparing the efficacy of ESK-NS versus quetiapine extended release, both in combination with an ongoing SSRI/SNRI, in patients with TRD (Reif et al. NEJM 2023; 389 1298–309). Remission was defined as a Montgomery-Åsberg Depression Rating Scale (MADRS) total score ≤10, and partial response and response as ≥25% and ≥50% improvements, respectively, in total MADRS score (or remission). Long-term outcomes were based on the best outcome on-treatment across 32 weeks (≥1 instance of response or remission) from earliest outcome endpoint onwards. Non-responder imputation (NRI) was applied after treatment discontinuations.

336 patients were randomised to ESK-NS; 334 received ≥1 dose. Table 1 shows long-term outcomes following at least partial response, response or no partial response at Weeks 4 and 8. For example, among those who had at least a partial response at Week 4, 94.1% and 79.8% had response and remission by Week 32, respectively.

Image 1:

This analysis demonstrated a relationship between short- and long-term outcomes. Presence of at least partial response at Week 4 led to more favourable outcomes by Week 32. Moreover, most patients with response by Week 4 achieved remission by Week 32. Continued symptom improvements were observed beyond the induction phase even in some patients with no partial response at Week 4.

None Declared

In the ESCAPE-TRD study, esketamine nasal spray (ESK-NS) significantly increased chance of remission at Week 8 versus (vs) quetiapine extended release (Q-XR) in patients (pts) with treatment resistant depression (TRD; Reif et al. NEJM 2023; 389:1298–309). Changes in disability and functional impairment due to depressive symptoms assessed with the Sheehan Disability Scale (SDS) are reported.

To assess the effect of ESK-NS vs Q-XR on pts’ daily functioning using SDS, considering their symptom evolution.

ESCAPE‑TRD was a randomised phase IIIb trial comparing the efficacy of ESK-NS vs Q-XR, both alongside an ongoing selective serotonin/serotonin-norepinephrine reuptake inhibitor, in pts with TRD. Clinical response (CRes) was defined as ≥50% improvement in Montgomery-Åsberg Depression Rating Scale (MADRS) score from baseline or total score ≤10, clinical remission (CRem) was defined as total MADRS score of ≤10, and functional remission (FRem) was defined as SDS total score ≤6. The Kaplan-Meier method was used for time to event analyses, and hazard ratios (HRs) were estimated using Cox regression models. Time in each state was estimated by treatment arm and compared between arms using analysis of covariance.

336 and 340 pts were randomised to ESK-NS and Q-XR, respectively. Significantly more ESK-NS treated pts achieved CRes, CRem and FRem (HRs: 1.848, 1.711 and 1.819, respectively; all p<0.001), and achieved these faster, compared to Q-XR (Figure 1). In each arm and at each time point, more pts reached CRes than CRem, and more reached CRem than FRem, illustrating that FRem is more difficult to achieve (Figure 1). Total time in CRes was 5.4 weeks greater for ESK-NS compared with Q-XR; total time in CRem was 3.7 weeks greater and in FRem 2.0 weeks greater for ESK-NS vs Q-XR, respectively (Table 1).

Image 1:

Image 2:

These data support a temporal cascade of events from CRes to CRem to FRem; ESK-NS improved time to, and in, each outcome vs Q-XR. Treatments that reduce clinical symptoms better and faster provide the best chance of improving functional impairment.

None Declared

Children from low-socioeconomic backgrounds exhibit more behavioural difficulties than those from more affluent families. Influential theoretical models specify family stress and child characteristics as mediating this effect. These accounts, however, have often been based on cross-sectional data or longitudinal analyses that do not capture all potential pathways, and therefore may not provide good policy guidance.

In a UK representative sample of 2399 children aged 5–15, we tested mediation of the effect of household income on parent and teacher reports of conduct problems (CP) via unhealthy family functioning, poor parental mental health, stressful life events, child physical health and reading ability. We applied cross-lagged longitudinal mediation models which allowed for testing of reciprocal effects whereby the hypothesised mediators were modelled as outcomes as well as predictors of CP.

We found the predicted significant longitudinal effect of income on CP, but no evidence that it was mediated by the child and family factors included in the study. Instead, we found significant indirect paths from income to parental mental health, child physical health and stressful life events that were transmitted via child CP.

The results confirm that income is associated with change in CP but do not support models that suggest this effect is transmitted via unhealthy family functioning, parental mental health, child physical health, stressful life events or reading difficulties. Instead, the results highlight that child CP may be a mediator of social inequalities in family psychosocial functioning.

To investigate the effect of cariprazine on cognitive symptom change across bipolar I disorder and schizophrenia.

Post hoc analyses of 3- to 8-week pivotal studies in bipolar I depression and mania were conducted; one schizophrenia trial including the Cognitive Drug Research System attention battery was also analyzed. Outcomes of interest: Montgomery-Åsberg Depression Rating Scale [MADRS], Functioning Assessment Short Test [FAST], Positive and Negative Syndrome Scale [PANSS]). LSMDs in change from baseline to end of study were reported in the overall intent-to-treat population and in patient subsets with specified levels of baseline cognitive symptoms or performance.

In patients with bipolar depression and at least mild cognitive symptoms, LSMDs were statistically significant for cariprazine vs placebo on MADRS item 6 (3 studies; 1.5 mg=−0.5 [P<.001]; 3 mg/d=−0.2 [P<.05]) and on the FAST Cognitive subscale (1 study; 1.5 mg/d=−1.4; P=.0039). In patients with bipolar mania and at least mild cognitive symptoms, the LSMD in PANSS Cognitive subscale score was statistically significant for cariprazine vs placebo (3 studies; −2.1; P=.001). In patients with schizophrenia and high cognitive impairment, improvement in power of attention was observed for cariprazine 3 mg/d vs placebo (P=.0080), but not for cariprazine 6 mg/d; improvement in continuity of attention was observed for cariprazine 3 mg/d (P=.0012) and 6 mg/d (P=.0073).

These post hoc analyses provide preliminary evidence of greater improvements for cariprazine vs placebo across cognitive measures in patients with bipolar I depression and mania, and schizophrenia, suggesting potential benefits for cariprazine in treating cognitive symptoms.

The coronavirus disease 2019 (COVID-19) pandemic represents an unprecedented threat to mental health. Herein, we assessed the impact of COVID-19 on subthreshold depressive symptoms and identified potential mitigating factors.

Participants were from Depression Cohort in China (ChiCTR registry number 1900022145). Adults (n = 1722) with subthreshold depressive symptoms were enrolled between March and October 2019 in a 6-month, community-based interventional study that aimed to prevent clinical depression using psychoeducation. A total of 1506 participants completed the study in Shenzhen, China: 726 participants, who completed the study between March 2019 and January 2020 (i.e. before COVID-19), comprised the ‘wave 1’ group; 780 participants, who were enrolled before COVID-19 and completed the 6-month endpoint assessment during COVID-19, comprised ‘wave 2’. Symptoms of depression, anxiety and insomnia were assessed at baseline and endpoint (i.e. 6-month follow-up) using the Patient Health Questionnaire-9 (PHQ-9), Generalised Anxiety Disorder-7 (GAD-7) and Insomnia Severity Index (ISI), respectively. Measures of resilience and regular exercise were assessed at baseline. We compared the mental health outcomes between wave 1 and wave 2 groups. We additionally investigated how mental health outcomes changed across disparate stages of the COVID-19 pandemic in China, i.e. peak (7–13 February), post-peak (14–27 February), remission plateau (28 February−present).

COVID-19 increased the risk for three mental outcomes: (1) depression (odds ratio [OR] = 1.30, 95% confidence interval [CI]: 1.04–1.62); (2) anxiety (OR = 1.47, 95% CI: 1.16–1.88) and (3) insomnia (OR = 1.37, 95% CI: 1.07–1.77). The highest proportion of probable depression and anxiety was observed post-peak, with 52.9% and 41.4%, respectively. Greater baseline resilience scores had a protective effect on the three main outcomes (depression: OR = 0.26, 95% CI: 0.19–0.37; anxiety: OR = 1.22, 95% CI: 0.14–0.33 and insomnia: OR = 0.18, 95% CI: 0.11–0.28). Furthermore, regular physical activity mitigated the risk for depression (OR = 0.79, 95% CI: 0.79–0.99).

The COVID-19 pandemic exerted a highly significant and negative impact on symptoms of depression, anxiety and insomnia. Mental health outcomes fluctuated as a function of the duration of the pandemic and were alleviated to some extent with the observed decline in community-based transmission. Augmenting resiliency and regular exercise provide an opportunity to mitigate the risk for mental health symptoms during this severe public health crisis.

This study estimates the maximum price at which mesenchymal stem cell (MSC) therapy is deemed cost-effective for septic shock patients and identifies parameters that are most important in making treatment decisions.

We developed a probabilistic Markov model according to the sepsis care trajectory to simulate costs and quality-adjusted life years (QALYs) of septic shock patients receiving either MSC therapy or usual care over their lifetime. We calculated the therapeutic headroom by multiplying the gains attributable to MSCs with willingness-to-pay (WTP) threshold and derived the maximum reimbursable price (MRP) from the expected net monetary benefit and savings attributable to MSCs. We performed scenario analyses to assess the impact of changes to assumptions on the study findings. A value of information analysis is performed to identify parameters with greatest impact on the uncertainty around the cost-effectiveness of MSC therapy.

At a WTP threshold of $50,000 per QALY, the therapeutic headroom and MRP of MSC therapy were $20,941 and $16,748, respectively; these estimates increased with the larger WTP values and the greater impact of MSCs on in-hospital mortality and hospital discharge rates. The parameters with greatest information value were MSC's impact on in-hospital mortality and the baseline septic shock in-hospital mortality.

At a common WTP of $50,000/QALY, MSC therapy is deemed to be economically attractive if its unit cost does not exceed $16,748. This ceiling price can be increased to $101,450 if the therapy significantly reduces both in-hospital mortality and increases hospital discharge rates.

Asenapine is indicated in adults for acute treatment of schizophrenia and manic or mixed episodes associated with bipolar I disorder with or without psychotic features. We report the safety, tolerability, and efficacy of asenapine in patients with bipolar I disorder completing up to 52 weeks of treatment.

Patients completing either of two 3-week efficacy trials and a 9-week double-blind extension were eligible for this 40-week double-blind extension. Patients in the 3-week trials were randomized to flexible-dose asenapine (5 or 10 mg BID), placebo, or olanzapine (5-20 mg QD; included for assay sensitivity only). Patients entering the extension continued their preestablished treatment; those originally randomized to placebo received flexible-dose asenapine (placebo/asenapine, 5 or 10 mg BID). Safety and tolerability endpoints included adverse events (AEs), extrapyramidal symptoms, laboratory values, and anthropometric measures. Efficacy was measured as the change in Young Mania Rating Scale (YMRS) total score from 3-week trial baseline to week 52; the placebo/asenapine group was included in the safety analyses.

Incidence of treatment-emergent AEs was 71.9%, 86.1%, and 79.4% with placebo/asenapine, asenapine, and olanzapine, respectively. The most frequent AEs included headache and somnolence (placebo/asenapine); insomnia, sedation, and depression (asenapine); and weight gain, somnolence, and sedation (olanzapine). Mean ± SD changes in YMRS score at week 52 among observed cases in the intent-to-treat population were -28.6±8.1 for asenapine and -28.2±6.8 for olanzapine.

In this 52-week study, asenapine was well tolerated and long-term maintenance of efficacy was supported in patients initially presenting with bipolar mania.

Disrupted sleep is common in depression.

Investigate effects of adjunct extended release quetiapine fumarate (QTP-XR) on sleep disturbance and quality in patients with MDD and inadequate response to antidepressant (AD) therapy.

Data were pooled from two (D1448C00006/D1448C00007) 6-week, double-blind, randomised, placebo (placebo+AD)-controlled studies of adjunct QTP-XR (15 0 mg/day and 300 mg/day). Primary endpoint: MADRS total score change versus placebo+AD. Secondary endpoints (post hoc): change from randomisation in MADRS item 4 (reduced sleep), HAM-D items 4, 5 and 6 (early-, middle- and late-insomnia), sleep disturbance factor (HAM-D items 4+5+6) and sleep quality (PSQI global score). MADRS total score change in patients with baseline HAM-D sleep disturbance factor score > = 4 or < 4 (high and low sleep disturbance, respectively) was evaluated.

919 patients received adjunct QTP-XR: 150 mg/day (n = 309), 300 mg/day (n = 307), placebo+AD (n = 303). At Week 6, adjunct QTP-XR (both doses) reduced MADRS item 4, HAM-D sleep disturbance factor, HAM-D items 4, 5 and 6 and PSQI global scores from baseline versus placebo+AD (p < 0.001). In patients with baseline HAM-D>=4 (n = 226, 215 and 210, respectively) adjunct QTP-XR (both doses) improved (p< 0.01) MADRS total score versus placebo+AD from Week 1 onward. In patients with baseline HAM-D< 4 (n = 83, 92, 93, respectively) adjunct QTP-XR (both doses) improved (not statistically significantly) MADRS total score versus placebo+AD at Week 6.

Adjunct QTP-XR significantly restored sleep and improved sleep quality in patients with MDD and inadequate response to AD. Significant improvement in depressive symptoms was demonstrated with adjunct QTP-XR in patients with MDD and high baseline sleep disturbance. AstraZeneca funded.

The use of patient-reported outcome measures in psychiatric practices in the United States is still in its beginning phases. More research is need to determine the usefulness of such measures and the optimal methods to present them to patients and practitioners in routine care settings.

This presentation will describe the research plan for testing a group of patient-reported outcome measures using digital applications. Potential opportunities for use in underserved refugee populations will be presented.

The outcome measures were selected from those recommended in DSM-5 Section III, including cross-cutting symptom and disability measures. A user-friendly digital application was developed for data collection, synthesis, and presentation. The research plan has three phases: focus groups with patients and clinicians, piloting of methods, and the main study, a pragmatic trial comparing treatment outcomes using outcome measurement versus usual care.

Results of the focus group sessions will be presented, along with changes made to the measures and the digital application in response to these results. Current status of the research project will be discussed.

The results of this research project will bring greater clarity to questions on the role of outcome measurements in improving quality of care and patient outcomes. With ever greater use of smart phones, tablets, and personal computers, digital technology has the potential to facilitate psychiatric assessment and treatment for underserved, difficult-to-reach populations such as refugees.

The authors have not supplied their declaration of competing interest.