Terminal cancer patients often endure significant distress, impacting their quality of life. Spiritual well-being provides peace and meaning during this challenging period.

Objectives. This study explored the spiritual well-being of terminally ill patients and their next-of-kin caregivers in hospice care, focusing on factors influencing their spiritual experiences.

This mixed-methods study included 30 terminally ill patients and 17 next-of-kin caregivers in hospice care. Spiritual well-being was assessed using the Functional Assessment of Chronic Illness Therapy – Spiritual Well-Being Scale (FACIT-Sp-12), and symptom distress with the Edmonton Symptom Assessment Scale. Qualitative data were collected through semi-structured interviews at baseline, 1 week, and 1 month. Data were analyzed using quantitative methods and thematic analysis.

Patients showed a significant improvement in spiritual well-being over time, with FACIT-Sp-12 scores increasing from 28.6 at baseline to 31.3 at 1 month (p < .01). Symptoms such as shortness of breath (β = –1.19, p < .001), drowsiness (β = –1.27, p = .01), and anxiety (β = –0.60, p = .03) were negatively associated with spiritual well-being. Caregiver spiritual well-being positively influenced patient scores, especially with female caregivers (β = 0.26, p < .001). Qualitative findings supported these results, revealing themes of spiritual adjustment, the impact of physical symptoms on spiritual well-being, and the crucial role of caregivers in providing emotional and spiritual support.

Early palliative care facilitates spiritual adjustment in terminally ill patients. A holistic approach addressing physical symptoms and psychological distress is essential. Supporting caregivers, particularly female ones, positively impacts patient spiritual well-being. Tailored interventions considering the unique needs of patients and caregivers are recommended to enhance palliative care quality.

Patients with major depressive disorder (MDD) commonly experience comorbid anxiety and somatization, which can complicate treatment. Adjunctive therapy with atypical antipsychotics can be an effective treatment option for patients with MDD who had inadequate responses to antidepressant therapy (ADT) alone. Cariprazine is a dopamine D3-preferring D3/D2 and serotonin 5-HT1A receptor partial agonist that is approved as an adjunctive treatment for MDD. This post hoc analysis examined the effect of adjunctive cariprazine therapy on anxiety and somatization symptoms in patients with MDD.

A post hoc analysis was conducted using data from a phase 3, double-blind, placebo-controlled, fixed-dose study of patients with MDD who had inadequate responses to ADT alone. Patients were randomized (1:1:1) to receive ADT plus cariprazine 1.5 mg/d, 3 mg/d, or placebo for 6 weeks. The least squares (LS) mean change from baseline to week 6 in Hamilton Rating Scale for Depression (HAM-D) Anxiety/Somatization subscale was measured. The Anxiety/Somatization subscale includes six HAM-D items: anxiety-psychic, anxiety-somatic, gastrointestinal somatic symptoms, general somatic symptoms, hypochondriasis, and insight. The modified intent to treat population included 751 patients (placebo=249; cariprazine 1.5 mg/d=250; cariprazine 3 mg/d=252).

The LS mean change from baseline in HAM-D Anxiety/Somatization subscale at week 6 was significantly greater than placebo + ADT for both cariprazine + ADT dose groups (placebo: -3.22; cariprazine 1.5 mg/d: -4.00, P<.001; 3 mg/d: -3.75, P<.05). LS mean change from baseline in the cariprazine 1.5 mg/d + ADT group was also significantly greater than placebo + ADT on the anxiety-psychic (placebo: -0.88; cariprazine 1.5 mg/d: -1.08, P<.01) and anxiety-somatic (placebo: -0.78; cariprazine 1.5 mg/d: -0.96, P<.05) items. In patients treated with cariprazine 3 mg/d + ADT, LS mean changes from baseline on anxiety-psychic and anxiety-somatic items were numerically larger than placebo + ADT but not statistically significant. Both cariprazine + ADT dose groups had significantly larger LS mean changes compared with placebo + ADT on the gastrointestinal somatic symptoms item (placebo: -0.51; cariprazine 1.5 mg/d: -0.66, P<.01; cariprazine 3 mg/d: -0.68, P<.01). General somatic symptoms, hypochondriasis, and insight items showed no significant difference between placebo + ADT and cariprazine + ADT groups.

Patients treated with adjunctive cariprazine demonstrated greater improvements than patients treated with adjunctive placebo on HAM-D Anxiety/Somatization subscale scores, as shown by reduced scores on anxiety-psychic, anxiety-somatic, and gastrointestinal items. These findings suggest adjunctive cariprazine therapy may be effective in reducing anxiety and somatization symptoms in patients with MDD.

AbbVie

Study Registration Number: NCT03738215

Anhedonia characterizes major depressive episodes in bipolar depression and is associated with more severe illness/poor prognosis. These post hoc analyses assess effect of cariprazine 1.5 and 3 mg/d on anhedonia symptoms in patients with bipolar I depression.

Data were pooled from 3 randomized, double-blind, placebo-controlled bipolar I depression trials in cariprazine. Cariprazine 1.5 and 3 mg/d versus placebo were evaluated in patient subgroups stratified by median baseline MADRS anhedonia score (higher anhedonia=score ≥19; lower anhedonia=score <19). Outcomes included mean change from baseline to week 6 in MADRS total and anhedonia factor score (sum of apparent sadness, reported sadness, concentration, lassitude, and inability to feel items). The proportion of patients with week 6 anhedonia factor response (≥50% improvement from baseline) was also determined. Changes from baseline were analyzed using a mixed-effect model for repeated measures.

There were 760 patients in the higher anhedonia subgroup (placebo=249, cariprazine: 1.5 mg/d=261; 3 mg/d=250) and 623 patients in the lower anhedonia subgroup (placebo=211, cariprazine: 1.5 mg/d=200; 3 mg/d=212). Mean baseline MADRS total score was higher in the higher anhedonia subgroup (total=33.6) than in the lower anhedonia subgroup (total=27.6). Change from baseline to week 6 in MADRS total score was greater for both cariprazine doses versus placebo in the higher anhedonia subgroup (least squares mean difference [LSMD] and 95% confidence interval [CI]: 1.5 mg/d=-3.01 [-4.84, -1.19], P=.0012; 3 mg/d: -3.26 [-5.12, -1.40], P=.0006); in the lower anhedonia subgroup, cariprazine 1.5 mg/d was statistically significant versus placebo (-2.61 [-4.28, -0.93], P=.0024). In the higher anhedonia subgroup at week 6, change from baseline in anhedonia factor score was significant versus placebo for both cariprazine doses (1.5 mg/d=-1.97 [-3.13, -0.81], P=.0009; 3 mg/d=-2.07 [-3.26, -0.89], P=.0006); in the lower subgroup, the difference was significant versus placebo for cariprazine 1.5 mg/d (-1.70 [-2.77, -0.62], P=.0021). After adjusting for changes in other depressive symptoms, LSMDs versus placebo in the anhedonia factor score remained significant for cariprazine 1.5 mg/d (-1.21 [-2.05, -0.36], P=.0052) and 3 mg/d (-1.00 [-1.86, -0.14], P=.0233) in the higher anhedonia subgroup, and for 1.5 mg/d (-1.06 [-1.92, -0.19], P=.0164) in the lower subgroup. In the higher anhedonia subgroup, rates of anhedonia factor response were greater versus placebo (31.7%) for cariprazine 1.5 mg/d (44.8%, P=.0028) and 3 mg/d (45.6%, P=.0019); in the lower subgroup, response rates were 39.3% for placebo, 48.0% for 1.5 mg/d, and 46.7% for 3 mg/d. Adverse events in ≥5% cariprazine and twice placebo were nausea, akathisia, restlessness, and EPS.

Those with bipolar depression and anhedonia cariprazine demonstrated a potent antidepressant and antianhedonic effect in higher/lower anhedonia subgroups.

AbbVie

This data was previously presented at the European College of Neuropsychopharmacology (ECNP) Congress; Barcelona, Spain; October 7 – 10, 2023.

Akathisia is a common adverse effect associated with use of dopamine receptor blocking agents.1,2 Symptoms of akathisia, in severe cases, may lead to discontinuation of treatment. Cariprazine is a dopamine D3-preferring D3/D2 receptor partial agonist and serotonin 5-HT1A receptor partial agonist approved to treat schizophrenia and acute manic, mixed, and depressive episodes of bipolar 1 disorder. Cariprazine is well tolerated in patients across its indications, but is associated with a higher incidence of akathisia compared with placebo.3,4 This pooled post hoc analysis of data from phase 3 clinical trials of adjunctive cariprazine aimed to characterize the incidence, severity, and management of akathisia and other extrapyramidal symptoms (EPS) in adult patients with MDD.

Patients with MDD and inadequate response to ongoing antidepressant therapy (ADT) were randomized to cariprazine 1.5 mg/d + ADT, cariprazine 3 mg/d + ADT, or placebo + ADT for 6 weeks of double-blind treatment. Post hoc analysis evaluated incidence, severity, and time to resolution of akathisia, restlessness, and other EPS; use of rescue medications; and the rate of discontinuation due to these treatment-emergent adverse events (TEAEs).

A total of 1508 patients (cariprazine + ADT: 1.5 mg/d, n=502, 3 mg/d, n=503; placebo + ADT, n=503) were included in these 2 studies. The incidence of akathisia was greater with cariprazine 3 mg/d + ADT (9.7%) than with cariprazine 1.5 mg/d + ADT (6.4%) and placebo + ADT (2.0%). Most patients treated with cariprazine + ADT (94%) experienced only mild or moderate akathisia. The incidence of restlessness was 3.8% for patients treated with cariprazine 3 mg/d + ADT, 3.6% for cariprazine 1.5 mg/d + ADT, and 1.8% for placebo + ADT. The incidence of EPS excluding akathisia and restlessness was 4.4% for patients treated with cariprazine 3 mg/d + ADT, 4.6% for cariprazine 1.5 mg/d + ADT, and 3.2% for placebo + ADT. For patients treated with cariprazine + ADT and placebo + ADT, respectively, EPS-related study discontinuations were 1.4% and 0.4% due to akathisia, 0.2% and 0.0% due to restlessness, and 0.1% and 0.4% due to EPS excluding akathisia and restlessness. Rescue medications were used to treat EPS-related TEAEs during the double-blind treatment period in 3% of cariprazine-treated patients and 0.4% of placebo-treated patients. The mean time to resolution of akathisia during treatment was slightly shorter in cariprazine-treated patients (15.6 days) versus placebo-treated patients (19.5 days).

Incidence of akathisia was higher for cariprazine than placebo, with a lower incidence observed for patients treated with cariprazine 1.5 + ADT than with cariprazine 3 mg/d + ADT, suggestive of a dose related effect. Most patients experienced mild or moderate akathisia. Rates of study discontinuation and rescue medication use due to akathisia were low, suggesting that akathisia was tolerated by most patients.

This data was previously presented at the CINP World Congress; Montreal, Canada; May 7-10, 2023.

AbbVie

Anhedonia, a multidimensional domain including the reduced ability to experience pleasure, is a core diagnostic symptom of major depressive disorder (MDD) and a common residual symptom. In patients with MDD, anhedonia has been associated with poor treatment outcomes, suicide and reduced functioning and quality of life. This post-hoc analysis of data from a phase 3 trial (NCT03738215) evaluated the efficacy of adjunctive cariprazine (CAR) treatment on anhedonia symptoms in patients with MDD.

Patients with MDD and inadequate response to ongoing antidepressant therapy (ADT) were randomized to CAR 1.5 mg/d + ADT, CAR 3 mg/d + ADT, or placebo + ADT for 6 weeks of double-blind treatment. Post hoc analyses evaluated the change from baseline to Week 6 in Montgomery–Åsberg Depression Rating Scale (MADRS) total score, MADRS anhedonia subscale score (items: 1 [apparent sadness], 2 [reported sadness], 6 [concentration difficulties], 7 [lassitude], and 8 [inability to feel]), and MADRS anhedonia item 8 in the overall modified intent-to-treat (mITT) population and in subgroups of patients with baseline MADRS anhedonia item 8 score of ≥4 or baseline anhedonia subscale score of ≥18. Least square (LS) mean change from baseline to Week 6 was analyzed using a mixed-effects model for repeated measures.

There were 751 patients in the mITT population (CAR + ADT: 1.5 mg/d=250, 3 mg/d=252; placebo + ADT=249). At baseline, 508 (67.6%) patients had MADRS anhedonia item 8 scores ≥4, and 584 (77.8%) had MADRS anhedonia subscale scores ≥18. In the overall mITT population, LS mean change from baseline to Week 6 in anhedonia subscale score was significantly greater for CAR 1.5 mg/d + ADT (-8.4) and CAR 3 mg/d + ADT (-7.9) than for placebo + ADT (-6.8; both P<.05). The LS mean change from baseline in MADRS individual item 8 was also significantly greater for CAR 1.5 mg/d + ADT (-1.7) vs placebo + ADT (-1.3; P=.0085). In both subgroups of patients with baseline anhedonia, CAR 1.5 mg/d + ADT was associated with significantly greater reduction in MADRS total score, MADRS anhedonia subscale score, and MADRS item 8 score compared with placebo + ADT (all P<.05). In the CAR 3 mg/d + ADT group, significantly greater reductions vs placebo + ADT were observed for MADRS total score and MADRS anhedonia subscale score in the subgroup of patients with baseline anhedonia subscale scores ≥18 (both P<.05).

Adjunctive treatment with CAR was associated with a reduction in symptoms of anhedonia relative to adjunctive placebo in patients with MDD and inadequate response to ADT alone. In subgroups of patients with moderate-to-severe anhedonia at baseline, CAR + ADT demonstrated greater improvements than placebo + ADT in overall depressive symptoms and symptoms of anhedonia. These results suggest that adjunctive CAR treatment may be effective for improving symptoms of anhedonia in patients with MDD who have symptoms of anhedonia.

AbbVie

Assess effect of predominant polarity on efficacy of cariprazine in patients with bipolar I (BP-I) disorder. Predominant polarity may be an important clinical consideration in BP-I disorder, with predominant depressive episodes associated with delayed diagnosis and higher rates of suicidality, while predominant manic episodes are associated with younger onset, manic/psychotic first episode, and more substance abuse [1].

Data were pooled from 3 randomized, double-blind, cariprazine trials in BP-I depression and 3 trials in BP-I mania. Post hoc analyses were performed in subgroups from the bipolar depression studies with/without predominant depression (≥2:1 ratio of prior lifetime depressive to manic episodes), and in subgroups from the bipolar mania studies with and without predominant mania (≥2:1 ratio of prior lifetime manic to depressive episodes). Change from baseline to week 6 in Montgomery-Åsberg Depression Rating Scale (MADRS) total score was evaluated for cariprazine 1.5 and 3 mg/d versus placebo (bipolar depression studies); change from baseline to week 3 in Young Mania Rating Scale total score was evaluated for cariprazine 3-12 mg/d versus placebo (bipolar mania studies). Change from baseline analyzed using mixed-effect model for repeated measures in pooled intent-to-treat population from each indication.

In bipolar depression studies, there were 624 patients (45% of total study population) in the predominantly depressive subgroup (placebo=197, cariprazine: 1.5 mg/d=217; 3 mg/d=210) and 750 patients (55%) in the subgroup without predominant depression (placebo=258, cariprazine: 1.5 mg/d=241; 3 mg/d=251). In the predominant depressive subgroup, LSMDs for MADRS total score change from baseline were significant versus placebo for cariprazine 1.5 mg/d (-2.49 [-4.30, -.68], P=.0071) and 3 mg/d (-2.48 [-4.31, -.65], P=.0079); in the subgroup without predominant depression, LSMDs were also significant versus placebo for both doses (1.5 mg/d=-3.30 [-5.06, -1.54], P=.0002; 3 mg/d=-2.53 [-4.29, -.77], P=.0049). In bipolar mania studies, there were 721 patients (73% of total study population) in the predominantly manic episode subgroup (placebo=307, cariprazine 3-12 mg/d =414) and 267 patients (27%) in the subgroup without predominant manic episodes (placebo=102, cariprazine 3-12 mg/d=165). In predominant mania subgroup, LSMD in YMRS total score change from baseline was significant for cariprazine 3-12 mg/d versus placebo (-4.65 [-6.29, -3.02], P<.0001); in subgroup without predominant mania, the LSMD for cariprazine versus placebo was also significant (-7.56 [-10.30, -4.82], P<.0001).

Cariprazine was efficacious in treating BP-I mood episodes regardless of predominant polarity for the presenting mood episode. Cariprazine was effective against symptoms of depression in patients with BP-I depression with/without predominant depressive episodes, and against symptoms of mania in patients with BP-I mania with/ without predominant manic episodes.

AbbVie

This data was previously presented at the Annual ECNP Congress; Barcelona, Spain; October 7-10, 2023.

Observational studies have shown a controversial relationship between dietary fat intake and Alzheimer's disease, and the causal effects are unclear.

To assess the causal effects of total fat, saturated fat and polyunsaturated fat (PUF) intakes on the risk of Alzheimer's disease.

A two-sample Mendelian randomisation analysis was performed using genome-wide association study summary statistics on different types of fat intake from UK Biobank (n = 51 413) and on late-onset Alzheimer's disease (LOAD; 4282 cases, n = 307 112) and all forms of Alzheimer's disease (6281 cases, n = 309 154) from the FinnGen consortium. In addition, a multivariable Mendelian randomisation (MVMR) analysis was conducted to estimate the effects independent of carbohydrate and protein intakes.

Genetically predicted per standard deviation increase in the total fat and saturated fat intakes were associated with 44 and 38% higher risks of LOAD (total fat: odds ratio = 1.44, 95% CI 1.03–2.02; saturated fat: odds ratio = 1.38, 95% CI 1.002–1.90; P = 0.049). The associations remained significant in the MVMR analysis (total fat: odds ratio = 3.31, 95% CI 1.74–6.29; saturated fat: odds ratio = 2.04, 95% CI 1.16–3.59). Total fat and saturated fat intakes were associated with a higher risk of all forms of Alzheimer's disease in the MVMR analysis (total fat: odds ratio = 2.09, 95% CI 1.22–3.57; saturated fat: odds ratio = 1.60, 95% CI 1.01–2.52). The PUF intake was not associated with LOAD or all forms of Alzheimer's disease.

This study indicated that total dietary fat intake, especially saturated fat, contributed to the risk of Alzheimer's disease, and the effects were independent of other nutrients. These findings informed prevention strategies and management for Alzheimer's disease directly towards reducing dietary saturated fat intake.

The comorbidity between schizophrenia (SCZ) and inflammatory bowel disease (IBD) observed in epidemiological studies is partially attributed to genetic overlap, but the magnitude of shared genetic components and the causality relationship between them remains unclear.

By leveraging large-scale genome-wide association study (GWAS) summary statistics for SCZ, IBD, ulcerative colitis (UC), and Crohn's disease (CD), we conducted a comprehensive genetic pleiotropic analysis to uncover shared loci, genes, or biological processes between SCZ and each of IBD, UC, and CD, independently. Univariable and multivariable Mendelian randomization (MR) analyses were applied to assess the causality across these two disorders.

SCZ genetically correlated with IBD (rg = 0.14, p = 3.65 × 10−9), UC (rg = 0.15, p = 4.88 × 10−8), and CD (rg = 0.12, p = 2.27 × 10−6), all surpassed the Bonferroni correction. Cross-trait meta-analysis identified 64, 52, and 66 significantly independent loci associated with SCZ and IBD, UC, and CD, respectively. Follow-up gene-based analysis found 11 novel pleiotropic genes (KAT5, RABEP1, ELP5, CSNK1G1, etc) in all joint phenotypes. Co-expression and pathway enrichment analysis illustrated those novel genes were mainly involved in core immune-related signal transduction and cerebral disorder-related pathways. In univariable MR, genetic predisposition to SCZ was associated with an increased risk of IBD (OR 1.11, 95% CI 1.07–1.15, p = 1.85 × 10−6). Multivariable MR indicated a causal effect of genetic liability to SCZ on IBD risk independent of Actinobacteria (OR 1.11, 95% CI 1.06–1.16, p = 1.34 × 10−6) or BMI (OR 1.11, 95% CI 1.04–1.18, p = 1.84 × 10−3).

We confirmed a shared genetic basis, pleiotropic loci/genes, and causal relationship between SCZ and IBD, providing novel insights into the biological mechanism and therapeutic targets underlying these two disorders.