Peripheral serotonin levels as a predictor of antidepressant treatment response: A systematic review.

There are currently no reliable biomarkers to predict clinical response to pharmacological treatments of depressive disorders. Peripheral blood 5-hydroxytryptamine (5-HT; serotonin) has been suggested as a biomarker of antidepressant treatment response, but there has not been an attempt to systematically summarize and evaluate the scientific evidence of this hypothesis. In this systematic review we searched MEDLINE, Embase, PsycINFO, and the Cochrane Central Register of Controlled Trials. Twenty-six relevant studies investigating peripheral 5-HT as an antidepressant biomarker were identified. In all, we did not find robust support for an association between baseline 5-HT and treatment response. Several larger studies with lower risk of bias, however, showed that higher baseline 5-HT was associated with a greater antidepressant response to SSRIs, prompting future studies to investigate this hypothesis. Our results also confirm previous reports that SSRI treatment is associated with a decrease in peripheral 5-HT levels; however, we were not able to confirm that larger decreases of 5-HT are associated with better treatment outcome as results were inconclusive.

Long-term remission and relapse of anxiety and depression in older adults after Cognitive Behavioural Therapy (CBT): A 10-year follow-up of a randomised controlled trial.

BACKGROUND: This study examined the long-term durability of cognitive behaviour therapy (CBT) for older adults with comorbid anxiety and depression 10 years after treatment, in comparison to an active control group. METHOD: Participants from a randomised controlled trial for older adults with comorbid anxiety and depression (Wuthrich et al., 2016) were re-contacted. Participants had received either group CBT or an active control treatment (Discussion Group). The final sample (N = 54; Aged 70-84, Mage = 76.07, SD = 3.83; 59 % of the eligible original sample) completed a diagnostic interview, cognitive assessment and self-report measures of symptoms and quality of life. RESULTS: CBT was associated with significantly improved long-term (10-year) efficacy for reducing anxiety and depression in older adults compared to the Discussion group. Effects included higher rates of remission (58 % remission of all diagnoses vs 27 %, 88 % of all depressive diagnoses vs 54 %, 63 % of all anxiety diagnoses vs 35 %, 67 % of primary diagnosis vs 42 %), lower rates of relapse (25-31 % vs 50-78 %) and lower rates of chronic treatment-resistance (8 % primary disorder vs 39 %, 21 % any disorder vs 58 %). Participants who showed an acute treatment response at post-treatment were 7-9 times more likely to be in remission after 10 years than those with residual symptoms. LIMITATIONS: Results may not generalise to those who do not complete CBT, and the time trajectory of symptom change is unclear. CONCLUSIONS: Long-term improvements in symptoms are specific to CBT. Results provide compelling evidence for CBT as an effective and durable treatment for late-life anxiety and depression.

Causal relationship between resting-state networks and depression: a bidirectional two-sample mendelian randomization study.

BACKGROUND: Cerebral resting-state networks were suggested to be strongly associated with depressive disorders. However, the causal relationship between cerebral networks and depressive disorders remains controversial. In this study, we aimed to investigate the effect of resting-state networks on depressive disorders using a bidirectional Mendelian randomization (MR) design. METHODS: Updated summary-level genome-wide association study (GWAS) data correlated with resting-state networks were obtained from a meta-analysis of European-descent GWAS from the Complex Trait Genetics Lab. Depression-related GWAS data were obtained from the FinnGen study involving participants with European ancestry. Resting-state functional magnetic resonance imaging and multiband diffusion imaging of the brain were performed to measure functional and structural connectivity in seven well-known networks. Inverse-variance weighting was used as the primary estimate, whereas the MR-Pleiotropy RESidual Sum and Outliers (PRESSO), MR-Egger, and weighted median were used to detect heterogeneity, sensitivity, and pleiotropy. RESULTS: In total, 20,928 functional and 20,573 structural connectivity data as well as depression-related GWAS data from 48,847 patients and 225,483 controls were analyzed. Evidence for a causal effect of the structural limbic network on depressive disorders was found in the inverse variance-weighted limbic network (odds ratio, [Formula: see text]; 95% confidence interval, [Formula: see text]; [Formula: see text]), whereas the causal effect of depressive disorders on SC LN was not found(OR=1.0025; CI,1.0005-1.0046; P=0.012). No significant associations between functional connectivity of the resting-state networks and depressive disorders were found in this MR study. CONCLUSIONS: These results suggest that genetically determined structural connectivity of the limbic network has a causal effect on depressive disorders and may play a critical role in its neuropathology.

[Usefulness of the Beck depression inventory in the diagnosis of depressive disorders in multiple sclerosis]. / Utilidad de la escala de depresión de Beck para el diagnóstico de los trastornos depresivos en la esclerosis múltiple.

INTRODUCTION: Depression is one of the most prevalent psychiatric conditions in adulthood, reaching figures of around 20%. The methodologies used to study depression are varied, and range from a self-administered test to structured psychiatric assessment. Several studies of patients with multiple sclerosis (MS) have been conducted in the last 20 years, and figures of around 35% have been found for depressive symptoms, while depressive disorders are less frequent, at approximately 21%. AIMS: The aim of this study is to evaluate the usefulness of patient self-reported scales such as the Beck depression inventory (BDI) for identifying depressive symptoms in patients with MS, and to analyse their correlation with the diagnosis of clinical depression or depressive disorder using the psychiatric clinical interview based on the criteria of the Diagnostic and statistical manual of mental disorders, fifth edition. PATIENTS AND METHODS: This is a multicentre descriptive cross-sectional study of patients with MS and depressive symptoms. The BDI and the Hamilton depression rating scale (HDRS) were used, and the patients with the highest scores underwent psychiatric assessment. RESULTS: A total of 191 patients were included; 81 of these (40.5%) had depressive symptomatology in the pathological range according to the BDI (cut-off point of 14), and 20 had a severe score (above 28). Nineteen patients with severe depressive symptoms according to both scales were selected and finally evaluated by a psychiatrist, who also assessed five patients who according to the neurologist had severe depressive symptoms despite a BDI score of almost 28, but did not reach that level. The suspected major depressive disorder was confirmed in only four (21%) cases with BDI scores indicative of severe symptoms. There is no correlation between the severity score as evidenced by the BDI and the psychiatric assessment. A major depressive disorder was diagnosed in 16 (66.6%) of the 24 patients with BDI > 26 evaluated by psychiatry. A score above 26 on the BDI enables identification of 75% of cases of depressive disorder without subtyping. The correlation between the HDRS and the BDI was statistically significant (r = 0.8; p < 0). CONCLUSIONS: The BDI is a useful screening test for identifying patients with depressive symptoms; in specific terms, a score above 26 is probably indicative of a depressive disorder that may benefit from psychiatric assessment.

TITLE: Utilidad de la escala de depresión de Beck para el diagnóstico de los trastornos depresivos en la esclerosis múltiple.Introducción. La depresión es una de las condiciones psiquiátricas con mayor prevalencia en la edad adulta y alcanza cifras alrededor del 20%. Las metodologías para el estudio de la depresión son varias y van del uso de un test autoadministrado a la valoración psiquiátrica estructurada. En los últimos 20 años se han realizado varios estudios en los pacientes con esclerosis múltiple (EM), y se han objetivado cifras alrededor del 35% para los síntomas depresivos, mientras que los trastornos depresivos son menos frecuentes, aproximadamente el 21%. Objetivos. El objetivo de este estudio es evaluar la utilidad de una escala autoinformada por el paciente, como la escala de depresión de Beck (BDI), para la detección de síntomas depresivos en pacientes con EM, y analizar su correlación con el diagnóstico de depresión clínica o trastorno depresivo realizado a través de la entrevista clínica psiquiátrica basada en los criterios del Manual diagnóstico y estadístico de los trastornos mentales, quinta edición. Pacientes y métodos. Es un estudio descriptivo transversal multicéntrico de pacientes con EM y síntomas depresivos. Se emplearon la BDI y la escala de valoración de la depresión de Hamilton (HDRS), y los pacientes con puntuaciones más altas se sometieron a una valoración psiquiátrica. Resultados. Se incluyó a 191 pacientes; de ellos, 81 (40,5%) presentaron sintomatología depresiva en el rango patológico de acuerdo con la BDI (punto de corte en 14), y 20, puntuación grave (superior a 28). Se ha seleccionado a 19 pacientes con síntomas depresivos graves según ambas escalas que finalmente han sido evaluados por un psiquiatra, que además ha valorado a cinco pacientes que según el neurólogo presentaban síntomas depresivos graves a pesar de una puntuación en la BDI cercana, pero inferior, a 28. Sólo en cuatro (21%) casos con puntuación indicativa de síntomas graves en la BDI se ha confirmado la sospecha de trastorno depresivo mayor grave. No hay correlación entre la puntuación de gravedad evidenciada por la BDI y la valoración psiquiátrica. Se ha formulado el diagnóstico de trastorno depresivo mayor en 16 (66,6%) de los 24 pacientes con BDI menor que 26 evaluados por psiquiatría. Una puntuación superior a 26 en la BDI permite identificar el 75% de los casos de trastorno depresivo sin subtipificar. La correlación entre la HDRS y la BDI fue estadísticamente significativa (r = 0,8; p menor que 0). Conclusiones. La BDI es un test de cribado útil para identificar a pacientes con síntomas depresivos; en particular, una puntuación superior a 26 es indicativa con buena probabilidad de un trastorno depresivo que se podría beneficiar de una valoración psiquiátrica.

Emotion Regulation and Mentalization in Patients With Depression and Anxiety.

OBJECTIVE: Theoretical conceptualizations of emotion and affect regulation have a considerable common ground. However, mentalization theory considers the ability to regulate affects as being contingent on the ability to mentalize. The aim of the present study is to examine the association between emotion regulation and mentalization, operationalized as reflective functioning, in a sample of patients with depression and/or anxiety. METHODS: The study used data from the TRAns-diagnostic Cognitive behavioural Therapy versus standard cognitive behavioural therapy (TRACT-RCT) trial. Patients with depression and/or anxiety (N = 291; 64.4% female; Mage = 32.2; SD = 11.0) completed the Emotion Regulation Strategies Questionnaire (ERSQ) and the Reflective Functioning Questionnaire (RFQ-6). Correlation and regression analyses were performed to determine associations of the measures of ERSQ and RFQ-6 in relation to the outcome variables, global well-being (World Health Organization Well-being Index; WHO-5) and social functioning (Work and Social Adjustment Scale; WSAS). RESULTS: Overall, the patients had a reduced level of emotion regulation (MERSQ_Total = 1.77; SD = 0.59). However, only mildly impaired reflective functioning was found (MRFQ-6 = 3.57; SD = 1.26). ERSQ correlated significantly with RFQ-6 (r = -0.31), that is, more frequent use of emotion regulation strategies was associated with less hypomentalization. ERSQ was a stronger predictor of well-being and social function than RFQ-6. CONCLUSION: In patients with anxiety and/or depression, hypomentalization as measured by the RFQ-6 is not a major problem, but emotion regulation is. It seems that these two, theoretically related constructs, do not necessarily co-occur. Alternatively, the RFQ-6 scale might not capture the mentalization construct in a valid way. Emotion regulation strategies are highly related to symptomatology; therefore, they are likely to be an important target for psychotherapy.

Cognitive-Behavioral Therapy Enhancement Strategies.

We review the literature on various strategies to augment cognitive-behavioral therapy (CBT). Although traditional pharmacotherapy has only a small additive effect, research demonstrates that it is possible to select interventions that potentiate known mechanisms of CBT. D-cycloserine appears to potentiate activity at the N-methyl D-ethyl aspartate receptor and thereby facilitates fear extinction. Exercise may increase neural plasticity and thereby increase the efficacy of CBT for depression and anxiety. Noninvasive brain stimulation is thought to target the specific cortical regions needed for CBT response, but results have been mixed. Several other compounds appear promising but await controlled research before their efficacy as an augmentation strategy can be determined.

Cognitive Behavioral Therapy for Anxiety and Depression in Children and Adolescents.

Anxiety and depression are prevalent and impairing psychiatric problems for children and adolescents. In this review, the authors summarize information about their prevalence and impact, the most common assessment methods, the main components of cognitive behavioral therapy (CBT), and research on the effectiveness of CBT for these disorders. Future directions, including improving access to CBT through technology-based approaches and increasing personalization of treatment, are discussed.

Concentrated transdiagnostic and cross-disciplinary micro-choice based group treatment for patients with depression and with anxiety leads to lasting improvements after 12 months: a pilot study.

BACKGROUND: A concentrated transdiagnostic and micro choice-based group treatment for patients with depression and anxiety has previously shown to yield significant reduction in symptoms and increased level of functioning from pre to 3-month follow-up. In the present study, we report the results after 12 months follow-up. METHODS: This was a non-randomized clinical intervention pilot study, conducted in line with a published protocol. Sixty-seven consecutively referred patients, aged 19-47 (mean age 32.5, SD = 8.0) were included and completed treatment. All had a severity of their problems that entitled them to care in the specialist public mental health care. Self-reported age at onset of symptoms was 17.6 (SD = 7.9) years. Mean number of prior treatment courses was 3.5 (SD = 3.3; range 0-20). The main objective was to assess the treatment effectiveness by questionnaires measuring relevant symptoms at pre-treatment, 7 days-, 3 months-, 6 months- and at 12-months follow-up. RESULTS: Validated measures of functional impairment (WSAS), depression (PHQ9), anxiety (GAD7), worry (PSWQ), fatigue (CFQ), insomnia (BIS) and illness perception (BIPQ) improved significantly (p < .0005) from before treatment to 12 months follow-up, yielding mostly large to extremely large effect sizes (0.89-3.68), whereas some moderate (0.60-0.76). After 12 months, 74% report an overall improvement in problems related to anxiety and depression. Utilization of specialist, public and private mental health care was reported as nonexistent or had decreased for 70% of the patients at 12-month follow up. CONCLUSIONS: The concentrated, micro-choice based group treatment approach yielded a highly clinically significant reduction in a wide range of symptoms already one week after treatment, and the positive results persisted at 12-month follow-up. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05234281, first posted date 10/02/2022.

The Effects of Patient Preference on Clinical Outcome, Satisfaction and Adherence Within the Treatment of Anxiety and Depression: A Meta-Analysis.

BACKGROUND: Taking patient preference into consideration has received increased attention in the last decades. We conducted a meta-analysis to estimate the effects of patient preference on clinical outcome, satisfaction and adherence regarding treatment of depression and anxiety. METHODS: Pubmed, Embase, PsycINFO and Scopus were searched for (cluster) randomized controlled trials. Twenty-six randomized controlled clinical trials were included, comprising 3670 participants, examining the effect of patient preference regarding treatment of anxiety and depression on clinical outcome, satisfaction and/or adherence. RESULTS: No effect of patient preference was found on clinical outcome [d = 0.06, 95% CI = (-0.03, 0.15), p = 0.16, n = 23 studies]. A small effect of patient preference was found on treatment satisfaction [d = 0.33, 95% CI = (0.08, 0.59), p = 0.01, n = 6 studies] and on treatment adherence [OR = 1.55, 95% CI = (1.28, 1.87), p < 0.001, n = 22 studies]. LIMITATIONS: Patient preference is a heterogeneous concept, future studies should strive to equalize operationalization of preference. Subgroup analyses within this study should be interpreted with caution because the amount of studies per analysed subgroup was generally low. Most studies included in this meta-analysis focused on patients with depression. The small number of studies (n = 6) on satisfaction, prevents us from drawing firm conclusions. CONCLUSIONS: While this meta-analysis did not find a positive effect of considering patient preference on clinical outcome, it was associated with slightly better treatment satisfaction and adherence. Accommodating preference of patients with anxiety and depression can improve treatment. TRIAL REGISTRATION: PROSPERO: CRD42020172556.

Suicidal behavior and all-cause mortality in depressed older adults aged 75+ treated with electroconvulsive therapy: A Swedish register-based comparison study.

OBJECTIVES: Electroconvulsive therapy (ECT) is effective in treating late-life depression. There is limited research on suicidal behavior and all-cause mortality in the oldest old after ECT. METHODS: Older adults aged 75 years and above who had been inpatients for moderate to severe depression between January 1, 2011, and December 31, 2017, were included in the study. We used exact and propensity score matching to balance groups. We compared suicidal behavior (fatal and non-fatal) and all-cause mortality in those who had received ECT and those with other depression treatments. RESULTS: Of the study population, 1802 persons who received ECT were matched to 4457 persons with other treatments. There were no significant differences in the risk of suicidal behavior between groups, (within 3 months: odds ratio 0.73; 95% confidence intervals (CI), 0.44-1.23, within 4 months to 1 year: aOR 1.34; 95% CI, 0.84-2.13). All-cause mortality was lower among ECT recipients compared to those who had received other treatments, both within 3 months (aOR, 0.35; 95% CI, 0.23-0.52), and within 4 months to 1 year (aOR 0.65; 95% CI, 0.50-0.83). CONCLUSIONS: Compared to other depression treatments, ECT is not associated with a higher risk of suicidal behavior in patients aged 75 and above. ECT is associated with lower all-cause mortality in this age group, but we advise caution regarding causal inferences.

Longitudinal associations between subjective cognitive impairment, pain and depressive symptoms in home-dwelling older adults: Modelling within-person effects.

OBJECTIVES: Cognitive impairment, pain and depressive symptoms are common and interrelated factors in older adults. However, the directionality and specificity of their association remains unclarified. This study explored whether these factors prospectively increase reciprocal risk and examined the longitudinal association between these factors and quality of life (QoL). METHODS: This study used longitudinal data from The Older Persons and Informal Caregivers Survey Minimal Data Set (TOPICS-MDS; the Netherlands). Older adults self-reported cognitive impairment, pain, depressive symptoms and QoL at baseline and after 6 and 12 months of follow-up. The Random Intercept Cross-Lagged Panel Model was used to assess the prospective association between the three factors, while a multilevel linear regression analysis in a two-level random intercept model was used to examine the longitudinal associations between the three factors and QoL at the within-person level. RESULTS: The data of 11,582 home-dwelling older adults with or without subjective cognitive impairment were analysed. At the within-person level, pain at 6 months was associated with subsequent depressive symptoms (ß = 0.04, p = 0.024). The reverse association from depression to pain, and longitudinal associations between pain and subjective cognitive impairment and between depressive symptoms and subjective cognitive impairment were non-significant. Pain, depressive symptoms and subjective cognitive impairment showed a significant association with poor QoL 6 months later. CONCLUSIONS: A directional relationship was observed from pain to depressive symptoms. Pain reduction holds a potential benefit in the prevention of depressive symptoms, ultimately optimising the QoL of older adults.

Mortality and adverse events associated with statin use in primary care patients with depression: a real-world, population-based cohort study.

BACKGROUND: New National Institute for Health and Care Excellence (NICE) guidance endorses the prescription of statins in larger population groups for the prevention of cardiovascular and cerebrovascular morbidity and mortality, especially in people with severe mental illness. However, the evidence base for their safety and risk/benefit balance in depression is not established. OBJECTIVES: This study aims to assess the real-world mortality and adverse events of statins in depressive disorders. METHODS: Population-based, nationwide (England), between-subject, cohort study. We used electronic health records (QResearch database) of people aged 18-100 years with first-episode depression, registered with English primary care practices over January 1998-August 2020 for 12(+) months, divided into statin users versus non-users.Primary safety outcomes included all-cause mortality and any adverse event measured at 2, 6 and 12 months. Multivariable logistic regression was employed to control for several potential confounders and calculate adjusted ORs (aORs) with 99% CIs. FINDINGS: From over 1 050 105 patients with depression (42.64% males, mean age 43.23±18.32 years), 21 384 (2.04%) died, while 707 111 (67.34%) experienced at least one adverse event during the 12-month follow-up. Statin use was associated with lower mortality over 12 months (range aOR2-12months 0.66-0.67, range 99% CI 0.60 to 0.73) and with lower adverse events over 6 months (range aOR2-6months 0.90-0.96, range 99% CI 0.91 to 0.99), but not at 1 year (aOR12months 0.99, 99% CI 0.96 to 1.03). No association with any other individual outcome measure (ie, any other neuropsychiatric symptoms) was identified. CONCLUSIONS: We found no evidence that statin use among people with depression increases mortality or other adverse events. CLINICAL IMPLICATIONS: Our findings support the safety of updated NICE guidelines for prescribing statins in people with depressive disorders.

The outcomes of mental health care for depression over time: A meta-regression analysis of response rates in usual care.

BACKGROUND: Over the past decades dozens of randomized trials have shown that psychological treatments are more effective than care-as-usual (CAU). It could be expected that these treatments are implemented in routine care and that the response rates in usual care improve over time. The aim of the current meta-analysis is to examine if response and remission rates in usual care have improved over time. METHODS: We used an existing meta-analytic database of randomized controlled trials examining the effects of psychological treatments of depression and selected CAU control groups from these trials. We only included CAU conditions in primary care, specialized mental health care, perinatal care and general medical care. The response rate (50 % symptom reduction) was the primary outcome. RESULTS: We included 125 CAU control groups (8542 participants). The response rate for all CAU control groups was 0.22 (95 % CI: 0.19; 0.24) with high heterogeneity (I2 = 83; 95 % CI: 80; 85), with somewhat higher rates in primary care (0.27; 95 % CI: 0.23; 0.31). We found hardly any indications that the outcomes have improved over the years. The meta-regression analysis with publication year as predictor in the full dataset resulted in a coefficient of 0.1 (SE = 0.01; p = 0.0.35). A series of sensitivity analyses supported the main findings. Remission rates and pre-post effect sizes also did not significantly improve over time. CONCLUSIONS: Response and remission rates in usual care are low, with the large majority of patients not responding or remitting, and the outcomes have probably not improved over time.

Association of CYP2D6 and CYP2C19 metabolizer status with switching and discontinuing antidepressant drugs: an exploratory study.

BACKGROUND: Tailoring antidepressant drugs (AD) to patients' genetic drug-metabolism profile is promising. However, literature regarding associations of ADs' treatment effect and/or side effects with drug metabolizing genes CYP2D6 and CYP2C19 has yielded inconsistent results. Therefore, our aim was to longitudinally investigate associations between CYP2D6 (poor, intermediate, and normal) and CYP2C19 (poor, intermediate, normal, and ultrarapid) metabolizer-status, and switching/discontinuing of ADs. Next, we investigated whether the number of perceived side effects differed between metabolizer statuses. METHODS: Data came from the multi-site naturalistic longitudinal cohort Netherlands Study of Depression and Anxiety (NESDA). We selected depression- and/or anxiety patients, who used AD at some point in the course of the 9 years follow-up period (n = 928). Medication use was followed to assess patterns of AD switching/discontinuation over time. CYP2D6 and CYP2C19 alleles were derived using genome-wide data of the NESDA samples and haplotype data from the PharmGKB database. Logistic regression analyses were conducted to investigate the association of metabolizer status with switching/discontinuing ADs. Mann-Whitney U-tests were conducted to compare the number of patient-perceived side effects between metabolizer statuses. RESULTS: No significant associations were observed of CYP metabolizer status with switching/discontinuing ADs, nor with the number of perceived side effects. CONCLUSIONS: We found no evidence for associations between CYP metabolizer statuses and switching/discontinuing AD, nor with side effects of ADs, suggesting that metabolizer status only plays a limited role in switching/discontinuing ADs. Additional studies with larger numbers of PM and UM patients are needed to further determine the potential added value of pharmacogenetics to guide pharmacotherapy.