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Med (New York, N.Y.) Mar 2024Psilocybin-assisted psychotherapy (PAP) has been associated with antidepressant effects. Trials to date have typically excluded participants with complex presentations.... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Psilocybin-assisted psychotherapy (PAP) has been associated with antidepressant effects. Trials to date have typically excluded participants with complex presentations. Our aim was to determine the feasibility of PAP in a complex population, including high levels of treatment resistance in major depressive and bipolar disorder and patients with baseline suicidality and significant comorbidity. We also evaluated flexible repeated doses over a 6-month period.
METHODS
Adults with treatment-resistant depression as part of major depressive or bipolar II disorder without psychosis or a substance use disorder were eligible to participate. Subjects were randomized to immediate treatment or waitlist control, with all eventually receiving PAP. Participants had one, two, or three psilocybin sessions with a fixed dose of 25 mg. Each dose was accompanied by preparation and integration psychotherapy sessions. Acceptability, safety, tolerability, and efficacy were evaluated (this study was registered at ClinicalTrials.gov: NCT05029466).
FINDINGS
Participants were randomized to immediate treatment (n = 16) or delayed treatment (n = 14). 29/30 were retained to the week-2 primary endpoint. Adverse events were transient, with no serious adverse events. Greater reductions in depression severity as measured by the Montgomery-Åsberg Depression Rating Scale (MADRS) were observed in the immediate treatment arm compared to the waitlist period arm with a large hedge's g effect size of 1.07 (p < 0.01). Repeated doses were associated with further reductions in MADRS scores compared to baseline.
CONCLUSIONS
PAP was feasible in complex patients with preliminary antidepressant efficacy and adequate safety and tolerability. Repeated doses were associated with greater reductions in depression severity.
FUNDING
This work was funded by Brain and Cognition Discovery Foundation (BCDF), Usona, and Braxia Scientific.
Topics: Adult; Humans; Psilocybin; Depressive Disorder, Major; Depressive Disorder, Treatment-Resistant; Antidepressive Agents; Psychotherapy
PubMed: 38359838
DOI: 10.1016/j.medj.2024.01.005 -
Acta Psychiatrica Scandinavica May 2024Long-term studies comparing nonresponse to antidepressants for major depressive disorder (MDD) are lacking. (Comparative Study)
Comparative Study
Comparative responses to 17 different antidepressants in major depressive disorder: Results from a 2-year long-term nation-wide population-based study emulating a randomized trial.
BACKGROUND
Long-term studies comparing nonresponse to antidepressants for major depressive disorder (MDD) are lacking.
AIMS
To present systematic population-based nation-wide register data on comparative 2-year non-response within six antidepressant drug classes and 17 different antidepressants in patients with MDD.
METHOD
The study included all 106,920 patients in Denmark with a first main index diagnosis of MDD at a psychiatric hospital inpatient or outpatient contact and who subsequently had a purchase of an antidepressant in the period from 1995 to 2018. Non-response to first antidepressant within a 2-year study period was defined as switch to or add-on of another antidepressant, antipsychotic medication, lithium, or hospitalization. Analyses emulated a targeted trial in populations standardized according to age, sex, socioeconomic status, and comorbidity with psychiatric and physical disorders.
RESULTS
Compared with sertraline, there was no difference for citalopram (RR: 1.00 [95% CI: 0.98-1.02]) but fluoxetine (1.13 [95% CI: 1.10-1.17]), paroxetine (1.06 [95% CI: 1.01-1.10]) and escitalopram (1.22 [95% CI: 1.18-1.25]) were associated with higher risk ratio of non-responses. Within selective noradrenaline reuptake inhibitors, sertraline outperformed reboxetine; within serotonin-norepinephrine reuptake inhibitors, venlafaxine outperformed duloxetine; within noradrenergic and specific serotonergic antidepressants, mirtazapine outperformed mianserin and within the class of other antidepressants, sertraline outperformed agomelatine and vortioxetine. Within tricyclic antidepressants, compared to amitriptyline, nortriptyline, dosulepin, and clomipramine had higher non-response, whereas there was no difference for imipramine.
CONCLUSIONS
These analyses emulating a randomized trial of "real world" observational register-based data show that 2-year long-term non-responses to some antidepressants within six different drug classes are increased over others.
Topics: Humans; Antidepressive Agents; Depressive Disorder, Major; Fluoxetine; Selective Serotonin Reuptake Inhibitors; Sertraline
PubMed: 38379028
DOI: 10.1111/acps.13673 -
Journal of Affective Disorders Jul 2023Early sexual intercourse and a greater number of sexual partners have been proved associated with depression. However, the causality of these associations is not clear.
Identifying causal associations between early sexual intercourse or number of sexual partners and major depressive disorders: A bidirectional two-sample Mendelian randomization analysis.
BACKGROUND
Early sexual intercourse and a greater number of sexual partners have been proved associated with depression. However, the causality of these associations is not clear.
METHODS
To unveil the causal associations between sexual factors and major depression disorder (MDD). The bidirectional, two-sample Mendelian randomization (MR) study was conducted, which used genetic variants associated with two sexual factors (age first had sexual intercourse, n = 406,457; lifetime number of sexual partners, n = 378,882) and MDD (n = 500,199) from the largest genome-wide association studies (GWASs) conducted by the UK biobank and the Psychiatric Genomics Consortium. The two-step MR analysis was applied to assess mediation. The Genetic predictors for five risky behaviors were also obtained from the most up-to-date GWAS conducted by the UK Biobank (ever self-harmed: 117,733; ever attempted suicide: 4933; psychoactive substance abuse, alcohol use, and tobacco use: 463,010).
RESULTS
MR analysis indicated a risky causal effect of age first had sexual intercourse (OR = 0.720, 95 % CI: 0.661-0.784, P = 2.45 × 10) and lifetime number of sexual partners (OR = 1.656, 95 % CI: 1.356-2.022, P = 7.46 × 10) on MDD. Mediation analysis showed the effects were mediated by tobacco use, with a proportion of 34.20 % on age first had sexual intercourse and 22.94 % on lifetime number of sexual partners separately.
LIMITATIONS
The overlap of participants in different traits and unclear gender.
CONCLUSIONS
Robust genetic evidence indicated that premature sexual intercourse and more sexual partners were risks for MDD. Risky behaviors, especially the tobacco use, mediated this effect.
Topics: Humans; Depressive Disorder, Major; Sexual Partners; Mendelian Randomization Analysis; Genome-Wide Association Study; Coitus; Polymorphism, Single Nucleotide
PubMed: 37086791
DOI: 10.1016/j.jad.2023.04.079 -
Pharmacological Research Sep 2023Depression is a highly prevalent disorder of the central nervous system. The neuropsychiatric symptoms of clinical depression are persistent and include fatigue,... (Review)
Review
Depression is a highly prevalent disorder of the central nervous system. The neuropsychiatric symptoms of clinical depression are persistent and include fatigue, anorexia, weight loss, altered sleep patterns, hyperalgesia, melancholia, anxiety, and impaired social behaviours. Mounting evidences suggest that neuroinflammation triggers dysregulated cellular immunity and increases susceptibility to psychiatric diseases. Neuroimmune responses have transformed the clinical approach to depression because of their roles in its pathophysiology and their therapeutic potential. In particular, activated regulatory T (Treg) cells play an increasingly evident role in the inflammatory immune response. In this review, we summarized the available data and discussed in depth the fundamental roles of Tregs in the pathogenesis of depression, as well as the clinical therapeutic potential of Tregs. We aimed to provide recent information regarding the potential of Tregs as immune-modulating biologics for the treatment and prevention of long-term neuropsychiatric symptoms of depression.
Topics: Humans; Depression; T-Lymphocytes, Regulatory; Anxiety; Biological Products; Depressive Disorder, Major
PubMed: 37611836
DOI: 10.1016/j.phrs.2023.106893 -
MMW Fortschritte Der Medizin Jun 2024
Topics: Humans; Depressive Disorder; Diabetes Mellitus, Type 2
PubMed: 38806899
DOI: 10.1007/s15006-024-4001-5 -
CNS Spectrums Dec 2023There is an urgent need to improve the clinical management of major depressive disorder (MDD), which has become increasingly prevalent over the past two decades. Several... (Review)
Review
There is an urgent need to improve the clinical management of major depressive disorder (MDD), which has become increasingly prevalent over the past two decades. Several gaps and challenges in the awareness, detection, treatment, and monitoring of MDD remain to be addressed. Digital health technologies have demonstrated utility in relation to various health conditions, including MDD. Factors related to the COVID-19 pandemic have accelerated the development of telemedicine, mobile medical apps, and virtual reality apps and have continued to introduce new possibilities across mental health care. Growing access to and acceptance of digital health technologies present opportunities to expand the scope of care and to close gaps in the management of MDD. Digital health technology is rapidly evolving the options for nonclinical support and clinical care for patients with MDD. Iterative efforts to validate and optimize such digital health technologies, including digital therapeutics and digital biomarkers, continue to improve access to and quality of personalized detection, treatment, and monitoring of MDD. The aim of this review is to highlight the existing gaps and challenges in depression management and discuss the current and future landscape of digital health technology as it applies to the challenges faced by patients with MDD and their healthcare providers.
Topics: Humans; Depressive Disorder, Major; Pandemics; Telemedicine; Mobile Applications
PubMed: 37042341
DOI: 10.1017/S1092852923002225 -
PloS One 2023Identifying modifiable risk factors early on is essential to prevent major depressive disorder (MDD). This study systematically investigated the causal relationship...
Identifying modifiable risk factors early on is essential to prevent major depressive disorder (MDD). This study systematically investigated the causal relationship between 19 modifiable risk factors and MDD. Single-nucleotide polymorphisms (SNPs) associated with 19 potentially modifiable risk factors were screened via the genome-wide association study (GWAS) enrolling individuals of European descent. Summary-level data for MDD (59,851 cases and 113,154 controls) were extracted from the UK Biobank. The inverse-variance-weighted (IVW) method was utilized as the primary analysis. Sensitivity analyses were performed using the MR-Egger method, the Maximum likelihood method, the MR-pleiotropy residual sum outlier (MR-PRESSO) method, and MR-robust adjusted profile score (MR-RAPS) method. MR-Egger regression, heterogeneity tests, pleiotropy tests, and leave-one-out tests were also performed to analyze sensitivity. The MR Steiger test was used to verify the directionality of the exposure to the outcome. Genetically predicted smoking initiation increased the risk of MDD (P = 6.00E-09), while smoking status: never and past tobacco smoking decreased the risk of MDD (all P < 0.01). In addition, education level was inversely associated with MDD risk (all P < 0.01). Genetically instrumented sleeplessness/insomnia, daytime naps, and nap during the day were positively related to the risk of MDD (all P < 0.01). Personal feelings, including guilt, hurt, tension, and worry too long after an embarrassing experience, had a suggestive increased risk for MDD (all P < 0.000). The remaining five modifiable risk factors were all causally associated with the risk of MDD, including neuroticism, neuroticism scores, body mass index (BMI), average total household income before tax, and types of physical activity in the last 4 weeks (all P < 0.01). All 19 potentially modifiable risk factors were causally associated with the risk of MDD. The main hypothesis of this MR study was that identifying and intervening in these 19 potentially modifiable risk factors could be beneficial to the prevention and treatment of MDD and further reduce mortality and economic burden.
Topics: Humans; Depressive Disorder, Major; Genome-Wide Association Study; Mendelian Randomization Analysis; Risk Factors; Smoking
PubMed: 37535610
DOI: 10.1371/journal.pone.0289419 -
Psychopharmacology Bulletin Aug 2023Transcranial magnetic stimulation (TMS) is effective in the management of treatment resistant major depressive disorder (MDD) and has recently become widely available.... (Review)
Review
BACKGROUND
Transcranial magnetic stimulation (TMS) is effective in the management of treatment resistant major depressive disorder (MDD) and has recently become widely available. Our aim was to explore the literature for evidence of the mechanism of action.
METHOD
We examined our own accumulating TMS library, the reference lists of all available papers and used a search engine to collect information. We collated and examined this information under relevant heading.
RESULTS
TMS produces a large number of physiological changes including site of stimulation neurochemical, brain wave and blood flow effects, and distant structure effects including neurotransmitter effects and volume increase. TMS also corrects generalized and local functional connectivity (FC) abnormalities which are a feature of MDD.
CONCLUSION
TMS produces a range of physiological changes. It is unclear which of these underpin its antidepressant. It is likely more than one work synergistically to this end-almost certainly the capacity to correct MDD induced FC abnormalities makes a strong antidepressant contribution.
Topics: Humans; Depressive Disorder, Major; Transcranial Magnetic Stimulation; Depressive Disorder, Treatment-Resistant
PubMed: 37601083
DOI: No ID Found -
The American Journal of Clinical... Jun 2024Depression commonly features the experience of hopelessness and a loss of the ability to imagine and believe in one's positive future. This article considers this... (Review)
Review
Depression commonly features the experience of hopelessness and a loss of the ability to imagine and believe in one's positive future. This article considers this important feature of depression and how effective recovery from depression includes the restoration of hope and a belief in actualizing a positive future. It provides in detail a treatment strategy that is focused on cocreating with the patient a positive therapeutic outcome in the patient's future and encourages patients to internalize a representation of the future experience of recovery and restoration of hope. This approach is described in detail and begins by guiding the client suffering from depression to experience a positive therapeutic outcome during hypnosis. This is followed by having the client internalize this positive resolution and recovery and integrate this experience on conscious and subconscious levels. As the client "returns from the future" to the present, bringing back with them this experience of having achieved a resolution and recovery from depression, this corrective emotional experience can affect their daily behavior in the present arising from a significant change in thoughts, feelings, and actions. Case examples that illustrate the use of the future focused strategy in clinical practice are included.
Topics: Humans; Hypnosis; Hope; Depressive Disorder
PubMed: 38166179
DOI: 10.1080/00029157.2023.2289657 -
Blood Advances Sep 2023Major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SCZ) are associated with an increased risk of cardiovascular diseases, including venous... (Meta-Analysis)
Meta-Analysis
Major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SCZ) are associated with an increased risk of cardiovascular diseases, including venous thromboembolism (VTE). The reasons for this are complex and include obesity, smoking, and use of hormones and psychotropic medications. Genetic studies have increasingly provided evidence of the shared genetic risk of psychiatric and cardiometabolic illnesses. This study aimed to determine whether a genetic predisposition to MDD, BD, or SCZ is associated with an increased risk of VTE. Genetic correlations using the largest genome-wide genetic meta-analyses summary statistics for MDD, BD, and SCZ (Psychiatric Genetics Consortium) and a recent genome-wide genetic meta-analysis of VTE (INVENT Consortium) demonstrated a positive association between VTE and MDD but not BD or SCZ. The same summary statistics were used to construct polygenic risk scores for MDD, BD, and SCZ in UK Biobank participants of self-reported White British ancestry. These were assessed for impact on self-reported VTE risk (10 786 cases, 285 124 controls), using logistic regression, in sex-specific and sex-combined analyses. We identified significant positive associations between polygenic risk for MDD and the risk of VTE in men, women, and sex-combined analyses, independent of the known risk factors. Secondary analyses demonstrated that this association was not driven by those with lifetime experience of mental illness. Meta-analyses of individual data from 6 additional independent cohorts replicated the sex-combined association. This report provides evidence for shared biological mechanisms leading to MDD and VTE and suggests that, in the absence of genetic data, a family history of MDD might be considered when assessing the risk of VTE.
Topics: Male; Humans; Female; Depressive Disorder, Major; Venous Thromboembolism; Bipolar Disorder; Schizophrenia; Risk Factors
PubMed: 37399490
DOI: 10.1182/bloodadvances.2023010562