Lifetime use of MDMA/ecstasy and psilocybin is associated with reduced odds of major depressive episodes

Background: Depression is a major mental health issue worldwide, with high rates of chronicity and non-recovery associated with the condition. Existing treatments such as antidepressant medication and psychological treatments have modest effectiveness, suggesting the need for alternative interventions. Aim: The aim of this study was to examine the relationships between MDMA (3,4-methylenedioxymethamphetamine)/ecstasy and psilocybin use and major depressive episodes (MDEs). Methods: This observational study used data from a large ( N = 213,437) nationally representative sample of US adults to test the association of lifetime use of MDMA/ecstasy, psilocybin and other classic psychedelics (lysergic acid diethylamide (LSD), peyote, mescaline), other illegal substances (e.g. cocaine, phencyclidine (PCP)), and legal/medicinal substances of misuse (e.g. pain relievers, tranquilizers) with lifetime, past year, and past year severe MDEs. Results: Results revealed that lifetime MDMA/ecstasy use was associated with significantly lowered odds of a lifetime MDE (adjusted odds ratio (aOR) = 0.84; p < 0.001), past year MDE (aOR = 0.84; p < 0.001), and past year severe MDE (aOR = 0.82; p < 0.001). Psilocybin was associated with significantly lowered odds of a past year MDE (aOR = 0.90; p < 0.05) and past year severe MDE (aOR = 0.87; p < 0.05). All other substances either shared no relationship with a MDE or conferred increased odds of an MDE. Conclusions: These results suggest that MDMA/ecstasy and psilocybin use is associated with lower risk of depression. Experimental studies are needed to test whether there is a causal association between use of these compounds and the alleviation of depressive symptoms.

Examining the Use of Antidepressants for Adolescents with Depression/Anxiety Who Regularly Use Cannabis: A Narrative Review

Depression and anxiety disorders are two of the most common and growing mental health concerns in adolescents. Consequently, antidepressant medication (AD) use has increased widely during the last decades. Several classes of antidepressants are used mainly to treat depression, anxiety, and obsessive-compulsive disorders by targeting relevant brain neurochemical pathways. Almost all randomized clinical trials of antidepressants examined patients with no concomitant medications or drugs. This does not address the expected course of therapy and outcome in cannabis users. Cannabis is the most commonly used illicit substance globally. Substantial changes in its regulation are recently taking place. Many countries and US states are becoming more permissive towards its medical and recreational use. The psychological and physiological effects of cannabis (mainly of its major components, tetrahydrocannabinol (THC) and cannabidiol (CBD)) have been extensively characterized. Cannabis use can be a risk factor for depressive and anxiety symptoms, but some constituents or mixtures may have antidepressant and/or anxiolytic potential. The aim of this literature review is to explore whether simultaneous use of AD and cannabis in adolescence can affect AD treatment outcomes. Based on the current literature, it is reasonable to assume that antidepressants are less effective for adolescents with depression/anxiety who frequently use cannabis. The mechanisms of action of antidepressants and cannabis point to several similarities and conjunctions that merit future investigation regarding the potential effectiveness of antidepressants among adolescents who consume cannabis regularly.

Revisiting the effectiveness of repetitive transcranial magnetic stimulation treatment in depression, again

Following on from the publication of the Royal Australian and New Zealand Journal of Psychiatry Mood Disorder Clinical Practice Guidelines (2020) and criticisms of how these aberrantly addressed repetitive transcranial magnetic stimulation treatment of depression, questions have continued to be raised in the journal about this treatment by a small group of authors, whose views we contend do not reflect the broad acceptance of this treatment nationally and internationally. In fact, the evidence supporting the use of repetitive transcranial magnetic stimulation treatment in depression is unambiguous and substantial, consisting of an extensive series of clinical trials supported by multiple meta-analyses, network meta-analysis and umbrella reviews. Importantly, the use of repetitive transcranial magnetic stimulation treatment in depression has also been subject to a series of health economic analyses. These indicate that repetitive transcranial magnetic stimulation is a cost-effective therapy and have been used in some jurisdictions, including Australia, in support of public funding. An argument has been made that offering repetitive transcranial magnetic stimulation treatment may delay potentially effective pharmacotherapy. In fact, there is considerably greater danger of the opposite happening. Repetitive transcranial magnetic stimulation is as, if not more effective, than antidepressant medication after two unsuccessful medication trials and should be a consideration for all patients under these circumstances where available. There is no meaningful ongoing debate about the use of repetitive transcranial magnetic stimulation treatment in depression – it is a safe, effective and cost-effective treatment.

Treatment-Specific Hippocampal Subfield Volume Changes With Antidepressant Medication or Cognitive-Behavior Therapy in Treatment-Naive Depression

Background: Hippocampal atrophy has been consistently reported in major depressive disorder with more recent focus on subfields. However, literature on hippocampal volume changes after antidepressant treatment has been limited. The first-line treatments for depression include antidepressant medication (ADM) or cognitive-behavior therapy (CBT). To understand the differential effects of CBT and ADM on the hippocampus, we investigated the volume alterations of hippocampal subfields with treatment, outcome, and chronicity in treatment-naïve depression patients.Methods: Treatment-naïve depressed patients from the PReDICT study were included in this analysis. A total of 172 patients who completed 12 weeks of randomized treatment with CBT (n = 45) or ADM (n = 127) were included for hippocampal subfield volume analysis. Forty healthy controls were also included for the baseline comparison. Freesurfer 6.0 was used to segment 26 hippocampal substructures and bilateral whole hippocampus from baseline and week 12 structural MRI scans. A generalized linear model with covariates of age and gender was used for group statistical tests. A linear mixed model for the repeated measures with covariates of age and gender was used to examine volumetric changes over time and the contributing effects of treatment type, outcome, and illness chronicity.Results: Of the 172 patients, 85 achieved remission (63/127 ADM, 22/45 CBT). MDD patients showed smaller baseline volumes than healthy controls in CA1, CA3, CA4, parasubiculum, GC-ML-DG, Hippocampal Amygdala Transition Area (HATA), and fimbria. Over 12 weeks of treatment, further declines in the volumes of CA1, fimbria, subiculum, and HATA were observed regardless of treatment type or outcome. CBT remitters, but not ADM remitters, showed volume reduction in the right hippocampal tail. Unlike ADM remitters, ADM non-responders had a decline in volume in the bilateral hippocampal tails. Baseline volume of left presubiculum (regardless of treatment type) and right fimbria and HATA in CBT patients were correlated with a continuous measure of clinical improvement. Chronicity of depression had no effect on any measures of hippocampal subfield volumes.Conclusion: Two first-line antidepressant treatments, CBT and ADM, have different effects on hippocampal tail after 12 weeks. This finding suggests that remission achieved via ADM may protect against progressive hippocampal atrophy by altering neuronal plasticity or supporting neurogenesis. Studies with multimodal neuroimaging, including functional and structural analysis, are needed to assess further the impact of two different antidepressant treatments on hippocampal subfields.

Predictors of successful discontinuation of antipsychotics and antidepressants

Background To offer support for patients who decide to discontinue antipsychotic and antidepressant medication, identifying which potentially modifiable factors correlate with discontinuation success is crucial. Here, we analyzed the predictive value of the professional support received, circumstances prior to discontinuation, a strategy of discontinuation, and use of functional and non-functional coping strategies during discontinuation on self-reported discontinuation success and on objective discontinuation. Methods Patients who had attempted discontinuing antipsychotics (AP) and/or antidepressants (AD) during the past 5 years (n = 316) completed an online survey including questions on subjective and objective discontinuation success, sociodemographic, clinical and medication-related factors, and scales to assess the putative predictors. Results A regression model with all significant predictors explained 20–30% of the variance in discontinuation success for AD and 30–40% for AP. After controlling for baseline sociodemographic, clinical and medication-related factors, the most consistent predictor of subjective discontinuation success was self-care behavior, in particular mindfulness, relaxation and making use of supportive relationships. Other predictors depended on the type of medication: For AD, good alliance with the prescribing physician predicted higher subjective success whereas gradual tapering per se was associated with lower subjective success and a lower chance of full discontinuation. In those tapering off AP, leaving time to adjust between dose reductions was associated with higher subjective success and fewer negative effects. Conclusions The findings can inform evidence-based clinical guidelines and interventions aiming to support patients during discontinuation. Further studies powered to take interactions between variables into account are needed to improve the prediction of successful discontinuation.

Antidepressant drug treatment protecting from COVID-19: one more piece in the repurposing puzzle

In the article Analysis of the impact of antidepressants and other medications on COVID-19 infection risk in a chronic psychiatric in-patient cohort, Catherine L. Clelland and colleagues for the first time suggest a protective effect of antidepressants against infection with coronavirus disease 2019 (COVID-19) itself. During the observation period of the first wave of the pandemic in New York, more than 50% of patients in the psychiatric hospital studied were infected. From retrospective analysis of the hospital medical records, the authors found a significantly lower risk for infection in patients with antidepressant medication compared to treatment with other psychiatric drugs. The findings of a reduced infection incidence in patients who were already on antidepressant drug therapy underlines a preventive efficacy of antidepressants against COVID-19. Taken together with the prior obtained data of efficacy against deterioration of COVID-19 disease, this study adds a piece of evidence to the positive benefit-risk of antidepressants in repurposing condition against COVID-19.

Digital Interventions for Generalized Anxiety Disorder (GAD): Systematic Review and Network Meta-Analysis

Background: Generalized anxiety disorder is the most common mental health condition based on weekly prevalence. Digital interventions have been used as alternatives or as supplements to conventional therapies to improve access, patient choice, and clinical outcomes. Little is known about their comparative effectiveness for generalized anxiety disorder.Methods: We conducted a systematic review and network meta-analysis of randomized controlled trials comparing digital interventions with medication, non-digital interventions, non-therapeutic controls, and no intervention.Results: We included 21 randomized controlled trials with a total of 2,350 participants from generalized anxiety disorder populations. Pooled outcomes using analysis of Covariance and rankograms based on the surface under the cumulative ranking curves indicated that antidepressant medication and group therapy had a higher probability than digital interventions of being the “best” intervention. Supported digital interventions were not necessarily “better” than unsupported (pure self-help) ones.Conclusions: Due to very wide confidence intervals, network meta-analysis results were inconclusive as to whether digital interventions are better than no intervention and non-therapeutic active controls, or whether they confer an additional benefit to standard therapy. Future research needs to compare digital interventions with one-to-one therapy and with manualized non-digital self-help and to include antidepressant medication as a treatment comparator and effect modifier.

The Connection Between Depression And Chronic Pain. A Cross-Sectional Study For Individuals With Chronic Pain In Hail Region

Chronic pain is a physical disorder and a critical factor in determining depression. Their synchronicity tends to worsen the risk of both disorders. The research to date has found little information about the relationship between them. This research aimed to provide new insights into the understanding of the relationship between chronic pain and depression among the residents of Hail city, to free patients from chronic pain-induced depression. Statistical data in this paper confirmed that more than half of patients with pain also suffer from depression or mood swings. Data were collected with an online, semistructured questionnaire; the obtained data were converted into statistical data using Microsoft Excel 2013. It was found that women are more likely than men to develop depression due to chronic pain. The main cause of depression in patients was a chronic headache, colitis, and rheumatoid arthritis respectively, and it was found that the most commonly used pain relief medications were NSAIDs and painkillers & on the other hand, the most frequently used antidepressants were selective serotonin reuptake inhibitors. According to our findings, the type of chronic disease and its link to the patient's gender, education level, and the type of pain relief drug taken are the major elements that determined this association. We must also remember the patient's extensive medical history with a chronic pain condition, which played a significant influence among our patients who took part in our survey. Moreover, it was noticed that most patients received adequate information from the pharmacist about their antidepressant medication. Finally, depression still ranks high as a major factor affecting an individual's life in general; therefore, this research could promote the identification of new causes and targets for chronic pain-induced depression.