MDMA Superior to Placebo in Treatment of Severe PTSD

February 23, 2022 · Posted in Peer-Reviewed Published Data, Potential Treatments · Comment 
post traumatic stress disorder

An article by researcher Jennifer M. Mitchell and colleagues published in the journal Nature in 2021 reported that MDMA was more effective than placebo at treating severe post-traumatic stress disorder in an 18-week phase 3 clinical trial.

The article reported on a randomized, double-blind, placebo-controlled, multi-site trial that took place in the US, Canada, and Israel. Participants in the trial had severe PTSD, and in some cases also had dissociation, depression, a history of alcohol or substance use disorders, or childhood trauma. In the trial, 91 participants were required to stop any current psychiatric medications for a “washout” period, and then were randomized to either a group that received 12 therapy sessions plus placebo or a group that received 12 therapy sessions and 3 doses of MDMA, which were administered in a clinical setting.

Two months after the last therapy session, participants who had received MDMA during the trial showed greater reductions in PTSD symptoms and less functional impairment than those who were assigned to the placebo group during the trial. At the endpoint of the study, 67% of participants in the MDMA group no longer met the criteria for a PTSD diagnosis, compared to 32% of the placebo group.

Side effects that were more prevalent among the MDMA group were typically transient and mild to moderate in severity. These included muscle tightness, decreased appetite, nausea, sweating, feeling cold, and increased blood pressure and heartrate. The MDMA group did not show any increases in drug abuse or suicidality compared with the placebo group, and MDMA had similar effects among those participants with and without comorbid conditions. The authors concluded that MDMA was highly efficacious, safe, and well-tolerated as a treatment for PTSD and urged that further study of the treatment be done without delay.

Currently, US Food and Drug Administration (FDA)–approved treatments for PTSD include the selective serotonin reuptake inhibitors (SSRIs) sertraline and paroxetine, but approximately half of PTSD patients do not respond to these drugs or to evidence-based trauma-specific psychotherapy or cognitive-behavioral therapies. The FDA has designated MDMA-assisted therapy for PTSD a “Breakthrough Therapy.” This designation indicates that the therapy may be a substantial improvement over existing therapies for a serious condition, and is intended to speed up the drug development and review process.

MDMA (or 3,4-methylenedioxymethamphetamine) is the same chemical used recreationally under the name ecstasy or molly. However, the positive effects in the trial followed careful dosing (which is impossible with street drugs) and targeted therapy sessions.

We’re back!

February 23, 2022 · Posted in About the BNN · Comment 

After a pandemic-related hiatus, we’re back, and we hope to bring you articles regularly. For print subscribers, we hope to send out a single large issue in the coming months.

Transcranial Direct Current Stimulation (tDCS) Induces Gray-Matter Increases in Depression

July 1, 2021 · Posted in Potential Treatments · Comment 
tDCS

At the 2021 meeting of the Society of Biological Psychiatry (SOBP), researcher Mayank Jog and colleagues described a study of transcranial direct current stimulation (tDCS) in 59 patients with moderate depression. The patients received either tDCS sessions that delivered electrical current at 2mA for 20 minutes or a same-length sham stimulation delivered using a double-blind stimulator, for a total of 12 sessions over 12 consecutive working days. Jog and colleagues found that compared to the sham stimulation, tDCS induced increases in gray matter volume in the left dorsolateral prefrontal cortex (DLPFC) target area, with a statistically large effect size (Cohen’s d = 1.3). The researchers plan to follow up this study that found structural changes to the brain after tDCS with more research on the antidepressant effects of the treatment.

Good Outcomes Among Patients with Major Depressive Disorder Treated with Transcranial Magnetic Stimulation in a Large Study

June 25, 2021 · Posted in Potential Treatments · Comment 
rTMS treatment

At the 2021 meeting of the Society of Biological Psychiatry (SOBP), researcher Harold Sackeim and colleagues reported on data collected from patients in clinical treatment for major depression who received transcranial magnetic stimulation (TMS) at 103 practice sites. A total of 5,010 depressed patients were included in the intent-to-treat sample, and 3,814 completed the study, meaning that they either reached remission or were treated at least 20 times and went through a final assessment. “Response (58–83%) and remission (28–62%) rates were notably high across self-report and clinician-administered assessments,” and women had better outcomes than men.  Sackeim and colleagues concluded, “Strong efficacy and the low side effect and medical risk profile suggest that TMS be evaluated as a first-line treatment for [major depressive disorder].”

Accelerated Intermittent Theta-Burst Stimulation (aiTBS) Quickly Improved Treatment-Resistant Depression

June 21, 2021 · Posted in Potential Treatments · Comment 
Transcranial magnetic stimulation (TMS).

At the 2021 meeting of the Society of Biological Psychiatry (SOBP), researcher Nolan Williams and colleagues described a sham-controlled trial of accelerated intermittent theta-burst stimulation (aiTBS) in patients with treatment-resistant depression. Theta burst stimulation is a specific protocol for rTMS, or repeated transcranial magnetic stimulation, a non-invasive form of brain stimulation. Magnets placed on a patient’s head provide bursts of high-frequency stimulation to the brain.

Participants in the study received 50 sessions over 5 days of either aiTBS or a sham procedure. Among those who received the real aiTBS treatment, 85.7% saw an improvement in their treatment-resistant depression, compared to only 26.7% of those in the sham group. AiTBS produced a rapid antidepressant response, which Williams and colleagues suggest could be useful for the treatment of patients in emergency rooms or inpatient settings.

Transcranial Near-Infrared Light May Treat Brain Injury and Neurodegeneration

June 15, 2021 · Posted in Potential Treatments · Comment 

At the 2021 meeting of the Society of Biological Psychiatry, there was a symposium on treatment with near-infrared light chaired by researchers Paolo Cassano and Dan Iosifescu. The treatment is known as transcranial photobiomodulation (PBM) with near-infrared light. A device worn on the head delivers infrared light that penetrates the cerebral cortex and can modulate cortical excitability. It has a variety of effects including promoting neuroplasticity, improving oxygenation, and decreasing inflammation and oxidative stress.

These studies used near infrared light.

A number of studies exploring the possibility that PBM could be used as a clinical treatment for conditions such as depression, brain injury, or dementia were presented at the symposium.

Researcher Lorelei Tucker discussed promising findings from an animal model in which rats with stroke or brain injuries showed improvement after being treated with PBM. 

Cassano discussed studies aimed at refining which brain areas should be targeted with PBM and how much light should be delivered in order to improve depression. In double-blind, sham-controlled studies in people with major depression, targeting the dorsolateral prefrontal cortex with PBM improved their symptoms.

Researcher Benjamin Vakoc discussed a study of low-level light therapy (LLLT) using near-infrared light compared to a sham procedure in 68 people with moderate traumatic brain injury. The researchers used magnetic resonance imaging (MRI) to assess changes in white matter in the brain over time in people recovering from an acute brain injury. Patterns of changes in white matter were different for those who received LLLT compared to those who received the sham procedure.

Researcher Linda Chao described a very small study to determine whether PBM could improve symptoms of dementia. Four patients received typical dementia care while four others underwent home treatments with the commercially available Vielight Neuro Gamma device, which delivers PBM via both the scalp and an insert in the nose. After 12 weeks, the PBM group showed improvements in cognition and brain connectivity.

The Vielight Neuro Gamma device

Editor’s Note: We will be watching the literature to follow advances in this promising novel method of neuromodulation.

Participation in Sports May Mitigate Genetic Risk for ADHD in School-Aged Children

June 9, 2021 · Posted in Risk Factors · Comment 

At the 2021 meeting of the Society of Biological Psychiatry, researcher Keiko Kunitoki and colleagues reported that participation in sports decreased behavior abnormalities in 9- and 10-year-old children at genetic risk for attention deficit hyperactivity disorder (ADHD). Sports were associated with greater hippocampal volume, which was associated with fewer behavioral abnormalities. Kunitoki and colleagues concluded that “participation in team sports mitigated genomic risk for psychopathology at age 9–10 in part through increased hippocampal volume.”

Editor’s Note: These data are consistent with a program called the Vermont Family-Based Approach developed by researcher James Hudziak, who heads the Vermont Center for Children, Youth and Families at the University of Vermont. The program encourages families to practice different domains of wellness, such as music, mindfulness, exercise, and nutrition, among others. The idea is to support emotional and behavioral health, and to do so intensively in families where children show signs of mood and behavioral difficulties or are at risk for these difficulties.

Hudziak analyzed brain scans of 232 children aged 6 to 18 and reported that “practicing an instrument such as the piano or violin increased working memory, gray matter volume in the brain, and the ability to screen out irrelevant noise. Practicing mindfulness increased white matter volume and reduced anxiety and depression. Exercise also increased brain volume and neuropsychological abilities.”

In 2015, researcher Benjamin I. Goldstein reported that 20 minutes of vigorous exercise on a bike improved cognition and decreased hyperactivity in the medial prefrontal cortex in adolescents with and without bipolar disorder, and researcher Danella M. Hafeman reported that offspring of parents with bipolar disorder who exercised more had lower levels of anxiety.

To summarize, engaging in exercise, team sports, music, and meditation/mindfulness are beneficial for all children, and can be especially helpful for those at risk for depression or bipolar disorder. Children who are already symptomatic should additionally be offered something like family focused therapy (FFT), a multi-faceted approach developed by researcher David Miklowitz, in which families of young people at risk for bipolar disorder take part in therapy, learning together about the illness and practicing strategies for communication and coping.

Surface Area of Cortex Is Reduced After Multiple Manic Episodes

cortex

In a 2020 article in the journal Psychiatric Research: Neuroimaging, researcher Rashmin Achalia and colleagues described a study of structural magnetic resonance imaging (MRI) that compared 30 people with bipolar I disorder who had had one or several episodes of mania to healthy volunteers. Compared to the healthy volunteers, people with bipolar disorder had “significantly lower surface area in bilateral cuneus, right postcentral gyrus, and rostral middle frontal gyri; and lower cortical volume in the left middle temporal gyrus, right postcentral gyrus, and right cuneus.”

The surface area of the cortex in patients with bipolar I disorder who had had a single episode of mania resembled that of the healthy volunteers, while those who had had multiple manic episodes had less cortical surface area.

The data suggest that compared to healthy volunteers, people with bipolar disorder have major losses in brain surface area after multiple episodes that are not seen in first episode patients. In addition, the researchers found that both the number of episodes and the duration of illness was correlated with the degree of deficit in the thickness in the left superior frontal gyrus. These decreases in brain measures occurred after an average of only 5.6 years of illness.

Editor’s Note:  These data once again emphasize the importance of preventing illness recurrence from the outset, meaning after the first episode. Preventing episodes may prevent the loss of brain surface and thickness.  

Clinical data has also shown that multiple episodes are associated with personal pain and distress, dysfunction, social and economic losses, cognitive deficits, treatment resistance, and multiple medical and psychiatric comorbidities. These and other data indicate that treatment after a first episode must be more intensive, multimodal, and continuous and include expert psychopharmacological and psychosocial support, as well as family education and support. Intensive treatment like this can be life-saving. The current study also supports the mantra we have espoused: prevent episodes, protect the brain and the person.

Left Prefrontal Strokes Linked to Depression

man touching head

In a 2021 article in the journal Stroke, researcher Julian Klingbeil and colleagues reported that left, but not right, ventrolateral prefrontal stroke lesions were associated with increased risk of depression at six months post-stroke.

The study included 270 participants who had their first-ever stroke. Six months following their strokes, 19.6% of the participants had depression. Those who scored higher on a scale of depression and anxiety symptoms in the first month after their stroke were more likely to have depression six months after the stroke.

The researchers identified a cluster of locations for stroke lesions, mostly within the left ventrolateral prefrontal cortex, that they linked to depression symptoms six months post-stroke. Klingbeil and colleagues hope that recognizing lesions in this region as risk factors for depression will help with early diagnosis of depression among people who recently had a stroke.

Editor’s Note: Antidepressants have been shown to improve post-stroke recovery of neurological functional (and depression) that is caused by the cutoff of blood supply during a stroke (ischemia). Patients and their family members should talk with their neurologist about treatment of ischemic strokes with antidepressants, especially when the lesions occur on the left side of the brain.  

Psychiatric Disorders Linked to More Physical Disease

May 19, 2021 · Posted in Comorbidities, Peer-Reviewed Published Data · Comment 
man seeing primary care physician

In an article in the journal JAMA Network Open, Leah S. Richmond-Rakerd and colleagues found that people with mental disorders had more physical disease at younger ages, they had more and longer hospitalizations and associated health care costs, and they were more likely to die at younger ages than people without mental disorders.

The research came from a population-based cohort study of more than 2.3 million citizens of New Zealand over three decades. The authors concluded, “These findings suggest that ameliorating mental disorders may have implications for improving the length and quality of life and for reducing the health care costs associated with physical diseases.” 

Editor’s Note: This editor would suggest the importance of also doing the opposite, that is, looking out for and treating and preventing the physical illnesses to which psychiatric patients are more vulnerable in order to improve the length and quality of life.

Either way, medical illnesses, both physical and psychiatric, are intimately intertwined, and both deserve careful and early intervention. Psychiatric and physical illnesses cause suffering, disability, and early demise. Major psychiatric illnesses need to be seen as potentially lethal medical illnesses, a fact that few people realize. Conversely, physical illnesses are often not treated as aggressively or intensively in psychiatric patients as in the general population. For example, patients with bipolar disorder get fewer interventions with stents and bypasses for the same heart problems as others. Special attention needs to be given to better encourage and support the medical health of psychiatric patients.

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