Antidepressant Effects of Psilocybin in Unipolar Depression
Highlights from the International Society for Bipolar Disorders Conference Posters and Presentations, Chicago, June 22-25, 2023
Alan Young reported on 233 patients with treatment refractory depression who were given 10mg then 25mg of psilocybin, 1 week apart.
There was intensive therapeutic support before, during, and after the ingestions. Patients experienced it as a waking dream. Response was rapid in onset and 20% response persisted at least through week 12.
Metabolic Changes in Brain of Bipolar at Autopsy
Highlights from the International Society for Bipolar Disorders Conference Posters and Presentations, Chicago, June 22-25, 2023
Graeme Preston reported on the brain of autopsied bipolar patients having increases aspartate and citrulline, while those with unipolar depression had decreases in the TCA cycle.
He saw increases in acetyl carnitine in manic bipolar patients versus bipolar depressed patients, which is of interest in relationship to the putative antidepressant effects of acetyl-L-carnitine in animal models of depression and in humans.
Positive Effects of Low-Dose Lithium (LDL)
Highlights from the International Society for Bipolar Disorders Conference Posters and Presentations, Chicago, June 22-25, 2023
Rebecca Strawbridge of the Institute of Psychiatry, Psychology & Neuroscience, King’s College London reported on 18 articles that were examined and grouped according to outcome domain (cognition, depression, mania, and related constructs e.g., suicidality). Significant benefits (versus placebo) were identified for attenuating cognitive decline, and potentially as an adjunctive therapy for people with depression/mania. Across studies, LDL (~serum level ?0.6 mmol/L) was reported to be safe.
Greater Severity of Depression in Youth With Bipolar Disorder versus Unipolar Depression
Highlights from the International Society for Bipolar Disorders Conference Posters and Presentations, Chicago, June 22-25, 2023
Aaron Silverman of the University of Toronto, CAMH found that “youth (age 13-21) with [Bipolar Disorders] compared to those with [unipolar] depression had significantly higher (more severe) ratings on depressed mood (p = .001), irritability (p = .037), anhedonia (p = .004), negative self-image (p < .001), hopelessness (p = .04), fatigue (p = .001), hypersomnia (p = .001), suicidal ideation (p = .04), and recurrent thoughts of death (p < .001).”
LITHIUM’S AMAZING DIVERSITY OF ASSETS
Editor’s Note: Lithium is vastly underutilized. There is wide spread ignorance about its many assets and misconceptions about its few side effects. Here is an update that should be of interest to potential users, family members, and clinicians.
Lithium:
- Prevents unipolar and bipolar depression
- Augments effects of antidepressants in unipolar depression
- Potentiates the effects of atypical antipsychotics in treating mania and depression
- Reduces inflammation
- Normalizes some aspects of cardiovascular risk
- Normalizes secretions for monocytes and leukocytes
- Increases neurogenesis, BCl-2, and hippocampal and thalamic volumes
- The increases in neuroprotective factors occurs at brain levels below typical therapeutic dosages
- Protects against memory deterioration
- Lowers dementia risk in old age
- Reduces suicide clinically and at minute concentrations in the water supply
- Lengthens telomeres and increases longevity
- Reduces size of lesions in models of stroke, AIDS, and Huntington’s chorea
- Normalizes circadian rhythms
- Reduces manic-like behavior induced by clock gene mutations
- Prevents calcium currents and increased firing rate in stem cells from bipolar patients
- Induces minimal to no weight gain on long term follow up
- Does not increase risk of kidney failure when given at blood levels of .6 to .8 blood levels
- Protects against spine and hip osteoporosis
Conclusion: With so many assets and so few liabilities, physicians and patients should reconsider the benefits of lithium and use it more often, not only in the few who respond to it as a monotherapy, but as a adjunct to the many other treatments of bipolar disorder. This should be a “no brainer” as lithium will very likely help some have fewer problems from their illness and may even help them live longer.
Many of these points are summarized in the open access publication: Robert M Post, The New News About Lithium: An Underutilized Treatment in The United States, Neuropsychopharmacology accepted article preview 4 October 2017; several new updates have been added from the International Society on Bipolar Disorders meeting, Chicago, June, 2023.
“Pharmacotherapy of Bipolar Depression”
Roger McIntyre gave a talk on the “Pharmacotherapy of Bipolar Depression” at the International Society for Bipolar Disorders Conference in Chicago, June 22-25, 2023
He pointed out that, contrary to the many approved agents for mania, there were few FDA-approved drugs for depression in patients with Bipolar Disorders. These approved drugs included: cariprazine (Vraylar); lumateperone (Caplyta); lurasidone (Latuda); quetiapine (Seroquel); and the olanzapine-fluoxetine combination (Symbyax). Other non-approved agents include: lithium, lamotrigine, antidepressants, MAOIs, pramipexole, carbamazepine, ketamine, bupropion+dextromethorphan, amantadine, memantine, and possibly minocycline and celecoxib. Surprisingly, more than 3,000 bipolar depressed patients have been reported to be taking ketamine and that this was not associated with the induction of hypomania or mania.
McIntyre reported on the antidepressant (AD) effects of intra-nasal (i.n.) insulin. The insulin receptor sensitizer metformin had AD effects, but only in those who converted to insulin sensitivity.
McIntyre reported on the mixed effects of the GLP-1 agonists in the prevention of depression (Cooper et al J. Psychiatric Res, 2023). This is of interest in relationship to the bidirectional relationship of diabetes mellitus and depression.
Liraglutide appeared to have an anti-anhedonia effect. Semaglutide had AD and antianxiety effects in animal models of depression.
Recent studies have explored the antidepressant effect of psilocybin. Small studies have indicated that it has rapid onset of AD effects, and, in contrast to ketamine where rapid onset AD and anti-suicidal effects are short lived, the AD effect of psilocybin may be more prolonged.
Ketamine repairs structure and function of prefrontal cortical neurons via glutamate NMDA receptor blocking action, while psilocybin and other psychedelics act via stimulating 5HT2A receptors. One single case study suggested that blocking 5HT2A receptors with trazodone could achieve a rapid onset of AD effects of psilocybin without the psychedelic effects, a very interesting finding that requires replication.
An Open Label Study of Synthetic Psilocybin in Bipolar Type II Depression
Highlights from Posters Presented at the Society of Biological Psychiatry Meeting, April 27-29, 2023 in San Diego
Scott Aaronson reported on patients receiving a single dose of synthetic psilocybin. All subjects had three preparatory sessions prior to dosing and three integration sessions post dosing and were followed for 12 weeks.
“At the three week primary outcome measure, 11 of 14 participants (78.6%) met remission criteria.” They concluded: “Most subjects reported significant improvement in chronic depressive symptoms without hypomania or suicidality and durability lasting for three months follow-up.”
The Addition of Fish Oil to Cognitive Behavioral Case Management is Not Effective for Youth Depression
In a relatively large placebo-controlled study adding a combination of 840 mg of eicosapentaenoic acid (EPA) and 560 mg of docosahexaenoic acid (DHA) versus placebo did not help treat depressed youth undergoing cognitive behavioral case management (CBCM) (Amminger et al, Biol. Psychiatry, June 22, 2023).
These findings add to the ongoing inconsistency of the effectiveness of Omega 3 Fatty Acids in treating depression. It had appeared more effective in younger than older depressed patients, but now even this trend appears unreliable.
A meta analysis does support use Omega 3 Fatty Acids for ADHD, however.
Serotonin is Back
A review by Moncrieff et al in Molecular Psychiatry 2022 concluded that : “there is no convincing evidence that depression is associated with, or caused by, lower serotonin concentrations or activity.” This was widely reported in the news media.
A new analysis by 26 experts in the field finds many faults with this analysis (Jauhar et al 2023). Instead, they conclude “A more accurate, constructive conclusion would be that acute tryptophan depletion and decreased plasma tryptophan in depression indicate a role for 5-HT in those vulnerable to or suffering from depression, and that molecular imaging suggests the system is perturbed. The proven efficacy of SSRIs in a proportion of people with depression lends credibility to this position.” Long live serotonin’s role in depression.
Probiotic as an adjunct to an antidepressant
Viktoriya L. Nikolova, et al reported in JAMA Psychiatry (2023) that the probiotic Bio-Kult Advanced; ADM Protexin was more effective than placebo as an adjunct to antidepressants for depression and anxiety.
