GLP-1s Might Decrease the Incidence of Depression and Anxiety
Lisa O’Mary of WebMD wrote: “People taking a popular type of drug for weight loss or to manage diabetes have a lower likelihood of being newly diagnosed with depression or anxiety, according to an analysis of millions of people’s health records.
The findings were published this week by researchers from the electronic health record company Epic. Researchers looked for new diagnoses of depression or anxiety among people who started taking drugs from a class called GLP-1 agonists that can help manage blood sugar or treat obesity by mimicking hormone levels in the body that can affect appetite and blood sugar. Many people who take the drugs experience significant weight loss.
The researchers found that people with diabetes who started taking most versions of GLP-1 agonists were between 11% and 65% less likely to be newly diagnosed with depression than people with diabetes who didn’t take one of the drugs. The greatest reduction in likelihood of a new depression diagnosis was observed among people taking tirzepatide, which is sold under the brand names Mounjaro and Zepbound.”
NEW FINDINGS BY COLVIN AWARD WINNER ROGER MCINTYRE
There is a convergence of finding of the occurrence of cognitive dysfunction in diabetes, obesity, and bipolar and unipolar mood disorders. This is based on new evidence of insulin resistance in the CNS found in examination of exosomes. Insulin is neuroprotective and neurotrophic much like lithium. People on lithium do not have evidence of loss of grey and white matter that other’s with bipolar disorder who are not on lithium have. Intra-nasal insulin can improve cognition. The widely used insulin sensitizers GLP-1s for diabetes and weight loss appear to also decrease cognitive decline. The GLP-1 liraglutide improves cognition in mood disordered patients, and increases brain NAA in obesity. The GLP-1 semaglutide appears to increase motivation, cognition and overcome reward deficits. These agents could have anti-depressant and depression preventing properties which remain to be further confirmed in ongoing clinical trials.
McIntyre finds that 80% of Alzheimer’s patients are insulin resistant and the GLP-1s are being studied for this illness as well. There is also a convergence of deficits in cognition, motivation, normal mood in Alzheimer’s patients.
“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.
