Intranasal Oxytocin for Internalizing Symptoms in Youth With Disruptive Behavior Disorders
Highlights from Posters Presented at the Society of Biological Psychiatry Meeting, April 27-29, 2023 in San Diego
E. Kendall reported that “Fifty-two youths with diagnoses of DBD [Disruptive Behavior Disorders] participated in [this] study, and twenty-five completed three weeks of treatment of intranasal OXT [oxytocin] and twenty-seven placebo (PBO)…. Youth who received OXT showed a significantly greater reduction of depression [ p=0.012] and anxiety [p=0.031] compared to the [placebo] group.”
They concluded that “Intranasal OXT can show efficacy in reducing internalizing symptoms in youth with DBD. This was accompanied by neural level changes implicated in emotion regulation (mPFC [medial prefrontal cortex] and ACC [anterior cingulate cortex]).”
Even Psychotic Mania Does Not Preclude Remarkable Success
Highlights from the International Society for Bipolar Disorders Conference Posters and Presentations, Chicago, June 22-25, 2023
Major (Two Star) General Gregg F. Martin described his lifetime hyperthermia (high energy) as a youngster morphing into full-blown mania and then a fulminatory psychotic mania. This was undiagnosed and untreated for almost 20 years and was accompanied by anxiety and Iraq war-induced PTSD and, eventually, terrifying delusions and hallucinations; all the while he was somehow functioning at a very high level and getting repeated promotions.
When finally and properly diagnosed, he was told he had to resign. He was treated with lithium and other agents, and achieved a complete recovery. He is now lecturing about his experience with bipolar illness and working on efforts directed at better illness recognition, treatment, and destigmatization. He is not only a war hero, but also an illness hero.
The Systematic Treatment Optimization Program for Early Mania
Highlights from the International Society for Bipolar Disorders Conference Posters and Presentations, Chicago, June 22-25, 2023
A. Rathseesh and L. Yatham reported on the importance of systematic vigorous treatment of a first manic episode. If more episodes occurred, losses in cognition did not fully recover. All patients remitted within 1 year of their first mania. Recurrence occurred in 58% by year 1 and 74% by year 4. Predictors of functional recovery included sustained euthymia, especially absence of depressive symptoms, good cognitive functioning, and maintaining a normal weight. More aggressive treatment to prevent relapses in years 1-4 after a first manic episode appears needed and how exactly to achieve this requires further study.
Effectiveness of Repeated Ketamine Infusions for Treatment Resistant Bipolar Depression
Highlights from the International Society for Bipolar Disorders Conference Posters and Presentations, Chicago, June 22-25, 2023
Farhan Fancy, of the University of Toronto, gave 66 highly treatment resistant (unselected) bipolar I or II patients four sub-anesthetic doses of IV ketamine (0.5-0.75mg/kg) over a two-week period. They saw significant reductions in depression, anxiety, suicidality, and disability. Response rates were 35% and remission rate was 20%. “Infusions were generally well tolerated with treatment-emergent hypomania observed in only three patients (4.5%) with zero cases of mania or psychosis.”
Nighttime Bedroom Light Exposure Increases Episode Relapses in Bipolar Disorder
Highlights from the International Society for Bipolar Disorders Conference Posters and Presentations, Chicago, June 22-25, 2023
Yuichi Esaki of Okehazama Hospital reported that “Of the 172 participants, 39 (22%) experienced manic or hypomanic episodes (during 2 years of follow up). In the Cox proportional-hazards model, the hazard ratio (HR) for manic/hypomanic episode relapses was significantly higher when the average nighttime illuminance was ?3 lux (n = 71) than when it was <3 lux (n = 101; HR, 2.54; 95% confidence interval (CI), 1.33–4.84)… Keeping the bedroom dark at night may prevent hypomanic and manic episodes.”
Disrupted Circadian Temperature Rhythm in Skin Temperature in Bipolar Mania
Highlights from the International Society for Bipolar Disorders Conference Posters and Presentations, Chicago, June 22-25, 2023
Andrea Stautland of University of Bergen studied the nocturnal temperature of sleeping participants in mania and during remission between 3:00am and 6:00am (n=12). In mania, but not in remission there were “highly significant mean changes (lack of night time decreases) between baseline and 4:30am and 6:00am, with p=0.012 and p=0.037, respectively.”
Editors Note: This data is of interest in light of the new subtype of unspecified bipolar disorder called Temperature and Sleep Dysregulation Disorder (TSDD) characterized by profound behavioral dyscontrol, marked sleep disturbance, and temperature dysregulation (red face and ears, being too hot, going out in the cold underdressed). This extremely dysfunctional syndrome responds to high dose lithium; melatonin, clonidine, and other cooling techniques; and ascending and then repeated doses of intranasal ketamine (as described by Papolos et al 2013; 2018).
“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.
Early Antidepressant Use is Associated with Rapid Cycling Bipolar Disorder
Highlights from Posters Presented at the Society of Biological Psychiatry Meeting, April 27-29, 2023 in San Diego
A.C. Courtes and Jair Soares reported that “Antidepressants were prescribed as the first psychiatry medication in 74/114 (65%) of BD patients.” This and alcohol use disorder were independent predictors of rapid cycling.
Lumateperone Normalizes Pathological Levels of Acute Inflammation and Stimulates Important Pathways Involved in Mood Regulation
Highlights from Posters Presented at the Society of Biological Psychiatry Meeting, April 27-29, 2023 in San Diego
Sophie Dutheil of Intra-Cellular Therapies, Inc. reported that “In male and female C57BL/6 mice subjected to an acute stress or immune challenge, lumateperone reduced elevated levels of key proinflammatory cytokines. A number of key genes and pathways associated with the maintenance of tissue integrity and blood-brain barrier function were also altered by a single dose of lumateperone. Furthermore, we found that lumateperone administration conferred anxiolytic- and antianhedonic-like properties while enhancing the mTORC1 signaling pathway in the PFC.”
Higher Brain Temperature in Youth Bipolar Disorder Using a Novel Magnetic Resonance Imaging Approach
Highlights from Posters Presented at the Society of Biological Psychiatry Meeting, April 27-29, 2023 in San Diego
Ben Goldstein of the University of Toronto reported that “Brain temperature was significantly higher in BD (bipolar youth) compared to CG (control group) in the precuneus. Higher ratio of brain temperature-to-CBF [cerebral blood flow] was significantly associated with greater depression symptom severity in both the ACC [anterior cingulate cortex] and precuneus within BD.”
These finding are of particular interest in light of the Unspecified Bipolar Disorder subtype called Temperature and Sleep Dysregulation Disorder (TSDD), where patients are over heated and respond to clonidine and other cooling techniques along with lithium and repeated intranasal ketamine insufflations.
