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.
Patterns of Pharmacotherapy for Bipolar Disorder
Highlights from the International Society for Bipolar Disorders Conference Posters and Presentations, Chicago, June 22-25, 2023
Balwinder Singh of the Mayo Clinic College of Medicine reported on “10,351 individuals from North America (n=3,985), Europe (n=3,822), and Australia (n=2,544), predominantly with cross-sectional data (80%)….They found that “Cross-sectionally, mood-stabilizing anticonvulsants (44%), second-generation antipsychotics (42%), and antidepressants (38%) were most prescribed. Lithium was prescribed in 29% of patients, primarily in Australian (31%) and European (36%) cohorts.” Lithium is remarkedly underutilized in North American cohorts.
Both Obesity and Bipolar Disorders in 2249 Individuals Show White Matter Microstructure Abnormalities
Lorielle Dietze of Dalhousie University “obtained body mass index (BMI) and diffusion tensor imaging derived fractional anisotropy (FA) values from 930 individuals with bipolar disorders (BD), and 1319 control individuals from 20 cohorts in the ENIGMA-BD Working Group.”
They “found that lower FA was associated with both BD and BMI, in five white matter tracts, including the corpus callosum and thalamic radiation. Nine ROIs were correlated with only BD, while higher BMI was uniquely correlated with lower FA in four white matter ROIs.”
They concluded: “For the first time we showed that both obesity and BD demonstrated lower FA in some of the same regions. The impact of obesity may be greater in some tracts in BD individuals.”
Cognitive Function and White Matter Integrity in Individuals With Bipolar Disorder
Highlights from Posters Presented at the Society of Biological Psychiatry Meeting, April 27-29, 2023 in San Diego
Jennifer McDowell reported that they found “significantly reduced FA (fractional anisotropy) values in 85 bipolar probands compared to 66 controls” in multiple (n=8) white matter tracts. There were significantly lower scores in bipolar probands compared to controls on composite scores, ( p = 0.007), verbal fluency, ( p < 0.001), and symbol coding, (p = 0.023). They concluded that: “ Impacted connectivity in critical fiber tracts may be key to understanding the neural underpinnings of deficits, like cognition, observed in this clinical population.”
Editors note: It is of interest that lithium has been shown to normalize some white matter abnormalities in youngsters and help preserve cognitive function in older individuals. On this and many other accounts, way too little lithium is being used in the treatment of patients with bipolar disorder. Lithium not only increases neurogenesis (new grey matter neurons) and hippocampal volume, but also has positive effects on white matter tracts and even increases the length of one’s telomeres (which keeps you more healthy). In other ungrammatical words, “If your brain is not connected right, it don’t work right.”
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).”
Intravenous Arketamine As Adjunctive Treatment for Bipolar Depression
Highlights from Posters Presented at the Society of Biological Psychiatry Meeting, April 27-29, 2023 in San Diego
I.D. Bandeira of Stanford University reported on the feasibility and safety of the (R)-enantiomer of ketamine (arketamine) in treating six patients with bipolar depression: “Subjects received two intravenous infusions of arketamine of 0.5mg/kg, followed by 1mg/kg one week later.” Patients improved after the first dose and after “1mg/kg dose, the mean MADRS [Montgomery–Åsberg Depression Rating Scale] total score before the second infusion was 32.0, which dropped to 17.66 after 24h (p<0.001).” All individuals tolerated both doses, exhibiting no dissociative or manic symptoms.
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.
