Vitamin B6 Plus Lithium Helps Ease Mania Symptoms in Patients With Bipolar Disorder

Daily vitamin B6 (40mg/day), but not B1 (100mg/day), as an adjunctive therapy to lithium was associated with the improvement of mood symptoms in hospitalized patients with bipolar disorder experiencing a manic episode, according to a study published in the Journal of Affective Disorders 2024; 345 103-111: Zandifar et al.

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.

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.

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.”

“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.

Sleep Disturbances in Pediatric Bipolar NOS is the Same as in BP I 

Gianni Faedda reported in Frontiers in Psychiatry (2012) that decreased need for sleep is as prominent in BP NOS children as in those with BP I.  So it appears that with the exception of only brief periods of mania in BP NOS, these children have similar characteristics to those with full blown BP I.  Thus in addition to the briefer periods of mania, one should be on the look out for all the symptoms of bipolar disorder that are not typical of ADHD, including brief or extended periods of euphoria, decreased need for sleep, more extreme degrees of irritability and poor frustration tolerance, hallucination, delusions, suicidal and homicidal ideation, more severe depression, and increases in sexual interest and actions.  When these are present, the bipolar mood instability should  be treated first and only then small doses of psychomotor stimulants can be used to treat what ever residual ADHD remains.  The typical symptoms of ADHD are very of present and comorbid in childhood onset bipolar disorder and cannot be used to discriminate the two diagnoses.  The children with BP NOS are as dysfunctional as those with BP I and take longer to stabilize, so pharmacological treatment may need to be intensive, multimodal, and supplemented by Family Focused Therapy (FFT) or a related family therapy.  It is most often not conceptualized as such, but BP NOS as well as BP I should be considered as a medical emergency and handled by a sophisticated pediatrician and/or referred for psychiatric consultation and therapy.  The longer bipolar disorder is not treated, the worse the outcome is in adulthood.

Lithium is a Lifesaver in Bipolar Disorder

Batya Swift Yasgur MA, LSW reported in Medscape Medical News on November 28, 2022 that “Mood stabilizers protect against suicide and all-cause mortality in patients with bipolar disorder (BD), including natural mortality, with lithium emerging as the most protective agent, new research suggests.

Investigators led by Pao-Huan Chen, MD, of the Department of Psychiatry, Taipei Medical University Hospital, Taiwan, evaluated the association between the use of mood stabilizers and the risks for all-cause mortality, suicide, and natural mortality in over 25,000 patients with BD and found that those with BD had higher mortality.

However, they also found that patients with BD had a significantly decreased adjusted 5-year risk of dying from any cause, suicide, and natural causes. Lithium was associated with the largest risk reduction compared with the other mood stabilizers.

PREVENT EPISODES, PROTECT YOUR BRAIN, BODY, AND SELF

December 1, 2022 · Posted in Course of Illness, Risk Factors · Comment 

Kessing and Andersen 2017 wrote:”Overall, increasing number of affective episodes seemsto be associated with:(i) increasing risk of recurrence, (ii) increasing duration of episodes, (iii) increasing symptomatic severity of episodes,(iv) decreasing threshold for developing episodes, and (v) increasing risk of developing dementia.

Conclusion: Although the course of illness is heterogeneous, there  is evidence for clinical progression of unipolar and bipolar disorder.”

These adverse outcomes emphasize the importance of early and sustained treatment to prevent the occurrence and accumulation of episodes.

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.

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