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We’re back!
After a pandemic-related hiatus, we’re back, and we hope to bring you articles regularly. For print subscribers, we hope to send out a single large issue in the coming months.
Review: Reconsideration of bipolar disorder as a developmental disorder
Reconsideration of bipolar disorder as a developmental disorder: Importance of the time of onset
Pierre Alexis Geoffroy et al, J Physiology Paris, 2013
Eight admixture studies have demonstrated three homogeneous subgroups of patients with bipolar disorder, identi?ed by their age at onset (early, intermediate and late age at onset), with two cutoff points, at 21 and 34 years.
The early onset group had more: Suicide attempts, rapid cycling, drug and alcohol abuse, psychotic symptoms, panic disorder, OCD, and a positive family history for affective disorder. Early onset illness should be recognized and treated earlier.
Trace lithium levels in drinking water reduce the risk of dementia: a systematic review
International Journal of Bipolar Disorders volume 12, Article number: 32 (2024)
The sample size varied in the studies from 37,597 to 35,000,000. Lithium levels ranged from 0.002 to 0.027 (mg/L).
“We systematically reviewed five available studies, which reported associations between trace-Li in water and incidence [of] or mortality from dementia. Association between trace-Li levels and a lower risk or mortality from dementia were observed at concentrations of Li in drinking water as low as 0.002 mg/L and 0.056 mg/L. Meanwhile, levels below 0.002 mg/L did not elicit this effect. Although three of the five studies found dementia protective properties of Li in both sexes, a single study including lower Li levels (0.002 mg/l) found such association only in women.
Conclusion
The reviewed evidence shows that trace-Li levels in the water are sufficient to lower the incidence or mortality from dementia. Considering the lack of options for the prevention or treatment of dementia, we should not ignore these findings. Future trials of Li should focus on long term use of low or even micro doses of Li in the prevention or treatment of dementia.
No HIV Infections After Twice-a-Year PrEP
Lenacapavir, a twice-yearly injectable HIV-1 capsid inhibitor, has shown 100% efficacy in preventing HIV in women at a high risk for infection, according to an interim analysis of the phase 3 PURPOSE 1 trial.
The results were so promising that the independent data monitoring committee recommended that Gilead Sciences stop the blinded phase of the trial and offer open-label lenacapavir to all participants.
The results were both unexpected and exciting. “I’ve been in the HIV field for a really long time, and there’s no other phase 3 PrEP trial that found zero infections,” said Moupali Das, MD, PhD, executive director of clinical development at Gilead Sciences, Foster City, California.
Editors Note: It would be nice if we knew anything about primary prophylaxis of bipolar disorder for high risk children.
Naltrexone Augmented with Prazosin Is Highly Effective for Alcohol Use Disorder
Murray Raskind, of the VA Northwest Mental Illness Research, Education, and Clinical Center, conducted a translational proof-of-concept randomized controlled trial (RCT) of the mu-opioid receptor antagonist, naltrexone, augmented with the alpha-1 adrenergic receptor antagonist, prazosin, for alcohol use disorder in veterans.
“Prazosin was titrated over 2 weeks to a target dose of 4 mg QAM, 4 mg QPM, and 8 mg QHS. Naltrexone was administered at 50 mg QD…. In the NAL-PRAZ condition, % reductions from baseline for all three primary outcome measures exceeded 50% and were at least twice as large as % reductions in the NAL-PLAC condition.
They concluded: “These results suggest that prazosin augmentation of naltrexone enhances naltrexone benefit for AUD. They are consistent with preclinical studies in rodent models of AUD and strengthen rationale for an adequately powered definitive RCT. “
Accelerated iTBS Treats Bipolar Depression in 5 Days
Yvette Sheline, of the University of Pennsylvania Perelman School of Medicine, reported that 10 intermittent theta burst stimulations (iTBS) per day for 5 days yielded dramatic improvement in patients with bipolar depression – both immediately after the iTBS as well as at 4 weeks.
Resting-state functional MRI was used to individually target the left dorsolateral prefrontal cortex (dlPFC), the region most anticorrelated with the subgenual anterior cingulate cortex (sgACC).
THE PATHOPHYSIOLOGY OF SCHIZOPHRENIA IS BECOMING CLEARER
David Lewis of U. Pittsburgh showed that the glutamate neurons in the prefrontal cortex of patients with schizophrenia are deficient in the gamma (30-50 Hz) oscillations that are responsible for normal working memory.
Not only are dendrites and spines deficient in these neurons in layer 3 of the cortex, but there is a deficit in parvalbumin GABA inhibitory neurons. The GABA enzyme GAD 67 is lower, producing less inhibition. The frontal neurons are hypoactive and there is less BDNF and oxidative phosphorylation present, yielding decreases in mitochondrial function.
A DESEASE MODIFYING DRUG, LECANEMAB, IS NOW AVAILABLE FOR ALZHEIMER’S DISEASE
C. H. van Dyck from Yale talked about the diagnosis and treatment of Alzheimer’s dementia.
New brain imaging data have revealed that Lecanemab cannot only highly significantly delay memory decline but also improve PET measures of amyloid and tau. Early illness in those with mild cognitive impairment (MCI) can be detected; results indicate better effects of treatment Lecanemab in those with earlier and milder illness compared to those with more severe illness.
Intramuscular versus Intravenous Ketamine for the Management of Treatment-Resistant Depression and Suicidal Ideation
Cristina Albott of the University of Minnesota Medical School reported relatively similar efficacy of intramuscular versus intravenous ketamine for the management of treatment-resistant depression and suicidal ideation in outpatient settings.
“Intramuscular (IM) delivery represents an underexplored and promising route of administration given its high bioavailability and low cost….Sixty-six patients underwent a series of 7 to 9 IV (n=35) or IM (n=31) administrations of 0.5mg/kg ketamine during a 21-28 day period. Both IV and IM showed similar magnitudes of improvement in depression, but surprisingly only the IM route was associated in a significant improvement in suicidal ideation in a within subjects change.”
“No adverse events occurred throughout the treatment series for either administration route…. This clinical case series provides preliminary support for the effectiveness and safety of IM compared to IV ketamine in TRD. “
Influence of Childhood Maltreatment on Morphometry and Brain Network Architecture in Bipolar Disorder
Martin Teicher of McLean Hospital, Harvard Medical School, reported on the influence of childhood maltreatment on morphometry and brain network architecture in Bipolar Disorder.
“Childhood maltreatment (MAL) is common in individuals with bipolar disorder (BP) and is associated with earlier onset, more severe course, and more comorbidities.” They found that reduced hippocampal volume and white matter alterations were present in those with a history of childhood maltreatment. They concluded that “MAL may act as a sensitizer promoting the emergence of bipolar symptoms in individuals with less severe network abnormalities” than in BP patients with no MAL.
Lithium Is Unparalleled in It Range of Efficacy in the Mood Disorders
Most clinicians are aware of lithium’s superiority over other mood stabilizers in bipolar illness prophylaxis. New data suggests this might also apply to the atypical antipsychotics.
Lithium is also not only an effective adjunct to antidepressant in unipolar depression, but has some of the best data for its use in long term prevention. In bipolar disorder prophylaxis it is particularly effective in those with classical presentations of discrete episodes of euphoric mania, treatment early in the course of illness, lack of anxiety and substance comorbidities, and a positive history of mood disorder in first-degree relatives.
New data indicates that it is also effective in childhood onset mania, and open long term follow ups indicate that it is more effective than other mood stabilizers or atypical antipsychotics.
Despite the compelling effectiveness data and many ancillary benefits, survey data indicates very low levels of current lithium use in both adult and child bipolar disorder. The conventional view, shared by most patients and many clinicians, underestimates its range of effectiveness and potential benefits while overestimating it is side effects. A more balanced view is needed as neglect of wider use of lithium is detrimental to the long term outcome of immense numbers of patients.
Robert M. Post, MD
