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

Quotes from Kay Jamison, PhD, Professor of Psychiatry at the Johns Hopkins School of Medicine

“There’s this notion that mania and depression are uncommon or certainly that mania is uncommon, and that is not true. The bipolar illness spectrum is associated with a lot of very damaging things, most importantly suicide, but also alcohol and drug use and violence. It’s a very early onset illness, so unlike dementia or heart disease, which hit people much later in life, these hit people when they’re young. They have to cope with [bipolar disorder] when they’re young, and they don’t have the experience of life to help them out. That tends to be overlooked, what it does to people and their families, and how devastating it is. First and foremost, I would want people to know that it’s treatable, imperfectly treatable, but treatable, and it’s important to get it treated….It’s completely reasonable to extend hope to somebody who has bipolar illness but to also make it very clear that it’s hard. But draw upon what you know. Read, read, read. Learn about it. Badger your doctors. Why are they doing this? What’s the point of this drug rather than that drug? Always question what’s happening to you. “

Editor’s Note: One of the most important things that people with mood disorder can do, is to every night chart chart their mood, functioning, sleep, medications, and other symptoms so that this graphic longitudinal assessment can be shown to their physician/therapist at each visit. This will help most efficiently refining the treatment regimen for an optimal long term outcome. See www.bipolarnews.org (click on Personal Calendar or Life Chart) for a good format for doing these daily ratings.
Parents of children (age 2-12) with mood and behavioral disorders can each week rate the severity of their child’s symptoms of anxiety, depression, ADHD, oppositional behavior, and mania on a secure website. This can be printed out to assist physicians with the assessment of need for treatment and of how well treatment is working. Informed consent for this system is available at www.bipolarnews.org (click on Child Network).

Antidepressant Use and Risk of Manic Episodes in Children and Adolescents With Unipolar Depression

Suvi Virtanen, PhD; et al in JAMA Psychiatry. September 27, 2023. report a low risk of switching in youngsters with unipolar depression. However, the odds ratio for a switch were significantly elevated when there was concomitant use of anticonvulsants and antipsychotics, and there was a four fold increased risk if a parent had bipolar disorder. Thus one should be particularly careful about treating depression with antidepressants (AD) when there is a positive parental history of bipolar disorder and one should think of other options, such as lamotrigine, an atypical with good AD effects, or lithium.

Pediatric Bipolar Disorder is Associated with Neurocognitive Deficits

Highlights from the International Society for Bipolar Disorders Conference Posters and Presentations, Chicago, June 22-25, 2023

Maria Paula Maziero of The University of Texas Health Science Center At Houston reported that while euthymic youths with BD (bipolar disorder) exhibited significant dysfunction in working memory (WM), verbal learning, and memory domains, fluctuation between the mood states affected the type of cognitive dysfunction. They concluded: “Pediatric bipolar disorder patients have marked cognitive dysfunction involving multiple domains, especially executive measures. The severity of mood symptoms influences cognitive performance, but even euthymic persons perform lower than matched controls.

Childhood Bullying and Maltreatment Yield A Worse Course of Bipolar Illness

Highlights from the International Society for Bipolar Disorders Conference Posters and Presentations, Chicago, June 22-25, 2023

Georgina Hosang of Bart’s & The London, Queen Mary’s School of Medicine reported that bullying and maltreatment together were associated with more suicidal behaviors than either childhood experience alone.

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).”

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]).”

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.

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.

Two different subtypes of early onset unspecified bipolar disorder (USBD)

The first subtype is classical BP NOS (Not Otherwise Specified) having all the characteristics of full-blown bipolar disorder except for only having brief durations of mania and responding to conventional treatment. The second is what is now called Temperature and Sleep Dysregulation Disorder (TSDD) and was formerly described by D. Papolos as the Fear of Harm (FOH) syndrome, and requires a different treatment approach.

Clinicians should be alert to unique symptoms in children who might have TSDD as such a diagnosis would lead to a unconventional treatment paradigm. We emphasize the importance of specifically asking parents about evidence of over heating (red face and red ears) and high tolerance for cold (going outside markedly under-dressed) and the presence of fear of sleep and horrific nightmares, as these may lead one to consider the diagnosis of TSDD.

If these two novel aspects (temperature and sleep dysregulation) occur in the presentation of a highly fearful and behaviorally dysregulated child with bipolar-like symptoms, these may lead to the consideration of an unconventional treatment paradigm. It utilizes 1) high dose lithium; 2) clonidine and other practical approaches to achieve cooling and relieve over heating; and 3) ascending doses of intranasal ketamine (as described by Papolos et al 2013; 2018). This may be of considerable clinical importance as a large group of children with this unique presentation respond very poorly to conventional treatments for bipolar disorder and remain highly impaired and dysfunction throughout their childhood and adolescence.

If these children instead are treated with: lithium (to achieve blood levels of 1.0 meq/L or higher); clonidine (0.1- 0.3mg IR and 0.1mg ER at noon and HS) and other practical ways to achieve cooling; followed by ascending intranasal doses of ketamine (starting at 20mg and increasing toward 80-260mg/day, repeated every 2-3 days), marked improvement can be achieved. This occurs in conjunction with ketamine’s positive effects on fear and aggressive behaviors in association with its ability to reduce core body temperature.

We highlight this potential alternative treatment approach as long term positive effects have been achieved with it in open case series (Papolos et al 2013; 2018 ). The efficacy of this treatment approach has not been validated in controlled clinical trials, but we believe wider recognition of the two subtypes of USBD– BPNOS and TSDD,– will lead to more systematic research on treatment. Actively looking for the unique features of TSDD and pursuing its unconventional treatment may lead to long term positive effects in a child previously viewed as having an intractable psychiatric illness.

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