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.

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.

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.

Familial Aggregation of Major Depression Predicts Risk of Major Depression

Gronemann et al reported in JAMA Psychiatry: “In this cohort study of 2,903,430 individuals, maternal, paternal, full sibling, or half-sibling with MD were associated with 2-fold higher risks of MD in men and women….(E)xposure to family MD during childhood and adolescence was associated with increased risk. The risk increased with number of affected family members; (however) individuals exposed when 30 years or older had markedly lower risk.

Editors Note: Even depression in grandparents adds further to the risk of depression.  When there is high familial loading for depression and other psychiatric illnesses, one should be alert to the possible onset of depression in young individuals and treat them early and well accordingly.

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.

Potential of Environmental Enrichment to Prevent Transgenerational Effects of Paternal Trauma

Gapp, K. et al. wrote about the “Potential of Environmental Enrichment to Prevent Transgenerational Effects of Paternal Trauma” in Neuropsychopharmacol 41, 2749–2758 (2016).

They “used a mouse model of unpredictable maternal separation combined with unpredictable maternal stress (MSUS) to examine the consequences of traumatic stress on coping behaviors in adulthood and across generations, and the potential contribution of (glucocorticoid receptors) GR. We show that MSUS affects avoidance behaviors and learning in aversive environments in exposed fathers and their male offspring. This is associated with an increase in GR expression in the hippocampus, and with decreased DNA methylation of GR promoter in the hippocampus and in germ cells. We show that transmission of the effects of paternal trauma can be prevented by paternal (environmental enrichment) EE, suggesting a reversibility of these effects.”

Editors Note: Dad’s early environmental adversity alter his response to traumatic stress as an adult, and this can be passed to the next generation via epigenetic changes in DNA methylation, histone and microRNA chemical changes persisting in sperm.  If the dad with early life adversity is housed in an enriched environment, he does not have the altered response to stress or the changes in GR, and his offspring do not have the transgenerational alterations in stress responsively.  This could probably happen in people if we could only figure out to super good environmental enrichment in those having early life adversity.  Having lots of stress as a neonate and then being adopted out to wonderful foster family could be the basis for a naturalistic study of this sort of result.

Lurasidone Effective Long-Term in Pediatric Bipolar Depression

September 30, 2020 · Posted in Potential Treatments · Comment 

At the 2020 meeting of the American Society of Clinical Psychopharmacology, researcher Manpreet Singh presented data showing that children aged 10–17 with bipolar depression had an excellent long-term response to the antipsychotic medication lurasidone (trade name Latuda).

Lurasidone has been approved by the US Food and Drug Administration as a monotherapy treatment of bipolar depression in children and adolescents since 2018. Following a six-week double-blind study comparing lurasidone with placebo in 305 children and adolescents, Singh and colleagues carried out an open-label extension study in which all of the young participants, including those in the placebo group, had the option of taking lurasidone for up to two more years.

Of those, 195 children completed one year of treatment, and 93 completed two years of treatment. Rates of response were 51.0% after the six-week preliminary study; 88.4% at one year; and 91.1% at two years. Rates of remission were 24.3% after the six-week study; 61.3% at one year, and 75.6% at two years, while rates of recovery were 17.7% after the preliminary study; 53.8% at one year; and 73.8% at two years.

This improvement in depression had a strong correlation with improvement in functioning, as measured by the Children’s Global Assessment score (CGAS). The results show progressive increases in rates of response, remission, and recovery with duration of treatment that are associated with improvement in functioning.

Early Precursors of Mood Disorders in Young Children of Parents with Bipolar or Unipolar Disorder

July 24, 2020 · Posted in Course of Illness, Risk Factors · Comment 

At the 2020 meeting of the International Society for Bipolar Disorders, researcher Caroline Vandeleur presented findings from a 13-year study of children in Switzerland who have a parent with bipolar disorder or major depressive disorder. In contrast to findings from the US presented by Danella Hafeman, Vandeleur and colleagues found no evidence of psychopathology in 4 year-olds. They did find that in 7-year-olds, children of a parent with major depressive disorder were four times more likely to have a separation anxiety disorder. In an overall sample of 449 children with a mean age of 10 who were followed up for 13 years, major depression tended to be preceded by anxiety disorders. Participants who went on to be diagnosed with bipolar disorder had earlier symptoms of depression, subthreshold hypomania, conduct disorders, and drug abuse. These were especially common in those who had a parent with bipolar disorder.

Editor’s Note: These data indirectly confirm other observations in which children at high risk for mood disorders in the US showed earlier signs of psychopathology than those in other countries including the Netherlands and Canada.

Next Page »