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.

Fish Oil Monotherapy on Depression in Adolescents at High Risk for Bipolar I Disorder: Ambiguity Persists

omega-3 fatty acids
Fish oil supplements

Researcher Robert K. McNamara and colleagues reported in the Journal of Child and Adolescent Psychopharmacology in a 2020 article that 12 weeks of treatment with omega-3 fatty acids in the form of fish oil did not reduce depression symptoms in adolescents at risk for bipolar disorder when compared to placebo. The primary outcome measured was the results of the Childhood Depression Rating Scale-Revised (CDRS-R).

Fish oil did perform better than placebo on two parts of the rating scale: symptom severity and symptom improvement, especially in weeks 11 and 12 of the study. Omega-3 fatty acids increased creatine and choline in the anterior cingulate, and also increased polyunsaturated fatty acids in red blood cells. The treatment was safe and well-tolerated.

A total of 42 patients between the ages of 9 and 21 who had been diagnosed with depression and had at least one parent with bipolar I disorder received either placebo or 3 fish oil capsules per day. Each capsule contained 450?mg EPA, 40?mg docosapentaenoic acid (DPA), and 260?mg DHA for a total daily dose of 2130?mg EPA + DHA.

Editor’s Note: Ambiguity persists about whether omega-3 fatty acids can improve unipolar or bipolar depression, attention-deficit hyperactivity disorder (ADHD), or prevent the progression of schizophrenia symptoms to the full syndrome. Given the lack of side effects, and the documented effects on red blood cells and brain choline, clinical use of these compounds could be considered in some circumstances.

Predicting Onset of Bipolar Disorder in Children at High Risk: Part I

April 3, 2020 · Posted in Diagnosis, Risk Factors · Comment 

teenage boy sitting on floor with arms on kneesAt the 2019 meeting of the American Academy of Child and Adolescent Psychiatry, one symposium was devoted to new research on predicting onset of bipolar disorder in children who have a family history of the disorder. Below are some of the findings that were reported.

Symptom Progression

In offspring of parents with bipolar disorder, researcher Anne Cecilia Duffy found that symptoms in the children tended to progress in a typical sequence. Childhood sleep and anxiety disorders were first to appear, then depressive symptoms, then bipolar disorder.

Different Types of Illness May Respond Best to Different Medications

Duffy’s research also suggested links between illness features and a good response to specific medications. Those offspring who developed a psychotic spectrum disorder responded best to atypical antipsychotic medication. Those with classical episodic bipolar I disorder responded well to lithium, especially if there was a family history of lithium responsiveness. Those offspring with bipolar II (and anxiety and substance abuse) responded well to anticonvulsant medications.
If parents with bipolar disorder had experienced early onset of their illness, their children were more likely to receive a diagnosis of bipolar disorder.

The offspring of lithium-responsive parents tended to be gifted students, while those from lithium non-responders tended to be poorer students.

Comparing Risk Factors for Bipolar Disorder and Unipolar Depression

Researcher Martin Preisig and colleagues also showed that parental early onset of bipolar disorder (before age 21) was a risk factor for the offspring receiving a diagnosis of bipolar disorder. Parental oppositional defiant disorder (ODD) was also a risk factor for bipolar disorder in the offspring. The emergence of depression, conduct disorder, drug use, and sub-syndromal hypomanic symptoms also predicted the onset of mania during childhood.

Conversely, sexual abuse and witnessing violence were strong risk factors associated with a diagnosis of major (unipolar) depressive disorder. Being female and experiencing separation anxiety were also factors that predicted unipolar depression.

Predicting Conversion to Mania

Researcher Danella M. Hafeman reported that mood swings (referred to in the literature as “affective lability”), depression/anxiety, and having a parent who had an early onset of bipolar disorder were linked to later diagnoses of mania. Immediate risk factors that predicted an imminent onset of mania included affective lability, substance abuse, and the presence of sub-threshold manic symptoms.

Positive Effects of a Brief Session of Aerobic Exercise for Sedentary Children

March 31, 2020 · Posted in Current Treatments · Comment 

At a symposium at the 2019 meeting of the American Academy of Child and Adolescent Psychiatry, researcher Benjamin I. Goldstein reported that a single 20-minute session of aerobic exercise (achieving 70% of maximal heart rate) was associated with improvement in cognition and in abnormalities seen on brain imaging in young people. Goldstein urged clinicians to do motivational interviews with sedentary children in their care, emphasizing the positive cardiovascular and cognitive effects of exercise. He indicated this would be more effective than a focus only on weight loss, which is much more difficult to achieve.

Lithium Effective for Maintenance Treatment of Childhood-Onset Bipolar Disorder

March 10, 2020 · Posted in Current Treatments · Comment 

little girl with therapist

Evidence has been accumulating that lithium is effective in the treatment of young people with bipolar disorder. In a study by Robert Findling and colleagues published in the Journal of the American Academy of Child and Adolescent Psychiatry in 2018, participants aged 7–17 who responded well to lithium during a 24-week study were then randomized to receive either lithium continuation (17 participants) or placebo (14 participants) for 28 more weeks.

Those who continued lithium treatment were more likely to stay in the study. Participants who discontinued the study mostly reported that they did so due to re-emergence of their mood symptoms (mostly in the placebo group).

Lithium was well-tolerated and was not associated with any more weight gain than placebo. This study adds to the growing literature on the effectiveness and tolerability of lithium both acutely and in maintenance treatment in childhood bipolar disorder.

Lithium Better than Other Mood Stabilizers for Youth with Bipolar Disorder

March 6, 2020 · Posted in Current Treatments · Comment 

A new study by Danella M. Hafeman and colleagues finds that lithium is superior to other mood stabilizers in young people. The data in this case come from 340 youth aged 7–17 who participated in a study known as Course and Outcome of Bipolar Youth (COBY).

At each visit over an average of 10 years, participants reported medications taken, symptoms they had experienced, etc. during the preceding six-month period. During times that participants had taken lithium (compared to other mood stabilizers) they were older, on fewer antidepressants, and they were less likely to have an anxiety disorder.

Those participants who took lithium had half as many suicide attempts, fewer depressive symptoms, less psychosocial impairment, and less aggression than those who took other mood stabilizers.

The researchers concluded, “Findings are consistent with adult studies, showing that lithium is associated with decreased suicidality, less depression, and better psychosocial functioning. Given the paucity of evidence regarding lithium in children and adolescents, these findings have important clinical implications for the pharmacological management of youth with bipolar disorder.”

Editor’s Note: Lithium should especially be considered in those with a family history of mood disorders, and in particular in those with a family history of good response to lithium. Lithium is under-prescribed in both adults and children and should be given much higher consideration in light of the multiple benefits it provides in addition to mood stabilization. These include maintenance of memory, increases in longevity (perhaps based in its ability to increase the length of telomeres, the bits of protective material at the end of DNA strands that deteriorate with age and illness), and neuroprotection against loss of gray and white matter volume in the brain, which often occurs in mood disorders.

Prazosin Effective and Well-Tolerated for PTSD in Young People

March 2, 2020 · Posted in Potential Treatments · Comment 

young woman sleeping

In a poster session at the 2019 meeting of the American Academy of Child and Adolescent Psychiatry (AACAP), three posters highlighted the efficacy and tolerability of prazosin, a drug typically used to treat high blood pressure, for the treatment of childhood-onset post-traumatic stress disorder (PTSD).

Researchers Samira Khan and Taniya Pradhan of West Virginia University reviewed cases in which 39 patients aged 8–19 received 1–5 mg of prazosin at bedtime. The mean dose was 1.72 mg. Sleep (including nightmares) improved in 92.3% of the youths, and mood improved in 33.3%. Sleep improved more in patients who received lower doses (1–2 mg) than those who received higher doses. About 70% of the patients whose data were included in the case series were also receiving psychotherapy while being treated with prazosin.

In another poster, researcher Vladimir Ferrafiat and colleagues from University Hospital of Rouen in France reported on a prospective study of 18 participants under age 15 with severe PTSD who were unresponsive to other medications. The participants were given 1 mg of prazosin at bedtime, which was increased to 3 mg in 20% of the participants. The youth were assessed weekly over a one-month period. Improvement was seen in all domains, including sleep, nightmares and daytime intrusive symptoms. Prazosin was well tolerated, with only one patient experiencing low blood pressure, which did not necessitate withdrawal from the study.

In the final poster, researcher Fatima Motiwala and colleagues reviewed the literature on the treatment of PTSD in children. Motiwala indicated that among the options, prazosin was widely used in her hospital, at doses starting at 1 mg given at bedtime and increasing to a mean of 4 mg at bedtime with excellent results and tolerability.

Editor’s Note: Although these were not double-blind controlled studies, the findings are noteworthy in that they provide consistent data on the effectiveness and tolerability of prazosin in low doses in children with PTSD, essentially mirroring controlled data in adults, where higher doses are typically required.

Lurasidone Highly Effective in Open Continuation in Youth with Schizophrenia

February 27, 2020 · Posted in Potential Treatments · Comment 

teen girlResearcher Michael Tocco and colleagues reported at the 2019 meeting of the American Academy of Child and Adolescent Psychiatry (AACAP) that in adolescents between the ages of 13 and 17 with schizophrenia, taking lurasidone for two years following a double-blind, placebo-controlled study led to steady improvement. There was a remarkably high 91% response rate and a 66% remission rate. Out of all the participants, 51.3% were rated as recovered.

Cannabis May Produce More Brain Changes in Teens with Bipolar Disorder than in Healthy Teens

October 31, 2019 · Posted in Risk Factors · Comment 

smoking

At the 2019 meeting of the International Society for Bipolar Disorders, researcher Benjamin Goldstein of Sunnybrook Research Institute in Toronto reported that adolescents with bipolar disorder who smoked marijuana had greater deficits in certain brain areas than did adolescents who did not have bipolar disorder. The areas affected included the dorsal lateral and rostral middle frontal cortex, and middle cortex. Goldstein concluded, “Adolescents with [bipolar disorder] may be particularly sensitive to the neurostructural effects of cannabis.”

Marijuana in general causes adverse changes in brain structure and cognition and vulnerability to paranoia and psychosis. Heavy use in adolescence is associated with an increased incidence of the onset of bipolar disorder and schizophrenia. The Goldstein data suggest several possible causal mechanisms. Those with bipolar disorder may already have brain abnormalities that are exacerbated by marijuana use. Alternatively, marijuana and bipolar disorder together may impact brain structure more than either factor alone would.

Comorbid Psychiatric Disorders Impair Response to Psychosocial Treatment in Adolescents with Bipolar Disorder

October 21, 2019 · Posted in Comorbidities · Comment 

teenagers

At the 2019 meeting of the International Society for Bipolar Disorders, researcher Marc J. Weintraub and colleagues followed 145 adolescents with bipolar disorder over a period of two years. The adolescents with comorbid disorders (compared to those with bipolar disorder alone) fared more poorly in response to psychosocial treatment.

Weintraub and colleagues found that the adolescents who had anxiety disorders in addition to their bipolar disorder spent more weeks depressed, had more severe symptoms of (hypo)mania, and had more family conflict over the course of the study than those adolescents who had bipolar disorder alone.

Participants who had attention deficit hyperactivity disorder (ADHD) in addition to their bipolar disorder had more weeks with (hypo)manic symptoms, had more severe (hypo)manic symptoms, and greater family conflict than those with bipolar disorder alone.

Those participants with comorbid oppositional defiant disorder (ODD) or conflict disorder in addition to their bipolar disorder had more depressive symptoms and family conflict throughout the study.

Editor’s Note: How to better approach treatment in these diagnostically complex young people is an urgent unmet need, as most research excludes participants with more than one psychiatric disorder. Clinicians treating young people with bipolar disorder and comorbidities such as anxiety disorder, ADHD, and ODD must generally rely on inferences from children with these illnesses, using their own intuition about best treatment approaches rather than having evidence from systematic studies about how best to treat these children. It appears that both psychosocial and pharmacological treatments must be tailored to these more complicated presentations.

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