# Presentation: 758899

## Child & Adolescent Bipolar Foundation

- Lithium testing in children: a Public Health Necessity
- June 11, 2002
-  Martha Hellander, J.D., Executive Director

**Notes:**
Good afternoon.

(Read Financial Interest statement)

I’m sure you’re all aware that we’ve got a public health crisis in the making due to the recent huge advances in our ability to diagnose children with bipolar disorder, and lack of evidence of how best to treat them.  I’m here to urge you to place lithium high on the priority list for testing in children, and to urge the FDA to do at least two types of studies that have never been done in children and are unlikely to be done by pharmaceutical companies.  

## Slide 2

**Notes:**

The Child and Adolescent Bipolar Foundation is a parent-led, not-for-profit organization with over 5,000 families raising kids diagnosed with BP. Many of our families have adults with bipolar illness in several generations. Recent advances in the detection of the disorder in children offer the hope of curing and even preventing this disorder in its earliest stages . However, data on treatment options to guide clinicians lag behind the identification of these children.   We urge the FDA to take a leadership role in establishing safety and efficacy data on lithium, which is mostly off patent and has been safely and effectively used in adults for over fifty years. 

As executive director of CABF, I’ve consulted on the design of treatment studies for adolescent bipolar disorder and am the bioethics consultant to a multi-site NIMH-funded treatment study scheduled to start in September.  I’ve participated in strategic planning for mood disorders research at the NIMH, and served on a recent NIMH grant review committee for studies in child psychiatry.  I am a member of the Pediatric Psychopharmacology Initiative workgroup of the American Academy of Child and Adolescent Psychiatry. 

My husband is an academic economist. The disorder has caused suicides and ruined lives in many generations of both families, which are also filled with accomplished and creative individuals. One of our children was diagnosed six years ago. Her suffering, early diagnosis and remarkable recovery, well before she reached adolescence, set me on the path to help others. 

## CABF Parents

- Age 30s-50s
- 98% female
- 71% married
- 26% hold graduate degrees
- 42% employed full-time

**Notes:**
Our members are by and large educated and resourceful with private insurance and access to medical care.  Our children are in good physical health, are not living in poverty, and were born or adopted into loving families.  
Over half our members have attended or graduated from college.  26% hold graduate degrees.  Most are married and 50% of their spouses hold executive, managerial or professional jobs.  Only 42% of these highly educated moms are able to work full time due to the needs of the children. 

## CABF Children

- Age 1-8  	24%
- Age 9-12  	36%
- Age 12-l8	37%
- Age 19+	 4%
- Hospitalized 1-9+ times 54%
- Never hospitalized 46%

**Notes:**
This is the age range of our kids. 60% are below age 12. 

Over half have been hospitalized. These hospitalization rates are tragic and an indication of the lack of knowledge in the community as to how to treat them.  To admit a child to an inpatient psych unit they must be in serious danger of suicide or harming someone

I won’t have time to go into diagnostic issues but in the handouts are a couple of general articles for practitioners,  one by child psychiatrist Mani Pavuluri at Univ of Illinois at Chicago,  and another one by a pediatrician, Adelaide Robb, at Children’s National Medical Center in Washington.    The main diagnostic issue in prepubertal kids is telling it apart from ADHD, as there is some overlap of symptoms.  

I’ve also included in the handouts an article by Dr. Barbara Geller that just appeared in Am J Psychiatry,  reporting her 2 year follow up on an NIMH-funded longitudinal study of about 90 prepubertal kids with mania.  Dr. Geller has served as a consultant or member of this committee, and is also the Chair of our Professional Advisory Committee.  

These kids are really sick and impaired in many crucial areas of functioning.  To learn more about the suffering of our children and families, I invite you to visit our Web site and read the message boards, filled with stories of missed opportunities for treatment, and also of  hundreds of childrenwho have have gained stability and are now able to attend school and have friends and enjoy their childhood. .

Dr. Geller’s paper in the Am J Child & Adolesc Psychopharmacology...

[if time or someone asks]
In a nutshell the overlap is 

(BP vs. ADHD--Geller's 8 signs (n=93 BP, 81 ADHD, 94 controls)

Mania Specific:
Elated Mood (89% v. 14%)
Grandiosity (86% v. 4.9%)
Flight of Ideas/Racing Thoughts (71% v 10%)
Hypersexuality (43% v. 6%)
Decreased Need for Sleep (40% v. 6%)

Of interest:
Suicidality (24.7% v. 0%)
Psychosis 60% v. 0%

ref: Geller, et al, DSM-IV Mania Symptoms in a Prepubertal and Early Adolescent Bipolar Disorder Phenotype Compared to Attention-Deficit Hyperactive and Normal Controls (J Child Adol Psychopharm, V. 12, No. 1, 2002)

## Addiction

- 39-60% risk of developing Substance Use Disorder
- Wilens, et al.  “Risk for Substance Use     Disorders in Youths With Child and Adolescent-Onset Bipolar Disorder.”  JAACAP***  ***38(6):680-685, 1999

**Notes:**
I’m going to focus on are 3 grave public health concerns that intersect with childhood bipolar disorder, and which are helped by lithium.  

These kids are biologically vulnerable to becoming addicts. 

Wilens T, Biederman J, et al.  “Risk for Substance Use Disorders in Youths With Child and Adolescent-Onset Bipolar Disorder.”  Journal of the American Academy of Child & Adolescent Psychiatry  38(6):680-685, 1999.

## Addiction (cont’d)

- Lithium reduces adolescent substance use and stabilizes mood in RCT
- Geller B et al (1998). Double-blind and placebo controlled study of lithium for adolescent bipolar disorders with secondary substance dependency.  JAACAP  37:171-178.

**Notes:**
In one 10 week, short term treatment trial with 25 teenagers, Dr. Barbara Geller found that lithium significantly reduces substance use and stabilizes mood in kids with dual diagnosis.  The implications of this finding are staggering, yet this finding has not been picked up by the substance abuse treatment community.

## Incarceration

- In 50 kids consecutively screened on intake in Texas detention center, 20% had acute mania (another 20% depression)
- Pliszka, et al, “Affective Disorder in Juvenile Offenders: A Preliminary Study,” Am J Psychiatry 157:1, Jan. 2000

**Notes:**
When unstable, like adults with mania, bipolar kids are impulsive and exercise poor judgment.  In a study in Texas looking at 50 kids subsequently brought into a juvenile detention center, Steven Pliszka found that 20% met full DSM-IV criteria for acute mania and another 20% had major depressive disorders.  If the illness is detected early enough and properly treated, this outcome could be avoided.  So here’s another public health crisis that involves kids with mood disorders. 

## Suicidality in BP Children

- 25% serious thoughts, plan or intent in prepubertal kids with mania
- Geller et al: Two-year prospective follow-up of children with a prepubertal and early adolescent bipolar disorder phenotype.
- 	Am J Psychiatry 159:927-933, 2002

**Notes:**

Dr. Geller found in her ongoing NIMH funded study of about 90 prepubertal kids with mania, a full 25% of them were suicidal on arrival at her outpatient clinic, with serious thoughts, a plan or intent. Other researchers find similarly high rates.  
Children often talk of wanting to “make themselves dead” starting as young as 3 and 4, and make real attempts such as trying to jump out of moving cars on the freeway.   

So here is a third, major public health crisis, that involves early onset mood disorders.  Suicide is the third leading cause of death in the 15- to 24-year-old age range, according to the Surgeon General’s office.

## Suicidality and Death In BP Adults 

- 18 % mortality
- Lithium reduces suicide regardless of whether it stabilizes mood
- Tondo and Baldessarini, “Reduced Suicide Risk During Lithium Maintenance Treatment,” J Clin Psychiatry 2000:61 (suppl)

**Notes:**
The lifetime mortality rate for bipolar disorder in adults is 18%,  which is higher than that for childhood leukemia

Lithium is known to reduce suicide sixfold to eightfold, even when ineffective in treating mood. (J Clin Psychiatry. 2000;61[suppl 9]:97-104).  No other drugs approved for mania have been shown to have an antisuicidal effect. 

## Timeline

- 1949 John Cade treats mania w/lithium
- 1952 18 cases of pediatric mania reported
- 1970 Lithium approved by FDA for mania
- 1975 NIMH recognizes pediatric depression
- 1995 NIMH recognizes pediatric mania
- 2002 No standard treatment for pediatric
-              mania

**Notes:**
Lithium has been on the market for over 50 years, and children with mania have been described in the medical literature for nearly that long, yet we still have no standard treatment for pediatric mania. 
There have been a number of small studies, and I’ve included an example in your handouts, a study by Elizabeth Weller and colleagues, published in l988.  Lithium was approved in l970 for mania and maintenance treatment down to age 12, but no pivotal studies were ever done and no post-marketing surveillance studies, or testing in juvenile animal models, was ever done. 

## Medications used to treat pediatric bipolar disorder symptoms

- ~ 40+ medications used clinically
- Indicated for mania >12  =   1 (Lithium)
- Indicated for mania <12  =   0
- Indicated for BP depression = 0

**Notes:**
In a recent survey, our members reported over 40 different medications used to treat the symptoms of bipolar disorder in their children, none of which are indicated for kids under 12 and only l (lithum) for adolescent mania.
\
(if time mention:))
Valproic acid has indication for acute mania in adults, no maintenance indication.  
Olanzapine recently got indication for acute mania in adults.

## CABF Survey 2002  n=854Medication Use:  Lifetime

- _No. of Meds _
- 1-3		15%
- 4-5		20%
- 6-10		34%
- 11-15		19%
- 16-20		 5%
- > 20		 6%

**Notes:**
This slide shows how many medications our children have been prescribed to treat their psychiatric symptoms in their lifetime. Of 854 kids, trials of five, ten, and even fifteen or more different medications are common, partly due to earlier misdiagnosis, but largely because even when they get the correct diagnosis, clinicians have no evidence-based data to guide their treatment. We’re getting frequent reports of kids being started on gabapentin, for example, as a first line mood stabilizer, despite the fact that placebo studies in adults show it not effective for treatment of mania and it has troubling side effects in children. 

## Medication Use:  Current

-       _No. of Meds_
- 1		13%
- 2		30%
- 3		28%
- 4		15%
- 5		 7%
- 6-10       7%

**Notes:**
This slide shows how many medications our children are currently taking to treat their symptoms and side effects.  57% are taking 3 or more medications.  Parents are faced with the terrible knowledge that while their child’s illness is life-threatening, and medications used in adults may be the only treatment available, we really don’t know what the long term side effects might be and which meds have a better long-term safety profile in which kids. 

The current issue of the American Journal of Psychiatry has three articles on childhood bipolar disorder as well as the editorial by Fred Volkmar, M.D.  who writes:  “the lack of treatment efficacy data on these conditions is most unfortunate.” 

## Medication Use: Class 

- Anticonvulsants 		79%
- Atypical anti-psychotics 	68%
- AD/SSRIs			33%
- Lithium                           30%
- Stimulants			26%
- Typical antipsychotics 	11%
- Anxiety/Sleep                   9%

**Notes:**
Of the anticonvulsants, most are still on patent except Tegretol. 
The same is true of the atypical antipsychotics and the SSRIS.
CABF strongly supports the further testing of all of these medications in children, but I am not focusing on those needs today since the topic of this hearing is off-patent medications. 

As you can see Lithium is being used in 30% of our kids.  I heard yesterday that approximately 93,000 children in America between 0-17 are taking lithium.  

## Summary

- Lithium is *widely used* in children and adolescents with bipolar disorder
- Lithium is *off patent* and unlikely to be tested by pharmaceutical industry
- Lithium *lacks data* for pediatric use
- New studies would produce *benefits* for children with pediatric bipolar disorder

**Notes:**
In summary, we propose that lithium meets all the requirements of the Best Pharmaceuticals for Children Act and that the urgent public health crises of teen substance abuse, incarceration and suicide, all of which include many kids we now know have early onset bipolar disorder,  require that lithium testing in children be given the highest priority by the FDA.  In particular, post marketing surveillance studies, and juvenile animal studies, should be requested and, if proposals are not forthcoming, should be funded by the money appropriated by Congress. 

## Slide 16

**Notes:**
Let’s take one more look at our Web site.  The little girl with the blonde hair and the yellow hat was suicidal at age 4 but has been well since age l0.  She’s 15 and in high school now and wants to be a therapist when she grows up.  The little girl at the top left is now 13, plays clarinet, and has her black belt in karate at age 13.  Both of these kids stabilized when lithium was added to their treatment (which includes other medications currently under patent). 

The boy with the turtle is Ben Carlson of Duluth, Minnesota. He had very early onset and like most of our kids was misdiagnosed with ADHD and conduct disorder but finally was diagnosed with bipolar disorder and stabilized on lithium at around age 12.  He felt really well and asked if he could stay on the lithium indefinitely. That was about l5 years ago and there was no maintenance data back then to tell the doctor how long kids should stay on lithium (there still isn’t), so the doctor took him off lithium to see if he still needed it.  He relapsed and killed himself before they could get his lithium back to a therapeutic level.  

Please urge the FDA to give lithium its highest priority for testing in children, and let me know if there is any way the Child & Adolescent Bipolar Foundation can help in this effort.  

Thank you.