Abilify

[Guest guest]

No, Karac's aggressive behavior increased and we had to put him in the

hospital. Pat K

[Guest guest]

And his mother still thinks it was the Abilify? Is he still in the

hospital? That is something I am used to hearing on the bipolar list but not

the autism list. So far none of our boys have had to go to the hospital but

's doctor wanted to put her in for her depression but she would not

go. If it was because of Karac's agression I hope that they are able to

find something that will work with him. I have learned with bipolar that

finding the right meds can be a long, hard process or you can be lucky and

find the right one at the beginning. Then after awhile that wonderful

combination will quit working and the process starts over again. So much

for chemical imbalances.

You know, I tried taking Evan off the Risperdal a couple of times and the

last time he got very agressive so it was made clear to me that he needs

something. These meds also need to be taken off slowly just as they are

built up slowly. We are weaning him slowly off the Risperdal as he uses

more of the Abilify.

Betty Ann-61 yo, possibly Bipolar but undx'd, Effexor, Buspar

grandma and guardian to

- 11 yo-- Bipolar/ADHD on Depakote, Adderall, Singular

Evan - 9 yo nonverbal autism on 2 mg Risperdal,

10 mg Abilify stated 3/11/03, raised 5/05/03

- 7 yo- Bipolar/ADHD/PTSD on Tegretol, Adderall, Clonidine .1 mg,

mother to -32 yo, their mom - Bipolar/ADHD on Topamax, Tegretol,

Singular

wife to Bob - 71 yo, Effexor and too more many meds to remember

Re: Abilify

> No, Karac's aggressive behavior increased and we had to put him in the

> hospital. Pat K

[Guest guest]

Karac is still in the hospital. They are trying him on Risperdal which I

have dreaded. He doesn't even seem like himself. It breaks my heart. They

x-rayed Karac again tonight to see if he still had blockage in his bowels; we

don't know the results. They are giving him a laxative to try to clear it out.

I

am glad the Abilify is working for you; I felt like it was working for Karac,

but you see, I am not the mother. Betty, I appreciate your concern; you are

so kind to respond. Pat K

[Guest guest]

Pat, I wonder if perhaps Karac is also Bipolar? There are several on two of

my bipolar lists where the child is bipolar and is on the autism spectrum.

Sometimes I wonder just how much we can handle with all the increase in the

problems for our kids. is manic again and seems to have no conscience

or even the ability to think of the consequences when he wants something. It

breaks my heart and we are sincerely worried that it will end up in prison

someday if he does not get it under control. We have taken his Play Stations

away from him and both because is back to stealing games again.

He stole one from his friend's sister and has lost another friend. He has so

few. is right in insisted that they be packed up and they will stay

locked up until his birthday in August. Then they must only play them for a

certain amount of time. If that does not work out then we will have to get

rid of them. And I just spent about $400 buying them the PS2 and several

games. We left them their gameboys but they have misplaced most of their

games and I refuse to buy any more. , as a recovering drug addict,

feels that these games are as additive to as crank was to her. if

that proves to be so, then we will have to just get rid of them.

I do hope that they find something to help Karac soon. I hate to see them

using the Risperdal since it has the eating side effect and for some, loss

of bladder control, but one must do what is necesssary for the child. They

might even have to try a combination of meds. It is too bad that they

cannot try the Abilify in the hospital to see if that would help him while

he is there. It does not take long to build up in the body and the body gets

rid of it pretty fast also so that is not the problem some meds have.

I never, in my wildest dreams, expected that any of these boys or myself for

that matter would end up on meds like this, but then I also did not realize

that it was Bipolar as well as ADHD that runs through our family. I really

think the autism comes from my husband's side of the family. His mother

could be Asperger's and he has a son that certainly fits the criteria.

Betty Ann-61 yo, possibly Bipolar but undx'd, Effexor, Buspar

grandma and guardian to

- 11 yo-- Bipolar/ADHD on Depakote, Adderall, Singular

Evan - 9 yo nonverbal autism on 2 mg Risperdal,

10 mg Abilify stated 3/11/03, raised 5/05/03

- 7 yo- Bipolar/ADHD/PTSD on Tegretol, Adderall, Clonidine .1 mg,

mother to -32 yo, their mom - Bipolar/ADHD on Topamax, Tegretol,

Singular

wife to Bob - 71 yo, Effexor and too more many meds to remember

[Guest guest]

Betty, has the Risperdal caused Evan to lose bladder control? How long has

he been on the Risperdal? There is Bipolar on my daughter in law's side of the

family. She has an aunt who committed suicide with it; a grandmother who has

it, and a first cousin who is schizophrenic. Her brother was speech delayed

until age 7. So, who knows? Pat K

[Guest guest]

Pat, Evan's telemedicine doctor denies that Evan having any problems with

bladder control can come from his use of Risperdal but after a year or so of

arguing with him over it I did a web search of Risperdal and side effects of

bladder control and it is a rare side effect. I know that plenty of parents

on the bipolar lists say that it happened to their children and one of

Evan's pediatricans told the company that delivers his pull-ups that he

probably would be needed the pull-ups as long as he was on the Risperdal.

Evan had complete bladder control both day and night until he started the

Risperdal. Evan has been on the Risperdal for almost two years now but we

are weaning him off it. Evan has been doing some screaming that is really

nerve racking but it is around meal times and at bedtimes so I think that it

is because he is hungry or tired. Sometimes he will take me to the

refrigerator when he wants something but other times he just screams.

Soooo much fun. He did have a picture of food he was suppose to bring me,

when he wanted anything to eat or drink, on a magnetic on the refrigerator

but he rip it to pieces. Sort of a clue that he did not like using it??

Bipolar and schizophrenia, now that is our inheritance. I have one sister

who has schizophrenia as did one of our uncles. With all that I have

learned about bipolar I believe most of my mother's brothers and sisters, as

well as my mom also were bipolar to some degree. I do not know how Karac's

mom would feel about it but she might want to bring that up to the doctors.

If you can get a book of The Bipolar Child from the library it is very

informative. There are several websites about childhood bipolar including

www.bipolarchild.com by the authors of The Bipolar Child and www.bpkids.org

It is bad enough to have one of these disorders but unfortunately it is more

common to have multiple disorders at the same time. neurobiological

disorders cover a lot of territory.

Betty Ann-61 yo, possibly Bipolar but undx'd, Effexor, Buspar

grandma and guardian to

- 11 yo-- Bipolar/ADHD on Depakote, Adderall, Singular

Evan - 9 yo nonverbal autism on 2 mg Risperdal,

10 mg Abilify stated 3/11/03, raised 5/05/03

- 7 yo- Bipolar/ADHD/PTSD on Tegretol, Adderall, Clonidine .1 mg,

mother to -32 yo, their mom - Bipolar/ADHD on Topamax, Tegretol,

Singular

wife to Bob - 71 yo, Effexor and too more many meds to remember

----- Original Message -----

From: <pkuenstler@...>

> Betty, has the Risperdal caused Evan to lose bladder control? How long

has

> he been on the Risperdal? There is Bipolar on my daughter in law's side

of the

> family. She has an aunt who committed suicide with it; a grandmother who

has

> it, and a first cousin who is schizophrenic. Her brother was speech

delayed

> until age 7. So, who knows? Pat K

[Guest guest]

How soon after taking the Resperdal did Evan lose bladder control? Pat K

[Guest guest]

I am sorry Pat but I do not remember. It was not long after though but not

everyone has this problem. At least it is suppose to be such a rare side

effect that it is not listed under the side effects that the company puts

out on the papers that go to the doctors.

Betty

----- Original Message -----

From: <pkuenstler@...>

> How soon after taking the Resperdal did Evan lose bladder control? Pat K

[Guest guest]

Betty, you are so kind to reply. I just admire you. You seem so very strong.

How do you manage?

Yes, I wouldn't be surprised if Karac wasn't bipolar in addition to the

autism. I think his mother is even though she hasn't been diagnosed. This has

put

her under a lot of stress.

Karac seems to be adjusting to the hospital; they are structured and he likes

routine. There are about four other patients; a young girl with an eating

disorder; a young man who had a drug problem, and two other young boys that I

don't know what they are there for. They all seem to like Karac. Sometimes

they play a little ball out in the hall together. They eat together in a little

kitchen. Tonight I left the hospital as they were beginning to eat. Karac

looked so normal sitting there with them.

Karac finally had a BM and I could tell he felt a lot better. He is calmer,

but he only talks in whispers, and I wonder if that is from the medication and

if he will ever get his voice back.

I hope Evan continues to do well on the Abilify; I wish we had continued with

it. Pat K

[Guest guest]

Kathie, Abilify made very sleepy when he first started on it. I think

he got sick a couple of times but I am not positive on that. He is now back

to his normal self with his sleeping. Evan had no side effects with it.

BETTY ANN-61 yo, possibly Bipolar but undx'd,

Effexor, Buspar, Lorazepam as needed, Serenity

grandma and guardian to

ANDREW - 11 yo-- Bipolar/ADHD, Homeschooled

Depakote 250 mg. 2 x daily, Adderall 30 mg daily, Abilify 7.5 mg 1 x daily

EVAN - 9 yo-- nonverbal autism

Risperdal 2.5 cc daily, Abilify 10 mg 1x daily

DAVID 7 yo Bipolar/ADHD/PTSD

Adderall 20 mg daily, .25 mg Risperdal 2 x daily

and mother to ANDREA -32 yo, their mom -

Bipolar/ADHD, Topamax, Tegretol, Singular, Serenity

wife to BOB - 72 yo, a very patient and tired grandpa

----- Original Message -----

From: <krdorran@...>

> Hi all,

> My friend's son was just dx'ed as ADHD, with some Bi-polar symptoms and

was

> given Abilify by a child Psychiartrist.

> He had one dose which was one quarter of a pill yesterday afternoon. Today

he

> fell into a deep sleep 4 hrs and woke up and vomited several times.

> Are these typical occurances with Abilify?

> He is only 4.

> Thank you ,Kathie

[Guest guest]

Karac didn't have that reaction to Abilify; if he had, I would have stopped

it immediately! Pat K

[Guest guest]

Heidi, I just went to the website and typed in Abilify to get information

about it when the doctor prescribed it for Karac. It was prescribed for Karac

for aggression. My understanding is that it is a relatively new drug in the

category of Risperdal, and Zydis without some of their side effects. Pat K

[Guest guest]

Hi, folks!

Can you tell me more about Abilify? What conditions/symptoms is it prescribed

for? Any info. would be greatly appreciated.

Thanks!

Heidi

Re: Abilify

Kathie, Abilify made very sleepy when he first started on it. I think

he got sick a couple of times but I am not positive on that. He is now back

to his normal self with his sleeping. Evan had no side effects with it.

BETTY ANN-61 yo, possibly Bipolar but undx'd,

Effexor, Buspar, Lorazepam as needed, Serenity

grandma and guardian to

ANDREW - 11 yo-- Bipolar/ADHD, Homeschooled

Depakote 250 mg. 2 x daily, Adderall 30 mg daily, Abilify 7.5 mg 1 x daily

EVAN - 9 yo-- nonverbal autism

Risperdal 2.5 cc daily, Abilify 10 mg 1x daily

DAVID 7 yo Bipolar/ADHD/PTSD

Adderall 20 mg daily, .25 mg Risperdal 2 x daily

and mother to ANDREA -32 yo, their mom -

Bipolar/ADHD, Topamax, Tegretol, Singular, Serenity

wife to BOB - 72 yo, a very patient and tired grandpa

----- Original Message -----

From: <krdorran@...>

> Hi all,

> My friend's son was just dx'ed as ADHD, with some Bi-polar symptoms and

was

> given Abilify by a child Psychiartrist.

> He had one dose which was one quarter of a pill yesterday afternoon. Today

he

> fell into a deep sleep 4 hrs and woke up and vomited several times.

> Are these typical occurances with Abilify?

> He is only 4.

> Thank you ,Kathie

[Guest guest]

This is wonderful information. Thanks for sending it. Pat K

[Guest guest]

UNIQUE AGENT OFFERS NOVEL ADVANCES IN ANTIPSYCHOTIC THERAPY

(from a symposium held during the American Psychiatric Association 54th

Institute on Psychiatric Services (IPS) October 11, 2002/Chicago, Illinois)

The Challenge in treating patients with Schizophrenia and schizoaffective

disorder is to alleviate both the positive and negative symptoms of

schizophrenia without causing serious and often devastating side effects.

First- generation antipsychotics like haloperidol and thorazine were hailed

as an advance when they were introduced, but these drugs were mainly

effective in reducing the positive symptoms of psychosis and had less effect

on negative symptoms, which are considered to be the most debilitating over

the long-term. These agents were also associated with serious irreversible

neurological symptoms called extrapyramidal symptoms (EPS).

Second-generation or atypical ant psychotics (ie, clopping, risperidone

[Risperdal: Janssen Pharmaceuticals, Inc,] olanzapine [Zyprexa; Eli Lilly

and Company], quatrain [seroquel; AstraZeneca], ziprasidone [Geodon; Pfizer

Inc] are considered a major improvement in treating psychosis, due to their

ability to reduce both positive and negative symptoms, as well as their low

potential for EPS. Over the past several years, however, it has become

evident that some atypical ant psychotic agents can have potentially serious

side effects of their own, including agranulocytosis, seizures,

prolactinemia, weight gain and glycemic dysregulation.

" Psychiatrists prefer atypical agents because they have a more favorable

side-effect profile an typical antipsychotics. We have resolved the EPS

issue with the atypical agents, but new side effects have emerged, " stated

Jean-Pierre Lindenmayer, MD. Who added that Aripiprazole presents a

particularly promising safety and tolerability profile, which appears to

have a low liability for EPS and, at the same time, no weight gain, glucose

dysregulation, dyslipidemia, or prolactin increase, as seen in clinical

studies. " This drug may offer us the Best of both worlds, he said.

Unique Mechanism of Action

The unique mechanism of action aripiprazole is its effect as a partial

agonist on the dopamine (D2) receptor, not as an antagonist, explained

L. Roth, MD, PhD. Aripiprazole is also a partial agonist at 5-HT 1A

receptors and an antagonist at a 5-HT 2A receptors. Its partial agonist

properties at the dopaminergic and serontoninergic receptors appear to

stabilize the dopamine-serotonin system.

One hypothesis is that the partial agonism at the D2 receptors means that

the drug acts as an antagonist under conditions of high dopaminergic

activity leading to relief of psychosis, and it acts as an agonist when too

little dopamine is present, leading to a low potential for EPS. Aripiprazole

also acts as an antagonist at the 5-HT 2A receptors, likely reducing the

risks of EPS and improving negative symptoms of schizophrenia. The potent

partial agonism at the 5-HT 1A receptors appears to lead to mood

stabilization and cognitive improvement, Dr. Roth explained

" This is a new concept--partial agonism and antagonism at th3 dopamine

receptor. It has never been brought to fruition in a drug until now. " Dr.

Lindenmayer emphasized.

Evidence for Efficacy

Schizophrenia represents a heterogeneous group of disorders with different

symptoms complexes that affect social, occupational, and interpersonal

domains. Positive symptoms, such as delusions, hallucinations, and

disorganized speech, have been historically most amenable to treatment.

Atypical antipsychotic agents appear to reduce negative symptoms, including

affective flattening, alogia, avolition and anhedonia, and may also improve

cognition and mood, explained Philip G. Janicak, MD.

Dr. Janicak believes that dosing strategies are of the utmost importance in

alleviating symptoms of schizophrenia and that for many years, patients have

been receiving doses of antipsychotics that are much too high. " We have

basically been intoxicating our patients over the past 40 years, " He told

listeners.

The goal of treatment is achieve optimal outcome with the lowest effective

dose, he continued. It may take weeks, months, and even years for a

substantial response to occur, depending on the drug. For example, clozapine

may take up to a year to reach maximal efficacy, while risperidone takes

weeks to months, Dr. Janicak explained.

Dr. Janicak reviewed studies of atypical antipsychotic agents, including

risperidone, olanzapine, quatrain, and ziprasidone, showing that th3se drugs

are effective in treating both positive and negative symptoms to a similar

extent. " But there is some evidence that we have traded servomotor effects,

such as EPS, for other effects with the second-generation atypical drugs, "

stated Dr. Janicak. Depending on which drug is used, these effects include

agranulocytosis, seizures, weight gain, diabetes, altered lipid profiles,

cardiac effects, orchestrates, sedation and sialorrhea.

Five short-term placebo-controlled trials, ranging from 4 to 6 weeks, were

cited as being suggestive of the efficacy of aripiprazole in hospitalized

patients with schizophrenia or schizoaffective disorder during acute

relapse. Three trials included a haloperidol group and one trial included a

risperidone group. These trials were designed to compare aripiprazole with

placebo and active control with placebo, Dr. Janicak reminded listeners.

Active drugs were not compared directly.

In one study, daily doses of aripiprazole 15 mg and 30 mg and haloperidol 10

mg were more effective than placebo (P<.05) on the PANSS Total Score and the

PANSS Negative Score (Kane et al. J clin Psychiatry, 2002, 63(9):763-71.)

Aripiprazole 20 mg and 30 mg also compared favorable with risperidone 6 mg

in the magnitude of effect on PANSS Total Score and PANSS Negative Score

(P<.05). Additional studies demonstrated efficacy at 15 mg. 20 mg. And 30

mg. It is recommended that physicians start patients at 15 mg. per day.

Dr. Janicak explained that clinical trials do not actually give a picture of

the 'real world,' because many patients with schizophrenia have

treatment-refractory psychosis. Drugs such as clozapine, risperidone, and

olanzapine have been studied in treatment-refractory psychosis, and for now,

clozapine appears to have a modest advantage over other atypicals in this

setting.

The most frequently used approach for treatment-resistant psychosis is

augmentation with anticonvulsants/mood stabilizers, and combinations of

antipsychotics. Antidepressants and electro convulsive therapy (ETC) in

combination with atypical antipsychotics may also be helpful. Some evidence

supports the strategy of augmentation with anticonvulsants/mood stabilizers,

but there are little date to support other augmentation strategies, Dr.

Janicak noted.

Need for Long-Term Therapy

Schizophrenia is a chronic illness that requires long-term treatment. Some

evidence suggest that early intervention improves long-term prognosis and

that antipsychotics reduce the risk of relapse. Also, patients who do

relapse on antipsychotic medications have less severe episodes than those

who discontinue their drugs.

Thus, adherence is an important issue, Dr. Janicak emphasized. 'Although

atypical antipsychotics offer the best hope of reducing relapse to date,

currently approved agents have significant limitations in broad efficacy,

safety, and tolerability.' he said.

Studies suggest that aripiprazole may improve the likelihood of adherence,

since this drug appears to have beneficial effects on positive and negative

symptoms as well as on cognition, and has a more favorable side effect

profile than currently available antipsychotic agents, according to Dr.

Janicak.

In particular, one study (Cornblatt B, et al. Int J Neurospychopharmacol.

2002:(suppl 1):S185) showed that aripiprazole had a similar effect on

cognitive and executive function compared with olanzapine, and the drug

significantly achieved significantly better results on verbal learning at

week 8 and week 26 (P<.05).

Side-Effect Profile

Studies to date suggest that the side-effect profile of aripiprazole

compares favorable with that of other atypicals, according to data presented

by Dr. Lindenmayer.

" Aripiprazole has an exceedingly low incidence of EPS; causes minimal

somnolence but some insomnia; and is associated with transient nausea,

minimal weight change, no significant elevations in total cholesterol,

triglycerides or glucose, no significant Qtc prolongation, minimal

orthostatic hypotension, or tachycardia, " Dr. Janicak told the audience.

All typical antipsychotic agents elevate prolactin, and this has potential

consequences that are problematic for patients. These include sexual

dysfunction, amenorrhea, glactorrhea, impotence, osteoporosis, and

gynecomastia. These side effects can lead to non-compliance. " The fact that

aripiprazole does not elevate prolactin levels will be a major

differentiating feature of this drug, " Dr. Lindenmayer predicted. Weight

gain occurs with haloperidol, as well as with atypical agents, he continued.

Weight gain is undesirable from a health and aesthetic point of view, and

pronounced weight gain can be associated with significant increases in

dyslipidemia and diabetes. Treatment with aripiprazole appears to be free of

weight gain according to a 26-week open label study (Cornblatt et al. Int J

Neuro Psycho Pharmacol. 2002; (suppl 1):S185) and does not elevate total

cholesterol (Bristol-Myers Squibb and Otsuka America Pharmaceutical. Data on

file).

Another important aspect of aripiprazole is that. As yet, unlike other

atypical antipsychotics, no worsening of diabetes or emergence of new

diabetes has been reported, Dr. Janicak stated. Additionally. QT

prolongation, which can lead to potentially life-threatening arrhythmia and

has been linked to seizures and sudden death, does not appear to be a

problem with aripiprazole, when compared with haloperidol or placebo (Stock

et al. Int J Neuro Psycho Pharmacol. 2002; (suppl 1):S185).

The most commonly reported side effects associated with aripiprazole have

been shown to be comparable with placebo in incidence. These are headache,

nausea, vomiting, insomnia, somnolence, and akathisia. Evidence suggest that

most of these symptoms resolve within two weeks, Dr. Janicak noted.

Intriguing Finding

Unpublished data suggest that aripiprazole may have a role in the treatment

of acute bipolar mania. Drugs currently used to treat acute mania include

lithium, carbamazepine, divalproex sodium [Depakote: Abbott Laboratories],

and olanzapine. Response rate with these drugs are approximately 50% to 60%,

and some of these drugs have potentially serious side effects.

These drugs are often continued after resolution of acutely manic episodes

for subsequent prophylaxis, " explained E Keck. Jr., MD. " There are

still a number of unmet needs in acute mania, and we still lack the ideal

treatment in manic and depressive episodes.

" These studies suggest that the partial dopamine agonist, aripiprazole, may

have a great promise in acute bipolar mania, " Dr. Keck continued. One study

compared aripiprazole versus placebo (Jody et al. Int J Neuro Psycho

Pharmacol. 2002), and another compaired aripiprazole versus haloperidol--'

the gold-standard ant-manic drug,' Dr. Keck said. (Bristol-Myers Squbb and

Otsuka American Pharmaceutical. Date on file).

Future treatment of acute bipolar mania may include combination therapy,

especially during early phases of treatment, Dr. Keck noted.

Summary

Aripiprazole is a novel agent with a unique mechanism of action that include

potent partial agonist activity at the dopamine D2 receptors, potent partial

agonism at 5-HT1A receptors, and it is an antagonist at 5-HT2A receptors.

This mechanism of action appears to translate to broad efficacy against

positive and negative symptoms of schizophrenia and acute bipolar mania as

well as improved mood and cognition. Recent studies suggest that these gains

are achieved without the undesirable side effects associated with currently

available agents. Aripiprazole appears to have low potential for side

effect, including weight gain, dyslipidemia, elevated prolactin, glucose

dysregulation, and prolonged Qtc intervals. Studies thus far support that

fact that aripiprazole represents a true advance in the treatment of

psychosis.

===========

Jean-Pierre Lindenmayer, MD, chairperson of the Symposium and Director,

Psychopharmacology Research Unit, Manhattan Psychiatric Center-- S.

Kline Institute for Psychiatric Research, Clinical Director; Manhattan

Psychiatric Center, and Clinical Professor Psychiatry, New York University

of Medicine, New York, New York.

L. Roth, MD, PhD. Associate Professor, Departments of Biochemistry,

Neurosciences, and Psychiatry: Director, NIMH Psychoactive Drug Screening

Program, Case Western Reserve University School of Medicine, Cleveland, Ohio

G. Janicak, MD. Professor of Psychiatry and Pharmacology, College of

Medicine, Medical Director, Psychiatric Research Center, and Associate

Program Director: NIH General Clinical Research Center, University of

Illinois, Chicago, Illinois

E. Keck, Jr. MD. Professor of Psychiatry and Pharmacology,

Nice-Chairman for Research, Department of Psychiatry, University of

Cincinnati College of Medicine, Co-Director, Biological Psychiatry Program,

University of Cincinnati Medical Center, Cincinnati, Ohio

==========

MEDIVIEW is an independent, professional news service provided by

Medical Intelligence Solutions ( MSI), reporting on selected topics

presented at worldwide medical meetings.

ABILIFY (Aripiprazole) Approved by U.S. Food and Drug Administration For

Treatment of Schizophrenia

http://www.prnewswire.com/cgi-bin/stories.pl?ACCT=105 & STORY=/www/story/11-18

-2002/0001843453

New antipsychotic offers combination of proven efficacy and favorable side

effect profile PRINCETON, N.J. And TOKYO, Nov. 18 /PRNewswire/ -- The U.S.

Food and Drug Administration (FDA) approved ABILIFY (aripiprazole), a

new antipsychotic medication indicated for the treatment of schizophrenia,

on Friday, November 15. Bristol-Myers Squibb Company (NYSE: BMY) and Otsuka

America Pharmaceutical, Inc. will jointly market ABILIFY in the United

States. The companies anticipate that ABILIFY tablets will be widely

available in pharmacies within two weeks. Clinical studies involving 1,238

patients with acute relapse of schizophrenia demonstrated that treatment

with ABILIFY provided significant improvements in the positive and negative

symptoms of schizophrenia. Importantly, treatment with ABILIFY was

associated with minimal weight change, minimal extrapyramidal symptoms (EPS

is a group of involuntary muscle movement disorders) and a modest difference

in sedation compared to placebo (11% vs. 8%). Additionally, the incidence of

QTc interval prolongation with ABILIFY treatment is not different from

placebo. " ABILIFY represents an important new treatment for schizophrenia, "

said Lieberman, M.D., vice chairman of psychiatry, professor of

psychiatry and pharmacology, University of North Carolina at Chapel Hill.

" Clinical data show that patients treated with ABILIFY experience

significant improvement of their symptoms, and the medication demonstrated

an excellent safety and tolerability profile. Given that a large percentage

of patients discontinue or switch antipsychotic medication due to inadequate

response or side effects, the addition of ABILIFY to our armamentarium is

very exciting. " Schizophrenia affects more than two million Americans, and

about one percent of the population worldwide. Schizophrenia interferes with

a person's ability to think clearly, manage emotions, make decisions and

relate to others. This illness tends to manifest itself in early adulthood

and is characterized by positive symptoms, such as hallucinations,

delusions, and paranoia, as well as negative symptoms, such as social

withdrawal and emotional flatness. While there is no cure for schizophrenia,

it is a treatable illness. " This approval will enable Bristol-Myers Squibb

to further realize its mission of extending and enhancing human life in

important new ways, " said R. Dolan, chairman and chief executive

officer. " For patients and their caregivers, as well as for physicians,

ABILIFY represents new hope for thousands of people with schizophrenia. For

Bristol-Myers Squibb, it marks the beginning of a promising new era for our

company when we will be providing a new generation of innovative medicines

for the benefit of patients everywhere. And I am pleased that we have Otsuka

at our side as we begin this great journey. " " We at Otsuka are very proud to

have discovered ABILIFY and to have developed it jointly with Bristol-Myers

Squibb into a product that represents an important option in the treatment

of serious mental illness, " said Tatsuo Higuchi, president, Otsuka

Pharmaceutical Co., Ltd. " ABILIFY highlights Otsuka's strong passion and

commitment to scientific discovery, and introducing this important new

compound in the United States is a great accomplishment for us. ABILIFY will

become a new and valuable treatment option to help many people who live with

schizophrenia to lead more productive lives. " ABILIFY Clinical Trials The

efficacy of ABILIFY in the treatment of schizophrenia was evaluated in

short-term (4- and 6-week), placebo-controlled trials of acutely relapsed

patients. The primary measures used to assess symptoms of schizophrenia were

the Positive and Negative Syndrome Scale (PANSS); the PANSS positive

subscale, which rates seven positive symptoms of schizophrenia; the PANSS

negative subscale, which rates seven negative symptoms of schizophrenia; and

the Clinical Global Impression (CGI) scale, which allows physicians to

assess the overall clinical state of the patient. In three studies involving

1,238 patients, ABILIFY was statistically superior to placebo in improving

the symptoms of schizophrenia as evaluated by PANSS total score, PANSS

positive score, PANSS negative score and CGI-severity score. The incidence

of reports of EPS as an adverse event in the short-term, placebo-controlled

trials with ABILIFY was 6% compared to 6% for placebo. ABILIFY demonstrated

a favorable weight profile in short-term clinical trials. In these studies,

there was a slight difference in mean weight change between ABILIFY and

placebo patients (0.7 kg versus -0.05 kg, respectively). The safety and

tolerability of ABILIFY has been established in studies involving more than

5,500 patients with approximately 3,600 patient-years of exposure, including

more than 1,250 patients who were treated for at least one year. In

short-term (4- and 6-week) placebo-controlled trials, there was no

difference in the incidence of discontinuation due to adverse events between

patients treated with ABILIFY (7%) and placebo (9%). The most commonly

reported adverse events with an incidence of greater than 15% and greater

than placebo in short-term clinical trials with ABILIFY were headache (32%

versus 25% for placebo), anxiety (25% versus 24% for placebo) and insomnia

(24% versus 19% for placebo). For more information, please see full

prescribing information. As with other drugs having efficacy in

schizophrenia, the mechanism of action of ABILIFY is unknown. However, it

has been hypothesized that ABILIFY works differently than other

antipsychotics. Specifically, it is proposed that the efficacy of ABILIFY is

mediated through a combination of partial agonist activity at dopamine D2

receptors and serotonin 5HT1A receptors, and antagonist activity at

serotonin 5HT2A receptors. Partial agonism refers to the ability to both

block a receptor if it is overstimulated and to stimulate a receptor when

activity is needed. ABILIFY is administered as a once-daily oral tablet. The

effective dose range of ABILIFY is 10 to 30 mg. The recommended starting and

target dose of 10 or 15 mg daily enables physicians to initiate therapy at

an effective dose without the need to titrate. Dosage can be subsequently

adjusted to optimize individual patient response. Tablets may be

administered at any time of the day, with or without food. ABILIFY is

available in 10 mg, 15 mg, 20 mg and 30 mg tablets. About Bristol-Myers

Squibb and Otsuka Bristol-Myers Squibb and Otsuka are collaborative partners

in the development and commercialization of aripiprazole in the United

States and major European countries. ABILIFY was discovered by Otsuka

Pharmaceutical Co., Ltd. Founded in 1964, Otsuka is a diversified health

care company guided by its philosophy: " Otsuka -- people creating new

products for better health worldwide " and dedicated to the research and

development of innovative medical, pharmaceutical, and nutritional consumer

products to improve the quality of human life. Otsuka has a diverse

portfolio including central nervous system, cardiovascular, circulatory,

gastro-intestinal, respiratory, dermatological, ophthalmologic, and is

pursuing research in genomics and protein function. The Otsuka Group is

comprised of 32 businesses around the world, earning total revenues of $4.5

billion annually. Bristol-Myers Squibb is a global pharmaceutical and

related health care products company whose mission is to extend and enhance

human life. For more information visit: http://www.abilify.com For full

prescribing information, please contact Jeff Macdonald at 609-252-5771 Visit

Bristol-Myers Squibb on the World Wide Web at: http://www.bms.com Visit

Otsuka Pharmaceutical Co., Ltd. at: http://www.otsuka.co.jp This press

release contains certain forward-looking statements within the meaning of

the Private Securities Litigation Reform Act of 1995 that may be identified

by terminology such as " anticipate " and other words or terms of similar

expression or meaning. Such forward-looking statements are based on current

expectations and involve inherent risks and uncertainties, including factors

that could delay, divert or change any of them, and could cause actual

outcomes and results to differ materially from current expectations. For

further details and a discussion of these and other risks and uncertainties,

see the company's Securities and Exchange Commission filings, including the

company's 2001 Annual Report on Form 10-K. We undertake no obligation to

publicly update any forward-looking statement, whether as a result of new

information, future events, or otherwise.

[Guest guest]

Aripiprazole (Abilify): A Novel Atypical Antipsychotic

Why this drug is so different, and why it may be uniquely helpful for

children with bipolar disorder, the mechanism of action, side effect

profile, dosing, drug-drug interactions, costs, reports from the research,

clinical, and home fronts.

Three years ago, we published the first issue of The Bipolar Child

Newsletter, and in the opening paragraph we outlined what we hoped to

accomplish: We wrote: " We thought an e-mail newsletter would be a good forum

in which to keep parents, educators, and mental health professionals abreast

of the newest findings in the fields of psychopharmacology, genetics, and

neurobiology as they relate to early-onset bipolar disorder. "

In keeping with that aim we'd like to focus this issue on a newly available,

novel, antipsychotic medicine, aripiprazole (ari-PIP-prazole; brand name

Abilify). Psychiatrists are starting to prescribe it, parents are writing to

us asking for information about it, and early, anecdotal reports are

promising. Much remains to be learned about this unusual new drug. Very

little is known about its potential clinical utility and relative

tolerability in children suffering with early-onset bipolar disorder, and

scientific studies of that application are only now beginning. Still, the

drug's unique properties and apparently excellent tolerability in adults

offer a great deal of hope.

Let us spell out what we know about Abilify in February 2003.

Aripiprazole was discovered in Japan by Otsuka Phramaceutical Co., Ltd. The

compound entered Phase II trials for patients with schizophrenia in that

country by 1995, followed by Phase III trials in Europe by 2000. In 1999,

Otsuka-America arranged with Bristol-Meyers Squibb to manage Phase III

clinical trials and marketing of the new drug in the US. Abilify received

FDA approval in November of 2002. It is so new that clinical experience with

it, particularly in children, remains very limited.

The Mechanism of Action

Aripiprazole is chemically different from other atypical antipsychotic

agents and is also believed to have unique pharmacological actions that are

different from other atypical antipsychotic drugs, including clopazine

(Clozaril), olanzapine (Zypexa), or quetiapine (Seroquel), risperidone

(Risperdal), or ziprasidone (Geodon). Aripiprazole acts as a weak stimulator

(so-called " partial " agonist) at dopamine D2 receptors, with the potential

for exerting either antagonistic (inhibitory) or agonistic (stimulating)

effects, depending on the sensitivity of the receptors and availability of

dopamine, its natural agonist in the brain. Aripiprazole also has similar

actions at serotonin 5-HT1A receptors, as well as acting as an antagonist at

serotonin 5-HT2A receptors, and having a number of other lesser actions.

In simple terms, partial agonism refers to the ability of a drug to block a

receptor if it is overstimulated or in competition with a natural agonist,

such as dopamine and serotonin themselves, but also to stimulate a receptor

when the natural agonist is unavailable. These unprecedented properties in a

clinically effective antipsychotic agent indicate that Abilify can be

considered a " next-generation " atypical antipsychotic.

Aripiprazole is the first dopamine partial-agonist approved in the US for

clinical use in adult patients with schizophrenia, although other dopamine

partial-agonsists (e.g., bromocriptine [Parlodel] and pramipexole [Mirapex])

have been used to treat Parkinson's disease for many years. Aripiprazole is

effective in reducing both the positive and negative symptoms of

schizophrenia, and is well tolerated by most patients. In addition,

promising research studies have been conducted with adults suffering with

bipolar disorder. A multi-center, double-blind randomized,

placebo-controlled trial included 262 adult patients diagnosed with acute

mania or mixed manic-depressive states. By day four of treatment,

aripiprazole was significantly better than placebo in reducing acute manic

symptoms, including elevated mood, irritability, disturbed thinking, and

disruptive-aggressive behavior.

These findings have prompted adult and child psychiatrists to begin to

prescribe Abilify for both indicated and off-label applications, including

for early-onset bipolar disorder in children and adolescents.

Advantages of Abilify

Like other atypical antipsychotics, aripiprazole has a low risk of producing

extrapyramidal symptoms (EPS)-the disorders of posture and movement that

some patients experience with the older neuroleptic-type antipsychotics,

such as chlorpromazine (Thorazine) and haloperidal (Haldol). Typical EPS

include early and later muscle contractions (dystonia), slowed movements

(akinesia, or parkinsonism), motor restlessness often accompanied by severe

anxiety (akathisia), and later-emerging tardive dyskinesia (TD).

In our newsletter of Fall 2000, we first sounded some concerns about a

series of general medical or metabolic problems that were being increasingly

reported in association with the atypical antipsychotic medications such as

Clozaril, Zyprexa, Risperdal, and Seroquel. These include new-onset, type II

(non-insulin dependent) diabetes mellitus, changes in lipid metabolism and

blood concentrations, sometimes severe and persistent elevation of prolactin

and other hormonal imbalances (milk oozes from children's nipples), and a

range of adverse cardiovascular effects that include low blood pressure and

abnormal functioning of the heart. The long-term implications of such

adverse effects are not known, particularly for youngsters who may require

such medications for decades.

Studies conducted with Abilify show that patients gain little if any weight;

and the drug seems to cause no changes in the plasma glucose levels that

might suggest risk of diabetes. Nor does it seem to increase serum

cholesterol or other lipids. Also, the drug does not increase prolactin

levels, and in fact appears to decrease them to normal levels, and there

have been no reports of heart rhythm abnormalities (such as a prolonging of

the electrical recovery time of the heart [QTc interval] in the

electrocardiogram), hematological changes, serum chemistry changes, or

thyroid problems.

Parents who wrote to us asked if there were any cases of tardive dyskinesia

(TD), the late appearing movement disorder that can present with involuntary

facial grimacing, lip-smacking, chewing and sucking movements, cheek

puffing, and worm-like movements of the tongue, as well as quick movements

of the fingers, toes, arms and legs, or dystonic, writhing postures. At this

point there have been no reports, but it will be years before anyone can

answer this question with any authority.

The other question we were asked was: " Does this med punk out like some of

the others and will the doctor have to keep increasing the dose? " Again, we

have few answers, but the clinical trials involving patients with

schizophrenia showed that Abilify sustained improvements in the positive,

negative, and depressive symptoms of schizophrenia for at least a year.

The drug has been evaluated for safety in at least 5,592 adult patients who

participated in multiple-dose, premarketing trials in schizophrenia, bipolar

mania, and dementia of the Alzheimer's type, for a total of approximately

3,639 patient-years of exposure. A total of 1,887 aripiprazole-treated

patients were treated for at least six months, and 1,251 for at least a

year.

Promising--so far, but what are the side effects and how effective is it for

children struggling with the symptoms of bipolar disorder?

The Side Effects

The most common adverse effects reported among adult bipolar disorder

patients, specifically, included headache (32%), nausea (14%), vomiting

(12%), constipation (10%), anxiety (25%), insomnia (24%), dizziness (11%),

and akathisia (10%). Sleepiness was found with higher doses. Placebo-treated

patients in the same study also suffered side effects such as headache,

agitation, nausea, indigestion, and anxiety. Few of the side effects for

either group lasted beyond the first week.

Although many patients report few side effects with the medication, in

children, specifically, we have heard of single cases: one very young child

was taken off the drug due to severe constipation, one 12-year-old had new

mania, and one youngster had a dystonic reaction-one of the movement

disorders we spoke of above (dystonic reactions can be quickly counteracted

by antihistamines such as diphenhydramine [benadryl], or by anticholinergic

drugs such as benztropine [Cogentin] or trihexyphenidyl [Artane]).

Dr. Behr, a highly respected child psychiatrist on the faculty of

the Albert Einstein College of Medicine and founder of the Child

Psychopharmacology Listserv for child psychiatrists is very impressed with

Abilify, but has reported five cases of akathisia (out of the first 34

patients for whom he has prescribed the medication). He explained that this

was not " agitation, " but " real akathisia. " While the risk of EPS is much

lower than with the older neuroleptic agents, akathisia probably has a

different basis than other movement disorders associated with antipsychotic

drugs, and can occur occasionally even with atypical agents. Parents should

be aware of akathisia and be alert to it.

According to Ross J. Baldessarini, M.D. of Harvard Medical School, and one

of the leading authorities on antipsychotic medications:

Akathisia is motor restlessness that can occur with all antipsychotics,

typical or atypical, but is more likely to occur with the older typical

agents and D2 blocking agents. It can occur occasionally and in subtle

fashion even with clozapine. Akathisia involves extreme subjective distress

with a kind of " anxiety " that involves a physical sense of discomfort, often

referred to the legs, and partially relieved by moving around, hence the

restless component. Sometimes it can be treated with propranolol (Inderal)

or benzodiazepines, but it may require removing the offending agent.

He added: " This common condition is often overlooked or misunderstood or

mislabeled as 'agitation' and it has been associated with aggressive or even

suicidal behavior. "

Since so many children with bipolar disorder suffer paradoxical reactions to

all drugs (even those thought to quell mania) the hypothetical risk of

inducing or worsening mania or psychosis by a dopamine partial-agonist still

remains a concern for us and many clinicians, and its clarification awaits

more clinical experience.

Reports from the Medical Front

Dr. Behr told us that " I have used Abilify in several kids and many

of the responses have been dramatically positive. My impression is that, if

it is going to work, there usually is a very quick response --within a few

days. It is very similar to the effect that one sees with Zyprexa

(olanzapine) but without the sedation and weight gain. "

We corresponded extensively with Mani N. Pavuluri, M.D. the director of the

Pediatric Mood Disorders Clinic at the Institute of Juvenile Research at the

University of Illinois at Chicago. In one e-mail, she told us of a five-

year-old child with bipolar disorder who was severely psychotic, suffering

delusions of reference, raging, and refractory to three previous trials of

mood stabilizers and two antipsychotics. The child is now doing well on 5 mg

of Abilify a day. (A four-year-old patient, however, could not tolerate the

drug due to constipation.)

Because Dr. Pavuluri and her colleagues were so impressed with their

observations of the effects of aripiprazole in difficult-to-treat children

who have bipolar disorder (and the results of the five clinical trials that

were completed at their center in adults) they have designed a research

protocol that proposes to examine Abilify in 7-17 year-olds with bipolar

disorder over a six-week period.

Cremer, M.D. a psychiatrist from Miami, Florida informed his collegues

on the Professional Listserv of the Juvenile Bipolar Research Foundation: " I

have two young patients who are bipolar and who have been on every

medication for therapeutic trials and were refractory, or who stopped

medications due to side effects, and they are both doing well on Abilify. "

When we contacted him and asked for some more details, he described one of

his children thus:

The first patient, KM, is seven-years-old and his core symptoms were rages,

sleeplessness, irritability with remorse, low frustration tolerance, fickle

changes in mood, rapid speech, and an ADHD profile.

He was refractory to every medication (all the anticonvulsants), he was

briefly responsive to the atypical antipsychotics and briefly responsive to

lithium. On Abilify he has been able to engage in play in the office and

used the time to discuss some of his feelings about how he has been feeling.

The ADHD-type picture has abated with the medication.

Dr. Cremer then wrote about his other patient, a nine-and-a-half-year-old

boy:

TF has severe separation anxiety, fickle moods, bursts of hyperactivity,

some bizarre behavior, moodiness, and spells of rages with pressured speech.

He has responded to an atypical antipsychotic, but with the side effects of

puffiness and weight gain. He is on carbamazepine without side effects.

Since starting him on Abilify, he lost his puffiness almost immediately and

is losing weight. His temper has stabilized. He still has his moments, but

they are within the realm of average for his social delay.

Dr. Cremer mentioned that both of these children showed improvement on their

mental status exams.

Reports from the Home Front

How are the children doing on Abilify-at home and in school? Several parents

wrote to us and again, the stories were positive (but please bear in mind

that the negative stories have not reached us yet, and that all children

will not have these superb reactions or be able to tolerate the drug). One

mother said:

Since started the drug, things have been so much better. He is on 10

mg and the first few days he was in a major " fog " and slept a lot, and had

an upset tummy. I thought we were going to have to lower the dose but waited

it out and things did get better and the sleepiness went away and he no

longer walks around in a fog. Things are starting to " click " in his head as

far as school work is concerned. His upsets are not rages anymore. And the

constant fighting with siblings......well, now it is just regular sibling

rivalry that we have never gotten to see before. He is much more compliant

and his aggression level has gone way, way down. He gets up in the morning

and says: " Good morning " instead of " I hate you! " Not sure how long it will

last, but I am enjoying it very much!

She added something that reminded us once again what this illness does not

only to the child, but to the entire family, and especially the siblings:

She said: " His little brother is still having a hard time understanding why

is being nice and not his usual self that he was used to. But we are

working on that. "

We've been corresponding with the grandfather of a young boy for some time

now and he wrote recently to tell us of his grandson's reactions to Abilify.

He said:

His daily reports from school are all positive, and both his special-ed

teachers are now able to concentrate on his education instead of his

behavior. I notice there is no more cycling and no more rages. He is more

calm; and when things go wrong, he doesn't explode as he did in the past. As

a result of the Abilify, he is a happier 9-year old, and I no longer walk on

egg shells when he is with me.

Another mother described her fourth-grader's reaction to the medication

thus:

He began the Abilify and on the third to fourth day, we saw dramatic

improvement. It was almost as if we were dealing with a different child. The

rages stopped. He has always been an affectionate child, but now his

affection shines through clearly. He's been getting wonderful reports from

his special- ed teachers at school. I still find myself preparing for battle

when I have to reprimand him, but I'm pleasantly surprised when he complies

with my requests now and there is no problem. This medication has been truly

amazing for my son and our family.

And because there is no such thing as too much good news to parents of

children suffering with bipolar disorder, we conclude with this mother's

description:

While it hasn't solved all of our son's problems, it has controlled his

paranoia and mania, decreased his grandiosity (but not eliminated it), made

it possible for him to read and focus better, and has done all of this

without major side effects (once we got up to 15 mg and eliminated the other

antipsychotic medications completely). He tells me that he feels much better

able to control himself. He says that he can now read without his mind

wandering off in different directions. He can also let negative issues drop,

rather than dwelling on them.

She continued:

We have noticed a big change in him. He gets up in the morning and stays

awake and alert all day (no sedation). He is generally more cooperative and

although he still does annoying things, I can now confront him without

feeling like I need the National Guard to back me up. His pediatrician, his

therapist, and teachers at school have all noticed the change for the

better.

There is something intriguing in this story and in Dr. Cremer's reports

above. The children's focus and attention seem to have improved on Abilify.

Indeed, Dr. Mani Pavuluri proposes to look at the drug's ability to improve

cognitive functioning in her study patients. The results should be

interesting for all in the field, and for all parents and educators.

Dosing

Abilify is supplied in 10, 15, 20, and 30 mg tablets--a disadvantage for

children, who are typically started on lower doses. Parents can cut tablets

into halves or even quarters, or bear extra costs in using the services of

compounding pharmacies. We understand from Bristol-Meyers Squibb that lower

milligram formulations as well as a liquid formulation will be available

some time " in the foreseeable future, " but we can't be any more specific

than that.

Typical adult doses for the treatment of psychotic disorders are 10-15

mg/day, with an overall range of 5-30 mg. Doses for children are not

established yet, but are likely to be about half those used for adults.

Moreover, the specific use of this drug to treat psychotic patients under

age 18, or for those diagnosed with bipolar disorder is not approved by the

FDA, though it is evidently starting to be used clinically on an off-label

basis in adolescents and children and for bipolar disorder patients.

Dr. Pavuluri reports that she starts youngsters weighing less than 110

pounds at 2.5 mg, and those over 110 pounds at 5 mg initially to avoid

nausea, and doubles the dose within a week if it is tolerated. Further dose

increases usually are not made for another week or two as steady state, or

stable, tissue concentrations are achieved.

It is a good idea to give the medication in the morning, with a meal or some

food in order to minimize risk of nausea and insomnia, which are among its

most common side effects. Also, parents should ensure that the child eats

fruit and vegetables, or high-fiber cereals, and drinks plenty of fluids in

order to prevent constipation.

Drug-to-Drug Interactions

The anticonvulsant mood stabilizer, carbamazepine (Tegretol), induces CYP3A4

and 2D6 liver enzymes which can increase the ability of the body to remove

Abilify, and so decrease Abilify's concentration in the blood. The

manufacturer recommends that the dosage of Abilify be doubled as long as

both drugs are taken at the same time. This consideration brings up the

question as to whether Trileptal (oxcarbazepine, an analogue of

carbamazepine) can cause this same increase in clearance as Trileptal also

has some effect on the liver enzyme CYP3A4 that normally removes Abilify.

The possibility seems to exist, but no one has a definitive answer about

this yet and careful dosing ad an attentive eye to the clinical picture will

be required.

Antidepressants such as fluoxetine (Prozac) fluvoxamine (Luvox) and

paroxetine (Paxil) can slow the body's ability to eliminate Abilify by

inhibiting CYP3A4 and CYP2D6 liver enzymes, and so increasing blood levels

of the drug. When any of these SSRIs are prescribed with Abilify, the

manufacturer recommends that the Abilify be reduced at least to one-half of

its current or usual dose.

Again, physicians who have patients on either class of these medications

will have to monitor the clinical picture carefully and make adjustments as

needed.

The Cost of the Medication

Abilify is very expensive. A Connecticut retail pharmacy quoted the

following prices for 30 tablets at each of three dosages: 10-mg or 15-mg,

$357, and 20-mg, $506. (We have seen cheaper prices so it behooves all

parents to shop around.)

For families who don't have prescription cards or the funds to pay for

Abilify, Bristol-Meyers Squibb moved quickly to set up a Patient Assistance

Program at 1-800-332-2056.

Conclusions

Because early anecdotal reports from researchers, clinicians, and parents

seem so positive, and because the drug's safety profile has been very

promising to date (and it doesn't confound a child's problems with weight

gain), it is hard not to be hopeful about this new medicine. However, it is

important to state again that Abilify is only beginning to be studied in

children, and a more balanced picture is certain to evolve as data

accumulates. (A study is currently enrolling at the NIMH comparing

risperidone to aripiprazole in youngsters aged 8-18 years, with psychotic

symptoms who have responded unsatisfactorily to at least one other adequate

trial of an antipsychotic. To read more about this study and to see if your

child qualifies, go to http://www.ClinicalTrials.gov and type in

aripiprazole.

We are forever walking a fine line between that all-important emotion called

hope, and a need to stay open-minded and await the data. One of the mothers

we quoted above, put it so wisely when she wrote:

Although this medication has been wonderful for my son, I would not want to

raise hopes for other bipolar parents by singing its praises too much. I

know how it felt when I heard wonderful things, hopeful things, about other

medications that were found to be effective with bipolar disorder. As the

parent of a bipolar child, when getting overly hopeful about a medication

and then going through the painful and frustrating experience of trying it

only to find it did not work (or worse--it exacerbated the symptoms of the

bipolar disorder), it was heartbreaking. I guess with all the variations in

brain chemistries unique to individuals with bipolar disorder (or any other

psychiatric illness), there can't be one medication, the medication, that

cures bipolar disorder. I think all parents need to be reminded of this so

they're not setting themselves up for a fall

We've said it before, and it bears repeating again: If your child is doing

well on his or her present medications, it is unwise to change the regimen

because you read about a new drug--here or anywhere. If your child is

stable, do nothing to rock that blessed boat.

We will continue to gather information about Abilify and its effect on

children suffering with bipolar disorder, both on the research and the

clinical fronts, and we would appreciate hearing from any of you whose

children have had experience with it.

At this time of mid-winter and always, we wish you and your children the

best,

Janice Papolos and Demitri F. Papolos, M.D.

Bibliography

*Baldessarini, R.J. E-mail correspondence of February 5, 6, and 10, 2003.

*Behr, . E-mail correspondence of February 4, 2003. Telephone

conversation Of February 10, 2003.

*Burris, KD, Molski TF, et al. Aripiprazole, A novel antipsychotic is a

high-affinity partial agonist at human dopamine D2 receptors. Journal of

Pharmacological Exp Ther 2002;302-389.

*Goodnick, PJ, and Jerry, JM. Aripiprazole: Profile on efficacy and safety.

Expert Opinion Pharmacotherapy 2002; 12: 1773-1781.

*Jody, Darlene, Marcus, Keck, et al. " Aripiprazole vs. placebo

in acute mania. (poster), Proc Am Psychiatr Assoc Annual Meeting, May 2002.

*McGavin JK, Goa KL. Aripiprazole. CNS Drugs 2002; 16: 779-786.

*Papolos, DF. and Papolos J. The Bipolar Child, Revised Edition. New York:

Broadway Books, 2002.

*Papolos, J and DF. Papolos. The Bipolar Child Newsletters Volumes 5 and 10.

(www.bipolarchild.com) *Pavuluri, MN. E-mail correspondence of Feburary 3

and 4, 2003.

The authors would like to thank Mani N. Pavuluri, M.D., Behr, M.D.,

Cremer, M.D., McQuade, Ph.D., Mort Fineberg, Fineberg,

Schwartz, Niki Tenn, and especially, Deborah Storms, for their

contributions to this newsletter. For his abiding interest, wisdom, and

friendship, as well as his specific help with this report, we acknowledge

Ross J. Baldessarini, M.D.

Copyright 2003

[Guest guest]

Heidi, Evan also uses Abilify for agressive behavior and hopefully to

stabilize his moods. uses it for his Bipolar. It does help as a

mood stabilizer but is a antipsychotic.

BETTY ANN-61 yo, possibly Bipolar but undx'd,

Effexor, Buspar, Lorazepam as needed, Serenity

grandma and guardian to

ANDREW - 11 yo-- Bipolar/ADHD, Homeschooled

Depakote 250 mg. 2 x daily, Adderall 30 mg daily, Abilify 7.5 mg 1 x daily

EVAN - 9 yo-- nonverbal autism

Risperdal 2.5 cc daily, Abilify 10 mg 1x daily

DAVID 7 yo Bipolar/ADHD/PTSD

Adderall 20 mg daily, .25 mg Risperdal 2 x daily

and mother to ANDREA -32 yo, their mom -

Bipolar/ADHD, Topamax, Tegretol, Singular, Serenity

wife to BOB - 72 yo, a very patient and tired grandpa

[Guest guest]

Thanks, Pat! How would you rate how it's worked for Karac's aggression? Had

Karac tried Risperdal and/or Zydis previously?

Thanks again!

Heidi

Re: Abilify

Heidi, I just went to the website and typed in Abilify to get information

about it when the doctor prescribed it for Karac. It was prescribed for Karac

for aggression. My understanding is that it is a relatively new drug in the

category of Risperdal, and Zydis without some of their side effects. Pat K

[Guest guest]

Our doctor just added Abilify to our list of meds we " should try out. " Has

anyone out there tried this one? The doc told us it is mainly for schizophrenia

(spelling???) but he tried it on some autistic patients with good results. I

am not sold yet. We got the prescription filled but we want to see if anyone

has had experience with this one.

C.

Georgi's mom

[Guest guest]

Our doctor just added Abilify to our list of meds we " should try out. " Has

anyone out there tried this one? The doc told us it is mainly for schizophrenia

(spelling???) but he tried it on some autistic patients with good results. I

am not sold yet. We got the prescription filled but we want to see if anyone

has had experience with this one.

C.

Georgi's mom

[Guest guest]

A friend was put on the above medicine..it can cause a

Neuroleptic Malignant Syndrome . Have ya'll ever heard of that? thank you!

Kim

[Guest guest]

NICE THANK YOU

WAS IT YOU?

FOR IF IT WERE ME, ID BE A BIT ANGERED, SPECIALLY FOR THERE IS THE ABILITY TO

REFUTE

WHAT IS IN A PERSONS SYSTEM.

Re: [ ] Abilify

A friend was put on the above medicine..it can cause a

Neuroleptic Malignant Syndrome . Have ya'll ever heard of that? thank you!

Kim

[Guest guest]

No it's for a friend..I don't understand really what you meant..Kim>

>

>

>

> NICE THANK YOU

> WAS IT YOU?

>

> FOR IF IT WERE ME, ID BE A BIT ANGERED, SPECIALLY FOR THERE IS THE ABILITY

> TO REFUTE

> WHAT IS IN A PERSONS SYSTEM.

> Re: [ ] Abilify

>

>

> A friend was put on the above medicine..it can cause a

> Neuroleptic Malignant Syndrome . Have ya'll ever heard of that? thank you!

> Kim

[Guest guest]

Some like the Abilify; it is an antipsychotic and is suppose to be less likely to cause TD than the other antipsychotics, but they said the same thing about Geodon, and Karac ended up with TD; so I personally am against all the antipsychotics unless the child is actually psychotic. So far, Karac is doing better on Xanax then on any other medication he has ever had. If it had been up to me, Karac would never have been on any medication. It has been two and half months since Karac has had a meltdown at my house, and he is doing so well at school now they are planning to let him gradually start doing his office help again. I t just seems to be trial and error for all these kids. Pat K

[Guest guest]

Oh, yes, we did switch from Risperdal to Abilify and then to Geodon. All of these meds had side effects. Pat K