5. DR CAROL GLOD.

[Guest guest]

Dr Glod appears to be the odd one out in this group of powerful pro-

pharmaceutical 'experts'.

http://barista.media2.org/?p=390

" ...The link between Prozac and increased suicide risk was first

suggested by Teicher, Carol Glod and Cole of McLean

Hospital in Belmont in an influential 1990 article. The study

immediately met with fierce opposition, and at hearings held by the

FDA in September 1991 a panel of 10 outside experts decided there was

not sufficient evidence to conclude that Prozac increased the risk of

suicide... "

HOWEVER, 13 years later, Glod did manage to author the following

trial and find that bupropion was good for adolescents:

http://findarticles.com/p/articles/mi_qa3892/is_200307/ai_n9294633

Open trial of bupropion SR in adolescent major depression

Journal of Child and Adolescent Psychiatric Nursing, Jul-Sep 2003

by Glod, Carol A, Lynch, Arlene, Flynn, , Berkowitz,

, Baldessarini, Ross J

Find More Results for: " Open trial of bupropion SR in adolescent

major depression "

Bupropion sustained...

Bupropion Sustained...

PROBLEM. There are few studies of sustained-release bupropion in

adolescents with major depression.

METHODS. Twenty-one adolescents with DSM-IV major depression were

recruited through advertisement and self-referral; 11 began study

medication and were rated weekly with an expanded Hamilton Depression

Rating Scale (SIGH-SAD), as well as Clinical Global Impression-

Improvement (CGI-I).

RESULTS. Of 11 subjects enrolled, 8 completed an 8-week trial of

bupropion SR. Mean baseline SIGH-SAD scores of 31.3 decreased

significantly by 74% to mean endpoint score of 8.2. Improvement on

CGI-I that agreed closely between raters and patients was found in 8

of 11 subjects (72.3%). The mean daily dose of bupropion SR was 362

mg + or - 52 mg and was well tolerated; insomnia and weight loss were

experienced by 55%; other adverse effects of dry mouth, headache,

agitation, light-headedness, diarrhea, or rash were noted in a

minority of subjects.

CONCLUSIONS. In this preliminary, small open study, depressed

adolescents showed a marked response to bupropion SR. "

I don't know whether the study was funded by the manufacturers,

Sandoz, but do see that Sandoz got a warning from the FDA last June

regarding violations related to the black box warning of suicidality

in children and ADOLESCENTS on buproprion:

http://www.pharmcast.com/warningletters/Yr2006/May2006/Sandoz0506.htm

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Released by FDA: 5/26/06. Posted by FDA: 5/30/06

Enna Krivitsky

Associate Director, Regulatory Affairs

Sandoz, Inc.

227-15 N. Conduit Avenue

Laurelton, NY 11413

Re: ANDA 75-932

Bupropion hydrochloride extended-release tablets (SR)

MACMIS 14211

Dear Ms. Krivitsky:

The Division of Drug Marketing, Advertising, and Communications

(DDMAC) has reviewed a professional print advertisement for bupropion

hydrochloride extended-release tablets (SR), submitted by Sandoz,

Inc. (Sandoz) under cover of Form FDA 2253. This promotional piece

is violative because it has the form of a reminder advertisement for

a drug whose labeling contains a boxed warning relating to a serious

hazard associated with the use of the drug product. Because the

reminder format was used, the print ad fails to include information

in brief summary relating to side effects, contraindications, and

effectiveness as required by regulation. Thus, the print

advertisement misbrands bupropion hydrochloride extended-release

tablets (SR) in violation of Sections 502(n) and 201 (n) of the

Federal Food, Drug, and Cosmetic Act (Act), 21 U.S.C. §§ 352(n) and

321(n) and FDA's implementing regulations 21 C.F.R. §§ 202.1(e)(1),(e)

(2)(i),(e)(3).

Background

According to its FDA-approved product labeling (PI), bupropion

hydrochloride extended-release tablets (SR) is approved for the

following indication (in pertinent part):

Bupropion hydrochloride extended-release tablets (SR) are indicated

for the treatment of depression. The efficacy of bupropion in the

treatment of depression was established in two 4-week controlled

trials of depressed inpatients and in one 6-week controlled trial of

depressed outpatients whose diagnoses corresponded most closely to

the Major Depression category of the APA Diagnostic and Statistical

Manual (DSM) (see CLINICAL PHARMACOLOGY).

The use of bupropion hydrochloride extended-release tablets (SR) is

associated with a boxed warning. Specifically, the PI states:

BOXED WARNING

Suicidality in Children and Adolescents

Antidepressants increased the risk of suicidal thinking and behavior

(suicidality) in short-term studies in children and adolescents with

Major Depressive Disorder (MDD) and other psychiatric disorders.

Anyone considering the use of Bupropion Hydrochloride Extended-

release Tablets (SR) or any other antidepressant in a child or

adolescent must balance this risk with the clinical need. Patients

who are stared on therapy should be observed closely for clinical

worsening, suicidality, or unusual changes in behavior. Families and

caregivers should be advised of the need for close observation and

communication with the prescriber. Bupropion Hydrochloride Extended-

release Tablets (SR) is not approved for use in pediatric patients.

(See WARNINGS and PRECAUTIONS: Pediatric Use)

Pooled analysis of short-term (4 to 16 weeks) placebo-controlled

trials of 9 antidepressant drugs (SSRIs and others) in children and

adolescents with major depressive disorder (MDD), obsessive

compulsive disorder (OCD), or other psychiatric disorders (a total of

24 trials involving over 4,400 patients) have revealed a greater risk

of adverse events representing suicidal thinking or behavior

(suicidality) during the first few months of treatment in those

receiving antidepressants The average risk of such events in patients

receiving antidepressants was 4%, twice the placebo risk of 2%. No

suicides occurred in these trials.

Violative " Reminder Ad "

According to 21 C.F.R. § 202.1(e)(2)(i) (in pertinent

part), " Reminder advertisements ... are not permitted for a

prescription drug product whose labeling contains a boxed warning

relating to a serious hazard associated with the use of the drug

product. " Therefore, because the labeling for bupropion hydrochloride

extended-release tablets (SR) contains a boxed warning related to a

serious hazard associated with the use of the drug product, it is a

violation to present this drug product in promotional material that

takes the form of a reminder advertisement.

All advertisements for any prescription drug, unless otherwise exempt

(such as permissible reminder advertisements), must include a true

statement of information in brief summary relating to side effects,

contraindications (including side effects, warnings, precautions, and

contraindications, etc.), and effectiveness as required by

regulation. (See 21 U.S.C. § 352(n), 21 C.F.R. §§ 202.1(e)(1), (e)

(3)) This print advertisement fails to present such a brief summary.

Conclusion and Requested Action

Your promotional piece is in the form of an impermissible reminder

advertisement that also fails to include information in brief summary

relating to side-effects, contraindications, and effectiveness for

bupropion hydrochloride extended-release tablets (SR) in violation of

21 U.S.C. §§ 352(n), 321(n); 21 C.F.R. §§ 202.1(e)(1), (e)(2)(i), (e)

(3).

DDMAC requests that Sandoz immediately cease the dissemination of

violative promotional materials for bupropion hydrochloride extended-

release tablets (SR) such as those described above. Please submit a

written response to this letter on or before June 12; 2006, stating

whether you intend to comply with this request, listing all violative

promotional materials for bupropion hydrochloride extended-release

tablets (SR) such as those described above, and explaining your plan

for discontinuing use of such materials. Please direct your response

to me at the Food and Drug Administration, Center for Drug Evaluation

and Research, Division of Drug Marketing, Advertising, and

Communications, 5901-B Ammendale Road, Beltsville, MD 20705-1266,

facsimile at (301) 796-9878. In all future correspondence regarding

this matter, please refer to MACMIS# 14211 in addition to the ANDA

number. We remind you that only written communications are considered

official.

The violations discussed in this letter do not necessarily constitute

an exhaustive list. It is your responsibility to ensure that your

promotional materials for bupropion hydrochloride extended-release

tablets (SR) comply with each applicable requirement of the Act and

FDA implementing regulations.

Sincerely,

B. Gray, PharmD

Acting Group Leader

Division of Drug Marketing,

Advertising, and Communications