UPJOHN'S DRUG XANAX ON TRIAL

Hirsch Davis hdavis at erolsNSP.com
Thu Mar 26 18:00:37 EST 1998


On 26 Mar 1998 18:44:08 GMT, sbharris at ix.netcom.com(Steven B. Harris)
wrote:

[snip]
>
>   Some people have tried to make a big deal out of "dependence" vs.
>"addiction", but I personally don't think it's a useful distinction. 
>The drug seeking behavior of the patient is the same, and so are the
>strains on the doctor and the patient's family and support system.  If
>you'll sell your grandma down the river to get one more dose, then
>you've got a problem.  What you call the problem is largely irrelevent.
>
>                                        Steve Harris, M.D.


Good grief.  Diabetics exhibit drug-seeking behavior when they ask for
insulin.  I guess that makes them junkies.  CYA Steve, don't give it
to them!  You'll just get sued for pandering to their addiction.

The "sell your grandma down the river" phenomenon is in fact typical
of the addict.  The problem is that patients with anxiety disorders
don't do that (yes, there is some overlap between anxiety sufferers
and drug abusers, but it's small).  However, you point out the
relevance of the addiction/dependence distinction yourself, when you
fail to distinguish between the necessary use of medication for a
disabling condition and drug abuse.  If you're afraid to prescribe a
benzo when medically necessary due to fear of "addiction", then let's
call it something else, perhaps "dependence", so you can get over that
fear and help your patients.

Bloom and Kupfer's "Psychopharmacology: The Fourth Generation of
Progress" has a couple of good chapters on anxiety disorders.  Until
you get around to it, here are a couple of abstracts from authors who
seem top have given a bit more thought to the problem of relieving
patient suffering with dependence-producing medications than you.

Hirsch


ARTICLE TITLE:  Panic disorder and addiction: the clinical issues of
comorbidity. 
ARTICLE SOURCE:  Bull Menninger Clin  (United States), Spring 1997,
61(2 Suppl A) pA54-65 
AUTHOR(S):  Du Pont RL 
AUTHOR'S ADDRESS:  Institute for Behavior and Health, Inc., Rockville,
MD 20852, USA. 
MAJOR SUBJECT HEADING(S):  Case Management [standards]; Panic Disorder
[epidemiology] [therapy]; Substance-Related Disorders [epidemiology]
[therapy] 
MINOR SUBJECT HEADING(S):  Comorbidity; Diagnosis, Dual (Psychiatry) 
INDEXING CHECK TAG(S):  Human; Support, Non-U.S. Gov't 
PUBLICATION TYPE:  JOURNAL ARTICLE 
ABSTRACT:  Panic disorder and addiction are occasionally
comorbid--4.5% of addicted patients have panic disorder, and 16% of
panic disorder patients are comorbid for addiction to alcohol and
other drugs. Despite these relatively low rates of comorbidity, the
treatment of these two disorders is commonly confounded by issues of
comorbidity, as many physicians avoid using benzodiazepines to treat
panic disorder out of inappropriate fear of addiction, and not a few
physicians treat panic disorder thinking that they will thereby end
comorbid addiction. Sound clinical practice calls for clear
identification of both panic disorder and addiction and fully
effective treatments of the diseases from which the patients suffer. 
MEDLINE INDEXING DATE:  199709 
ISSN:  0025-9284 
LANGUAGE:  English 
UNIQUE NLM IDENTIFIER:  97293499 

ARTICLE TITLE:  Clinical aspects of chronic use of alprazolam and
lorazepam. 
ARTICLE SOURCE:  Am J Psychiatry  (United States), Aug 1995, 152(8)
p1161-7 
AUTHOR(S):  Romach M; Busto U; Somer G; Kaplan HL; Sellers E 
AUTHOR'S ADDRESS:  Clinical Research and Treatment Institute,
Addiction Research Foundation, Toronto, Ont., Canada. 
MAJOR SUBJECT HEADING(S):  Alprazolam [therapeutic use]; Lorazepam
[therapeutic use]; Mental Disorders [drug therapy]; Substance-Related
Disorders [diagnosis] 
MINOR SUBJECT HEADING(S):  Alprazolam [administration & dosage]
[adverse effects]; Ambulatory Care; Anxiety Disorders [drug therapy];
Depressive Disorder [drug therapy]; Drug Administration Schedule;
Lorazepam [administration & dosage] [adverse effects]; Middle Age;
Patient Acceptance of Health Care; Recurrence; Risk Factors; Sex
Factors; Substance Withdrawal Syndrome [epidemiology] [etiology];
Substance-Related Disorders [epidemiology] 
INDEXING CHECK TAG(S):  Female; Human; Male 
PUBLICATION TYPE:  JOURNAL ARTICLE 
ABSTRACT:  OBJECTIVE: The authors' goal was to determine the clinical
characteristics of persistent users of alprazolam or lorazepam who
wished to discontinue their medication. METHOD: Long-term users (daily
use for more than 3 months) of alprazolam (N = 34) or lorazepam (N =
97) who entered an outpatient treatment program for discontinuation of
benzodiazepines were carefully assessed. Detailed histories of
benzodiazepine use were obtained; a structured interview was used to
make psychiatric diagnoses based on DSM-III-R criteria. RESULTS: The
majority of patients were using low therapeutic doses of medication
(lorazepam: mean = 2.7 mg/day; alprazolam: mean = 1.2 mg/day) and had
either maintained their initial daily dose over time or decreased it.
Individuals tended to shift their use of medication from an
as-prescribed to an as-needed pattern. Forty-seven percent of the
patients were diagnosed with at least one current anxiety disorder,
most commonly generalized anxiety. At least one diagnosable
personality disorder was found in 45% of the patients, most commonly
obsessive-compulsive personality disorder. Patterns of benzodiazepine
use were influenced by age, gender, and past history of alcohol
dependence. CONCLUSIONS: Long-term users of alprazolam/lorazepam
seeking treatment for discontinuation had clinically important past
and current psychiatric histories. They used a constant or decreasing
dose of medication and made attempts to stop their use. Persistent use
of alprazolam/lorazepam for therapeutic purposes did not represent
abuse or addiction as the terms are usually understood. A substantial
proportion of these patients may be receiving appropriate maintenance
therapy for a chronic psychiatric condition. 
MEDLINE INDEXING DATE:  199511 
ISSN:  0002-953X 
LANGUAGE:  English 
UNIQUE NLM IDENTIFIER:  95351392 
CAS REGISTRY/EC NUMBER(S):   28981-97-7 (Alprazolam); 846-49-1
(Lorazepam) 

ARTICLE TITLE:  Alprazolam and benzodiazepine dependence. 
ARTICLE SOURCE:  J Clin Psychiatry  (United States), Oct 1993, 54
Suppl p64-75; discussion 76-7 
AUTHOR(S):  Sellers EM; Ciraulo DA; Du Pont RL; Griffiths RR; Kosten
TR; Romach MK; Woody GE 
AUTHOR'S ADDRESS:  Department of Pharmacology, University of Toronto,
Canada. 
MAJOR SUBJECT HEADING(S):  Alprazolam [adverse effects];
Benzodiazepines [adverse effects]; Substance-Related Disorders
[epidemiology] 
MINOR SUBJECT HEADING(S):  Adult; Alcoholism [epidemiology];
Comorbidity; Diazepam [adverse effects]; Incidence; Methadone
[therapeutic use]; Middle Age; Opioid-Related Disorders [epidemiology]
[rehabilitation]; Substance Abuse Detection; Substance-Related
Disorders [etiology] 
INDEXING CHECK TAG(S):  Female; Human; Male 
PUBLICATION TYPE:  JOURNAL ARTICLE; REVIEW (97 references); REVIEW,
TUTORIAL 
ABSTRACT:  The incidence of nonmedical use of alprazolam is very low
relative to its widespread legitimate medical use; in fact, given the
millions of patients who have received this medication, the incidence
is remarkably small. In particular, among patients with anxiety
disorders, dependence does not appear to be a clinically important
problem. Alprazolam abuse and dependence represent only a small
fraction of the large and serious nonmedical use problem in the United
States, and when they occur, are among individuals who abuse other
drugs. For example, a serious problem of alprazolam abuse may exist
among patients in methadone maintenance treatment. A similar problem
exists with diazepam. Alcohol abusers and alcohol-dependent
individuals are another group among whom concern about benzodiazepine
and alprazolam abuse exists. However, more and better information
about the extent and nature of this use is needed. Many patients with
alcohol or drug abuse also have anxiety disorders for whom effective
pharmacotherapy may be needed. In the interim, caution but not
prohibition to use should prevail in prescribing alprazolam to such
patients. To the extent that nonmedical alprazolam use exists,
evidence suggests that the vast majority of such use is the
consequence of the inappropriate prescribing of the medication by a
small number of physicians. One way to reduce the inappropriate use of
benzodiazepines in methadone programs is to drug test the
methadone-maintenance patients and to link positive urine tests to
contingency-management strategies. The available data provide some
support to the idea that alprazolam and diazepam have more abuse
liability than other benzodiazepines. 
MEDLINE INDEXING DATE:  199403 
ISSN:  0160-6689 
LANGUAGE:  English 
UNIQUE NLM IDENTIFIER:  94086456 
CAS REGISTRY/EC NUMBER(S):   0 (Benzodiazepines); 28981-97-7
(Alprazolam); 439-14-5 (Diazepam); 76-99-3 (Methadone) 

ARTICLE TITLE:  Addiction to benzodiazepines--how common? [see
comments] 
COMMENTS:  Comment in: Arch Fam Med 1996 Jul-Aug; 5(7):383-4; Comment
in: Arch Fam Med 1996 Jul-Aug; 5(7):384 
ARTICLE SOURCE:  Arch Fam Med  (United States), Nov 1995, 4(11)
p964-70 
AUTHOR(S):  Piper A Jr 
MAJOR SUBJECT HEADING(S):  Benzodiazepines; Substance-Related
Disorders [etiology] 
MINOR SUBJECT HEADING(S):  Physician's Practice Patterns;
Prescriptions, Drug; Prevalence; Substance-Related Disorders
[epidemiology] 
INDEXING CHECK TAG(S):  Human 
PUBLICATION TYPE:  JOURNAL ARTICLE; REVIEW (111 references); REVIEW,
TUTORIAL 
ABSTRACT:  Benzodiazepines have compiled an impressive record of
safety and efficacy. Despite this record, however, physicians and
laypersons frequently worry about the drugs' addictive potential.
Overemphasizing these concerns may discourage prescription of
benzodiazepines, thereby impeding treatment of anxiety disorders. This
review first defines the term addiction. It then examines how
frequently conditions meeting that definition occur in patients
without histories of substance abuse, who are prescribed
benzodiazepines under medical supervision. In such patients,
benzodiazepines almost never induce behavior that satisfies any
reasonable definition of addiction. 
MEDLINE INDEXING DATE:  199602 
ISSN:  1063-3987 
LANGUAGE:  English 
UNIQUE NLM IDENTIFIER:  96074207 
CAS REGISTRY/EC NUMBER(S):   0 (Benzodiazepines) 

ARTICLE TITLE:  Current benzodiazepine issues. 
ARTICLE SOURCE:  Psychopharmacology (Berl)  (Germany), Mar 1995,
118(2) p107-15; discussion 118, 120-1 
AUTHOR(S):  Woods JH; Winger G 
AUTHOR'S ADDRESS:  Department of Pharmacology, University of Michigan
Medical School, Ann Arbor 48109, USA. 
MAJOR SUBJECT HEADING(S):  Benzodiazepines [adverse effects];
Substance-Related Disorders [etiology] 
MINOR SUBJECT HEADING(S):  Age Factors; Benzodiazepines
[pharmacokinetics] [therapeutic use]; Memory Disorders [chemically
induced]; Risk Factors; Substance Withdrawal Syndrome [etiology];
Triazolam [pharmacology] 
INDEXING CHECK TAG(S):  Human; Support, Non-U.S. Gov't; Support, U.S.
Gov't, P.H.S. 
PUBLICATION TYPE:  JOURNAL ARTICLE; REVIEW (86 references); REVIEW,
TUTORIAL 
ABSTRACT:  This article deals with some of the recent evidence bearing
on the issues of the liability of benzodiazepines to lead to abuse,
dependence, and adverse behavioral effects. Reviews of
epidemiological, clinical and experimental literature indicated that
the previous conclusion about abuse of these drugs still holds: the
vast majority of the use of benzodiazepines is appropriate. Problems
of nonmedical use arise nearly exclusively among people who abuse
other drugs. Nevertheless, there are reasons for concern about
patients who take benzodiazepines regularly for long periods of time.
These drugs can produce physiological dependence when taken
chronically, and although this does not appear to result in dose
escalation or other evidence of "psychological dependence,"
physiological dependence can result in patient discomfort if drug use
is abruptly discontinued. Also, physicians are currently prescribing
shorter-acting benzodiazepines in preference to longer-acting
benzodiazepines. The shorter-acting drugs can produce a more intense
withdrawal syndrome following chronic administration. Furthermore,
rates of use of benzodiazepines increase with age, and elderly
patients are more likely than younger ones to take the drug
chronically. The clearest adverse effect of benzodiazepines is
impairment of memory. This, too, may be particular concern in older
patients whose recall in the absence of drug is typically impaired
relative to younger individuals, and who are more compromised
following drug administration. 
MEDLINE INDEXING DATE:  199510 
ISSN:  0033-3158 
LANGUAGE:  English 
UNIQUE NLM IDENTIFIER:  95343042 
CAS REGISTRY/EC NUMBER(S):   0 (Benzodiazepines); 28911-01-5
(Triazolam) 
GRANT ID NUMBER:  DA-00254-DA-NIDA 


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