Salzman C, Fisher J, Nobel K, Glassman R, Wolfson A, Kelley M.
Cognitive Improvement Following Benzodiazepine Discontinuation in Elderly
Nursing Home Residents.
International Journal of Geriatric Psychiatry 1992; 7: 89-93.

In a controlled study, benzodiazepine treatment was gradually discontinued from a group of
elderly nursing home residents. In comparison with similar residents who continued on
benzodiazepines, measures of memory and cognitive functioning showed significant improvement
following discontinuance. There was no associated increase in anxiety, agitation, or
sleeplessness. These data are consistent with previous observations suggesting that
benzodiazepines impair cognitive function in the elderly and further indicate that such impairment
is reversible upon benzodiazepine discontinuance. [SUMMARY p. 89]

[Key words; memory impairment, cognitive impairment, the elderly]

Scharf MB, Jacoby JA.
Lorazepam - Efficacy, Side Effects, and Rebound Phenomena.
Clinical Pharmacology and Therapeutics 1982; 31: 175-179.

" The spontaneous reports of amnesia by three of our subjects after oral doses of lorazepam
strongly suggest that this side effect, thought to occur rarely after oral doses of other
benzodiazepines, may be a more frequent side effect of lorazepam." [p. 178]

[Key words; Ativan, lorazepam, amnesia, memory impairment]

Schlicht HJ, Gelbke HP.
[ Frequency of Positive Diazepam-Screening in Post-Mortem Examinations.]
German Zeitschrift für Rechtsmedizin 1979; 82: 271-277.

" The proportion of diazepam-positive samples was increased in the groups of suicide and
poisoning (alcohol and opiates). The association between diazepam intake and poisoning was
statistically highly significant. " [p. 271]

[Key words; Valium, diazepam, poisoning, suicide]

Schneider-Helmert D.
Why Low-Dose Benzodiazepine-Dependent Insomniacs Can't Escape Their
Sleeping Pills.
Acta Psychiatrica Scandinavica 1988; 78: 706-711.

" Comparison with drug-free insomniacs showed that LBD (= low-dose benzodiazepine
dependence) leads to a complete loss of hypnotic activity and substantial depression of delta and
REM sleep."

" Upon withdrawal, recovery from this suppression, especially in REM sleep, occurred, while
insomnia did not increase. The patients, however, reported sleeping longer while taking the drug
compared with withdrawal. This misperception seems to be a specific effect of benzodiazepines,
and contrasts with the full awareness of insomnia upon withdrawal. It is concluded that these
effects play a leading role in the patient's inability to escape their sleeping pills. "

" It has recently been recognised that the widespread use of benzodiazepines bears a
considerable risk for patients to develop dependence on therapeutic dosage. One of the major
reasons to use these substances on a long-term basis is chronic insomnia.

Half of the patients reporting to the Medical Center Mariastein are dependent on benzodiazepines
according to clinical criteria. They typically defend their persistent use of sleeping pills with the
claim that they experience such poor sleep when stopping medication for only one or two nights
and they therefore feel forced to continue drug intake despite fading hypnotic efficacy. In fact,
insomnia has been reported to be among the most frequent withdrawal symptoms after somatic
dependence has developed with the use of benzodiazepines in therapeutic dosage for months or
years. " [p. 706]

[Key words; dependence, tolerance, insomnia, hypnotics]

Schneider-Helmert D.
[ Confusional States Due to the Hypnotic Midazolam.]
German Schweizer Medizinische Wochenschrift 1985; 115: 247-249.

Five cases are reported in which confusional states and total anterograde amnesia occurred after
oral intake of recommended doses of midazolam, a new ultra-short acting benzodiazepine.
Particular risk factors were not present, and in three out of five patients the complications
occurred with the first administration. Analysis of these cases and experimental data reported in
the literature suggest t hat the extreme response curve of midazolam may be responsible for these
complications. The potential danger of the patient's actions is pointed out. [SUMMARY p. 247]

[Key words; Versed, midazolam, confusion]

Schweizer E, Case WG, Rickels K.
Dr. Schweizer and Associates Reply.
American Journal of Psychiatry 1989; 146: 1242.

" It is our position that most of these patients did not require long-term benzodiazepine therapy -
certainly not continuously for many years. In fact, we have unpublished data which demonstrate
that many patients, once they have been withdrawn from their maintenance benzodiazepines,
show more improvement on clinical measures of anxiety and depression than they did during their
chronically medicated state. " [p. 1242]

[Key words; detoxification, long-term effects]

Seivewright N, Dougal W.
Withdrawal Symptoms from High Dose Benzodiazepines in Poly Drug Users.
Drug and Alcohol Dependence 1993; 32: 15-23.

" Finally, it is clear that the phenomenon of benzodiazepine dependence in the case of poly drug
users encompasses a much wider range of aspects of usage and behaviours than has hitherto
been observed in conventional users. We found that escalation of daily dosage up to 50 times
therapeutic dosage had occurred, and taking of 5-10 times therapeutic dosage was

Extreme behaviours were reported in the obtaining of continued supplies and avoidance of
interruption of supply and in drug seeking behaviour when withdrawing. Our subjects offered
descriptions of alarmingly disturbed behaviour when intoxicated with benzodiazepines,
characterised particularly by amnesia, which early reports suggest is common..." [p. 22]

[Key words; addiction, abuse, dependence, amnesia, memory impairment]

Sheehan MF, Sheehan DV.
Snorting Benzodiazepines.
American Journal of Drug and Alcohol Abuse 1991; 17: 457-468.

Two cases of intranasal benzodiazepine use are presented. The methods of preparation and
administration of the powder and accounts of the pharmacological effects of the drugs used are
described. The pattern of development and progress of the habit and its associated features are
delineated. Snorting benzodiazepines appears to be more common than is currently appreciated,
and the clinical complications and implications of this habit are discussed. [ABSTRACT p. 457]

" After 3 years on alprazolam (4 mg/d by mouth), he [a 25-year old male] found that this dose
was not as effective as before in controlling his panic disorder. Intermittently, he used up to 6
mg/d when his panic disorder worsened. " [p. 459]

" Whether these first reported cases of benzodiazepine snorting are a prelude to more
widespread use or to an epidemic is to early to tell. The implications are serious, the
pharmacokinetic profile different, the possible complications hazardous, and the need for
physicians and drug enforcement agencies to be forewarned is apparent. " [p. 467]

[Key words; Xanax, alprazolam, addiction, abuse, dependence, tolerance]

Shorr RI, Bauwens SF, Landefeld CS.
Failure to Limit Quantities of Benzodiazepine Hypnotic Drugs for
Outpatients: Placing the Elderly at Risk.
American Journal of Medicine 1990; 89: 725-731.

"In summary we have demonstrated that, in our hospital, elderly patients, who are at the highest
risk for experiencing adverse effects from long-term use of benzodiazepine hypnotics, receive a
disproportionate number of prescriptions that permit such use o f these agents. It is important to
determine whether similar patterns of benzodiazepine hypnotic prescribing exist in other outpatient
settings. If similar patterns are found, widespread efforts will be needed to reduce quantities of
hypnotics pre scribed to elderly outpatients." [p. 731]

[Key words; hypnotics, the elderly]

Short TG, Maling T, Galletly DC.
Ventricular Arrhythmia Precipitated by Flumazenil.
BMJ 1988; 296: 1070-1071.

" The patient was extubated 20 hours after admission by which time her electrocardiogram was
normal. Further questioning disclosed that she had a nine year history of physical dependency on
benzodiazepines and had developed insomnia, anxiety, and phobias on attempted withdrawal. "
[p. 1071]

[Key words; dependence, withdrawal, phobias]

Skegg K, Richards SM, Doll R.
Minor Tranquillisers and Road Accidents.
BMJ 1979; 1: 917-919.

" A large, randomised controlled trial would be needed to disentangle the effects of drugs and
underlying diseases. From a practical point of view, however, it is important to know that drivers
taking minor tranquillisers are at increased risk of having a road accident (for whatever reason);
and the results of our small study suggest that the risk may be substantial.

This has implications for the safety of other road users as well as the patients themselves. If our
results prove to be typical, patients given tranquillisers should at least be warned that they are at
special risk and that, if they must drive, they should take particular care not to exceed the
prescribed dose or to combine their drugs with alcohol. " [p. 919]

[Key words; accidents, traffic]

Skinner PT.
Skills not Pills: Learning to Cope with Anxiety Symptoms.
Journal of the Royal College of General Practitioners 1984; 34: 258-260.

A pilot project to assess the benefit of a psychology service in general practice for patients with
anxiety is described. A course of lessons in "anxiety management skills" was provided at two
practices. At a follow-up appointment one year later two thirds of the 35 patients studied had
stopped taking anxiolytic medication and two thirds reported and elimination of their anxiety
symptoms. It is proposed that a psychology service be provided for general practitioner in health
centres and health clinics, as a possible alternative to repeat prescribing of anxiolytic medication.
[SUMMARY p. 258]

[Key words; anxiety, withdrawal]

Smart RG, Fejer D.
Drug Use Among Adolescents and Their Parents : Closing the Generation
Gap in Mood Modification
Journal of Abnormal Psychology. 1972; 79: 153-160.

"...It is clear that much adolescent drug use probably takes place in families where parental pill is
common. It is possible that much adolescent drug use or abuse cannot be reduced without
parallel reductions in parental use. " [p. 159]

[Key words; addiction, abuse, dependence]

Smith AJ.
Self-Poisoning with Drugs: A Worsening Situation.
BMJ 1972; 4: 157-159.

" This report is intended to draw attention to the worsening situation in one English city and not to
discuss prevention in any detail. Nevertheless, it is difficult to escape some conclusions about
prophylaxis. Clearly the medical profession itself by increasing the prescribing of psychoactive
drugs (often for trivial causes that should be handled by simple reassurance, counsel, or support)
is in danger of breeding an attitude of dependence on pharmacological crutches for all crises. In a
drug-conscious society self-poisoning must always be a hazard. Greater care and responsibility in
prescribing would undoubtedly reduce the size of the problem. " [p. 159]

" With the inevitable increase in availability of new psychotropic drugs in the future it is difficult to
foresee any improvement in the self-poisoning problem without careful thought and planning. The
time may have come for an official appraisal of the situation on a national basis and for a
concerted discussion of preventive measures. " [p. 159]

[Key words; poisoning, suicide]

Smith RJ.
Study Finds Sleeping Pills Overprescribed.
Science 1979; 204: 287-288.

" Sleeping pills, the most prescribed medication in the world, are more dangerous and less useful
than either physicians or patients realize, according to a recent report by the Institute of Medicine
(IOM) - National Academy of Sciences. " [p. 287]

" Currently, more than 25 million such prescriptions are written annually in the United States
alone, and more than 8 million persons use the pills sometimes during the year.

The panel is particularly concerned that persons are taking the pills for to many consecutive
nights, beyond the period of proved effectiveness, and to a point where the hazard s may be
severe: Physicians should rarely, if ever, prescribe hypnotic drugs for periods beyond 2 to 4

Clinical trials cited by the panel show that the effectiveness of most pills begins to drop off after 7
nights. Currently, most prescriptions are for 30 tablets or more, however. " [p. 287]

" ... the IOM report concludes that, although barbiturates are indeed as hazardous as everyone
thinks, the chief alternatives, benzodiazepines, may be just as risky, and in some ways may be
even more risky than barbiturates. " [p. 287]

" In addition, the panel reported, Dalmane may not have some of the attributes ascribed to it by
its manufacturer, Hoffmann-La Roche Inc. Labelling in the Physician's Desk Reference and in the
company's advertising, for example claims, "Sleep laboratory studies have objectively determined
that Dalmane is effective f or at least 28 consecutive nights of drug administration." Nowhere, the
IOM panel says, "do these advertisements reveal that the claim of effectiveness for 28 nights is
based on studies of only ten patients and that hundreds of individuals with sleep complaints had to
be screened to select these severe insomniacs for research purposes. " [p. 287]

" ... the panel concluded that what was thought to be Dalmane's greatest attribute was, for all
practical purposes, unimportant. Unlike barbiturates, Dalmane is not lethal by itself in overdose.
But the panel discovered that an increasing proportion of drug-related deaths involve alcohol;
because both drugs are lethal in combination with alcohol, Dalmane does not offer any significant
advantage in diminishing the overall number of deaths related to sleeping pills. " [pp. 287-288]

" "The committee finds information from these sources tends to be incomplete and of questionable
value to the physician." One example is the current PDR listing for Dalmane, which claims that
Dalmane is effective for a month of consecutive use. This listing is based on only two studies in
sleep laboratories with five people each. Asked about this, a company spokesman admits that
"perhaps this is not satisfactory." Also, no mention of Dalmane's long-acting metabolite was made
until last year, 5 years after the characteristic became known.

When the information was added, consequent adverse effects were not mentioned; the company
instead brags that the drug is even more effective than known earlier. " [p. 288]

[Key words; Dalmane, flurazepam, hypnotics, drug manufacturers]

Snaith RP, Hindmarch I.
Psychotropic Drugs and Road Accidents.
BMJ 1977; 2: 263.

" Sedative drugs, of course, are not detected in the breathalyser and if they were there would be
no legal implications. Yet there is good evidence that the sedative drugs commonly prescribed
(previously the barbiturates and now the benzodiazepines) do potentiate the effect of alcohol."
[p. 263]

" Prescriptions for sedative drugs and hypnotics now run into millions a year. The people to
whom they are prescribed are also likely to be using alcohol... yet there is no requirement placed
upon the medical profession to issue a warning of this interaction effect when the drugs are
prescribed." [p. 263]

" We believe that research in this field has been to long delayed and that it should now be
accorded priority... Complaints may be made that issuing such warnings and recommendations
will inevitably decrease treatment compliance, but if this is to be set against the potential saving of
life then the balance will be favourable, for sedative drugs are frequently prescribed for trivial
reasons. " [p. 263]

[Key words; accidents, traffic]

Soldatos CR, Sakkas PN, Bergiannaki JD, Stefanis CN.
Behavioral Side Effects of Triazolam in Psychiatric In-Patients: Report of
Five Cases.
DICP 1986; 20: 294-297.

Triazolam was administered to five psychiatric in-patients for a two-week period. This period
was preceded by a one-week placebo baseline and followed by another week of placebo
administration. All conditions were double blind. By the second week of active drug
administration, psychopathology greatly intensified across all of the patient with the emergence of
anxiety, memory impairment, confusion, paranoid ideation, and hallucinations. The drug-induced
behavioral changes induced persisted during the initial withdrawal period, but then gradually
subsided. Also following drug withdrawal, four patients showed a marked worsening of their
sleeplessness for several nights. [ABSTRACT p. 294]

[Key words; Halcion, triazolam, dependence, withdrawal, anxiety, amnesia, memory impairment,
confusion, paranoia, hallucinations, psychosis, paradoxical effects]

Speight ANP.
Floppy-infant Syndrome and Maternal Diazepam and/or Nitrazepam.
Lancet 1977; ii: 878.

" There is a general lack of awareness of the hazards of long-term diazepam in pregnancy.
Unfortunately, many women on diazepam will continue to take the drug by repeat prescriptions,
even when they become pregnant, and the liberal use of diazepam and nitrazepam on general
medical and surgical wards seems to extend to antenatal wards. Where severe psychiatric
disturbance makes prescription essential the pediatric staff should be alerted. In all but the mildest
cases a period in a special-care nursery is desirable because of the danger of apnea. Apart from
the danger, the sedated infant will have less chance of being breast fed, and his participation in the
process of mother-child bonding will be impaired. "

[Key words; pregnancy, infants, apnea]

Sunter JP, Bal TS, Cowan WK.
Three Cases of Fatal Triazolam Poisoning.
BMJ 1988; 297: 719.

" Triazolam, which is widely prescribed as a hypnotic, is considered to be safe even in overdose.
In elderly patients, however, overdose may be fatal, particularly in patients taking concomitant
drug treatment or with serious disease. "

" The hazards of overdose led to barbiturates being replaced as hypnotics by drugs such as
triazolam. Our recent experience indicates that patients who have taken triazolam should be
monitored closely as this drug may not be as safe as is commonly supposed when taken in
overdose by debilitated elderly patients. "

[Key words; Halcion, triazolam, poisoning, suicide]

Surendrakumar D, Dunn M, Roberts CJC.
Hospital Admission and the Start of Benzodiazepine Use.
BMJ 1992; 304: 881.

" The identification of 17 potential new users of benzodiazepines after admission to the general
beds in one district in two weeks was higher than expected and is unacceptable. If the study is
representative it implies a considerable potential risk for subsequent dependence. ( - - - )

Our study suggests that hospital prescribing continues to contribute to benzodiazepine use in the
community as half the group had first been prescribed the drugs in hospital.

In addition to the inappropriate supply of drugs at the end of a hospital stay, poor prescribing was
evident by the drug's apparently unwarranted use in an elderly demented patient and continuous
use in a stroke victim. There was also clear evidence that benzodiazepine hypnotics were being
prescribed at the time of admission, before an assessment of the need could have been made.
There is no room for complacency in hospitals regarding benzodiazepine prescribing. This study
highlights the need for prescribing policies to be formulated and instituted. "

[Key words; addiction, dependence, the elderly]

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