Ward MG, Schuckit MA.
Factors Asociated with Suicidal Behavior in Polydrug Abusers.
Journal of Clinical Psychiatry 1980; 41: 379-385.

In 155 polydrug abusers, druguse patterns that were associated with serious suicidal behavior
included preference for depressant drugs, history of withdrawal from barbiturates, and lower
frequency of PCP use. Diagnostic factors associated with increased suicidal behavior included
history of depression in the subject's mother and a diagnosis of antisocial personality in the
subjects themselves. These findings are discussed in relation to Winokur's concept of broad
spectrum depressive disease. [ABSTRACT p. 379]

[Key words; dependence, addiction, abuse, depression, suicide]

Wardle J.
Behaviour Therapy and Benzodiazepines: Allies or Antagonists?
British Journal of Psychiatry 1990; 156: 163-168.

Behaviour therapy and benzodiazepines are directed towards common problems and are often
used in combination. At present we know little about the beneficial or adverse interactions of
these two treatments. This paper reviews the available literature and suggests that there are
important theoretical and clinical issues to be resolved. [ABSTRACT p. 163]

" The result of the post-treatment assessment indicated that patients on benzodiazepines did worse
overall. This it not surprising in view of the likelihood that long-term users of benzodiazepines
have more serious and resistant disorders. However, there was also a trend in the data for a more
deleterious effect of concurrent benzodiazepine use in the behaviour therapy than in the cognitive
therapy. The results from the one-year follow-up revealed these differences more clearly. Only 8
percent of the behaviour therapy patients who had received benzodiazepines were in the
"markedly improved" category at follow-up compared with 86 percent of those who had not
been taking benzodiazepines; the cognitive therapy group showed a 50 percent marked improve
ment rate regardless of concurrent medication. This study was not designed to investigate these
questions, so there was of course no random assignment of patients. Nevertheless this result cast
concurrent benzodiazepine use in a less benevolent light than the studies using short-term
administration of benzodiazepines."

[Key words; long-term effects]

Weedle PB, Poston JW, Parish PA.
Use of Hypnotic Medicines by Elderly People in Residential Homes.
Journal of the Royal College of General Practitioners 1988; 38: 156-158.

Data relating to the use of hypnotic medicines from a descriptive epidemiological study of drug
use in 55 residential homes for elderly people were analysed. Of the 1888 residents included in
the study, 435 (23,0%) were receiving a total of 448 hypnotic medicines. There was preferential
prescribing of short-acting benzodiazepines but long-acting benzodiazepines represented 31,7%
of all hypnotic drugs prescribed. The median duration of treatment with temazepam was 0,8 years
and with nitrazepam 2,5 years. The proportion of residents receiving hypnotic medicines in each
home varied from 3,6% to 60,0% with a median of 24,1%. This study indicates a need for
general practitioners to review their prescribing of hypnotic medicines for elderly people, paying
particular attention to the duration of treatment. [ABSTRACT p. 156]
[Key words; Euhypnos, Mogadon, Normison, nitrazepam, temazepam, hypnotics, the elderly]

Whitcup SM, Miller F.
Unrecognized Drug Dependence in Psychiatrically Hospitalized Elderly
JAGS 1987; 35: 297-301.

" Although underlying medical illness could not be completely ruled out as the etiology of
symptoms and signs interpreted as evidence of complicated withdrawal, the patients did not have
symptoms or history of underlying cardiac, respiratory, or CNS disease, and their medical
evaluations on admission were normal. As a result of their clinical condition, three patients with
complicated withdrawal were transferred to medical intensive care units and two to medical
floors. Nevertheless, a thorough medical work-up of patients with complicated withdrawal did
not reveal a diagnosis other than withdrawal to explain their clinical course, making the possibility
of significant and confounding underlying medical illness unlikely. "

" Women may be at increased risk for misdiagnosis because they use benzodiazepines rather than
alcohol resulting in an underestimation of their chemical dependence. "

" Finally, when chemical dependence was recognized and treated, complications were minimal,
but when unrecognized, withdrawal lead to significant morbidity. " [p.300]

[Key words; addiction, dependence, withdrawal, the elderly]

WHO Review Group.
Use and Abuse of Benzodiazepines.
Bulletin of the World Health Organisation 1983; 61: 551-562.

Benzodiazepines are widely used for the treatment of anxiety, insomnia, and certain
neuromuscular and convulsive disorders. However, their widespread availability has given rise to
fears that they are over-prescribed. The problem is compounded by the fact that there is no
universal agreement among medical practitioners as to the clinical indications warranting the use of
these drugs. Although most industrialised countries exercise control over the sale and manufacture
of benzodiazepines, many developing countries do not have sufficient control of these drugs. As a
result, information on drug utilisation and associated problems is difficult to obtain and there is a
lack of comparative data on drug consumption in different countries. The present article describes
the current knowledge on the pharmacological, clinical, and epidemiological characteristics of
benzodiazepines, and the problems associated with their use, and indicates areas where more
research is needed. Recommendations are made for future work. [ABSTRACT p. 551]

"Various benzodiazepines have been demonstrated to have an adverse effect on psychomotor
and cognitive functions. Performances on a vigilance task for example where impaired in normal
human subjects given diazepam at doses employed therapeutically. The benzodiazepines vary in
the degree to which they produce sedation and behavioural impairment. Comparative studies of
these drugs employing a range of doses, will be necessary to determine the extent and significance
of these differences.

Substantial intoxication and gross behavioural and cognitive impairments have been noted in
people abusing high doses of benzodiazepines on an acute or chronic basis. Striking deterioration
in personal care and social interactions has been reported. Other studies suggest that chronic
administration of benzodiazepines produces impairment in learning, memory and psychomotor

Studies have shown that benzodiazepines, alone and particularly in combination with alcohol,
have deleterious effects on driving performance. On the basis of such observations health
authorities in Scandinavia, in collaboration with the drug manufacturers, have decided to label
benzodiazepine preparations with a special warning symbol.

When some benzodiazepines are given at bed time for the treatment of insomnia deficits in
psychomotor and cognitive performances have been observed in tests the following morning.
Studies have revealed marked differences among the benzodiazepines in terms of their production
of such "hangover" effects, which are presumably related to their duration of action.

A variety of behavioural and mode disturbances have been reported in association with repeated
administration of some benzodiazepines in clinical situations, including increased hostility,
depression, antisocial behaviour, paranoid ideation, and suicidal tendencies. Because the
frequency of such observations has been relatively low, it has often been assumed that these
effects represent idiosyncratic reactions. However, a series of controlled studies of
chlordiazepoxide and diazepam in non-anxious subjects, has suggested that increased hostility
may represent a regular rather than an idiosyncratic, effect of some of these drugs. Several
reports have mentioned an aggravation of depressive symptoms by certain benzodiazepines in
patients not treated concurrently with antidepressants." [p. 560]

[Key words; Valium, Librium, diazepam, chlordiazepoxide, cognitive impairment, amnesia,
memory impairment, psychomotor impairment, depression, aggression, hostility, paranoia,
disinhibition, paradoxical effects, long-term effects, traffic]

Wilbur R, Kulik V.
Abstinence Syndrome from Therapeutic Doses of Oxazepam.
Canadian Journal of Medicine 1983; 28: 298-300.

A patient developed severe anxiety, moodswing, depression, and thinking disorder 24 hours after
abruptly stopping oxazepam, of which he had taken 30 mg 3 times a day for two months, for
anxiety and panic attacks. Oxazepam was restarted and tapered off gradually; nevertheless, a
relatively severe abstinence syndrome occurred. Muscular fasciculations and moodswing were
very marked. The patient also experienced significant anxiety, depression, moodswing, and
muscular fasciculations for two months after detoxification from oxazepam. Subsequently, the
patient's panic attacks were treated successfully with propranolol hydrochloride. This report
concludes with a brief review of the literature on benzodiazepine withdrawal. [SUMMARY p.

[Key words; Serax, Serenid, Serepax, oxazepam, dependence, withdrawal, depression]

Wolf B, Griffiths RR.
Physical Dependence on Benzodiazepines: Differences within the Class.
Drug and Alcohol Dependence 1991; 29: 153-156.

" As stated earlier, there is a concordance in the literature that quickly eliminated BZD are
associated with a higher incidence of physical dependence and more severe withdrawal
syndromes. In addition to pharmacokinetic properties, pharmacodynamic factors may be
important. The potency of a compound, which correlates with receptor affinity seems to co-vary
with the liability of a BZD to induce physical dependence. Thus, there seem to be at least three
factors which may be predictive of the severity of the withdrawal syndrome: (1) short elimination
half-life; (2) high potency; (3) use of relatively high doses. " [p.155]

[Key words; addiction, dependence, withdrawal]

Wysowski DK, Barash D.
Adverse Behavioral Reactions Attributed to Triazolam in the Food and Drug
Administrations Spontaneous Reporting System. Archives of Internal Medicine 1991; 151: 2003-2008.

Reports of adverse behavioral reactions to triazolam, a triazolobenzodiazepine ultra-short-acting
hypnotic, were examined in the postmarketing surveillance Spontaneous Reporting System of the
Food and Drug Administration. Reports for triazolam of confusion, amnesia, bizarre behavior,
agitation, and hallucinations were compared with reports of these reactions for temazepam,
another short-acting hypnotic. Analysis of individual case reports from marketing through 1985
for triazolam vs temazepam showed 133 vs two for bizarre behavior, 58 vs four for agitation, and
40 vs one for hallucinations. Considering extent of use, reporting rates for triazolam were 22 to
99 times those for temazepam, depending on the reaction. Reactions to triazolam tended to occur
at higher doses and in older patients. This and an updated analysis of aggregate reports for the
first 7 years of marketing of each drug with reporting rates and adjustment for various factors
suggest a higher occurrence of these reactions with triazolam, but selection factors cannot be
completely ruled out. When treating insomnia, physicians should emphasize sleep hygiene
practices as alternatives to drug therapy; if drug therapy is required, they should prescribe
hypnotics at the lowest recommended doses for the shortest clinically necessary durations and
discontinue medication use should any adverse reactions occur. [SUMMARY p. 2003]

[Key words; Halcion, triazolam, aggression, paradoxical effects, hypnotics]

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