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Dependence on Hypnotic/Sedative Drugs.
In: Pharmacological Treatment of Anxiety. National Board of Health and Welfare, Drug
Information Committee, Sweden 1988; 1: 135-143.
" In spite of good socioeconomic conditions the long-term prognosis for patients with
hypnotic/sedative dependence seems to be similar to that encountered in e.g. alcohol abuse. "
[Key words; addiction, abuse, dependence, social decline, long-term effects
Breier A, Charney DS, Nelson JC.
Seizures Induced by Abrupt Discontinuation of Alprazolam.
American Journal of Psychiatry 1984; 141: 1606-1607.
Two patients had grand mal seizures following abrupt discontinuation of short-term
treatment with alprazolam. Alprazolam\'abs pharmacokinetic and clinical properties are
discussed in relation to withdrawal reactions.
[ABSTRACT p. 1601]
[Key words; Xanax, alprazolam, addiction, dependence, withdrawal, seizures]
British National Formulary
1993; 26: 132-136.
"Most anxiolytics ('sedatives') will induce sleep when given in large doses at night and most
hypnotics will sedate when given in divided doses during the day. Prescribing of these
drugs is widespread but dependence (either physical or psychological) and t
olerance to their effects occurs. This may lead to difficulty in withdrawing the drug after the patient has been taking it regularly for more than a few
weeks (---). Hypnotics and anxiolytics should not therefore be precribed indiscriminately and
should, instead, be reserved for short courses to alleviate acute conditions after causal factors have been established.
Prescribing of more than one anxiolytic or hypnotic at the same time is not recommended. It may constitute a hazard and there is no evidence that side-effects are
Benzodiazepines are the most commonly used anxiolytics and hypnotics; they act at benzodiazepine receptors which are
associated with gamma-aminobutyric acid (GABA) receptors. Barbiturates are no longer
recommended. Benzodazepines have fewer side-effects than barbiturates and are much le
ss dangerous in overdosage. They are also less likely to interact with other drugs because
unlike barbiturates they do not induce liver microsomal enzymes.
A paradoxical increase in hostility and aggression may be reported by patients taking
benzodiazepines. The effects range from talkativeness and excitement, to aggressive and antisocial acts.
Adjustment of the dose (up or down) usually attenuates the impulses. Increased anxiety
and perceptual disorders are other paradoxical effects. Increased hostility and aggression after barbiturates and alcohol usually indicate intoxication.
DEPENDENCE AND WITHDRAWAL. The benzodiazepine withdrawal syndrome may not
develop until up til 3 weeks after stopping a long-acting benzodiazepine, but may occur
within a few hours in the case of a short-acting one. It is characterised by insomnia, anxiety, loss of appetite,
and body weight, tremor, perspiration, tinnitus, and perceptual disturbances. These
symptoms may be similar to the original complaint and encourage further precribing. Some symptoms may continue for weeks or months after stopping benzodiazepines
entirely. Withdrawal of a benzodiazepine should be gradual as abrupt withdrawal may
produce confusion, toxic psychosis, convulsions, or a condition resembling delirium tremens.
DRIVING. Hypnotics an anxiolytics may impair judgement and increase reaction time, and
so affect ability to drive or operate machinery; they increase the effects of alcohol. Moreover
the hangover effects of a night dose may impair driving on the following day."
[Key words; addiction, dependence, withdrawal, tolerance, anxiety, confusion, aggression,
hostility, tinnitus, paradoxical effect, disinhibition, traffic]
The Use of Benzodiazepines in Prison Populations.
Journal of Clinical Psychiatry 1978; 39: 219-222.
" Experiences at the Utah State Prison with the use of psychotropic medication... indicated
that the indiscriminate use of benzodiazepines could lead to more detriment than benefit."
" During 1974 when several tranquillizers and pain killers were being used relatively
indiscriminately... the incidence of riots, stabbings, cuttings, murders and attempted
suicides and self-mutilations were extremely high. 22 cases of sputum injections, deliberate self-mutilations, were reported during that period. In addition there were two major riots and five minor riots,
one murder, two suicides, 44 self mutilations, 6 stabbings of other individuals, 8 attacks on
guards, and innumerable verbal assaults on guards and other inmates.
" Several prisoners had acute withdrawal symptoms and some who were addicted to Valium
and other benzodiazepines had a prolonged withdrawal effect, much longer than even the
heroin and methadon addicts. " [p. 221]
[Key words; Valium, diazepam, addiction, dependence, abuse, withdrawal, depression,
suicide, aggression, hostility]
Browne JL, Hauge KJ.
A Review of Alprazolam Withdrawal.
DICP 1986; 20: 837-841.
" A cumulative review of case reports in the literature describing withdrawal reactions
secondary to alprazolam is presented. In four of eight reports, the primary withdrawal
reactions were grand mal seizures. One case was characterized by painful myoclonos. In the remaining three cases, the major complications consisted of rebound anxiety with
psychotic features. Despite tapering of the daily dosage according to manufacturer
guidelines, a withdrawal syndrome was precipitated in three cases.
As a result of alprazolam\'abs atypical pharmacodynamic profile, the issue is raised as to
whether alprazolam is pharmacologically cross-tolerant with other benzodiazepines. "
[SUMMARY p. 837]
[Key words; Xanax, alprazolam, addiction, abuse, dependence, anxiety, withdrawal]
Burke KC, Meek WJ, Krych R, Nisbet R, Burke JD.
Medical Services Use by Patients before and after Detoxification from Benzodiazepine
Psychiatric Services 1995; 46: 157-160.
Objective: The authors examined use of medical and mental health services before and
after detoxification among a group of patients detoxified from benzodiazepines to see if the
data suggested a reduction in service use and costs after detoxification, the
so-called offset effect observed for treatment of alcohol and mental disorders. Methods:
Through a medical record review, information was collected about medical service use for patients aged 40 and older who were
detoxified from benzodiazepines at Scott and White Clinic and Hospital between 1997 and
1991. Results: Among the 76 patients, medical and mental health outpatient visits fell
from an average rate of 25.4 visits per year before detoxification to 4.4 per year after
detoxification. For the 44 patients with at least one inpatient stay besides the admission for
detoxification, the mean number of inpatient days remained constant at
three days per year before and after detoxification. Conclusions: Although a retrospective
review suffers from a range of limitations, the findings suggest that detoxification from
benzodiazepines may be effective in reducing use of outpatient medical and
mental health services and presumably in reducing costs of care. "
[\~SUMMARY p. 157]
[Key words; addiction, dependence, costs, detoxification]
Burnakis TG, Berman DE.
Hostility and Hallucinations as a Consequence of Midazolam Administration.
DICP 1989; 23: 671-672.
A 74-year-old woman experienced an apparent psychotic reaction several hours after
administration of iv midazolam as a predimedicant for gastroscopty. The reaction included
confusion, hallucinations, and hostility and required administration of haloperidol
to calm her. The woman subsequently underwent colonoscopy with meperidine as a
premedication and experienced no behavioral changes. Although other causes cannot be
completely ruled out, the evidence points strongly to midazolam as the precipitating agent for the psychotic reaction.
[ABSTRACT p. 671]
[Key words; Versed, midazolam, aggression, hostility, psychosis, hallucintions, confusion,
Busto U, Fornazzari L, Naranjo CA.
Protracted Tinnitus after Discontinuation of Long-Term Therapeutic Use of
Journal of Clinical Psychopharmacology 1988; 8: 359-362.
The presence of protracted tinnitus after discontinuation of long-term therapeutic doses of
diazepam (---) is described in three patients. In one of these patients, the association of the tinnitus appearance with the drug
discontinuation was documented in a double-blind, randomized, crossover single case
study. Objective confirmation of drug use or of abstinence was performed by obtaining
plasma benzodiazepine concentrations. The findings provide further documentation that sensory
disturbances of short- and long-term duration are among the most distinctive clinical
features of the benzodiazepine withdrawal syndrome.
[ SUMMARY p. 359]
[Key words; Valium, diazepam, dependence, withdrawal, protracted withdrawal syndrome,
Alprazolam-Induced Rage Reaction.
Journal of Clinical Psychopharmacology 1985; 5: 186-188.
" ... this case lends support to the observation that alprazolam shares with other
benzodiazepines the capacity to produce rage reactions at therapeutic drug levels. "
" ... it seems that alprazolam should be used at least as cautiously as other
benzodiazepines in patients who experience anxiety in the context of suppressed rage at
hostile or conflict-ridden environments. "
[Key words; Xanax, alprazolam, aggression, hostility, paradoxical reactions]
Benzodiazepines: The End of a Dream.
Australian Family Physician 1994; 23: 1584-1585.
" Benzodiazepine tranquillisers were introduced in 1960 after brief clinical tests at the
University of Texas in 1959. Controlled trials were not required for evaluation and "efficacy"
was demonstrated by anectdotes and testimonials. If introduced today they would probably
only be approved for limited indications." [p. 1584]
" Some critical authors have suggested that the medical profession and drug companies
have been guilty of knowingly ignoring the dangers of tranquillisers. " [p. 1584)
Side-effects, including instability and falls in the elderly, memory disturbance, abnormal
sleep patterns, sexual disturbance, depression, fatigue and habituation are all well
" Use of these drugs for minor complaints, or as first line of management is no longer
justified. " [p. 1584]
"Some patients can withdraw from these drugs rapidly without great trouble. For others, it is
a long, harrowing experience. "
" The dream of the perfect sedative has not come true. For some, it has become a recurrent
nightmare. Chloral, bromides, barbiturates, meprobamate and even heroin were all touted in
their turn as the ideal, non addictive calming agents. There is still no perfect drug for primary insomnia or anxiety. Benzodiazepines are a limited tool in the
pharmacopoeia, but not the panacea once thought. " [p. 1585]
[Key words; addiction, dependence, withdrawal, amnesia, memory impairment, depression,
fatigue, drug manufacturers]
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