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Rapaport M, Braff DL.
Alprazolam and Hostility.
American Journal of Psychiatry 1985; 142: 146.
" Monoamine oxidase inhibitors suppress the REM sleep and are correlated with patient self-reports of decreased dreaming.
Recently we treated a patient who said she began having violent sadomasochistic nightmares and the return of self-mutilatory impulses after 0.25 mg t.i.d. of alprazolam was added to her regimen of tranylcypromine, 30 mg/day. Both the patient\'abs sa
domasochistic nightmares and her self-mutilatory impulses ceased 24 hours after her last dose of alprazolam."
[Key words; Xanax, alprazolam, nightmares]
Regestein QR, Reich P.
Agitation Observed During Treatment with Newer
Journal of Clinical Psychiatry 1985; 46: 280-283.
Side effects involving agitation, e.g. sleepwalking, anger, and panic, were observed in 10 insomniac patients treated with temazepam or triazolam but not other benzodiazepines. E
ach patient described these side effects as uncharacteristic. Milder agitation was observed in 2 cases. In 4 cases, these effects were doubted by the precribing physician. This type of side effect has been only slowly recognized for other benzodiazepines a
nd has not been much reported for these newer agents. Agitation observed during treatment with these agents may be related to their short elimination half-lives.
[SUMMARY p. 280]
[Key words; Halcion, Euhypnos, Normison, triazolam, temazepam, anxiety, aggression, hostility, paradoxical effects]
Rejent TA, Wahl KC.
Diazepam Abuse: Incidence, Rapid Screening and Confirming Methods.
Clinical Chemistry 1976; 22: 889-891.
" The abuse of drugs continues unabated in the United States. Awareness of "hard drug" use predominates in the news media and funded programs, but the facts concerning other drug misuse are generally hidden. Diazepam (and probably others) are heavily misus
ed, but are not the subject of critical editorialization."
" Highly prescribed psychotropic drugs can easily end up in the hands of many others. Threfore, the clinical analyst should be aware of drug popularity, which in our present society leads to overuse, abuse, and often requires medical intervention in a clinical emergency
. " [p. 891]
[Key words; addiction, abuse, dependence]
Rementeria JL, Bhat K.
Withdrawal Symptoms in Neonates From Intrauterine Exposure to Diazepam.
Journal of Pediatrics 1977; 90: 123-126.
Three infants are presented who had withdrawal symptoms af
ter prolonged, intrauterine exposure to diazepam. Symptoms, clinical course, management, and laboratory findings are described. Some physiologic aspects of diazepam in the fetus and neonate are discussed. One infant died at six weeks of age; death was attr
ibuted to the sudden infant death syndrome. [ABSTRACT p.123]
[Key words; Valium, diazepam, dependence, withdrawal, infants, pregnancy]
Rickels K, Case WG, Schweizer EE, Swenson C, Fridman RB.
Low-Dose Dependence in Chronic Benzodiazepine Users:
A Preliminary Report on 119 Patients.
Psychopharmacology Bulletin 1986; 22: 407-415.
" In fact, one hard-earned lesson is that long-term BZ users are in need of much more intensive psychiatric and social support than other anxious or depressed patients. " [p. 414]
[Key words; long-term effects]
Rickels K, Schweizer E, Case G, Greenblatt DJ.
Long-Term Therapeutic Use of Benzodiazepines.
I. Effects of Abrupt Discontinuation.
Archives of General Psychiatry 1990; 47: 899-907.
" Patients who were able to remain free of benzodiazepines for at least 5 weeks obtained lower levels of anxiety than before benzodiazepine discontinuation. " [p. 899]
[Key words; long-term effects, detoxification]
Rigby J, Harvey M, Davies DR.
Mania Precipitated by Benzodiazepine Withdrawal.
Acta Psychiatrica Scandinavica 1989; 79: 406-407.
A case of mania following abrupt benzodiazepine withdrawal in an 83-year-old woman is described. It is argued that the withdrawal state acted as a significant life event in precipitating the manic episode.
[ABSTRACT p. 406]
[Key words; Ativan, lorazepam, addiction, dependence, withdrawal, mania]
Risse SC, Whitters A, Burke J, Chen S, Scurfield RM, Raskind MA.
Severe Withdrawal Symptoms after Discontinuation of Alprazolam in Eight Patients with Combat-Induced Posttraumatic Stress Disorder.
Journal of Clinical Psychiatry 1990; 51: 206-209.
Eight patients with combat-induced p
osttraumatic stress disorder (PTSD) receiveing long-term alprazolam therapy for anxiety or depression (maximum dose of 2-9 mg/day for 1-5 years) had alprazolam therapy withdrawn. Most of the patients underwent gradual medication withdrawal. All patients ha
d a prior history of alcohol abuse or benzodiazepine dependence. During withdrawal, all patients had severe reactions including anxiety, sleep disturbance, rage reactions, hyperalertness, increased nightmares, and intrusive thoughts; and 6 of the 8 patient
s had homicidal ideation. As a result of this report, the authors suggest that the potential for severe withdrawal reactions, even with gradual tapering, should be considered before prescribing alprazolam therapy for this group of patients.
[ABSTRACT p. 206]
[Key words; Xanax, alprazolam, addiction, dependence, withdrawal, detoxification, hostility, aggression, nightmares, insomnia]
Rivas F, Hernandez A, Cantu JM.
Acentric Craniofacial Cleft in a Newborn Female Prenatally Exposed to a High Dose of Diazepam.
Teratology 1984; 30: 179-180.
A newborn female with craniofacial clefts, including cleft lip and palate, was studied. The mother had ingested 580 mg of diazepam in a single dose at about the 43rd day of gestation.
The synchronism of drug intake and the embryological development of the affected structures suggests an etiopathogenic relationship. [ABSTRACT p. 179]
[Key words; teratogenic effects, infants]
Roberts K, Vass N.
Schneiderian First-Rank Symptoms Caused by Benzodiazepine Withdrawal.
British Journal of Psychiatry 1986; 148: 593-594.
Benzodiazepine withdrawal has been found to give rise to numerous physical and psychological symptoms. This paper describes, for the first time, Schneiderian first-rank symptoms
of schizophrenia caused by such withdrawal.
[SUMMARY p. 593]
[Key words; addiction, withdrawal, abuse, dependence, withdrawal psychosis]
Roche Products Inc. Manati, Puerto Rico.
[ In advertisement for "Valium", Archives of General Psychiatry 1990; 47: 893.]
" The effectiveness of Valium in long-term use, that is,
more than 4 months, has not been assessed by systematic
clinical studies. " [p.893]
" SIDE EFFECTS: Drowsiness, confusion, diplopia, hypotension, changes in libido, nausea, fatigue, depression, dysarthria, jaundice, skin rash, ataxia, constipation, headache, incontinence, changes in salivation, slurred speech, tremor, vertigo, urinary ret
ention, blurred vision. Paradoxical reactions such as acute hyperexcited states, anxiety, hallucinations, increased muscle spasticity, insomnia, rage, sleep disturbances, stimulation have been reported; should these occur, discontinue drug. "
Romney DM, Angus WR.
A Brief Review of the Effects of Diazepam on Memory.
Psychopharmacology Bulletin 1984; 20: 313-316.
" Moreover, it [i.e. diazepam] appears to produce side effects, previously unnoticed, both on mood, causing depression and rage, and on cognitive and psychomotor functioning. " [p. 313]
[Key words; Valium, diazepam, depression, aggression, cognitive impairment, psychomotor impairment]
Lorazepam-Associated Drug Dependence.
Journal of the Royal College of General Practioners
1986; February: 86.
" I should like to draw attention to what, in my opinion, are the unequivocal risks of lorazepam-associated drug dependence and exaggerated withdrawal symptoms. In my experience, this can occur often with low dosage, short courses and for many months after
cessation of therapy.
It is common to find other general practioners and psychiatrists who share
this view and there is also widespread lay awareness of the problem. For the last year and a half I have been communicating with the Committee on Safety of Medicines about the problem. They answer that they have received few yellow card reports on this pro
My personal view is that this is because doctors do not realize that reporting an expected side-effect of a drug is as useful for epidemiological purposes as is reporting an unexpected side-effect for general scientific purposes. I should like, th
erefore, to appeal to all the general practioners who must be seeing this problem, to report any cases to the Committe on Saftety of Medicines. " [p. 86]
[Key words; Ativan, lorazepam, addiction, dependence, abuse, withdrawal]
Rosenbaum JF, SW Woods, Groves JE, Klerman GL.
Emergence of Hostility During Alprazolam Treatment.
American Journal of Psychiatry 1984; 141: 792-793.
Of 80 patients given alprazolam, eight became hostile early in treatment. The authors suggest that alprazolam-induced hostili
ty may be more likely in patients with well-supressed chronic anger and resentment and cite reports of hostility associated with other benzodiazepines. [SUMMARY p. 792]
[Key words; Xanax, alprazolam, aggression, paradoxical effects]
Effects of Maternal Diazepam.
BMJ 1978; 1: 985.
" High doses (30 mg or more) of diazepam administered during labour cause, in the infant, fail
ure to start breathing, shallow, inadequate respirations, periodic cessations of respiration, floppiness, subnormal temperature, and poor sucking. These effects last several days and significant plasma levels of diazepam and of its active metabolites persist for up to eight days. Diazepam accumulates in tissue of the fetus, and is metabolised and excreted slowly by the newborn baby. "
" The depressant effects of pethidine and other drugs given during labour would be made worse by diazepam. "
" Diazepam is excreted in breast milk, which may sedate the baby and cause feeding difficulty. Finally, there is the fear of impairing future intellectual development by exposing the developing brain to the influence of tranquillizers.
" How often must we be reminded of the ancient precept primum non nocere ? "
[Key words; Valium, diazepam, pregnancy, infants]
Ryan HF, Merrill FB, Scott GE, Krebs R, Thompson BL
Increase in Suicidal Thoughts and Tendencies
Association with Diazepam Therapy.
JAMA 1968; 203: 1137-1139.
Seven cases occurred in which there was an association in time between the institution of diazepam therapy and the onset of suicidal thoughts and tendencies, which tended to be concealed by patients who were at the time receiving psychiatric treatment.
An additional patient demonstrated deepening of depression while receiving diazepam. Physicians should consider the possible adverse depressive effect of diazepam when prescribing it as an antianxiety agent. [SUMMARY p. 1137]
" The major adverse side effects have been considered to be the possible development of ataxia and confusion. However, the report by Feldman of the progressive development of dislike and hate in some patients, manifested in one by an overt act of violence, may not be
totally unrelated to the problem to which we here adress ourselves. " [p. 1137]
" There has been no clear warning that diazepam may have this kind of adverse effect in psychiatric patients, only that it cannot be expected to do the job of the accepted an
tidepressants in patients with severe depression. It would seem that caution should be exercised in the use of diazepam in all patients in order to promptly detect adverse depressive effects. The use of diazepam
in even mild depressions, in our view, requires consideration of the potential onset of suicidal thoughts and tendencies which may not be readily recognized. " [p. 1137]
[Key words; Valium, diazepam, depression, suicide, paradoxical effects]
Salzman C, Fisher J, Nobel K, Glassman R, Wolfson A,
Cognitive Improvement Following Benzodiazepine Discontinuationin Elderly Nursing Home Residents.
Internationl Journal of Geriatric Psychiatry 1992; 7:
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 anxiet
y, agitation, or sleepnessness. 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 disdcontinuance. [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."
[Key words; Ativan, lorazepam, amnesia, memory impairment]
Schlicht HJ, Gelbke HP.
[ Frequency of Positive Diazepam-Screening in Post-Mortem Examinations.]
German Zeitschrift fur 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]
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 sleepin pills. "
" It has recently been recognized 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 af
ter somatic dependence has developed with the use of benzodiazepines in therapeutic dosage for months or years. "
[Key words; dependence, tolerance, insomnia, hypnotics]
[ Confusional States Due to the Hypnotic
German Schweizer Medizinische Wochenschrift 1985; 115: 247-249.
Five cases are reported in which confusional states and total anterograde amnesia ocurred 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 patie
nts 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 withdrawan 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 dependen
ce in the case of poly drug users encompasses a much wider range of aspects of usage and behaviours than has hitherto been observed in coventional 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 commonplace.
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 alarmingl
y disturbed behaviour when intoxicated with benzodiazepines, characterized particularly by amnesia, which early reports suggest is common..." [p. 22]
[Key words; addiction, abuse, dependence, amnesia, memory impairment]
Sheehan MF, Sheehan DV.
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 apperars to be more common than is currently appreciated, and thge 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 n
eed 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 Arrythmia Precipitated by Flumazenil.
BMJ 1988; 296: 1070-1071.
" The patient was extubated 20 hours after admisson 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]
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 eliminatio
n of their anxiety symptoms. It is proposed that a psychology service be provided for general practitioner in health centers 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]
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 c
rutches 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]
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 weeks.
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. "
" ... 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 dru
g-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 characteric 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 pot
entiate 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 a
gainst 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]
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 desireable because of the danger of apnea. Apart from the danger, the sedated infant will have less chance of being breast fed,
and his particpation in the process of mother-child bonding will be impaired. "
[Key words; pregnancy, infants, apnea]
[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 patien
ts 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]
Tata PR, Rollings J, Collins M, Pickering A, Jacobson RR.
Lack of Cognitive Recovery Following Withdrawal from Long-Term Benzodiazepine Use.
Psychological Medicine 1994; 24: 203-213.
Twenty-one patients with significant long-term therapeutic benzodiazepine (BZ) use, who remained abstinent at 6 months follow-up after successfully completing a standardized inpatient BZ withdrawal regime, and 21 normal controls matched for age and IQ but
not for anxiety, were repeatedly tested on a simple battery of routine psychometric tests of cognitive function, pre- and post- withdrawal and at 6 months follow-up. The results demonstrated significant impairment in patients in verbal learning and memory, psychomotor, visuo-motor and visuo-conceptual abilities, compared with controls, at all three time points. Despite practice effects, no evidence of immediate recovery of cognitive function following BZ withdrawal was found. Modest recovery of certain deficits emerged at 6 months follow-up in the BZ group, but this remained significantly below the equivalent control performance. The implications of persisting cognitive deficits
after withdrawal from long-term BZ use are discussed. [SUMMARY p. 203]
" The main cognitive functions assessed in this study include working memory, verbal learning and memory, visuo-motor and visuo-conceptual skills. The lack of evidence for clinically significant cognitive recovery raises concern about the severity and reversibility of any underlying BZ-induced organic impairment."
" The adverse effects of acute diazepam administration on memory and arousal in man are well known (Lister &
File, 1984; Lister, 1985), and have been linked to the high density of BZ receptors in the hippocampus and reticular formation (Wolkowitz et al. 1987), although the neurochemical basis of chronic post-withdrawal deficits has yet to be demonstrated. " [p.
" Persisting neuropsychological deficits affecting psychomotor function and new verbal learning have occupational implications. Driving and safety at work with machinery may both be impaired (Skegg et al. 1979, Roy-Byrne & Cowley, 1990).Patients' impairment, following withdrawal from long-term BZ use, is likely to be less than that due to acute drug ingestion or the early withdrawal phase. Yet, one must be cautious in predicting either rapid or comprehensive cognitive recovery for those patients con
templating or undergoing a withdrawal regime, or in estimating the cognitive effects of mood dysfunction, which require further investigation. " [p. 211]
[Key words; memeory impairment, cognitive impairment,
Teo SH, Chee KT, Tan CT.
Psychiatric Complications of Rohypnol Abuse.
Singapore Medical Journal 1979; 20: 270-273.
Rohypnol has become a new drug of abuse in the Singapore drug scene. Five cases with psychiatric complications admitted to Woodbridge hospital are described and the probable aetiology discussed. Its potential danger is emphasized.
[ SUMMARY p. 270]
[Key words; Rohypnol, flunitrazepam, addiction, abuse, dependence, psychosis, paradoxical reactions]
Thomson M, Smith WA.
Prescribing Benzodiazepines for Noninstitutionalized Elderly.
Canadian Family Physician 1995; 41: 792-798.
" Benzodiazepines were dispensed to about 24% of the nonistitutionalized elderly in British Columbia during 1990. Amounts prescribed to almost 4% of the population appeared to be in excess of guidelines. Physicians need to know how their prescribing practi
ces relate to guidelines. Individuals who are made aware of discrepancies often adopt more appropriate prescribing practices. " [p. 797]
[Key words; the elderly]
Withdrawal from Benzodiazepines.
Journal of the Royal College of General Practioners
1983; 33: 608.
" I have started a support through withdrawal scheme for people coming off benzodiazepines. The enormous amount of suffering I see makes me wonder how much information on the toxic effects of these drugs, and illness caused by their withdrawal, reaches the
doctors. The pharmacological manuals grossly understate the dangers of tolerance, dependence and withdrawal that have been demonstrated so clearly after the use of these drugs. This is not only after long-term use at high dosage, but also after very short-term use (two weeks), on a normal therapeutic dose.
We must look urgently for the most effective treatment, since a quarter of benzodiazepine users will become severly physically dependent. Widespread dependence, as much as overprescribing,
must be the reason for the enormous use of these drugs.
The withdrawal syndrome has many unique features and needs to be treated as a new disease. In acute withdrawal, psychosis, convulsions and suicides are a great deal more common than the literature would suggest. The physical symptoms, many of which are not typical of anxiety, are the worst aspect of the illness.
Some of the symptoms are belated and are not associated with the drugs by patient or doctor. Rebound insomnia is a persistent symptom. Unfortunately, and so often, doctors prescribe another benzodiazepine for night sedation when the patient complains of this.
Psychological dependence is less of a problem. Many users report craving for the drugs, but at the same time feel revolted by them, and angry that they have to take them to avoid withdrawal symptoms.
Thousands of people could not possibly invent the bizarre symptoms caused by the therapeutic use of benzodiazepines and reactions to their withdrawal. Many users have to cope, not only with a frightening range of symptoms, but also with the disbelief and hostility of their doctors and families. It is not uncommon for patients to be "struck off" if they continue to complain about withdrawal symptoms. Even when doctors are concerned and understanding about the problem, they often have little knowledge of withdrawal procedure, and even less about treatment. The drugs newsletter on benzodiazepines issued in this region will
help them. Is anything being done elsewhere ?
Banning benzodiazepines would be unrealistic; there is nothing to replace them. But I would urge doctors to seek more information about them, and to listen to what their patients are saying. Release and self-help groups all over the country have done wonderful work, but why should people need to form groups for an urgent medical problem ? This is drug-induced disease, not drug abuse. "
[Key words; addiction, dependence, withdrawal, withdrawal psychosis, seizures, insomnia, depression, suicide]
Tune LE, Bylsma FW.
Benzodiazepine-Induced and Anticholinergic-Induces Delirium in the Elderly.
International Psychogeriatrics 1991; 3: 397-408.
Encompassing the range from subtle cognitive impairments to frank delirium, toxicity due to benzodiazepines and to anticholinergic-containing compounds is reviewed. For benzodiazepines, an extensive literature suggests that they impair immediate and delayed memory, psychomotor performance, and subjective complaints of station. This, in several studies, results in increased patient morbidity (e.g., increasing risk of hip fractures). Anticholinergic compounds are widely utilized in managing elderly patients particularly nursing home residents. Toxicitiy from anticholinergic
compounds, detected by anticholinergic drug levels, is significantly correlated with the presence and severity of delirium in a number of settings including postoperative patients and elderly nursing home residents. Possible means of identifying the syndrome by prediction of dose and type of medication, as well as by quantitative EEG, are reviewed.
[SUMMARY p. 397]
[Key words; cognitive impairment, amnesia, memory impairment, psychomotor impairment, fractures, the elderly]
Turkington D, Gill P.
Mania Induced by Lorazepam Withdrawal:
A Report of Two Cases.
Journal of Affective Disorders 1989; 17: 93-95.
Although depression is a well recognised component of the benzodiazepine withdrawal syndrome there have, as yet, been no convincing reports of mania. We report two cases of mania induced by abrupt discontinuation of lorazepam. Both cases were treated by re
introduction of the benzodiazepine followed by gradual dose reduction. [SUMMARY p. 93]
[Key words; Ativan, lorazepam, dependence, withdrawal, mania]
The Benzodiazepine Post-Withdrawal Syndrome.
Stress Medicine 1991; 7: 1-2.
" Much more needs to be done to establish the post-withdrawal syndrome as a clinical and pharmacological entity, but it is unlikely to be an artifact or entirely "mediogenic" (created by the media). The subject certainly deserves more attention from research workers in the stress disciplines. " [p. 2]
[Key words; addiction, dependence, withdrawal, protracted withdrawal syndrome]
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