H
Haacki M.
[ Amnestic Episodes after Ingestion of Midazolam Hypnotics, Effect or Side
Effect ? ]
Schweiz Med Wochenschrift 1986; 116: 42-44.

Five patients are reported who experienced amnestic episodes a short time after oral intake of the recommended dose (7.5-15 mg) of the new benzodiazepine hypnotic midazolam. Patients were able to perform complex activities or to talk freely with other persons, and seemed to be awake
and attentive. However, next morning they had complete anterograde amnesia from intake of the drug. No other psychotropic medication or alcohol was involved. This type of drug-induced amnesia seems to be more frequent than so far reported, since all these episodes were observed
in fewer than 30 cases in which the drug was prescribed. This means a considerable risk forpatients and for others, and serious questions arise which should be carefully investigated. [SUMMARY p.42]

[Key words; Versed, midazolam, amnesia, memory impairment]

Hall RCW, Joffe JR.
Aberrant Response to Diazepam: A New Syndrome.
American Journal of Psychiatry 1972; 129: 738-742.

" Six patients with a demonstrated aberrant response to diazepam showed a cluster of symptoms
consisting of tremulousness, apprehension, insomnia, and depression, followed by ego-alien suicidal ideation. In this series, the syndrome was abrupt in onset and marked in severity and appeared in individuals who had been previously emotionally stable. All of the patients had been
taking greater than maximally recommended doses of diazepam (i.e., greater than 40 mg. every day), primarily for medical conditions.

The significance of this syndrome lies in the quality of the suicidal ideation, which negates the usual indicators of suicidal intent. The appearance of any of the preliminary symptoms of this syndrome is therefore an immediate indication for the withdrawal of diazepam and the protection of the
patient against suicidal impulses. Furthermore, it is strongly suggested that physicians adhere to the maximum recommended dosages and be aware of the possibility that peripheral vascular disease and age may be a factor in the appearance of cumulative toxic effects. " [p. 741]

[Key words; Valium, diazepam, depression, suicide, paradoxical effects]

Hansson O, Tonnby B.
[ Serious Psychological Symptoms Caused by Clonazepam.]
Läkartidningen 1976; 73: 1209-1210.

Minor transient or permanent behavioural deviations are not the only results from ingestion of clonazepam. Far more serious side effects have been noted in connection with this anti-epileptic drug. The flora of symptoms is illustrated by some case reports. The authors question the choice
of clonazepam for the treatment of epilepsy in children. The manufacturer of the drug should provide the medical profession with supplementary information. [SUMMARY p. 1210]

[Key words; clonazepam, psychosis, paradoxical effects, drug manufacturers]

Haque W, Watson DJ, Bryant SG.
Death Following Suspected Alprazolam Withdrawal Seizures: A Case Report.
Texas Medicine 1990; 86: 44-47.

" This case is not unique in that it reports psychosis following alprazolam withdrawal. Nor is this the first report of withdrawal seizures. What is unusual and alarming is that the seizures recurred late in the drug s tapering schedule at a daily dose of only 1 mg. The unfortunate outcome in this
case is its most regrettable aspect. It serves as a powerful remainder of the potential risks of seizure activity. " [p. 46]

[Key words; Xanax, alprazolam, addiction, dependence, withdrawal]

Haskell D.
Withdrawal of Diazepam.
JAMA 1975; 233: 135.

" The manufacturer's literature warns of physical addiction to diazepam or other benzodiazepines, mainly with excessive doses. However, I have seen several patients experiencing barbiturate-type withdrawal symptoms after four to six months of diazepam therapy in doses as low as 15 mg/day.
Symptoms such as tremors, agitation, fearfulness, stomach cramps, and sweating made patients extremely uncomfortable, but dangerous reactions, such as convulsions, did not occur. All of these patients had been admitted to a psychiatric hospital for depression. They were generally
reluctant to stop using diazepam, but when the symptoms subsided after two to four weeks, they were usually happy to be free of medication.

" Also, the possibility of depression after prolonged diazepam treatment, as reported in another letter (226; 1572:1973), underscores the need for further study and caution with this drug. "

[Key words; Valium, diazepam, addiction, dependence, withdrawal, depression, long-term effects]

Haskell D, Cole JO, Schniebolk S, Lieberman B.
A Survey of Diazepam Patients.
\-\-Psychopharmacology Bulletin 1986; 22: 434-438.

" The major conclusions that may be drawn from this survey are:
1) that most patients at this clinic on diazepam have been taking it a long time; and
2) that they are generally n o t asymptomatic. In fact, they may be more symptomatic than
patients ordinarily considered for antianxiety drug studies. They appear to believe they are obtaining continued benefit from their medication and have difficulty tapering or stopping it. It remains unclear whether this difficulty is caused by chronic anxiety symptoms only partially relieved by BZs, or results from some degree of physical dependence requiring BZ maintenance
to suppress withdrawal symptoms. " [p. 437]

[Key words; addiction, dependence, long-term effects]

Hauser P, Devinsky O, De Bellis M, Theodore WH, Post RM.
Benzodiazepine Withdrawal Delirium with Catatonic Features Occurrence in Patients with Partial Seizure Disorders
Archives of Neurology 1989; 46: 696-699.

We report the cases of 3 patients with medically intractable seizures in whom withdrawal of treatment with a long-acting benzodiazepine (clorazepate dipotassium, 2 patients; clonazepam, 1 patient) was followed by delirium with catatoniclike features. While an increase in seizure
fequency occurred during withdrawal and prior to the onset of behavioural changes, electroencephalograms did not show epileptiform activity during the delirium. We compared these 3 patients with 10 others with intractable seizures in whom antiepileptic therapy was withdrawn without subsequent behaviour changes. High-dose benzodiazepine therapy and a history of viral
encephalitis may be risk factors for withdrawal delirium. [ABSTRACT p. 696]

[Key words; Tranxene, Klonopin, clorazepate, clonazepam, addiction, dependence, withdrawal, seizures]

Hawthorne M.
Any Questions
BMJ 1991; 302: 1266.

[regarding treatment of tinnitus]
" Anxiolytics, such as benzodiazepines, were a popular treatment some years ago but as their long term use is detrimental should not be used. " [p. 1266]

[Key words; tinnitus, long-term effects]

Hecker R, Burr M, Newbury G.
Risk of Benzodiazepine Dependence Resulting from Hospital Admission.
Drug and Alcohol Review 1992; 11: 131-135.

" Benzodiazepines may result in dependence after relatively brief periods of prescription. This study reports the continued use of either temazepam or nitrazepam as a hypnotic 3-4 months after the provison of the drugs as a discharge prescription following an acute hospital stay. Of 160
patients contacted by telephone, 68 (42.5%) were still taking the hypnotic when contacted and 23 (14%) of these had not previously used a hypnotic regularly prior to hospital admission... Patients should be counselled about the risks of the development of dependence and withdrawal
insomnia. Discharge prescription of benzodiazepine hypnotics should not exceed three days duration and preferably be avoided altogether " [p. 131]

[Key words; addiction, dependence, withdrawal]

Hendler N, Cimini C, Ma T, Long D.
Comparison of Cognitive Impairment Due to Benzodiazepines and to
Narcotics.
American Journal of Psychiatry 1980; 137: 828-830.

" ... the use of benzodiazepines in patients with chronic pain would theoretically be ill-advised because they reduce the turnover of serotonin, thus interfering with natural sleep and lowering the tolerance to chronic pain.

However, the most significant problem that benzodiazepines create seems to be cognitive impairment with associated EEG changes (---). Acute, single dose administration of diazepam does seem to produce impairment in learning, memory, and psychomotor functioning. " [p. 828]

" ... the evaluating psychiatrist noted that a great deal of cognitive impairment seemed to occur more often in patients using benzodiazepines than in patients using only narcotics. " [p. 828]

" ...one could conclusively state that benzodiazepines were far more likely to produce cognitive impairment, with concomitant EEG changes, than were narcotics. " [p. 830]

" While neither narcotics nor benzodiazepines should be used on a long-term basis, cognitive impairment was far more apparent with the latter class of drugs.

The question of the reversibility of the benzodiazepine effect is the subject of current research, but at this time one may only underscore a recent suggestion by the Food and Drug Administration that benzodiazepines be limited to short-term use. " [p. 830]

[Key words; amnesia, cognitive impairment, long-term effects]

Herman JB, Brotman AW, Rosenbaum JF.
Rebound Anxiety in Panic Disorder Patients Treated with Shorter-Acting
Benzodiazepines.
Journal of Clinical Psychiatry 1987; 48 (suppl 10): 22-28.

" Patients otherwise satisfactorily treated with alprazolam will comment that they begin to get a little "fidgety" or "nervous" 3 to 4 hours after their last dose. " [p. 22]

" "Rebound" is defined as the relative worsening of symptoms on discontinuation of treatment as compared with symptoms present on baseline. We have observed, however, that with the short-
and intermediate-acting benzodiazepines, treatment does not actually have to be discontinued for rebound phenomena to exist. " [p. 22]

[Key words; Xanax, alprazolam, addiction, dependence, withdrawal, tolerance, rebound]

Herxheimer A.
Driving under the Influence of Oxazepam: Guilt without Responsibility ?
Lancet 1982; ii: 223.

" Benzodiazepines can blunt perception, confuse thought, and cause amnesia. The defendant described feeling "fuddled and muddled" and driving less sharply than usual. This state of mind, if it was induced by the drug, would aggravate the difficulty of understanding that something was
wrong, and of taking appropriate action, let alone suspecting a connection between the state of mind and taking the drug. "

" The case underlines the importance of warning patients about the possible effects of drugs on driving and other potentially dangerous activities. A doctor who fails to warn his patient at least shares the responsibility for any accident that occurs as a result; in such a case the patient would
seem to be entitled to recover damages from the doctor. " [p. 223]

[Key words; cognitive impairment, amnesia, memory impairment, psychomotor impairment, driving, accidents]

Heyndrickx B.
Fatal Intoxication Due to Flunitrazepam.
Journal of Analytical Toxicology 1987; 11: 278.

" Flunitrazepam is used in many hospitals and prescribed by physicians for use in daily life. (- - - )
These pharmaceutical compounds are very dangerous and one should take care when prescribing them to elderly people. " [p. 278]

[Key words; Rohypnol, flunitrazepam, poisoning, the elderly]

Higgitt AC, Lader MH, Fonagy P.
Clinical Management of Benzodiazepine Dependence.
BMJ 1985; 291: 688-690.

" Withdrawal symptoms have been reported after treatment for as little as four to six weeks. The withdrawal symptoms observed are wide ranging, and, while they include some related to anxiety,
they are clearly distinguishable from a simple reemergence of pre-existing anxiety. Particularly frequently reported are instances of increased sensory perception such as hyperacusis, photofobia, paraesthesia, hyperosmia, and hypersensitivity to touch and pain, but gastrointestinal disturbances, headaches, muscle spasms, vertigo, and sleep disturbances are also frequent.

The proportion of long term users of benzodiazepines in whom withdrawal symptoms may be expected to emerge has been variably estimated to be between 15% and 44%. The symptoms typically emerge in the first week after stopping the drug but may develop after a reduction in dosage. Until recently the withdrawal syndrome was reported as lasting for up to three months, but we are now seeing more patients whose symptoms have persisted for more than six months - in some cases for a year or more.

Yet no one doubts that most patients currently taking benzodiazepines should stop them. " [p.688]

[Key words; addiction, dependence, withdrawal, protracted withdrawal syndrome]

Higgitt A, Fonagy P, Toone B, Shine P.
The Prolonged Benzodiazepine Withdrawal Syndrome: Anxiety or Hysteria ?
Acta Psychiatrica Scandinavica 1990; 82: 165-168.

"... the results offer no support for either the continued-anxiety or the conversion-disorder accounts of PWS [i.e. Prolonged Withdrawal Symptoms] suggested in the introduction. No evidence was found that psychophysiological indicators of anxiety were marked in this group.
(---) The observation that this group is psychophysiologically hard to distinguish from normal controls suggests that PWS is unlikely to be an affective disturbance and lends support to the view that it represents a genuine iatrogenic condition that may be best treated as a complication of
benzodiazepine treatment. (---)

It is fortunate that patients who continue to manifest symptoms long-term following withdrawal are relatively small in number (although they may amount to 30% of a benzodiazepine dependent sample.) This study has failed to elucidate the mechanisms underlying their problems but the
similarity of findings from the PWS and normal groups may be regarded as encouraging in terms of the long-term prognosis for these individuals. " [p. 167]

[Key words; addiction, dependence, withdrawal, protracted withdrawal syndrome]

Hippius H.
[ Complications of Long-Term Therapy with Psychotropic Drugs.] German Landarzt 1965; 41/22: 933-940.

"Gewöhnlich wie beim Meprobamat kommen bei langfristiger Therapie mit
Benzodiazepin-Derivaten als Intoxikations-Symptome vor: Müdigkeit, Somnolenz, allgeimeine Schwäche und Antriebslosigkeit, Vergesslichkeit, verwaschene Sprache, Kopfschmerzen, Schwindel, Crampi, Ataxie und Reflexsteigerungen. Auch delirante Syndrome sind schon
beobachtet worden. Paradoxe Symptome, wie Schlaflosigkeit und unruhige Umtriebigkeit, sind selten. " [p. 936]

[Key words; amnesia, memory impairment, long-term effects, paradoxical effects]

Holm M.
One Year Follow-Up of Users of Benzodiazepines in General Practice.
Danish Medical Bulletin 1990; 37: 188-191.

" Shortly after their introduction, it was stressed that benzodiazepine tranquillisers and hypnotics/sedatives should only be used for short periods to help patients over periods of stress and crisis. If these recommendations were followed, one would expect the majority of new patients on benzodiazepines to have stopped within a year. The finding in the present study that 45% of new users of benzodiazepines were still on them one year later compares with 20% after six months reported by Williams et al. " [p. 191]

" In line with other studies, there was a tendency for greater psychiatric morbidity in patients on heavy-dose long-term benzodiazepines. (---) A study from the United States showed that long-term users of anxiolytics tended to be older persons with high levels of emotional distress
and chronic somatic health problems.

The other risk factors for long-term use in the present study (female sex, living alone, use of benzodiazepine hypnotics/ sedatives) are of major importance, and the GP must focus on them to reduce the frequency of benzodiazepine misuse. " [p. 191]

[Key words; addiction, dependence, long-term effects]

Horwitz N.
[Acute Hypnotic Poisoning with Flunitrazepam (Rohypnol).]
Ugeskrift for Laeger 1980; 142: 2429-2430.

A healthy man aged 83 years ingested 4 mg flunitrazepam (two Rohypnol tablets) and became deeply unconscious with hypotension and depression of respiration. Flunitrazepam should be administered with great caution to elderly persons (1/4-1/2 tablet is usually sufficient.) On account
of the rapid action, the preparation should be administered immediately before bedtime.
[SUMMARY p. 2429]

[Key words; Rohypnol, flunitrazepam, poisoning, respiratory depression, the elderly]

Huff JS, Plunkett HG.
Anterograde Amnesia Following Triazolam Use in Two Emergency
Physicians.
Journal of Emergency Medicine 1989; 7: 153-155.

Anterograde amnesia following triazolam ingestion lasting beyond the sedative-hypnotic effect of the drug has recently been reported. Two additional cases are presented involving emergency physicians. [ABSTRACT p. 153]

[Key words; Halcion, triazolam, amnesia, memory impairment]

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