Karch FE.
Rage Reaction Associated with Clorazepate Dipotassium.
Annals of Internal Medicine 1979; 91: 61-62.

" Although paradoxical rage reactions associated with clorazepate have been rare, patients and physicians should be aware of possible paradoxical reactions with the use of clorazepate, and appropriate caution should be taken when prescribing this drug. " [p. 62]

[Key words; Tranxene, clorazepate, aggression, paradoxical reactions]

Karkos J.
[ Neurotoxicity of Benzodiazepines.]
Fortschr Neurol Psychiat 1991; 59: 498-520.

" The experimental data obtained after prenatal application indicate that BDZs can cause malformations, functional deficits and long-lasting behavioural anomalies. (---) The consequences of prenatal exposition to BDZs in m an, particularly their behavioural aspects, have not been
sufficiently investigated as yet. Postnatal BDZs application can bring about behavioural disturbances and neurological deficits in animals and man. " [p. 498]

[Key words; teratogenic effects]

Katz RL.
Sedatives and Tranquilizers.
New England Journal of Medicine 1972; 286: 757-760.

" These agents ( i.e. the benzodiazepines), which were introduced after meprobamate, are widely used in the treatment of anxiety. As with meprobamate, the reasons for their tremendous popularity are not fully clear, but some of the same reasons may apply. " [p. 758]

" The use of drugs to alleviate the stress and strains of daily living may be harmful in many ways.
In addition to the side effects and abuse of drugs, dependence on drugs to solve all problems may prevent personal growth. As Ban has stated, "It is reassuring and supportive to self esteem for most patients to find an acute anxiety state can be alleviated without the use of medication. Since e
most acute anxiety states remit promptly pharmacological conservatism is desirable." In addition, one cannot help wondering how much of the drug problem of contemporary children is due to the pill popping that they have observed in their parents. " [p. 760]

" Another harmful effect of drugs is that they may prevent the patient from getting to the source of the problem and taking appropriate action. "

" What can be recommended is that every time a physician reaches for his prescription pad, he ask himself if he is prescribing a sedative or tranquilizer because he has a roomful of patients waiting and is in a hurry to get on to the next patient... or whether he has carefully considered all the evidence, has found that sympathy, understanding, suggestion and reassurance are not
sufficient, and has decided to prescribe a sedative or tranquilizer for positive reasons rather than as an easy way out." [p. 670]

[Key words; addiction, dependence]


Keller AM.
Benzodiazepine Withdrawal.
Am J Med  1988; 85: 755.

"Although research in this area often originates from within the psychiatric community, it is important to note that the majority of prescriptions for this class of drugs are written not by psychiatrists, but by general psychiatrists. Unfortunately, the widespread use of these medications in the general medical community has not been accompanied by concomitant general knowledge of their potential adverse effects. All to often, biased information from pharmaceutical representatives is used to guide therapy with benzodiazepines.


In my own experience, I have encountered far more problems with patients who have become inadvertantly dependent on benzodiazepines than with patients who refuse to take these medications due to concerns about possible addiction. In particular, I have seen a number of very severe withdrawal reactions from alprazolam, including one death as a result of subdural hematomas incurred during a withdrawal seizure." [p.755]



Kellett JM.
The Benzodiazepine Bonanza.
Lancet 1974; ii: 964.

" Dr Tyrer is certainly right to draw attention to the multiplicity of benzodiazepines (---). Not only are there to many, but one suspects that they are too often prescribed in ways which cause harm to the patient.

In the past three months I have seen 3 patients who were all receiving over 50 mg. of diazepam daily and had been doing so for several months. They were all young women of unstable personalities who had shown no improvement in their behaviour while on diazepam: if anything,
suicide attemps had increased."

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

Keup W.
[ Flunitrazepam (Rohypnol) Reaches the Leading Position of Abuse among Benzodiazepine Derivative. ]
Sucht 1992; 38: 3-6.

Flunitrazepam (Rohypnol) in a random access sample of 8.165 persons with substance abuse problems of the German Substance Abuse Warning System (---) has reached in the past few years the leading position of abuse among benzodiazepine derivatives. A stricter control seems urgently needed, e.g. by establishing an additional Schedule in drug related legislation, between simple prescription and narcotic prescription, to allow a more effective control of this and other similar substances. [ SUMMARY p. 3]

[Key words; Rohypnol, flunitrazepam, addiction, abuse, dependence]

Kemper N, Poser W, Poser S.
[ Addiction Potential of the Benzodiazepines Is Greater Than Previously Assumed. ]
Deutsche Medizinische Wochenschrift 1980; 105: 1707-1712.

The position of benzodiazepine dependence among addiction diseases was studied retrospectively by analysing the case reports of in-patients at the Psychiatric Clinic, Göttingen.
Addicts constitute the largest group of patients in this clinic, a situation probably true in general of psychiatric hospitals in the Federal Republic of Germany. Isolated alcoholism is the most frequent addiction, followed by combined alcohol-drug dependence and pure drug dependence. At
present, benzodiazepines are the most commonly used addictive drugs. Although most of benzodiazepine dependants have changed to it from another drug, primary benzodiazepine dependence is increasing. Among the benzodiazepines, lorazepam seems to have a particularly high addiction potential. On withdrawal of benzodiazepines, symptoms were less marked than after stopping a combination of benzodiazepines and alcohol, and (or) barbiturates; they generally developed with some time delay. [SUMMARY p. 1707]

[Key words; addiction, abuse, dependence]

Kennebäck G, Hollstedt C, Persson A.
[ Complex Partial Seizures with Focal EEG Abnormalities During
Benzodiazepine Withdrawal.] Läkartidningen 1992; 89: 2523-2525.

The clinical and electroencephalographic features of three women presenting with complex partial seizures during benzodiazepine withdrawal are presented and discussed. [SUMMARY p. 2525]

[Key words, addiction, abuse, dependence, seizures]

Khan A, Joyce P, Jones AV.
Benzodiazepine Withdrawal Syndromes.
New Zealand Medical Journal 1980; 92: 94-96.

" We report eight cases of benzodiazepine withdrawal syndromes seen in a general psychiatric hospital. These consisted of acute organic brain syndrome, grand mal convulsions and abstinence syndromes. All of the cases were using benzodiazepines in prescribed therapeutic doses. These
problems appear to be more common than are generally acknowledged. " [SUMMARY p. 94]

All of the reported cases were using benzodiazepines in therapeutic doses and were documented within a short period of time in a relatively small population, alarming us regarding the true incidence of these problems. ( - - - )

Amongst the group who manifested the abstinence syndrome certain common features were discerned. These were women who had been prescribed a benzodiazepine in therapeutic doses over a minimum of three years for persisting anxiety and/or depression. On withdrawal they
uniformly suffered from insomnia, panic attacks, agitation, depersonalisation and an increase in depression. Their suffering was obvious and they all described it as being the worst experience of their lives. " [p. 96]

[Key words; addiction, abuse, dependence, depression, withdrawal psychosis,

Kielholz P.
[ A National Inquiry on the Frequency of Drug Abuse in Switzerland.]
German Schweizerische Ärztezeitung 1968; 40: 1077-1110.

" Tranquilizer werden nur in Einzelfällen als Hauptsuchtmittel angegeben, wobei es sich um Valium, Librium, Petranquil, Quaname, Oblivon und Seresta handelt. Etwas häufiger werden sie als Nebensuchtmittel benutzt. Wegen der noch zu kurzen Beobachtungszeit fur diese Medikamente kann aus diesen Befunden noch kein endgultiger Schluss gezogen werden. " [p.

" Alle Packungen suchtgefährdender Mittel sollten an gut sichtbarer Stelle eine Warnung vor missbräuchlicher und regelmässiger Verwendung enthalten. (---)

Die Bevölkerung ist laufend mit allen zur Verfugung stehenden Mitteln uber die Suchtgefahr aufzuklären. Es muss immer wieder betont werden, dass Hypnotica, Analgetica, Tranquilizer und Stimulantien keine harmlosen Medikamente sind, sondern zur Drogenabhängigkeit und
Gesundheitsschädigung fuhren können. " [p. 1092]

[Key words; Librium, Valium, chlordiazepoxide, diazepam, addiction, abuse, dependence, long-term effects]

King SA, Strain JJ.
Benzodiazepines and Chronic Pain.
Pain 1990; 41: 3-4.

"... their [i.e. the benzodiazepines] frequent prescription is disturbing for several reasons. The benzodiazepines are not innocuous drugs. They are addicting and their sudden discontinuation can result in serious withdrawal reactions. They can produce a variety of side effects, most notably
sedation, impairments in cognition, and depression ..." [p. 3]

[Key words; addiction, abuse, dependence, withdrawal, depression, cognitive impairment]

Kornhuber HH.
[ The Benzodiazepine Risk.] German
Deutsches Ärzteblatt 1988; 85: B-405.

" Die Schwere der Benzodiazepinabhängigkeit wird durch die grosse Häufigkeit von Ruckfällen nach Entziehung und die lange Dauer der Entzugssymptome (meist uber Monate) bewiesen.
Leistungsversagen, beruflicher Abstieg, Unfälle, vorzeitige Berentung, Ehescheidung und Selbstmordversuche kommen bei Benzodiazepinabhängigkeit häufig vor. Der Absetzversuch fuhrt
regelmässig zu jenen Symptomen, deretwegen sie ursprunglig genommen wurden: Unruhe, Angst, Schlaflosigkeit.

Ob die Kollegen, die heute noch das Benzodiazepinproblem herunterspielen, nicht einmal daruber nachdenken sollten, dass man die enormen Mittel fur Kosten und Folgekosten der Benzodiazepine zum Wohle der Patienten nutzlicher anwenden könnte - zumal in dieser Zeit harter "Kostendämpfung" im Gesundheitswesen. Daruber hinaus ist im Blick auf das Leid, das die
Benzodiazepine verursachen, an den hippokratischen Eid zu erinnern. Die Pharmaindustrie aber, die grosse Leistungen vollbracht hat, ist schlecht beraten, wenn sie das verteidigt, was sie am meisten angreifbar macht: den Missbrauch von Benzodiazepinen. "

[Key words; addiction, dependence, withdrawal, depression, suicide, social decline, costs, drug

Krakowski AJ, Langlais LM.
Acute Psychiatric Emergencies in a Geriatric Hospital.
Psychosomatics 1974; 15: 72-75.

" Psychotropic drugs are probably overused in the senile group for the alleviation of behaviour disturbances, especially anxiety and overactivity. The excessive doses and prolonged use may result in paradoxical effects and in confusional states, especially when polypharmacy is applied.
(- - - )

The polypharmacy may, however, be responsible for the reciprocal potentiation of untoward effects and be motivated less by the need of the patient than the need of the prescribing physician."
[p. 73]

[Key words; addiction, dependence, long-term effects, paradoxical effects, polypharmacy, the elderly]

Kripke DF, Garfinkel L.
Excess Nocturnal Deaths Related to Sleeping Pill and Tranquilliser Use.
Lancet 1984; i: 99.

" The group 1 subjects (who took no sleeping pills or tranquillisers) showed disproportionately fewer deaths during the usual hours of sleep, but group 2 subjects showed an excess of deaths during the same hours. The two groups differed significantly in the temporal distribution of deaths."
[p. 99]

" These results are consistent with the hypothesis that barbiturate sleeping pills and tranquillisers, in normal use, cause extra deaths during sleep. " [p. 99]

[Key word; hypnotics, the elderly]

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