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Doctors who treat the symptom tend
to give a prescription;
Doctors who treat the patient are
more likely to offer guidance.
Diazepam Addiction: A Case Report.
Canadian Psychiatric Association Journal 1978; 23: 35-37.
" A case of addiction to Diazepam is reported. Severe withdrawal symptoms such as
tremulousness, irritability, increased psychomotor activity, generalized muscle cramps,
abdominal cramps, photophobia, retro-orbital pains and insomnia are described. Visual
hallucinations, illusions, and paranoid features are also present in this case. Detoxification
and management were accomplished by gradual withdrawal and the addition of another
tranquilizer, anticonvulsant and muscle relaxant.
The author reviews other such reports of abuse and addiction in the literature which call for
wide recognition of the addictive properties of Diazepam and for restrictions on its
indiscriminate prescription by physicians. " [p. 36]
[Key words; Valium, diazepam, addiction, dependence, withdrawal, withdrawal psychosis,
insomnia, hallucinations, paranoia]
Allgulander C, Borg S.
[ A Patient Group Dependent on Sedative-Hypnotics -
Dependence Development, Medical Consultations and Choice of Drugs.]
Läkartidningen 1977; 74: 2429-2431.
Fifty-five patients with an exclusive dependence on sedative/hypnotics were investigated
with regard to dependence development, drug consumption and prescribing physicians.
Half of those investigated had used more then ten drugs with addictive properties, usually
for many years. The prescribing physicians were mostly private practioners, often qualified
psychiatrists. Parallel visits to different doctors were common, which again raises the issue
of further measures to prevent iatrogenic drug dependence.
[ SUMMARY p. 2431]
[Key words; addiction, dependence, multiple prescribing]
Allgulander C, Borg S.
Case Report: A Delirious Abstinence Syndrome Associated with
British Journal of Addiction 1978; 73: 175-177.
" The main diagnoses offered in this case include psychogenic psychosis, intracerebral
hemorrhage, alcohol withdrawal, cerebral anticholinergic effects of amitryptiline, and
psychosis due to infectious agents. This patient had not used alcohol to excess, and the
amitryptiline dosages she took do not produce such extensive cerebral symptoms. There
was no sign of infection or physical trauma. In view of the absence of a psychogenic
trauma, her recent exposure to high doses of a benzodiazepine derivative and the presence
of vegetative symptoms, confusion and hallucinations,
a withdrawal syndrome caused by clorazepate appears to be the most probable diagnosis. "
[ p. 176]
[Key words; Tranxene, clorazepate, addiction, dependence, withdrawal, hallucinations,
Altshuler LL, Szuba MP.
Course of Psychiatric Disorders in Pregnancy
Dilemmas in Pharmacological Management.
Neurologic Clinics 1994; 12: 613-635.
" ... there are well-documented reports of adverse neonatal effects when infants are
exposed either to chronic benzodiazepines in utero or to relatively small amounts only at
parturition or in the last trimester of pregnancy. Symptoms include muscular hypo
tonicity, failure to feed, impaired temperature regulation, apnea, and low Apgar scores." [p.
" Behavioral techniques (cognitive therapy) for both pa
nic disorder and OCD during the first trimester should be strongly considered as an
alternative to medication. Some reports suggest an association of diazepam with oral clefts,
so this medication is best avoided in the first trimester. " [p. 627]
" Large prospective and retrospective studies suggest a relative safety of use of tricyclic
antidepressants during pregnancy. Data available for neuroleptics, lithium,
benzodiazepines, and the anticonvulsants valproic acid and carbamazepine, although
mixed, point to increased risks of congenital malformations in the children of mothers
exposed to these agents in the first trimester of pregnancy. Very little is known about the
behavioral abnormalities in offspring of mothers exposed to these agents. Animal studies
suggest changes in brain receptor number and function in the offspring of mothers on a
variety of psychotropic drugs studied to date. " [p. 628]
[ Key words; pregnancy, apnea, low Apgar scores, oral cleft]
Action on Addiction to Tranquillizers.
Lancet 1985; i: 1521.
" MIND, the National Association for Mental Health, is calling for Goverment action to help
people addicted to minor tranquillizers. MINDs director, Mr Christopher Heginbotham, has
Mr Kenneth Clarke, Minister of Health, declaring that enormous profits have been made by
the pharmaceutical industry as a result of overprescription of minor tranquillisers and urging
the Goverment to tap this source for money to finance adequate withdrawal support
services. Mr Heginbotham recalls the similar situation in the '60s of barbiturate addiction
and emphasises the present weakness of primary care facilities. He attributes
the extent of tranquilliser dependence to the scale of demand levied on general practioners
and argues for a review of primary care.
It is estimated that about 500 000 people are addicted to barbiturates and benzodiazepines
(ten times the official figure given for the numbers addicted to opioids). Meanwhile, Mr
Heginbotham suggests, drug prescription should be accompanied by a detailed sheet of
information for the consumer covering adverse effects, dangerous interactions, the purpose
of the drug, and its proper use. "
[Key words; addiction, dependence, drug manufacturers]
Arana GW, Pearlman C, Shader RI.
Alprazolam-Induced Mania: Two Clinical
American Journal of Psychiatry 1985; 142: 368-369.
Two patients treated with alprazolam had histories suggestive of a bipolar disorder and
developed lithium-responsive manic episodes. The authors caution that treatment with
alprazolam may be complicated by the induction of mania.
[SUMMARY p. 368]
[Key words; Xanax, alprazolam, mania]
Risks of the New Psychotropic Drugs.
Journal of the Louisiana State Medical Society
1961; 113: 372-376.
" The third psychological risk is "addiction". This is placed in quotes since this is quite an
arbitrary classification. Although as yet no definite increase in tolerance with prolonged use
has been reported with any of the psychotropic agents, there have
been withdrawal symptoms reported in groups of patients on particularly high doses of the
meprobamates (Equanil, Miltown) and chlordiazepoxide (Librium). "
" More particularly, we are concerned with the fact that many patients who feel the need of
these medications, frequently become quite dependent on them psychologically. These
types of patients tend to utilize these drugs more and more to meet everyday pro
blems of living, which under normal circumstances, the individual should tolerate without
requiring pharmacological assistance. " [p. 373]
[Key words; Librium, chlordiazepoxide, addiction, dependence, withdrawal]
Adverse Effects of Prolonged Benzodiazepine
Adverse Drug Reaction Bulletin 1986; 118: 440-443.
" Symptoms appearing after long-term benzodiazepine use include
(a) dose-related extensions of the initial pharmacological actions, and (b) withdrawal
symptoms resulting from the development of tolerance and drug dependence. " [p. 440]
" Chronic benzodiazepine usage can cause both depression and "emotional anaesthesia",
an apathetic state with dulling of all emotions. In patients with depressive illness,
can aggravate the depression and provoke suicide.
On the other hand, some individuals experience euphoria, and benzodiazepines have
abuse liability when used intravenously.
Occasionally, benzodiazepines produce apparently paradoxical stimulant effects. (---)
Patients on low chronic doses of benzodiazepines sometimes commit uncharacteristic
such as shoplifting or sexual offences, while higher doses may produce outbursts of rage
and violent behaviour, especially in anxious patients.
Chronic benzodiazepine use has been suggested to be a contributory cause of "baby-
battering" and "grandma-bashing"; these paradoxical effects have been attributed to
disinhibition of behaviour previously suppressed by social restraints, fear, or anxiety, a
nd are most likely to occur in aggressive or anxious individuals. "
[Key words; addiction, dependence, abuse, withdrawal, paradoxical effects, depression,
suicide, hostility, aggression, disinhibition, suicide, shop-lifting]
Benzodiazepine Withdrawal: Outcome in 50
British Journal of Addiction 1987; 82: 665-671.
"...the study shows that long-term benzodiazepine use is associated with a considerable
morbidity. " [p. 670]
" None of these symptoms or behaviours were the original indication for starting on
benzodiazepines but developed during chronic use. It is arguable whethe
r the patient would have developed the symptoms over time in the absence of
benzodiazepines, but the fact that they were not present before benzodiazepine use, were
not amenable to treatment during benzodiazepine use, yet largely disappeared when the
drugs were stopped, suggests that benzodiazepines may actually cause or aggravate a variety of
psychological and psychosomatic symptoms. " [p. 670]
[Key words; addiction, dependence, withdrawal, long-term effects]
Anything for a Quiet Life ?
New Scientist 1989; 6: 34-37.
" Valium, Librium and Mogadon once seemed to provide the perfect answer to stress. We
now know how this group of drugs alters the chemistry of the brain; no wonder they create
more problems than they solve. " [SUMMARY p. 52]
" The problems begin with chronic use; that is, regular use for more than a week or two.
Harmful effects fall into two categories that may coexist: the drugs may begin to have
powerful but unwanted side effects, and also to become less effective. The indi
vidual taking them may develop tolerance, dependence and the symptoms of withdrawal.
Unwanted effects can be pronounced. Many benzodiazepines are eliminated from the body
only slowly and may accumulate, causing drowsiness, a lack of coordination, impairment of
memory and concentration, and confusion. These effects are most marked in the el
derly, making them more likely to suffer falls and fractures. Benzodiazepines taken as
sleeping pills often give rise to a "hangover", impairing performance the following day.
Benzodiazepines may contribute to traffic and industrial accidents and worsen the effects of
other depressant drugs, including alcohol.
Taking benzodiazepines over the long term can cause both depression and "emotional
anaesthesia", an apathetic state in which people are unable to feel pleasure or pain. The
drugs can aggravate depressive illness and provoke suicide. On the other hand, benz
odiazepines sometimes produce apparently paradoxical stimulant effects. Patients may
commit uncharacteristic antisocial acts such as shoplifting or sexual offences, or becoming aggressive with
outbursts of rage and violence. Some researchers have suggested that chronic use of
benzodiazepines may contribute to "baby-battering", "wife-beating" or "grandma-bashing."
[Key words; Librium, Valium, Mogadon, chlordiazepoxide, diazepam, nitrazepam, addiction,
dependence, withdrawal, tolerance, confusion, amnesia, memory impairment, depression,
suicide, hostility, shop-lifting, paradoxical effects, accidents, fractures]
Protracted Withdrawal Syndromes from
Journal of Substance Abuse Treatment 1991; 8: 19-28.
" Even with long-acting benzodiazepines such as diazepam, there is usually a history in
long-term users of steadily increasing anxiety, with the development over the years of new
symptoms such as agoraphobia, often with perceptual distorsions and depersona
lization, despite continued usage of these supposedly anxiolytic drugs. " [p. 22]
" Depression can be caused or aggravated by chronic benzodiazepine use, yet it also
appears to be a feature of the withdrawal syndrome. It may be severe enough to qualify as
a major depressive disorder and may persist for some months. (---)
It is not clear whether protracted depressive symptoms are more common in patients with a
previous history of depression or whether it recurs in subsequent years after withdrawal. [p.
" Tinnitus is a common symptom of benzodiazepine withdrawal
and may initially result from the characteristic general hypersensitivity to sensory stimuli. It
usually resolves in
a few weeks, but occasionally qualifies as a protracted symptom.
Busto et al. (1988) describe two cases in which tinnitus persisted for 6 and 12 months after
withdrawal and mention a third patient who was unable to withdraw from benzodiazepines
because of severe tinnitus at each attempt. Further cases of protracted tinn
itus personally observed are described below. " [p. 25]
" Tinnitus is fairly common in the general population, and
the apparent relation to benzodiazepine use may be incidental,
but these cases raise the suspicion that benzodiazepines may occasionally cause
permanent or only slowly reversible brain damage. " [p. 25]
" Formication is also common during benzodiazepine withdrawal, and many patients temporarily complain of a feeling of insects crawling on the skin or of lice
or nits in the hair. Occasionaly, more bizarre sensations are reported, such as a feeling of
slime or water running over the body, a sense of inner vibration, or a feeling of "trembling inside", and these symptoms may be protracted. [p. 26]
" Occasionally muscle jerking persits for a year or more after withdrawal and the clinical
picture may suggset myoclonus, tics, or exaggerated startle reactions. (---) Restless legs
syndrome may also be protracted. [p. 26]
" Gastrointestinal symptoms are extremely common during chronic benzodiazepine use and
in withdrawal. Many chronic benzodiazepine users have been investigated by
gastroenterologists and found to have "irritable bowel syndrome." [p. 26]
[Key words Valium, diazepam, withdrawal, anxiety, depression, tinnitus, depersonalization,
A Critical Appraisal of Chlordiazepoxide.
Journal of Neuropsychiatry 1962; 3: 177-180.
" It is obvious that Librium is not an innocuous compound.
It is capable of making latent psychopathology overt and of aggravating existing neurotic
and psychotic ailments. "
[Key words; Librium, chlordiazepoxide, paradoxical effects]
Baker PM, Bartholomeusz DB, Siskind M, Whitlock FA.
Drug-Induced Depression and Attempted
Medical Journal of Australia 1977; 2: 322-324.
" A study of 135 cases of suicide in Brisbane revealed that many of the victims were taking
one or more drugs, particularly alcohol, barbiturates, benzodiazepines and analgesics,
before their deaths. Most of these subjects were deeply depressed and it seemed possible
that their disturbances of mood were partly caused by the mixture of medicaments being
consumed beforehand. "
" In the end, two important prophylactic factors have to be considered when treating
emotionally disturbed patients;
the assessment of suicidal risk, and the hazard of giving potentially depressant drugs to
patients with a past or present history of depression, suicidal attempt, or alcoholism. In such
cases, multiple prescribing should be avoided lest the outcome be the death of the patient
being treated. " [p. 324]
Key words; depression, suicide, multiple prescribing]
Ban TA, Da Silva T, Gagnon MA, Lamont CT, Lehmann HE, Lowy FH, Ruedy J, Sellers
Therapeutic Monograph on Anxiolytic-Sedative
Canadian Medical Association Journal 1981; 124: 1439-1446.
" Various unusual responses have been documented, including nightmares, paradoxical
delirium and confusion, depression, aggression and hostile behaviour. Some patients
experience a dry mouth, a metallic taste or headaches.
Awareness of the sometimes bizarre effects of these drugs
is important. " [p. 1443]
[Key words; addiction, dependence, depression, aggression, hostility, nightmares,
headaches, paradoxical effects]
Bayer AJ, Bayer EM, Pathy MSJ, Stoker MJ.
A Double-Blind Controlled Study of Chlormethiazole and Triazolam in the Elderly.
Acta Psychiatrica Scandinavica 1986; 73 (suppl 329): 104-111.
This study compared the hypnotic efficacy and the psychometric effects of treatment with
either chlormethiazole or triazolam for 9 weeks in elderly patients with sleep disturbance.
Chlormethiazole and triazolam were found to be similarly effective in short-term use. However, evidence of sustained hypnotic
efficacy throughout the 9 weeks of treatment was obtained for chlormethiazole but not for
triazolam. There were daytime withdrawal effects with triazolam,
but none with chlormethiazole.
[ ABSTRACT p. 104 ]
" Our study suggests that the use of triazolam in older patients, even in conservative doses,
may have significant disadvantages and gives further support to the view that
chlormethiazole is, at present, the hypno
tic drug of choice for use in this age group. "
[Key words; Halcion, triazolam, dependence, withdrawal, the elderly]
Benzodiazepines and Tinnitus.
BMJ 1991; 302: 1465.
" In his discussion of the causes and managements of tinnitus
Mr M Hawthorne points out that benzodiazepines should not be
used to treat tinnitus because their long term use is detrimental.
I should like to add to this that withdrawal of benzodiazepines after long term use is a well
documented but often unrecognized cause of tinnitus. It may be realated to the hyperacusis characteristic of
benzodiazepine withdrawal, and it usually disappears once withdrawal is complete - but I
have seen patients in whom tinnitus persisted for many months after withdrawal from
benzodiazepines was complete, and similar cases have been reported. In one of the
reported cases the tinnitus was relieved by diazepam.
Tinnitus is common and has many causes, but questioning patients about their use of
benzodiazepines may elicit a cause that usually has a good prognosis. "
[Key words; addiction, dependence, withdrawal, tinnitus]
Berger R, Green G, Melnick A.
Cardiac Arrest Caused by Oral Diazepam Intoxication.
Clinical Pediatrics 1975; 14: 842-844.
Respiratory an cardiac effects have been reported as manifestations of diazepam toxicity.
Cardiac arrest may occur in the intravenous administration of diazepam, but we beleive this
case to be the first reported episode of cardiac arrest caused by oral ingestion in a child. [ABSTRACT p. 842]
[Key words; Valium, diazepam, poisoning, children]
Bergman H, Borg S, Engelbrektson K, Vikander B.
Dependence on Sedative-Hypnotics:
Neuropsychological Impairment, Field Dependence and Clinical Course in a 5-Year Follow-
British Journal of Addiction 1989; 84: 547-553.
" Despite some neuropsychological improvement in a group of 30 patients who had been
hopsitalized for primary abuse of sedatives or hypnotics 4-6 years earlier, the prevalence of
intellectual impairment was still increased and about as high as before.
As in alcoholic patients CAT scan of the brain showed an increased prevalence of dilatation of the ventricular system, but unlike alcoholics not of
widened cortical sulci. Field dependence and visuo-spatial skills during treatment predicted
abuse status at follow-up. Patients with improved drug habits had less pronounced withdrawal symptoms during treatment and a better social situation at follow-up
than patients without improvement of drug habits. The results suggest that despite some
neuropsychological improvement cerebral disorder diagnosed
in patients abusing sedatives or hypnotics is often permanent
through the years and that neuropsychological status is linked
to long-term prognosis. [SUMMARY p. 547]
[Key words; addiction, abuse, dependence, cognitive impairment]
Bergman U, Griffiths RR.
Relative Abuse of Diazepam and Oxazepam: Prescription Forgeries and Theft/Loss Reports
Drug and Alcohol Dependence 1988; 16: 293-301.
" The classic drug-seeking patterns through different physician which are sometimes asociated with drugs of abuse
been reported to be unusual for the benzodiazepines, However, in Sweden, which has had
a low use of barbiturates in recent years, rate of prescription forgeries (corrected for usage) for diazepam were similar to those for barbiturates (Bergman, unpublished
data). Surveys in Iceland, another country with low use of barbiturates at that time, revealed
drug seeking with the 10-mg tablets of diazepam by a substantial number of patients. This observation led to removal of 10-mg diazepam tablets from the Icelandic
market. As use of the psychotropic barbiturates
[Key words; Valium, Serax, Serenid, Serepax, diazepam, oxazepam, addiction, abuse,
Anxiety and Antianxiety Drug Use in Sweden.
In: Pharmacological Treatment of Anxiety. National Board of Health and Welfare, Drug
Information Committee, Sweden 1988; 1: 63-74.
"... there remain marked inter- and intra-regional differences in the utilization of these drugs
which are not easily accounted for." [p. 63]
"... a previously umknown problem with benzodiazepine dependence developing with
therapeutic doses has become generally recognized." [p. 72]
" The large geographic variations within Sweden in the sales of these anxiolytic drugs, most
of which have an inherent abuse potential, however remain a source of concern. This points
to the need for local therapeutic auditing, to obtain and maintain an acceptable standard of prescribing. " [p. 72]
[Key words; addiction, dependence, low-dose-dependence]
Insomnia and Pills in Sweden.
In: Treatment of Sleep Disorders. National Board of Health and Welfare, Drug Information
Committee, Sweden 1988; 4: 65-80.
"... large geographical differences in the utilization of hypnotics/sedatives exist within
Sweden. The close relation between misuse and availability of these drugs demonstrated in
the county of Malmö in the period 1975-1984, emphasizes the need at the local level for regular surveillance of
drugs with an inherent abuse potential, to obtain and maintain an acceptable standard of
prescribing. However, according to a legal statement from June 1986 (...) there is probably
no such surveillance of psychotropic drug utilization being performed anywhere
in Sweden today. "
" Swift et al conclude that " the desirability of protracted benzodiazepine hypnotic use in the
elderly must continue to be questioned, particularly in view of the doubtful rationale for
continued use found in the case of so many patients. " [p. 75]
" Hypnotics are also subject to abuse. This is an adverse reaction rarely reported in
voluntary adverse drug reaction reporting systems. " [p. 75]
" The discrepancy found in the province of Saskatchewan, Canada between the
recommendation of short-term treatment and the extent of chronic use, may actually be
explained by post-treatment re- bound symptoms seen when discontinuing treatment with
[Key words; Halcion, triazolam, addiction, abuse, dependence, the elderly]
Berlin RM, Conell LJ.
Withdrawal Symptoms after Long-Term Treatment with Therapeutic Doses of Flurazepam:
A Case Report.
American Journal of Psychiatry 1983; 140: 488-490.
A male patient with chronic insomnia experienced withdrawal symptoms when flurazepam
(30 mg h.s.), which he had taken nightly for 8 years, was abruptly discontinued. Problems
associated with sedative-hypnotic medication and the long-term treatment of chron
ic insomnia are discussed. [SUMMARY p. 488]
[Key words; Dalmane, flurazepam, addiction, dependence, withdrawal]
Betts TA, Birtle J.
Effect of Two Hypnotic Drugs on Actual Driving Performance Next Morning.
BMJ 1982; 285: 852.
[ regarding flurazepam and temazepam ]
" A single night-time dose of both hypnotics caused changes in driving behaviour next
morning that increased the chance of a road accident. Whether the effect wears off in the day (and if so, when), whether subjects
adapt to repeated dosing, whether the effect is dose dependent, and whether men would be affected we cannot say; we suggest, however, that doctors should advise
patients to avoid morning driving for the first few days of taking one of these hypnotics. " [p. 852]
[Key words; Dalmane, Euhypnos, flurazepam, temazepam, driving, accidents]
Three Case Reports of Behavioral Disinhibition with Clonazepam.
General Hospital Psychiatry 1987; 9: 151-153.
" These three patients had worsening symptoms while their dose of clonazepam was being
increased. " [p. 152]
" Clinicians should be careful that additional clonazepam is not given as this would
obviously worsen the situation." [p. 152]
[Key words; Klonopin, clonazepam, disinhibition, paradoxical effects]
Possible Effect of Chlordiazepoxide on the Fetus.
Canadian Medical Association Journal 1969; 100: 351.
" Cerebral hemorrhage would not cause leukopenia, and since all cultures were negative, it
was felt that the depression and leukopenia could both best be explained by
chlordiazepoxide toxicity. It is conceivable, of course, that some underlying neurological disorder is present but not
apparent at this time. " [p. 351]
[Key words; Librium, chlordiazepoxide, pregnancy]
Bleich A, Grinspoon A, Garb R.
Paranoid Reaction Following Alprazolam Withdrawal.
Psychosomatics 1987; 28: 599-600.
"Since the clinical course of our case is so strongly suggestive of a withdrawal reaction, we
believe it imperative to call attention to the unanticipated possibility that even a modest and
gradual reduction of this short-acting minor tranquillizer may provoke a paranoid reaction." [p. 600]
[Key words; Xanax, alprazolam, addiction, dependence, withdrawal, paranoia]
Blennow G, Romelsö A, Leifman H, Leifman A, Karlsson G.
Sedatives and Hypnotics in Stockholm: Social Factors and Kinds of Use.
American Journal of Public Health 1994; 84: 242-246.
" It is reasonable to believe that being unemployed or on a disability pension may be
associated with number of psychological problems caused by, for instance, social isolation. However, drug use in itself may be the reason for unemployment or a disability pension.
[Key words; addiction, dependence]
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