Agrawal P.
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.
Case Report: A Delirious Abstinence Syndrome Associated with Clorazepate (Tranxilen).
British Journal of Addiction 1978; 73: 175-177.

" The main diagnoses offered in this case include psychogenic psychosis, intracerebral haemorrhage, 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,
psychosis, confusion]

Action on Addiction to Tranquillisers.
Lancet 1985; i: 1521.

" MIND, the National Association for Mental Health, is calling for Government action to help people addicted to minor tranquillisers. MINDs director, Mr Christopher Heginbotham, has written to 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 Government 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 practitioners 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 Cases.
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]

Arnesson GA.
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 utilise these drugs more and more to meet everyday problems of living, which under
normal circumstances, the individual should tolerate without requiring pharmacological assistance. " [p. 373]

[Key words; Librium, chlordiazepoxide, addiction, dependence, withdrawal]

Ashton H.
Adverse Effects of Prolonged Benzodiazepine Use.
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, benzodiazepines 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 antisocial acts 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, and are most likely to occur in aggressive or anxious individuals. " [p. 441]

[Key words; addiction, dependence, abuse, withdrawal, paradoxical effects, depression, suicide, hostility, aggression, disinhibition, suicide, shop-lifting]

Ashton H.
Benzodiazepine Withdrawal: Outcome in 50 Patients.
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 whether 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]

Ashton H.
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 individual 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 co-ordination, impairment of memory and concentration, and confusion. These effects are most marked in the elderly, 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, benzodiazepines 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." [p. 54]

[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]

Ashton H.
Protracted Withdrawal Syndromes from Benzodiazepines.
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 distortions and depersonalisation, 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. 25]

" 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 tinnitus 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. Occasionally, 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 persist for a year or more after withdrawal and the clinical picture may suggest 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, long-term effects]

Ayd FJ.
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. " [p. 180]

[Key words; Librium, chlordiazepoxide, paradoxical effects]

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