van Balkom AJLM, de Beurs E, Koele P, Lange A, van Dyck R.
Long-Term Benzodiazepine Use Is Associated with Smaller Treatment Gain
in Panic Disorder with Agoraphobia.
Journal of Nervous and Mental Disease 1996; 184: 133-135.

" Given the large number of patients with PA using benzodiazepines, the predictor "long-term
benzodiazepine use" remains of clinical importance and deserves more attention in future
research. " [p. 134]

[Key words; long-term effects]

van der Kroef C.
Reactions to Triazolam.
Lancet 1979; ii: 526.

" During the past nine months I have been confronted in my psychiatric practice with a syndrome
which is almost certainly induced by the benzodiazepine triazolam ("Halcion")

Triazolam can produce the following symptoms: severe malaise; depersonalisation and
derealisation; paranoid reactions; acute and chronic anxiety; continuous fear of going insane;
depression and deterioration of existing depression; hyperaesthesia, especially for sound but also
for smell, taste and light; sometimes hypoaesthesia for the same stimuli; nightmares; restlessness;
inability to concentrate; verbal and physical aggression; conflicts with entourage; severe suicidal
tendencies; hypnagogic hallucinations; impulse actions; amnesia; dysphagia, accompanied by
nasty taste, painful tongue and mucous membranes, dry mouth, loathing of food, rigid feeling in
the throat and emaciation up to 2½ stone; cervical pains; headaches that are often extremely
sensitive to sound; pressure on the ears; numb and cold feeling in fingers and toes, extending to
the distal parts of the extremities; tingling feeling, muscular cramps and paralyses, often at the
sinistral side; catatonically impaired motor functioning; reading complaints and blurred vision;
dysfunctional speaking and writing; sweating.

This syndrome must be classified with the exogenous syndrome of Bonhoeffer. Symptoms
ususally disappear within a couple of days after stopping triazolam; sometimes there are
withdrawal symptoms, such as rapidly mounting panic and heavy sweating.

These side-effects appear in patients who are taking other drugs and in those who are not and in
patients who have never had psychiatric treatment as well as in those with a psychiatric history.
Patients with this syndrome may be admitted on suspicion of brain tumour or schizophrenia. They
impress the observer as seriously ill and the patients themselves often feel desperate and have to
fight an almost irresistible impulse to commit suicide. I know of one patient who did commit

The Netherlands Centre for Monitoring of Adverse Reactions to Drugs has received several
reports of patients with similar features while on triazolam and the centre issued (July 16) a letter
to Dutch doctors, dealing with this matter. "

[Key words; Halcion, triazolam, depression, suicide, aggression, psychosis, paranoia,

Vellucci SV.
Chlordiazepoxide Loses Its Anxiolytic Action with Long-Term Treatment.
Psychopharmacology 1979; 62: 61-65.

" In short-term clinical trials (lasting 28 days or less) it has been demonstrated that the
benzodiazepines are consistently more effective than placebo. However, in the long term,
anxiolytic efficacy is still not well established, despite the fact that the benzodiazepines are so
widely prescribed for the treatment of anxiety. There is an extreme paucity of data from both
clinical and animal studies on the long-term effect of these drugs (---). The few clinical studies that
have been carried out have suggested that there is a marked decrease in the drug-placebo
difference during extended treatment. " [p. 65]

[Key words; tolerance]

Viscott DS.
Chlordiazepoxide and Hallucinations.
Archives of General Psychiatry 1968; 19: 370-376.

Hallucinations are reported in seven cases of patients taking chlordiazepoxide. They were noted
to occur during what would have been part of the patient's sleep cycle. This paper proposes that
chlordiazepoxide causes a transient impairment of the ego's ability to suppress dream material
into the waking state as hallucinations. Unlike the hallucinations seen in patients recovering from
dextroamphetamine sulfate addition, these are weaker and no alteration of the sensorium is seen.
Moreover, they are terminated with reality testing. Some speculations concerning the therapeutic
action of the drug are also given. [SUMMARY p. 376]

[Key words; Librium, chlordiazepoxide, hallucinations, paradoxical effects]

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