Psychological Medicine
Association
香港社區精神醫學會
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your patients.
Abstract
This article reviews the history, the use and misuse of benzodiazepines. A small trick,
CIDER, is introduced to help doctors to remember and to follow the Revised Guidelines on
the Proper Prescription and Dispensing of Dangerous Drugs by Registered Medical
Practitioners.
The History
Librium was the first benzodiazepine to be marketed, by Roche in March 1960, after its
approval by the FDA in February 1960. Its discovery was by no means accidental, unlike
the discoveries of many wonder drugs. It was one of the research products by Dr. Leo
Sternbach in an attempt to find a substitute for the phenothiazines, which were the treatment
of choice for anxiety at that time. However, the many side-effects and the addictive
potential of phenothiazines tended to limit their use in ambulatory patients. The
pharmaceutical companies were actively looking for new substitutes to continue their share
in this porfitable market.
In 1963 Valium was introduced as a more potent tranquilizer. The third benzodiazepine,
Serax, was introduced in June 1965. (1)
The Use
Since their introduction, benzodiazepines became the most commonly prescribed group of
psychotropic drugs.
However one should be reminded that in fact the labeled uses of benzodiazepines are
confined to alcohol withdrawal psychosis, anxiety, insomnia and muscle spasm.
Common unlabeled uses include atonic seizures, atypical absence seizures, infantile spasms,
myoclonic epilepsy adjunct treatment, neonatal abstinence syndrome, night terrors, opioid
withdrawal symptoms, panic disorder, sedation in pediatric patients, tension headache and
tremors. (2)
The Misuse
The recognition of the development of drug dependency, withdrawal symptoms and thus
abuse potential of benzodiazepines has raised much concern after the exponential increase
of their uses in the 1970s.
Use for as short as 2 weeks had been reported to cause dependence.
Withdrawal syndrome can be very difficult to deal with especially for patients predisposing
to chemical dependence. However, paradoxically, many of them are in fact the target group
of patients for the prescription of benzodiazepines.
It is quite common for any articles concerning benzodiazepines in journals or magazines to
be flooded with response letters from “angry patients” who claimed to have sufferred from
benzodiazepine dependence and withdrawal synddrome.
I think many doctors would also have the experience of encountering patients telling you
that they have been taking some benzodiazepines daily for over 20 years. They are quite
satisfied with the fact, living with the drug, and resist any suggestion of tailing off them.
To combat these problems, many regulations and guidelines have been developed by
various authorities to regulate and to guide the use of benzodiazepines by doctors.
There has been a recent increase in the public’s awareness of mood disorders, anxiety
disorders and problems of insomnia. Patients tend to be more ready to seek help for these
problems from the general practitioners and their family physicians. This might result in an
increase in the use of benzodiazepines. It is time to review some of these guidelines, among
which the “Revised Guidelines on the Proper Prescription and Dispensing of Dangerous
Drugs by Registered Medical Practitioners” promulgated by the Medical Council of Hong
Kong will concern us most.
The Precautions
General
To use benzodiazepines only when indicated, in the lowest dose, for the shortest duration
possible.
Abuse potential and risk of dependence
The abuse potential and risk of development of drug dependence of a particular
benzodiazepine is inversely related to its half-life and directly related to the duration of
continuous use.
Benzodiazepines with short half lives will be of higher risks of being abused and drug
dependence. Hence they should be prescribed with care (or to be avoided) especially for
the at risk groups.
(Benzodiazepines with short half life (<6 hr): Midazolam (Mayne), Triazolam (Halcion);
Benzodiazepines with intermediate half life (around 12 hr): Alprazolam (Xanax), Loramet,
Lorazepam (Ativan), Bromazepam (Lexotan), Temazepam;
Benzodiazepines with long half life: Clonazepam (Rivotril), Estazolam, Flunitrazepam
(Rohypnol), Chlordiazepoxide (Bralix), Diazepam (Valium), Flurazepam, Nitrazepam,
Pinazepam (Domar).)
To use benzodiazepines intermittently or on a p.r.n. basis instead of continuous use can also
help to lower the risk of developing dependence.
Treatment of Anxiety
Benzodiazepines are indicated for the short-term relief (two to four weeks only) of anxiety
that is severe, disabling or subjecting the individual to unacceptable distress, occurring alone
or in association with insomnia or short-term psychosomatic, organic or psychotic illness.
The use of benzodiazepines to treat short-term ‘mild’ anxiety is inappropriate and
unsuitable. (3)
Treatment of Insomnia
Benzodiazepines should be used to treat insomnia only when it is severe, disabling, or
subjecting the individual to extreme distress
Treatment of panic disorders
With panic disorders (with or without agoraphobia) resistant to antidepressant therapy ,a
benzodiazepine (lorazepam 3–5 mg daily or clonazepam 1–2 mg daily [both unlicensed])
may be used.
Treatment of depression
Benzodiazepines should not be used as the sole agent in the treatment of depression.
A benzodiazepine may be used as short-term adjunctive therapy at the start of
antidepressant treatment to prevent the initial worsening of symptoms. (4)
The Regulations
In Hong Kong the prescription and supply of benzodiazepines by doctors is mainly
governed by the Dangerous Drugs Regulations (Cap. 134) and the Professional Code and
Conduct. Regulations 5 and 6 of the Dangerous Drugs Regulations (Cap. 134) criminally
sanction for any failure to keep proper records and requirements as to registers of
dangerous drugs supplied. These have received much attention and most doctors should be
familiar with, or at least be aware of, them after the repeated convition of doctors in breach
of the Regulations and the report of such cases in the HKMA Newsletter.
While breaching the Dangerous Drugs Regulations would result in criminal consequences, a
breach of the Professional Code and Conduct would result in diciplinary action. Part III
Section 11 of the Code conerns with the “Supply of dangerous or scheduled drugs”.
Subsection 11.1 states that: “ Medical practitioners are advised to acquaint themselves with
the Guidelines on the Proper Prescription and Dispensing of Dangerous Drugs promulgated
by the Medical Council. Disciplinary proceedings may be taken in any case in which a
medical practitioner prescribes or supplies drugs of addiction or dependence otherwise than
in the course of bona fide and proper treatment.”
The “Revised Guidelines on the Proper Prescription and Dispensing of Dangerous Drugs by
Registered Medical Practitioners” was promulgated by the Medical Council of Hong Kong
in October 2003.
Section (A), (2) and (3) state that “These guidelines reflect currently accepted professional
standards on the use of such agents in the local context, and are intended to provide general
guidance to medical practitioners for the promotion of good clinical practice.
The Practice Directions under Section (E) should be followed. Breach of these directions
may be construed as improper use of dangerous drugs.”
Section (E), (1) concerns the “Practice Directions for use of benzodiazepines”
Since the test for professional misconduct is “a fall short of accepted professiomal
standards”, and the Guidelines reflect the currently accepted professional standards on the
use of such agents in the local context; failure to follow the guidelines would highly likely to
result in a successful conviction of professional misconduct. (5)
The “CIDER”
It is important for doctors to pay attention to these guidelines and to be familiar with them
so as not to get caught by them.
I have designed a small trick to remember them (for those concerning benzodiazepines only):
The word CIDER is used to remember the essential points of the guideline:
C- Complete history, physical examination, investigation and diagnosis.
I- Inform your patients about your diagnosis, plan of management, duration of treatment,
other treatment alternatives, and the side effects and abuse potential of the medication.
D- Document your findings, plan of management and most important, the justification of
prescribing benzodiazepines to this particular patient
E- Evaluate the patient’s abuse potential (eg. History of substance abuse, alcoholic), judge
it against the therapeutic benefits, and document it in your notes
R- Reassess the need for continual treatment regularly, (monthly, as recommended) and tail
off whenever possible. (Remember to document this)
Refer the patient to specialist care when necessary.
So, doctors, please have a CIDER before prescribing benzodiazepines to your patients!
(The Origins of Cider
It’s almost impossible to pinpoint the origins of cider. The existence of apples is
easier to establish, but when it comes to actual cider making, documentary evidence
remains frustratingly patchy.
Most cider is made from fermented apple juice. Natural cider has nothing added and
relies, for fermentation, upon the wild yeast present in the apples. For mass-produced
ciders, a yeast culture is added in order to achieve consistency. Although much of
today’s cider is produced from apple concentrate, many traditional cider-makers use
only cider apples, cultivated specifically for the purpose.) (6)
Reference
1. Dilip Ramchandani. The Librium Story. History Notes, Psychiatric News.
2. First Databank
3. Advice form Committee on Safety of Medicines
4. BNF
5. The “Revised Guidelines on the Proper Prescription and Dispensing of Dangerous Drugs
by Registered Medical Practitioners”
6. History-of-cider.com