ANXIETY STATES
Classification of Anxiety Disorders
Anxiety States or Disorders as they are currently known include a group
of diseases characterized by mobilization of the fight-flight natural mechanism
in the absence of a real danger to life or safety of the person. Thus the body
reacts by over-sympathetic activity including fast heart beats, cold extremities, sweating, tremors, gastric
spasm, muscle tension, and hyper-vigilance.
·
Phobic disorder
1. Social phobia
2. Specific phobia
3. Simple phobia
4. Agoraphobia
·
Panic disorder
·
Generalised
anxiety disorder
·
Mixed anxiety and depressive
disorder
·
Obsessive compulsive disorder
·
Reactions to severe stress and adjustment disorders
·
Acute stress reaction
·
Post-traumatic stress disorder
·
Anxious (avoidant) personality disorder
·
Other anxiety disorder
Phobic disorder
Under phobic disorder are to be included
those conditions of abnormally intense dread in the presence of an object or
situation often amounting to panic.
Agoraphobia is the commonest phobia.
Anxiety is produced by, or in anticipation of, going out alone. Fear often increases progressively the
further the patient is away from home. Anxiety tends to occur in crowded places
such as trains, buses, shops, restaurants and cinemas or where the patient may
feel trapped eq. lifts or hairdressers.
Certain key items were identified.
The stimulus (presence of situation causing anxiety)
A response
(tried to avoid that situation)
Somatic symptoms and Signs
(hand shaky, weak at the knees. sweating. clammy hands. hot and cold
feelings, pallor)
The autonomic symptoms
include butterflies in the stomach, heart pounds or flutters. dry mouth,
dizziness or faintness, difficulty in getting breath, tightness in the
chest.
Specific situations
staying at home alone. going out alone, being in an enclosed space and
being in crowds.
Personality factors
differ in normal controls and those with phobic anxiety states which if
persistent can become chronic anxiety states.
On the Maudsley Personality Inventory which depicts personality on an
introversion/extraversion continuum and this is usually pictured on the
horizontal axis whereas rising neuroticism is depicted on the vertical
axis. Normal controls are midway on the
introversion/extraversion continuum but low on neuroticism.
Patients with generalised anxiety disorder (chronic anxiety) had
very high neuroticism scores and were found to be the most introverted of any
group. Patients with phobic disorders
were less neurotic and less introverted than those with generalised anxiety
disorder. These personal findings have
been supported by other workers.
Acute stress reaction
tends to be
short-lived and related to major stress,
occurs in those
with a stable pre-morbid
personality and generally there is no fami
history.
Post-traumatic stress disorder (PTSD) develops after an acute stress
reaction. It is characterised by
insomnia, nightmares and flashbacks, during which the original trauma is
relived. This helps to 'fix' the trauma
more firmly in the nervous system. During World War I prolonged stress in the
trenches led to exhaustion and 'shell-shock’, which would now be called PTSD.
The lessons were well learned in World War II when front-line sedation was
extensively employed. This resulted in a diminution of insomnia, nightmares and
flashbacks and less PTSD. Although
unfashionable, there is still a place for sedation after very traumatic experiences.
This is a good way of diminishing the likelihood of PTSD developing later.
Generalised anxiety disorder is
persistent and recurrent.
Exacerbations of anxiety are precipitated by minor stress. There is usually an
abnormal pre-morbid personality with anxious, histrionic or obsessional
features and there is generally a
family history of a similar disorder.
Differential Diagnosis of Anxiety Disorders
Alcohol withdrawal
Caffeinism
Amphetamines or other stimulant drugs
Hyperthyroid ism
Partial complex seizures
Hypoglycaemia
Cushing' s syndrome
Cardiac arrhythmias (Paroxysmal tachycardia)
Asthma
Genetic loading and sex
difference:
Nervous disorder in the family of the patient being treated.
fathers also required treatment in 13%
of cases
mothers 28%
brothers/sisters in 35%.
The mean age of onset is between 20 and 30 years of age.
In the National Agoraphobia Survey which consisted of a random sample of
100 cases, agoraphobic sufferers reported factors which made them feel worse
The most common situation reported by 96% was:
"having to queue at shops. etc."
followed by:
"having a definite appointment"
'feeling trapped at hairdressers.
etc."
"domestic arguments and stress"
"increase in distance away from
hoine"
"thinking about £ny problems"
"particular places in the neighbourhood"
"cloudy1 depressing
weather" 'which was reported by 56%.
In the same study the factors 'which made patients feel better
included:
"when cut1 having a way open for a
quickreturn home" (91%)
"being accompanied by husband or wife"
"sitting near a door in hall. restaurant
etc."
"focusing my mind on something
else"
"when out for a walk, taking dog, pram1 etc."
"talking problem over with a friend"
"talking problem over with my doctor"
"being accompanied by a friend"
“talking sense to myself" (reassuring myself)
(52%)
"wearing sunglasses" (36%).
Who do agoraphobics consult?
In the National Agoraphobic survey it was found that
96% consulted their local doctor
77% a psychiatrist
16% a religious or spiritual healer
9% a non-medical hypnotherapist
3% a psychologist
1% phobic societies
The outcome of treatment in this very selected sample is illuminating.
Treatments % Receiving Treatment % Finding it very helpful
a) Tablets/medicine 96 17
b) Relaxation 29 18
c) Psychotherapyl
Psychoanalysis 28 15
d) Behaviour therapy/
Desensitization 11 31
Flooding
etc.
e) Religion/faith
Healing 13 15
f) Hypnotherapy 15
Can depression and anxiety states be differentiated?
There is a tremendous overlap between the symptoms of depression and
anxiety. In doubtful cases there are some facts which help make the
primary diagnosis. The problem
arises because many people with primary depressive disorders develop panic
attacks for the first time in their lives.
As the depression recedes, so the panic attacks diminish. In cases of primary depression there
is generally loss of interest, loss of appetite, loss of
libido, retardation and the illness develops later in life. In primary anxiety states there is
initial insomnia (difficulty in going off to sleep), phobias, sexual
difficulties especially in men, previous attacks of anxiety and the onset is
earlier in life.
Most people indulge in alcohol as
their first line of self-help. It is
essential to take an accurate history because of the patients vested interest in disguising their drinking
habits from their medical advisers. Alcohol is particularly unhelpful since it
potentiates the effects of
benzodiazepines, reduces the plasma levels of tricyclic antidepressants.
and produces well-known medical complications.
THE TREATMENT OF ANXIETY
ANXIOLYTICS
The benzodiazepines have been phenomenally successful and in 1977 8.000
tonnes of benzodiazepines were consumed annually in the USA. Since then there
has been a considerable decline in the prescribing of these very valuable
drugs. In 1983 there were approximately
30 million prescriptions written for benzodiazepine and hypnotics in the UK.
It has been estimated by Professor Lader that 15% of the population in
developed countries use tranquillisers at some time each year. He estimates
that during the past 25 years over 500 million people world wide have taken
benzodiazepines.
It is therefore legitimate to ask how do benzodiazepines decrease
anxiety? This can be summarised as follows:-
1) The
discovery of benzodiazepine receptors in the brain.
2) The discovery that benzodiazepines work by
enhancing the inhibitory neurotransmitter GABA.
3) Thus
it appears that the benzodiazepines, anti-anxiety action may be a result of
increasing GABA to quiet brain cell activity.
Supporting evidence for the role of benzodiazepines
has been determined from animal studies. It was found that a decreased number
of benzodiazepine receptors appeared in fearful compared with non-fearful rats
and emotional compared with non-emotional mice. It could be, therefore, that genetic transmission determines the number of
benzodiazepine receptors in man. If
this theory were correct one could postulate that there are fewer
benzodiazepine receptors in anxious compared to non-anxious people
Benzodiazepine receptor antagonists have now been
developed and it has been shown that if these are given to normal healthy
volunteers there are increases in hormonal levels, which generally occur with
stress, ie. there is an increase in cortisol growth hormone and prolactin. After the benzodiazepine receptor
antagonist was administered the hormonal changes were associated with feelings
of sudden panic, agitation, confusion and impending death. The classical signs of central and
peripheral anxiety were observed.
The tricyclics and MAOIs exert an anti-anxiety effect
by a completely different mechanism.
They affect noradrenergic, adrenergic and serotonergic neurones, which
are found especially in the medullary nuclei.
Physiological arousal is due directly to activation of relevant medullary
nuclei which can act independently
of higher centres which are likely to
be susceptible to effects of tricyclics and MAOIs but which are
relatively immune to the direct effects of benzodiazepines.
The reaction to withdrawal of benzodiazepines
When a benzodiazepine is acutely withdrawn, three things can
happen. If the drug were totally
ineffective, then abrupt withdrawal of it will lead to no increase in symptoms
of anxiety. This is the neutral reaction. Because benzodiazepines have long-lasting effects1 when
they are withdrawn, there can be a pharmacological withdrawal. Reaction
with a peak of symptoms of anxiety at day 14.
If the drug was having no long-term clinical therapeutic benefit, after
the pharmacological effect or withdrawing a powerful tranquilliser, the
symptoms abate between days 14 and 28 and the patient is no worse off than he
was before.
If the medication had been valuable however, acute withdrawal will lead
to rise in symptoms over the following 14 days and a persistent level of
symptoms, because the original state of anxiety is no longer being controlled.
Choice of benzodiazepines
Table II classifies some of the currently available benzodiazepines
according to their elimination half-lives
Table
II
Classification of some currently available benzodiazepines accorrding to
their elimination half-life
Short
half-life Long
half-life
Alprazolam Bromazepam Flurazepam
Lorazepam Chlordiazepoxide Ketazolam
Loremtazepam Clobazam Medazepam
Oxazepam Clorazepate Nitrazepam
Temazepam Diazepan Prazepam
Triazolam Flunitrazepam
Those with a short half-life are generally good hypnotics because they
do not produce as much daytime sedation the following day as benzodiazepines
with a long half-life, e.g. temazepam (Normison, Euhypnos).
Some studies indicated that triazolam produced more memory disturbance
than temazepam. Largely because of this1
it was withdrawn from the U.K. but is still available in Europe and the
USA. It has a very short half-life and
was an excellent hypnotic if getting off to sleep was the major problem. It was even possible for the medication to
be taken at 2 a.m. if patients could not go off to sleep, without leaving much
of a hangover.
Buspirone (Buspar)
is thought to reduce the activity of 5HT pathways. It is unrelated to the benzodiazepines. It is an Azapirone. The
onset of action is much slower than a benzodiazepine and is an alternative to
them. It is ineffective against the rebound anxiety associated with withdrawal
of benzodiazepines. It takes 3 weeks to have its full effect and many people
withdraw it after 6 weeks.
The benzodiazepines with long half-lives can be given as a hypnotic but
they will also produce some sedation the following day. This is often desirable for psychiatric
patients. Chlordiazepoxide (Librium)
which is less sedative than diazepam (Valium),
clobazam (Frisium) is less sedative than either clorazepate (Tranxene) is
becoming more popular, flurazepam (Dalmane and nitrazepam (Nogadon) can lead to
quite a lot of sedation the following day.
Flunitrazepam (Rohypnol) has been used in other countries for a long
time, but has limited use in Great Britain.
If an intravenous benzodiazepine is to be used, diazepam can cause
problems because the solvent is acid.
This can lead to pain at the site of injection radiating down the arm
and it may be followed by venous thrombosis.
A good tip is to withdraw venous into the syringe to dilute the solvent
and then inject it slowly back into the vein.
Pain will then not be experienced and the risk of venous thrombosis
diminished. When diazeparn is given for
minor surgery or to produce sleep, the best physical sign is to watch the
eyelid, as the patient becomes sleepy so the lid will droop. By the time the
eyelid has covered half of the pupil most patients will be amnesic from that
point onwards. The new intravenous benzodiazepine, midazolam (Hypnovel) is more
satisfactory because of its fast onset of recovery and minimal local venous a
half-life of two hours and is water soluble compared with diazepam which has an
organic solvent. The dose is 2.5 to 7.5 mg. The ampoules are 10 mg in 2 ml.
It should be recalled that benzodiazepines are powerful muscle relaxants;
they should be given with caution to the elderly because big doses can reduce
muscle tone. Old ladies are notoriously prone to trip. This can result in the
fracture of the neck of the femur and long-acting benzodiazepines can
accumulate in the brain. They are best used intermittently or for
short courses to reduce the risk of habituation and can be given-2 hours before
entering a stressful situation.
Barbiturates are
seldom employed now except for rapid sedation for acute anxiety states. They
can also be given as a pre-med prior to ECT. Their ability to produce
habituation/addiction, withdrawal fits and to lower the plasma levels of
tricyclic antidepressants, are all reasons why their popularity has declined. The
major tranquillisers do have a part to play. They can help some chronic anxiety
states and they do not produce habituation or addiction and perphenazine
(Fentazin) or fluphenazine (Moditen), flupenthixol (Depixol) or trifluoperazine
(Stelazine) can all be used in small doses during the day. If sedation at night is required
chlorpromazine (Largactil) can be usefull.
Antidepressants
can play a valuable part in the treatment of anxiety. Of the first generation antidepressants clomipramine (Anafranil),
imipramine (Tofranil) and dothiepin (Prothiaden) are the ones which are used most
commonly. Dothiepin produces many fewer
side-effects than clomipramine. These
drugs can block panic attacks as can monoamine oxidase inhibitors, although one
should try the tricyclics initially.
There are some people who do not respond but do extremely well with
MAOIs. Tranylcypromine (Parnate) is the
most powerful; phenelzine (Nardil) is highly effective and isocarboxazid
(Marplan) can also be valuable. The incidence
of a hypertensive cheese reaction is greatest with tranylcypromine and least
with isocarboxazid. Recent work has
demonstrated the safety and efficacy of combined amitriptyline and
tranylcypromine. Indeed it has been
demonstrated that amitriptyline will prevent the cheese reaction of monoamine
oxidase inhibitors (Pare et al, Lancet, July 24, 1982. p. 183-186). This work illustrates that it is safer to
use combined antidepressants than the MAOI alone. Amitriptyline modifies the
rise of blood pressure caused by tyramine.
If certain MAOIs are to be combined with certain tricyclics great care
must be taken however. They should be started in small doses simultaneously,
giving the sedative tricyclic amitriptyline or trimipramine (Surmontil) at
Might with the.MAOI during the day-morning and lunchtime. If given later these psychic energisers can
induce insomnia.
Certain combinations can be lethal; clomipramine (Anafranil) should
never be combined with an MAOI; deaths have been reported from this
combination.
Second Generation antideressants can also be used to treat anxiety states. Trazodone
(Molipaxin) is said not to interact with MAOIs. It is sedative and can cause
weight loss. Mianserin is also sedative (Bolvidon. Norval). Lofepramine
(Gamanil) is a tricyclic with fewer anticholinergic side-effects. On the whole
the second generation antidepressants are less effective than the first
generation but with the exception of maprotiline (Ludiomil) they are safer if
taken in overdosage).
The beta-adrenergic blocking drugs have a valuable part to play in the
treatment of certain anxiety states.
Symptoms
of Anxiety
Somatic
and autonomic Psychic
(psychological)
Palpitations Feelings
of dread and threat
Difficulty
in breathing Irritability
Dry
mouth Panic
Nausea Anxious
anticipation
Frequency
of micturition Inner
(psychic) tension
Dizziness Worrying
over trivia
Muscular
tension Difficulty in concentrating
Sweating Initial
insomnia
Abdominal
churning Inability
to relax
Tremor
Cold
skin
Beta-blockers are best for the treatment
of palpitations, tremor, difficulty in breathing, although very
occasionally they can precipitate asthma. On the whole they do not influence
sweating, gastro-intestinal symptoms, frequency of micturition, nausea or a dry
mouth but they can diminish dizziness.
Tremor can be particularly troublesome if it affects a professional
musician or a dentist. Propranolol (Inderal)
or oxprenolol (Trasicor) 40 mg, given 2 hours before entering a
stressful situation is are useful. The dose may occasionally need to be
increased to 80-mg. They can be useful
in approximately 10% of anxiety states and their value can be determined very
quickly. Habituation and addiction do
not occur.
Beta-blockers can be combined,
with advantage, with benzodiazepines which are on the whole
superior for treating psychic anxiety.
Benzodiazepines should only be used for short courses of treatment. The benzodiazepines can produce over-sedation
whereas small doses of beta adrenergic blocking drugs do not cross the
blood-brain barrier and may control tremor, which can be troublesome at
interviews and pounding of the heart1 which can be distressing,
while leaving intellectual function entirely unimpaired.
Benzodiazepines as hypnotics can be given
every 3rd night to prevent habituation.
individual, group and marital
psychotherapy, psychoanalysis, behaviour and cognitive therapy.
Increasing importance is being given to
relaxation techniques, the main one being the use of relaxation tapes.
Patients are instructed to use it for 20 minutes twice a day, or if they
start to panic or if they have trouble getting to sleep, or wake in the night.
biofeedback helps to motivate patients and increases
the speed of learning deep muscular relaxation.
Other patients prefer yoga or autogenic training.Transcendental
Meditation (TM) has been shown to benefit anxiety states, anxiety and
alcoholism, mild hypertension, insomnia and stress-related disorders. Patients are taught to meditate and practise
for 20 minutes twice a day. Studies
have shown that regular meditation can decrease anxiety on a number of anxiety
scales. TM can also result in a lower
heart rate, blood pressure, respiration rate, basal metabolic rate. It is also associated with a reduction of
alcohol intake, cigarette smoking and the use of minor
tranquillisers and hypnotics. It can
also reduce the incidence of hospitalization.
Admissions for heart disease and diseases of the nervous system decreased
by 87%, benign and malignant tumours decreased by 55% and mental disorders
decreased by 31%. The most likely
explanation for these findings is that the regular use of TM reduces stress.
This, in turn, has an effect on the immune system of the body.
Other non-drug treatments of anxiety disorders
include general reassurance, explanation of symptoms, support, anxiety
management and counselling.
It should never be forgotten that the therapist plays
an enormous part in the recovery of anxious patients. There are certain personality types and modes of behaviour, which
are helpful. In a study carried out at
Johns Hopkins Hospital, registrars were measured for the three therapeutic virtues
of empathy, genuineness and warmth. It was found that registrars possessing
these qualities produced a better therapeutic outcome than their psycho-toxic
colleagues who were non-empathic, insincere and cold. Whatever other methods of reducing anxiety are employed; empathy,
genuiness and warmth are likely to contribute to the recovery process.