Introduction.

This essay will set out a brief description of the beliefs around the use of drugs to affect neurotransmission in the brain, and the effect of these drugs on emotion and behaviour. There will be a short description of the mechanics of where and how it is believed that specific drugs work in the treatment of depression and anxiety. This will lead on to a description of the effects that these drugs have on other parts of the brain and body and how they react with each other.

The Medical Model.

The medical model began to take hold around the 18th century, the so-called age of enlightenment (1) . It was at this time that the idea of demons being responsible for abnormalities started to be replaced with a concept of illness caused by physical disorders. That an abnormality could be caused by a physical disorder lead to the conclusion that it could be corrected by a similar physical intervention. Early discoveries produced information about the brain structure. Further investigation led to information about the effects of electricity on brain function and most recently specific chemicals have been used to produce a therapeutic effect.

It is my belief that the way that drugs have been used to treat various solely psychological conditions is deeply rooted in the history of the development of medicine. A religious approach to health and illness gave way to the rationalist approach and the clockwork universe as espoused by Newton et al. Now, new systems thinking(2) attempts to provide a model that is more inclusive and holistic than previous ones.

Drug Mechanisms.

The brain makes its connections to other parts of the body, and within itself, via the neurones in the nervous system. This system has two main transmitters that work in balance with each other. These are acetylcholine in the parasympathetic nervous system and noradrenaline in the sympathetic nervous system. However, in order to have as many connections, and therefore options, as possible and to prevent an impulse from moving in the wrong direction there are many brakes in the system called synapses or the synaptic cleft. These synapses are junctions where the electrical impulse is converted to a chemical transmitter. This chemical transmitter, the neuro- transmitter, then stimulates another neurone and the impulse is continued. It is at the synaptic cleft that the drugs to treat both depression and anxiety are thought to have their effect.

The diagram shows the basic structure of the synapse. As the electrical impulse reaches the end of the neurone it causes the vesicles to release the neuro-transmitter into the synaptic cleft. The neurotransmitter flows across the synaptic cleft and excites the post synaptic receptors to continue the impulse. The synapse has only a limited amount of the transmitter available at any given time, so there are areas of the synapse, coloured in red, that act to reabsorb the transmitter for re-use.

A number of neuro-transmitters have been identified. In 1965 Schildkraut proposed that too much noradrenaline could result in mania whereas too little in depression(3). However, later research has showed that the relationship may not be as simple as this. It has been found that in bodies of people with depression who have committed suicide there were lower amounts of serotonin than expected, this was also the case in the cerebrospinal fluid taken from patients with depressive illness(4).

Now, it is believed that serotonin, another neurotransmitter, is implicated in the development of depression. It is thought that the amount of serotonin produced is insufficient such that the quality of the impulse propagated between neurones in the brain is poor. Serotonin appears to have an inhibitory effect on parts of the limbic system that are concerned with the conscious experience of emotion. If this is true, then the removal of the inhibitory effect of serotonin would allow this part of the limbic system to be stimulated which may give rise to both depressive and anxiety states.

Depression.

Serotonin control lies at the heart of a number of classes of drugs used in the treatment of depression. They all have the effect of raising the levels of serotonin, and possibly other neuro transmitters, that are present within the synaptic cleft. These are:

With many of these drugs, particularly with those developed early in the study of depression, there were undesirable side effects showing that these neuro-transmitters clearly had much wider effects than at first thought. For instance a patient using the MAOI type drugs must have a special diet and amine-rich foods such as red wine and hard cheese must to be avoided. The amines derived from these foods build up in the body and may cause hypertension, and in severe cases, may even cause cerebral haemorrhage. The tricyclics can cause cardiac arrhythmia, drowsiness, blurred vision and dry mouth. The modern SSRI drugs have reduced these effects but some still remain. For example, fluoxetine can cause impotence in men; particularly undesirable in a patient already suffering from depression. The presence of such side-effects shows that the body is a complex system where processes are interrelated.

Anxiety.

The drugs used to treat anxiety have an approximately opposite effect to those described above in that they are classified as depressants. Tranquillisers can be further sub-divided into broadly the neuroleptics such as chlorpromazine, and the minor tranquillisers such as diazepam. As a group, they have a calming effect on patients to a greater or lesser degree, but the choice of drug used depends greatly on the degree of anxiety experienced by the patient. Examples of such drug are:

As with the drugs for depression there are a number of undesirable side effects. These can include drowsiness, lethargy, a tolerance for the drug needing greater quantities, a dependence on the drug leading to tremors and convulsions on withdrawal.

The neuroleptics such as chlorpromazine and prochlorperazine are also associated with a drug induced condition similar to Parkinson's Disease which may simply add to the patient's problems.

The benzodiazepines are associated with dependency and may also be associated with rebound anxiety where on withdrawal of the drug, the patient becomes even more anxious than before. Again even the newer drug report some side effects showing the systemic nature of the body mechanism.

Drug interactions

Drug interactions can be defined as "..when the effects of one drug are altered by the effects of another drug(5)." Whereas these interaction are mostly adverse they can in some instances be beneficial. There are two types of possible interaction:

i Drugs that cause or precipitate an interaction

These may be drugs that are highly bound to proteins and will therefore displace others drugs from specific binding sites, or drugs which inhibit the breakdown of other drugs, or compete for the elimination of other drugs in the kidneys. Drugs which are strongly bound to blood proteins, so competing for binding sites with other drugs which they potentiate include aspirin and sulphonamides. Drugs which alter the metabolism of other drugs include the monoamine oxidase inhibitors which inhibit the metabolism of other drugs. Some drugs may compete with others for excretion into the urine, so increasing the length of time taken to eliminate a dose of the drug from the body thus potentially lengthening the duration of its effects. Patients may also be taking diuretics which will affect renal function and therefore alter the rate at which drugs and other substances are eliminated from the body and reducing the time for which a given dose of a drug is present in the body.

ii Drugs that likely to be acted upon i.e. be the object of an interaction

These are drugs that have what is termed a steep dose-response curve. This is where a small change in dose results in a relatively large change in therapeutic effect. These drugs may have a high toxic-therapeutic ratio. By this it is meant that the level at which the drug is toxic to the body is very close the level that is therapeutic. Many of the drugs used in the treatment of anxiety and depression fulfil this criteria. Other drugs that might be being taken by the patient and may fall in this category are the oral contraceptives, immuno-suppressant drugs and some antibiotics.

Conclusion.

It is clear that the use of psychotherapeutic drug therapies has contributed to the well-being of many people over the years. However, it was suggested by SANE in 1993(6) that one quarter of all the medications prescribed in Britain by the NHS are psychotherapeutic drugs. Further, given the recorded side-effects of the drugs in use today, as well as the non-therapeutic use of "designer drugs" such as Ecstasy, and our relatively limited knowledge on brain structure and function it is possible that we may be storing up more problems for the future by following a solely bio-chemical regime. Further, drug therapy does not solve the problems of these patients permanently. Often, once the drugs are discontinued, their anxiety or depressive states return. Drug therapy does however provide a way of controlling their more florid symptoms, providing a supportive environment in which psychotherapeutic interventions may be made.

MARTIN WEAVER

August 1998

References