Addiction Treatment Blog

In 1954, Olds and Milner discovered that there appeared to be pleasure spots in the brain. Implanting electrodes in certain areas of the brain, through which a rat can give itself an electric current by pressing on a lever, produced in most brain areas nothing of note. In some areas, however, the rats seemed keen on the effects of self-stimulation and, in some cases, if left to their own devices would self-stimulate to the exclusion of all else – even food and drink.

As mentioned, noradrenaline was discovered in the brain in 1954. In 1959, a second catecolamine, dopamine, was identified, which was shown to be deficient in Parkinson’s disease.

The later mapping of dopamine-containing neurones has shown that they too, like noradrenergic neurones, tend to originate in a discrete area, the ventral tegmentum. Some of these neurones run to strictly motor areas of the brain and constitute the nigrostriatal system, and it is loss of nerve calls in this pathway that leads to Parkinson’s disease. Read more…

Schizophrenia can be dangerous to yourself and others around you if treated incorrectly.

In any consideration of the dopamine hypothesis of schizophrenia, one of the arguments invariably put forward is that psychostimulant drugs, in particular the amphetamines, lead to a mental disorder characterised by prominent paranoid feelings, or outright paranoid delusions. This many authorities have suggested, is a state that is very similar to some schizophrenic states. As the psychostimulants increase brain dopamine levels or neurotransmission, schizophrenia must therefore involve increased dopamine functioning and accordingly dopamine antagonists are its appropriate treatment.

However, the picture in real life is considerably more ambiguous. In the first place there has long been a substantial amount of evidence that up to a third of individuals with ‘schizophrenia‘ actually do well on psychostimulants. Read more…

Anticholinergics

The anticholinergics are a group of drugs, examples of which are given in the table below, which antagonise the action of the neurotransmitter acetylcholine (Ach) at one of its receptors – the muscarinic receptor.

These drugs were initially used to treat Parkinson’s disease. They have since largely been superseded by the use of L-dopa. As most neuroleptics commonly cause parkinsonian symptoms, the anticholinergics have been used routinely to alleviate side effects, where the effect of L-dopa would be blocked by the neuroleptics themselves.

It has been suggested that they have been used too routinely. In many instances it has been common practice to prescribe an anticholinergic agent along with a neuroleptic, when the neuroleptic is first given – that is even before side effects have appeared. The rationale for this has been that the emergence of side effects may compromise an individual’s willingness to continue with medication. The more cynical view is that an early prescription of an anticholinergic drug means that hospital staff or general practitioner will not be called out of hours by a distressed patient, who has just been paralysed by a dystonic reaction or had some other side effect. This of course ensures that they both get a night’s sleep. Read more…

As with most of the drugs, Neuroleptics may have some serious side effects.

Neuroleptics all bind to dopamine receptors. Almost all bind to at least one other receptor as well but not all of them bind to the same other receptor. People also differ. The combination of these two principles means that the side effects of a neuroleptic may differ from one individual to another.

The side effects listed seem fearsome. But most are readily reversible by reducing the dose, changing or halting the drug or using an antidote.

Treatment, however, may involve a trade-off. In practice, it seems that many individuals are prepared to tolerate the interference with daily living that some of the side effects listed may cause, in exchange for peace of mind. The reason for listing these side effects in full is not to deter prescribers from prescribing or takers from taking but rather to involve the taker in making the trade-off rather than having it imposed insensitively on them, and to give prescribers some feel for the nature of that trade-off. Read more…

History of the Neuroleptics

There is considerable controversy over who discovered the neuroleptics, one that is highly relevant to the question of just what these drugs do. Chlorpromazine was first synthesised in 1950, with the intention of producing centrally acting antihistamine for the control of cardiorespiratory sock or collapse. It was first used widely in humans in 1952, along with other agents, as part of an anaesthetic cocktail, when its effects were noted by a chlorpromazine – they were neither sedated in the usual way with anaesthetic agents or analgesic, but rather appeared to become indifferent. This he described as an ataractic effect. A notable point here is that the effect must have come on within an hour or so after having had the drug – and it came on in normal subjects.

In 1952, Jean Delay and Pierre Deniker reported that chlorpromazine was of benefit in controlling states of manic and psychotic agitation. Around the time of its launch in 1954, there was no suggestion that chlorpromazine was likely in any way to be specific to schizophrenia. That came later. In the mid-1950s, chlorpromazine was being reported as being useful for almost every psychiatric condition (hence its trade name Largactil – Large Action).

Laborit has always claimed priority in the discovery of chlorpromazine. Delay and Deniker and others have disputed this. To some extent taking sides in the dispute depends on whether you see the neuroleptics as being in some way curative of psychotic illness or as producing an anti-agitation effect – an effect that is produced equally in all takers who are agitated, whether or not they have a psychological problem. Laborit’s descriptions are in line with the approach that is adopted in this article, which is that neuroleptics act by inducing a state of psychic indifference – in everyone who has them, and that they do this within a short period of time. Delay and Deniker’s approach is the approach that later led to the notion that neuroleptics were anti-schizophrenic.

Within a few years of their use, it became  clear that the new group of drugs produced extrapyramidal side effects. As further compounds came on stream, it seemed that only those that produced extrapyramidal effects brought about benefits in the psychoses. This led to two things. One was that the drugs as a group came to be called neuroleptics by Delay, a term which literally means ‘nerve seizing‘. The second effect was that, for 30 years, little effort was put into finding ‘antipsychotic‘ agents that would not produce extrapyramidal effects – atypical neuroleptics as such agents are now called. It is only in recent years with the rediscovery of clozapine – a drug almost devoid of extrapyramidal effects – that the picture is changing.

Are Neuroleptics Anti-Schizophrenic?

It is commonly believed that neuroleptics drugs are anti-schizophrenic.

The evidence that neuroleptics are anti-schizophrenic comes from a series of research projects which have shown that subjects who take them after discharge from hospital are much less likely to be readmitted than those who do not.

The dopamine hypothesis of schizophrenia has been developed based on this kind of evidence. Briefly, this hypothesis states that as all neuroleptics block the dopamine system in the brain, and as they are beneficial in schizophrenia, therefore there must be something wrong with the dopamine system in the brains of individuals with schizophrenia. A major research enterprise has developed around attempts to test this hypothesis. From a sociological point if view, there have been two consequences of this. One is that many current researchers have had a vested interest in believing that neuroleptics are anti-schizophrenic. Another has been given the ‘known’ abnormalities in the dopamine system in schizophrenia, the fact that the drugs work on the dopamine system means that they are anti-schizophrenic.

For those who take the approach that neuroleptics do reverse the core disturbance in schizophrenia, the usual response to patients not getting better has been to give more of the drugs, and the idea that an individual might not take their drugs is viewed very seriously. In addition, the idea of paying much heed to what the takers of the drugs have to say about whether they are helpful or not seemed irrelevant – after all, these drugs are curative of an illness, a cardinal manifestation of which is supposedly lack of judgement.

The view taken throughout this chapter is that neuroleptics are not specifically anti-schizophrenic but that they are useful for anyone who is agitated, rather than just for people who have schizophrenia. The evidence for this comes from daily practice. Anyone who is agitated will usually be prescribed neuroleptics, whether or not they have schizophrenia. They may have depression, mania or just be agitated. Read more…