Addiction Treatment Blog

Lithium Pellets

There are some suggestions from as early as the 2nd century AD that spring waters that were alkaline (which would be expected with a high concentration of lithium salts) were known to be of some use in the treatment of overactive states such as mania (1).

Lithium itself was isolated first by August Arfwedson in 1817. It was named lithium as it was found in stone – lithos being the Greek for stone. During the 1850s alkaline compounds, like lithium, were known to be of some use in preventing gout by interfering with the precipitation of uric acid in the blood and joints. At the time mania and melancholia were often seen as being part of the same family of diseases as gout and this led to the use of lithium for these conditions also. As early as 1880, the use of lithium in this manner led Carl Lange to suggest that it might have a role in preventing episodes of periodic depression.

Surprisingly, however, despite these discoveries and what would now appear to be correct hunches, lithium slipped out of use for mood disorders and had to be rediscovered in 1949. In part this was because of its side effects. In the middle of the 19th century, several investigators took lithium and noted that it caused increased urine flow, tremor of the hands and difficulties with memory or concentration, which led to wariness regarding its use. Later in the 1930s, it was used as part of a salt restriction diet in the United States and in many cases it caused such clear cut toxicity that its use was banned by the Foods and Drugs Administration (FDA). Read more…

Mania is for practical purposes the mirror image of depression. Approximately 50% of people affected present with an elated, euphoric mood. They may be grandiose in their attitudes and beliefs uninhibited in their behaviour. However, the remainder may be irritable and tetchy rather than elated and euphoric and paranoid rather than grandiose. Common to both groups is an increased level of activity, so that hyperactivity is perhaps the most consistent diagnostic feature of mania. In addition, there is typically an increase in appetite and a decrease in time spent asleep.

In 1853, Falret and Baillarger independently described a bipolar disorder, in which affected individuals cycled between periods of elation, or mania, and depression. This was variously called folie circulaire or folie à deux periodes. It forms the basis for what is now recognised as manic-depressive disorder. In 1896, Emil Kraepelin divided the major psychiatric illnesses into manic-depressive illness and schizophrenia. The former was primarily a disorder of mood, the latter a disturbance of cognitive functions. The former usually followed an episodic course with individuals recovering to normal between episodes. The latter was more likely to become a chronic illness with a majority of affected individuals not every fully recovering. These distinctions have broadly speaking held to this day. Read more…

There are seven major physical treatments for depression at present.

• Tricyclic Antidepressants (Table 1). These have until recently been by far the most widely used.
• The Monoamine Oxidase Inhibitors (MAOIs) (Table 2).
• Reversible Inhibitors of Monoamine Oxidase (RIMAs) (Table 3).
• 5-HT Reuptake Inhibitors (Table 4).
• Other Antidepressants (Table 5).
• Treatments for Bipolar Disorders or Prophylaxis of Recurrent Disorders (Table 6).
• Others (Table 7)

In the last category, a number of other treatments are marketed for or used for depression and they often work, but whether they are antidepressants in the same sense as electroconvulsive therapy (ECT), imipramine or phenelzine is a matter of dispute. The 5-HT-1a agonist, buspirone, has in addition been marketed as an antidepressant, and a further compound from this group, flesinoxan, looks as though it may also emerge as an antidepressant.

Finally, there is also ECT, the mechanism of action of which, and its use clinically will not be discussed at any length in this article. Its role when antidepressants fail to work and in cases of mania will be considered at a later stage. Read more…

Coping with stress can be hard at times.

The term ‘affective disorder‘ is sometimes taken to encompass both the mood and anxiety disorders. In this blog, it will be restricted to the former. Two disorders will be considered, depression and mania. Depression will be covered first followed by a consideration of mania and then the question of prophylaxis of recurrent episodes of a bipolar disorder, be they depressive or manic.

It is perhaps more difficult to specify exactly what antidepressants do than it is for any other drug that acts on the brain. In the following articles, I will employ an ulcer model of depression in an attempt to clarify the issues. This model, however, simplifies both ulcers and depression and this should be borne in mind. In clear cut cases of depression, an ulcer model performs passably. But in less clear-cut cases, the difficulty in pinpointing what it is that antidepressants do re-emerges.

Another way to consider the issues is by considering what the terms ‘mood’ and ‘emotion’ mean. These are notoriously difficult to define, but one way the problem has been approached is to define them in relation to each other – to compare, for instance, the relation of mood to emotions with the relation between climate and weather, or the relation between the pedal and the keys of the piano. 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…

Traditionally, three psychoses or major categories of psychiatric illness have been described. These are schizophrenia, manic-depressive psychosis and a third group, variously termed the paranoid, reactive or sensitive psychoses, which more recently have been called the delusional disorders.

This seeming diagnostic precision, however, masks a situation in which, since World War II, there has been a tendency to label all serious psychiatric conditions as schizophrenia. Accordingly, the pharmacological management of the psychoses, in practice, reduces to the management of schizophrenia. It has also reduced in the past 30 years, to the clinical employment of a group of drugs called the neuroleptics, which have been supposed to be in some way specifically therapeutic for schizophrenia. Read more…

The number of children contemplating suicide has increased by fourteen per cent over the past year.

Up to fifteen to twenty per cent of unresponsive manic depressives kill themselves. When the condition is poorly controlled through incorrect medication, or combinations of them, and in harrowing life circumstances, suicide can happen, and it is vital to encourage sufferers to keep as much contact with carers as they can and, if possible, so that when things start to go wrong there is help to prevent these crises.

Statistics

Around 4500 people kill themselves in England and Wales each year (one in 100 deaths), while at least ten times that number of people attempt suicide.

In almost all cultures, the suicide rate rises with age, with the highest rates in the UK for those over seventy-five. In recent years, suicide has also increased in young man, and it is now the second leading cause of death in the fifteen to twenty-four age group, after accidents.

Certain factors are known to be associated with increased risk, including drug and alcohol misuse, unemployment, social isolation and family breakdown. People with diagnosed mental health problem are at  particular risk. Indeed, up to ninety per cent of suicide victims have been reported to have been suffering from a psychiatric disorder at the time of their death. Read more…

In children, manic depression is rarely diagnosed in the United Kingdom.

In children manic depression is rarely diagnosed in the United Kingdom; in the United States it is diagnosed quite frequently. Cardinal symptoms used to support a diagnosis of manic depression are insomnia and grandiosity (where the child has a persisting and genuine belief in his own self-importance – as opposed to temporary play acting which is of course normal). There is often co-morbid drug use which can obfuscate the picture. The area is of major importance as parents may wonder if their adolescent mischief-maker is ‘organically’ sick or just going through the growing pains of youth in a disorderly manner. There is value in early diagnosis of manic depression, though it is often only made retrospectively, and early management is important. In reality, the older the youth is the more likely manic depression is to be correct diagnosis. There is an increasing incidence into the early twenties (being the maximum age of onset).

The adolescent should have a careful evaluation by an experienced psychiatrist. Differentiation from ADHD (Attention Deficit Hyperactivity Disorder), ‘personality disorder’, drug use and behavioural disorders in a healthy child brought up in a dysfunctional manner are key. An accurate and careful diagnosis is important. Clear diagnosis may not be possible where there is a combination of these elements initially. Read more…

Neuroimaging

Neuroimaging means looking at the brain with tools such as X-rays, CAT scans and MRI scans (the latter being done by powerful magnets not using X-rays).

There are various techniques with MRI at present, including ’structural’ imaging which looks at the brain in a static state (which looks as it, as the word implies, actively, as it functions). There are few consistent findings, which is partly due to the fact that the studies are relatively new. One apparently consistent finding is that the system that bathes the brain, called the ventricles, does appear enlarged in manic depressive illness. In very unwell patients, there may be a difference in an area with a tongue-twisting name: the subgenual prefrontal cortex in the anterior cingulate gyrus. However, the relevance of these findings has not yet been determined. One of the problems is that the brain ‘normally’ varies, therefore it is difficult to ascertain the relevance of individual differences. Read more…

MDF Bipolar Organisation is a user-led charity working to enable people affected by manic depression to take control of their lives.

MDF Bipolar Organisation Charity

Contact Details

08456 340 540 (UK Only)
0044 207 793 2600 (Rest of world)

Email: mdf@mdf.org.uk

Websites

• www.mdf.org.uk
• www.mdfwales.org.uk (Wales site)
• www.pendulum.org.uk (Pendulum journal site)
• www.steady.org.uk (STEADY self-management course site)

Membership

You can become a member of MDF through the website. As a member you will receive the following benefits:

• The organization’s quarterly journal, Pendulum. This is full of current debate about manic depression, overseas news, forthcoming events, etc.
• Advice. A twenty-four hour line providing legal advice, employment advice and advice about benefits and debt. Your questions will be answered by qualified solicitors. Read more…