Delirium tremens

Delirium tremens (colloquially, the DTs, "the horrors", "the fear", or "the rats"; afflicted individuals referred to as "jitterbugs" in 1930s Harlem slang; literally, "shaking delirium" or "trembling madness" in Latin) is an acute episode of delirium that is usually caused by withdrawal or abstinence from benzodiazepines or barbiturates (and other minor tranquilizers). When caused by alcohol, it occurs only in individuals with a history of constant, long-term alcohol consumption. Occurrence due to benzodiazepine or barbiturate withdrawal does not require as long a period of consistent intake of such drugs. Prior use of both tranquilizers and alcohol can compound the symptoms and, while extremely rare, is the most dangerous, especially if untreated.
Five percent of acute ethanol withdrawal cases progress to delirium tremens. Unlike the withdrawal syndrome associated with opiate dependence, delirium tremens (and alcohol withdrawal in general) can be fatal. Mortality can be up to 35% if untreated; if treated early, death rates range from 5-15%.
==Symptoms==
The main symptoms are confusion, disorientation, agitation, and other signs of severe autonomic instability (fever, tachycardia, hypertension). Other common symptoms include intense hallucinations such as visions of insects, snakes, or rats (or stereotypically, pink elephants or tiny figures). These may be related to the environment, e.g., patterns on wallpaper that the patient would perceive as giant spiders attacking him or her. Unlike hallucinations associated with schizophrenia, delirium tremens hallucinations are primarily visual, but are also associated with tactile hallucinations such as sensations of something crawling on the subject - a phenomenon known as formication. Delirium tremens can sometimes be associated with severe, uncontrollable tremors of the extremities and secondary symptoms such as anxiety, panic attacks, and paranoia.
Delirium tremens (DT) should be distinguished from alcoholic hallucinogens, the latter occurring in approximately 20% of hospitalized alcoholics and not carrying a significant mortality. In contrast, DT occurs in 5-10% of alcohol-dependent people and carries up to 5% mortality with treatment and up to 35% mortality without treatment. DT is characterized by the presence of altered sensory; that is, a complete hallucination without any recognition of the real world. DT has extreme autonomic hyperactivity (high pulse, blood pressure, and rate of breathing), and 35-60% of patients have a fever. Some individuals experience seizures.
==Causes==
Delirium tremens can occur after a period of heavy alcohol drinking, especially when the person does not eat enough food. It may also be triggered by head injury, infection, or illness in people with a history of heavy use of alcohol.
It is most common in people who have a history of alcohol withdrawal, especially in those who drink the equivalent of 7-8 pints of beer (or 1 pint of "hard" alcohol) every day for several months. Delirium tremens also commonly affects those with a history of habitual alcohol use or alcoholism that has existed for more than 10 years.
The exact pharmacology of ethanol is not fully understood: however, it's theorized that delirium tremens is caused by the effect of alcohol on the benzodiazepine-GABAA-chloride receptor complex for the inhibitory neurotransmitter GABA. Constant consumption of alcoholic beverages (and the consequent chronic sedation) causes a counter regulatory response in the brain in attempt to regain homeostasis.
This causes down regulation of these receptors, as well as an up-regulation in the production of excitatory neurotransmitters such as norepinephrine, dopamine, epinephrine, and serotonin - all of which further the drinker's tolerance to alcohol and may intensify tonic-clonic seizures. When alcohol is no longer consumed, these down-regulated GABAA receptor complexes are sensitive to GABA that the typical amount of GABA produced has little effect; compounded with the fact that GABA normally inhibits action potential formation, there are not as many receptors for GABA to bind to - meaning that sympathetic activation is unopposed. This is also known as an "adrenergic storm". Effects of this "adrenergic storm" can include (but are not limited to) tachycardia, hypertension, hyperthermia, hyperreflexia, diaphoresis, heart attack, arrhythmia, stroke, anxiety, panic attacks, paranoia, and agitation.
This is all made worse by excitatory neurotransmitter upregulation, so not only is sympathetic nervous system over-activity unopposed by GABA, there is also more of the serotonin, norepinephrine, dopamine, epinephrine, and particularly glutamate. Excitatory NMDA receptors are also unregulated, contributing to the delirium and neurotoxicity (by excitotoxicity) of withdrawal. Direct measurements of central norepinephrine and its metabolites is in direct correlation to the severity of the alcohol withdrawal syndrome.
It is possible that psychological (i.e., non-physical) factors also play a role, especially those of infections, malnutrition, or other underlying medical disorders - often related to alcoholism.
==Treatment==
Pharmacotherapy is symptomatic and supportive. Typically the patient is kept sedated with benzodiazepines, such as diazepam, lorazepam, or oxazepam and in extreme cases low-levels of antipsychotics, such as haloperidol or even stronger benzodiazepines like temazepam or midazolam until symptoms subside. Older drugs such as paraldehyde and clomethiazole were the traditional treatment but these have now largely been superseded by the benzodiazepines, although they may still be used as an alternative in some circumstances. Acamprosate is often used to augment treatment, and is then carried on into long term use to reduce the risk of relapse. If status epilepticus is present, seizures are treated accordingly. Controlling environmental stimuli can also be helpful, such as a well-lit but relaxing environment to minimise visual misinterpretations such as the visual hallucinations mentioned above.
Delirium tremens at NIH
Delirium tremens at Wikipedia