Delirium agitation and

Use of die MAOIs must be discontinued 2 weeks before the administration of die SSRIs. When the SSRIs are administered witii die tricyclic antidepressants, tiiere is an increased risk of toxic effects and an increased tiierapeutic effect. When sertraline is administered witii a MAOI, a potentially fatal reaction can occur. Sjymptoms of a serious reaction include hyper-tiiermia, rigidity, autonomic instability witii fluctuating vital signs and agitation, delirium, and coma Sertraline blood levels are increased when administered witii cimetidine. 

Serious reactions, such as hyperthermia, rigidity, myoclonus, extreme agitation, delirium, and coma, will occur if the patient takes an MAOl concurrently or fails to let enough time elapse when switching from an MAOl to nefazodone or vice versa. 

Delirium tremens usually arises in chronic alcohol abusers. The clinical features may include hallucinations, intense fear, sleeplessness, restlessness, agitation, delirium, and sometimes grand mal convulsions. In addition, tachycardia, hypotension, and clover-shaped ST changes in the electrocardiogram are evident. 

Intoxication with MAO inhibitors is unusual. Agitation, delirium, and neuromuscular excitability are followed by obtunded consciousness, seizures, shock, and hyperthermia. Supportive treatment is usually all that is required, though sedative phenothiazines with adrenoceptor-blocking action, such as chlorpromazine, may be useful. 

Acute cocaine toxicity produces a sympathomimetic response that may result in mydriasis, diaphoresis, hyperactive bowel sounds, tachycardia, hypertension, hyperthermia, hyperactivity agitation, seizures, or coma. Sudden death due to cardiotoxicity may occur following cocaine use. Death may also occur following the sequential development of hyperthermia, agitated delirium, and respiratory arrest. Excited delirium and extreme physical activity may lead to rhabdomyolysis, acute renal failure, and disseminated intravascular coagulopathy. 

Toxicity Adverse effects include insomnia, mood changes, dyskinesias, gastrointestinal distress, and hypotension. Meperidine in combination with selegiline has caused agitation, delirium, and death. Selegiline has been implicated in the serotonin syndrome when used in patients taking selective serotonin reuptake inhibitors (see Chapter 30). 

Patients in thyrotoxic crisis usually have multiple system involvement. The cardiovascular system is particularly susceptible, and severe tachycardia, arrhythmias, and heart failure are common. The sympathetic nervous system is hyperactive, and this is one of the major causes of the cardiovascular effects. The CNS is also affected, and signs may include severe agitation, delirium, and coma. 

Anxiety, agitation, delirium, diaphoresis, myoclonus, tremors, and seizures... 

In the epidemiological tracking of agitated delirium victims in Metropolitan Dade County, men with preterminal delirium comprised approximately 10% of the annual number of cocaine overdose deaths. The demographic trends show that the proportion of these cases remains consistent throughout the epidemic of cocaine abuse and tends to track the annual frequency of cocaine-related sudden deaths. This observation suggests that a certain percentage of cocaine addicts may be at risk for cocaine delirium with chronic abuse. 

At present it is not clear whether extreme agitation, delirium, hyperthermia, and rhabdomyolysis are effects of cocaine that occur independently and at random among cocaine users, or whether these features are linked by common toxicologic and pathologic processes.20 Ruttenber and colleagues20 have examined excited delirium deaths in a population-based registry of all cocaine-related deaths in Dade County. This study has led to clear description of the cocaine delirium syndrome, its pattern of occurrence in cocaine users over time, and has identified a number of important risk factors for the syndrome. 

The use of benzodiazepines should be avoided. There are other safer pharmacological alternatives. Benzodiazepine withdrawal may play a role in the occurrence of delirium in the elderly. Other withdrawal symptoms include tremor, agitation, insomnia and seizures (Turnheim 2003). Thus, when there is long-term use of benzodiazepines abrupt discontinuation might be difficult. Discontinuation should however not be withheld but done slowly and step-wise. If benzodiazepines are used in the elderly, short-acting benzodiazepines such as oxazepam are preferred, because they do not accumulate in the elderly to the same extent (Kompoliti and Goetz 1998). If short-acting benzodiazepines are used they should be prescribed with caution, at low doses, and for short periods. As with all pharmacotherapy the effects should be evaluated. Benzodiazepines are sometimes used as a behavioural control. One should always ask if this use is for the benefit of staff or the benefit of the patient. The presence of staff may be sufficient for behavioural control. 

Memantine is approved for treatment of moderate to severe Alzheimer s disease. It is an antagonist at glutamatergic NMDA-receptors. Memantine is well tolerated and has a small beneficial effect at six months in moderate to severe AD (McShane et al. 2006). For patients with dementia one has to be careful wit all kind of medications that may affect the central nervous system. Delirium and hallucinations are common adverse effects in patients with dementia. Agitation may be due to delirium and external causes should be ruled out before adding another psychoactive drug. Sleep disturbance is common in demented elderly patients. Sleep deprivation may in a patient with dementia induce delirium. Nonpharmacological treatment for delirium or hallucinations should be considered first. 

We ve already described in considerable detail the many complications of dementia including depression, psychosis, delirium, and agitation. In general, the evolution of treatments for these symptoms has been straightforward. 

Serotonin syndrome Some TCAs inhibit neuronal reuptake of serotonin and can increase synaptic serotonin levels (eg, clomipramine, amitriptyline). Either therapeutic or excessive doses of these drugs, in combination with other drugs that also increase synaptic serotonin levels (such as MAOIs), can cause a serotonin syndrome consisting of tremor, agitation, delirium, rigidity, myoclonus, hyperthermia, and obtundation. 

Rabies. An acute infectious disease of the central nervous system affecting most mammals including humans, caused by rhabdovi-rus. Typical symptoms include paresthesia and a burning sensation or pain at the site of inoculation, periods of hyperexcitability, agitation, delirium, hallucinations, and bizarre behavior, between which the person is often cooperative and lucid. 

Withdrawal delirium (delirium tremens), which usually appears 1 to 4 days after abstinence and peaks at about 72 to 96 hours. The mortality rate may be as high as 15% if serious complicating medical problems are also present. Clinical signs and symptoms include profound confusion, illusions, delusions, vivid hallucinations, agitation, insomnia, and autonomic hyperactivity. Death results from infection, cardiac arrhythmias, fluid and electrolyte abnormalities, or suicide (e.g., in response to hallucinations, illusions, or delusions). 

The combination of pethidine with monoamine oxidase inhibitors (MAOIs) can cause serious adverse reaction, which can present in two distinct forms. The excitatory form is characterised by sudden agitation, delirium, headache, hypo- or hypertension, rigidity, hyperpyrexia, convulsions and coma. It is thought to be caused by an increase in cerebral 5-HT concentrations because of inhibition of monoamine oxidase. This is potentiated by pethidine, which blocks neuronal uptake of 5-HT. The depressive form, which is frequently severe and fatal, consists of respiratory and cardiovascular depression and coma. It is the result of the inhibition of hepatic microsomal enzymes by the MAOI, leading to accumulation of pethidine. Phenoperidine should also be avoided in patients taking MAOI drugs but other opioids appear to be safe. 

The classic anticholinergic (technically, "antimuscarinic") syndrome is remembered as "red as a beet" (skin flushed), "hot as a hare" (hyperthermia), "dry as a bone" (dry mucous membranes, no sweating), "blind as a bat" (blurred vision, cycloplegia), and "mad as a hatter" (confusion, delirium). Patients usually have sinus tachycardia, and the pupils are usually dilated (see Chapter 8). Agitated delirium or coma may be present. Muscle twitching is common, but seizures are unusual unless the patient has ingested an antihistamine or a tricyclic antidepressant. Urinary retention is common, especially in older men. 

Because of disturbing side effects including horrible nightmares, delusions, hallucinations, agitation, delirium, disorientation, and difficulty speaking, PCP use on humans is stopped in the United States. PCP continues to be sold as a veterinary anesthetic under the brand name Sernylan. 

Repeated GHB use is associated with mood swings, liver tumors, violent behavior, and dependence. If the drug is discontinued, the user can experience withdrawal. Severe withdrawal symptoms include extreme agitation, delirium, insomnia, tremor, rapid heart rate, and anxiety. 

In addition to acute and chronic schizophrenia, the neuroleptics are sometimes used in the management of mania, delirium, and severe agitation, whatever the cause of these symptom complexes. It must be noted that unlike parkinsonism, where a definite dysfunction in the DA system has been established, for schizophrenia and other psychiatric diseases, no unequivocal evidence has yet been presented to prove that there is a disturbance of the DA system (e.g., dopaminergic overactivity or receptor hypersensitivity). In untreated schizophrenics the production of DA metabolites is normal. Conflicting results have been obtained in studies of the DA receptors in schizophrenics (11,12,13), but in the case of patients who have not received neuroleptics, the receptor density and affinity appear to be normal (13). The "dopamine hypothesis" in these disorders derives from the beneficial effects of drugs that block DA receptors. 

Rebound psychosis or delirium or both have been reported after withdrawal of clozapine (207-212). Clozapine withdrawal has also been associated with nausea, vomiting, diarrhea, headache, restlessness, agitation, and sweating (213,214), which occur as the result of cholinergic rebound and which may respond to anticholinergic drugs (215), and with dystonias and dyskinesias. Delirium and the return of dyskinetic movements can occur within days after clozapine withdrawal. 

A 69-year-old man developed acute benzodiazepine withdrawal delirium following a short course of flunitrazepam after an acute exacerbation of chronic obstructive pulmonary disease. He was not an alcohol-or drug-abuser and he had not previously taken benzodiazepines. Six days after withdrawal of flunitrazepam he became agitated and confused, and had visual hallucinations, disorganized thinking, insomnia, increased psychomotor activity, disorientation in time and place, and memory impairment. Tachycardia and significant anxiety were also noted. He fulfilled the DSM IV criteria for withdrawal syndrome and delirium, and had spontaneous remission of symptoms within 48 hours. 

Sevoflurane often causes postoperative delirium and agitation in children, and this may be severe. The effect of intravenous clonidine 2 pg/kg on the incidence and severity of postoperative agitation has been assessed in a double-blind, randomized, placebo-controlled trial in 40 boys who had anesthetic induction with sevoflurane after oral midazolam premedication (32). There was agitation in 16 of those who received placebo and two of those who received clonidine the agitation was severe in six of those given placebo and none of those given clonidine. 

A 39-year-old man who was a recreational user of alcohol and cocaine presented with agitation, hallucinations, and delirium. He had a dry flushed skin, tachycardia, dilated, minimally reactive pupils, urinary retention, and absent bowel sounds. He was treated with intravenous fluids and a sedative. There were cocaine metabolites in the urine. Reanalysis of a urine sample by thin layer chromatography confirmed the presence of the anticholinergic drug atropine. 

An 81-year-old woman took celecoxib 100 mg/day, and over the next 2 weeks developed delirium and auditory and visual hallucinations (146). Celecoxib was withdrawn and her symptoms resolved over several days. She took a few doses of rofecoxib 12.5 mg/ day 6 months later without any problem. She began to take rofecoxib regularly again 2 months later, and after 1 month developed agitation, confusion, and hallucinations. Physical examination suggested no cause of the delirium other than rofecoxib. A CT scan was negative. The rofecoxib was withdrawn, and over the next 2 days her symptoms resolved... 

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