What is Neuroleptic Malignant Syndrome?

From the Merck Manual Website

[The website talks about Schizophrenia, but my dad doesn't have that. Somehow it's tied into the NMS, but I'm not sure yet how. I'll try to find out more about it.]

What Is Neuroleptic Malignant Syndrome?

Neuroleptic malignant syndrome is a state of unresponsiveness caused by use of certain antipsychotic drugs. It develops in up to 3% of people who are treated with antipsychotic drugs, usually within the first few weeks of treatment. The syndrome is most common among men who, because they are agitated, are given rapidly increased doses of the drugs or high doses initially.
Symptoms include muscle rigidity, a high temperature, a fast heart rate, a fast breathing rate, high blood pressure, and coma. Damaged muscles release the protein myoglobin, which is excreted in the urine. Myoglobin turns the urine brown (myoglobinuria), and myoglobinuria can result in kidney damage or even kidney failure.
People with this syndrome are usually treated in an intensive care unit. The antipsychotic drug is discontinued, fever is controlled (usually with ice baths and wet towels or with special cooling blankets), and a muscle relaxant (such as bromocriptineSome Trade Names PARLODELor dantroleneSome Trade Names DANTRIUM) is given. Giving sodium bicarbonate intravenously helps prevent myoglobulinuria by making the urine alkaline. Most people recover completely; however, almost 30% of people with this syndrome die. After recovery, up to 30% of people develop the syndrome again if they are given the same antipsychotic drug.

Treatment

The general goals of treatment are to reduce the severity of psychotic symptoms, prevent the recurrence of symptomatic episodes and the associated deterioration in functioning, and provide support to allow functioning at the highest level possible. Antipsychotic drugs, rehabilitation and community support activities, and psychotherapy represent the three major components of treatment.


Antipsychotic Drugs: Drugs can be effective in reducing or eliminating symptoms, such as delusions, hallucinations, and disorganized thinking. After the immediate symptoms have cleared, the continued use of antipsychotic drugs substantially reduces the probability of future episodes.

Unfortunately, antipsychotic drugs have significant side effects that can include sedation, muscle stiffness, tremors, weight gain, and motor restlessness. Antipsychotic drugs may also cause tardive dyskinesia, an involuntary movement disorder most often characterized by puckering of the lips and tongue or writhing of the arms or legs. Tardive dyskinesia may not go away even after the drug is discontinued. For tardive dyskinesia that persists, there is no effective treatment. Another side effect of antipsychotic drugs, although rare but potentially fatal, is neuroleptic malignant syndrome, which is characterized by muscle rigidity, fever, high blood pressure, and changes in mental function (for example, confusion and lethargy).
A number of new antipsychotic drugs that cause fewer side effects have become available. These drugs may relieve positive symptoms (such as hallucinations), negative symptoms (such as lack of emotion), and cognitive impairment (such as reduced mental functioning and attention span) to a greater extent than the older antipsychotic drugs.

ClozapineSome Trade Names CLOZARILhas proven to be effective in up to half of the people for whom other drugs do not work. However, clozapineSome Trade Names CLOZARILcan cause serious side effects, such as seizures or potentially fatal bone marrow suppression; thus, it is generally used only for people who have not responded to other antipsychotic drugs. People who take clozapineSome Trade Names CLOZARILmust have their white blood cell count measured weekly, at least for the first 6 months, so that clozapineSome Trade Names CLOZARILcan be discontinued at the first indication that the number of white blood cells is dropping.

Rehabilitation and Community Support Activities:

Community support activities, such as on-the-job coaching, are directed at teaching the skills needed to survive in the community. These skills enable a person with schizophrenia to work, shop, care for himself, manage a household, and get along with others. Although hospitalization may be needed during severe relapses, and involuntary hospitalization may be needed if the person poses a danger to himself or others, the general goal is to have the person live in the community. To achieve this goal, some people may need to live in a supervised apartment or group home where someone can ensure that drugs are taken as prescribed.

A small number of people with schizophrenia are unable to live independently, either because they have severe and unresponsive symptoms or because they lack the skills necessary to live in the community. They usually require full-time care in a safe and supportive setting.
Psychotherapy: Generally, the goal of psychotherapy is to establish a collaborative relationship between the person, family, and doctor. That way the person might learn to understand and manage his disorder, to take antipsychotic drugs as prescribed, and to manage stresses that can aggravate the disorder. A good doctor-patient relationship is often a major determinant of successful treatment. Psychotherapy reduces symptoms in some cases and helps prevent relapse in others.

Antipsychotic Drugs
Type
Drug
Selected Side Effects
Comments
Older antipsychotics

· Chlorpromazine
· Fluphenazine
· Haloperidol
· Loxapine
· Mesoridazine
· Molindone
· Perphenazine
· Pimozide
· Thioridazine
· Thiothixene
· Trifluoperazine
Dry mouth, blurred vision, seizures, increased heart rate, decreased blood pressure, constipation, sudden but often reversible tremor and muscle stiffness that may progress to rigidity, uncontrolled movements of the face and arms (tardive dyskinesia), fever and muscle damage (neuroleptic malignant syndrome)
Side effects are much more likely in older people and in people with impaired balance or serious medical disorders. Long-acting injectable forms of haloperidolSome Trade Names HALDOLand perphenazineSome Trade Names TRILAFONare available
Eye examination and electrocardiography (ECG) are recommended while taking thioridazineSome Trade Names MELLARIL
Newer antipsychotics

· Aripiprazole
· Clozapine
· Olanzapine
· Quetiapine
· Risperidone
· Ziprasidone
Drowsiness and weight gain, which can be substantial, are the most common side effects. May increase the risk of new-onset type II diabetes and high levels of triglycerides in the blood. Muscle tremor, uncontrolled movements of the face and arms (tardive dyskinesia), and muscle damage possible but occur less often compared to older antipsychotics.
Newer antipsychotics are less likely to cause tremor, muscle stiffness, uncontrolled movements, and fever and muscle damage
ClozapineSome Trade Names CLOZARILis used much less often because it can cause bone marrow suppression, reduced white blood cell count, and seizures. However, it is often effective in people who are not responsive to other drugs
ClozapineSome Trade Names CLOZARILand olanzapineSome Trade Names ZYPREXAare most likely to cause weight gain; aripiprazole is the least likely
ZiprasidoneSome Trade Names GEODONdoes not cause weight gain but may lead to abnormalities on electrocardiogram (my dad was given multiple doses of this)

Antipsychotic Drugs: How Do They Work?

Antipsychotic drugs appear to be most effective in treating hallucinations, delusions, disorganized thinking, and aggression. Although antipsychotic drugs are most commonly prescribed for schizophrenia, they appear to be effective in treating these symptoms whether they arise from mania, schizophrenia, dementia, or acute intoxication with a substance such as amphetamines.
Antipsychotic drugs work by influencing how information is transmitted between individual brain cells. The adult brain is made up of more than 10 billion individual cells called neurons. Each neuron in the brain has a single long fiber called an axon, which transmits information to other neurons. Like wires connected in a vast telephone switchboard, each individual neuron makes contact with several thousand other neurons.
Information travels down a cell's axon as an electrical impulse. When the impulse reaches the end of the axon, a tiny amount of a specific chemical called a neurotransmitter is released to pass information on to the next cell down the line. A receptor on the receiving cell detects the neurotransmitter, which causes the receiving cell to generate a new signal.
Symptoms of psychosis appear to be caused by excessive activity of cells sensitive to the neurotransmitters dopamineSome Trade Names INTROPINand serotonin. Therefore, antipsychotic drugs work by blocking receptors so that communication between groups of cells is dampened.
Different antipsychotic drugs block different types of neurotransmitters. Every effective antipsychotic drug known blocks dopamineSome Trade Names INTROPINreceptors. The new antipsychotic drugs (risperidoneSome Trade Names RISPERDAL, olanzapineSome Trade Names ZYPREXA, quetiapineSome Trade Names SEROQUEL, ziprasidoneSome Trade Names GEODON, and clozapineSome Trade Names CLOZARIL) may be more effective because they also block serotonin receptors. They also appear to cause fewer side effects.