Antipsychotic Drugs

Antipsychotic drugs work by influencing how information is transmitted between individual brain cells.

The adult brain is made up of more than 10 billion nerve cells called neurons. Each neuron in the brain has a single long fiber called an axon, which transmits information to other neurons (see figure Typical Structure of a Nerve Typical Structure of a Nerve Cell ). Like wires connected in a vast telephone switchboard, each 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 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 impulse.

Symptoms of psychosis appear to be caused by excessive activity of cells sensitive to the neurotransmitter dopamine. Therefore, antipsychotic drugs work by blocking receptors so that communication between groups of cells is reduced.

How well different antipsychotic drugs block different types of neurotransmitters varies. Every effective antipsychotic drug known blocks dopamine receptors. The newer antipsychotic drugs (asenapine, clozapine, iloperidone, lurasidone, olanzapine, quetiapine, risperidone, and ziprasidone) also block receptors for serotonin, another neurotransmitter. Experts thought that this property might make these drugs more effective. However, recent studies have not supported this view.

Clozapine, which also blocks many other receptors, is clearly the most effective drug for psychotic symptoms. But it is not commonly used because of its serious side effects and the need for monitoring with blood tests.

Antipsychotic drugs are divided into two groups:

Currently, about 95% of antipsychotics prescribed in the United States are second-generation antipsychotics. Doctors have thought that second-generation antipsychotics were somewhat more effective, but recent evidence casts doubt on this. They may have lower likelihood of some of the more serious adverse effects of first-generation drugs.

Second-generation antipsychotic 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). However, doctors are not sure whether they relieve symptoms to a greater extent than the older antipsychotic drugs or whether people are just more likely to take them because they have fewer side effects.

Clozapine, the first of the second-generation antipsychotic drugs, is effective in up to half of people who do not respond to other antipsychotic drugs. However, clozapine can have serious side effects, such as seizures or potentially fatal suppression of bone marrow activity (which includes making white blood cells). Thus, it is usually used only for people who have not responded to other antipsychotic drugs. In the United States, people who take clozapine must have their white blood cell count measured weekly, at least for the first 6 months, so that clozapine can be stopped at the first indication that the number of white blood cells is decreasing.

Some conventional and second-generation antipsychotics are available as long-acting injectable preparations that need to be given only once every month or two. These preparations are useful for many people, including those who cannot reliably take oral drugs every day.

Antipsychotics with novel actions are currently being studied and may become available.

Antipsychotic drugs have significant side effects, which can include

Some newer second-generation antipsychotic drugs have fewer side effects. The risk of tardive dyskinesia, muscle stiffness, and tremors is significantly lower with these drugs than with the conventional antipsychotics. However, some of these drugs seem to cause significant weight gain. Some also increase the risk of metabolic syndrome Metabolic Syndrome Metabolic syndrome is characterized by a large waist circumference (due to excess abdominal fat), high blood pressure, resistance to the effects of insulin (insulin resistance) or diabetes,... read more . In this syndrome, fat accumulates in the abdomen, blood levels of triglycerides (a fat) are elevated, levels of high-density cholesterol (HDL, the “good” cholesterol) are low, and blood pressure is high. Also, insulin is less effective (called insulin resistance), increasing the risk of type 2 diabetes Diabetes Mellitus (DM) Diabetes mellitus is a disorder in which the body does not produce enough or respond normally to insulin, causing blood sugar (glucose) levels to be abnormally high. Urination and thirst are... read more .

Tardive dyskinesia is a hyperactive involuntary movement disorder that can be caused by chronic antipsychotic drugs. It is more likely with first-generation than second-generation drugs. Tardive dyskinesia is 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 stopped. For tardive dyskinesia that persists, there is no effective treatment, although the drugs clozapine or quetiapine may relieve symptoms a little. However, the drug valbenazine has been found to be effective in improving symptoms of tardive dyskinesia. People who must take antipsychotic drugs for a long time are checked every 6 months for symptoms of tardive dyskinesia.

Neuroleptic malignant syndrome Neuroleptic Malignant Syndrome Neuroleptic malignant syndrome is confusion or unresponsiveness, muscle rigidity, high body temperature, and other symptoms that occur when certain antipsychotic (neuroleptic) drugs or anti-vomiting... read more is a rare but potentially fatal side effect of antipsychotic drugs. It is characterized by muscle rigidity, fever, high blood pressure, and changes in mental function (such as confusion and lethargy).

Long-QT syndrome Torsades de Pointes Ventricular Tachycardia Torsades de pointes ventricular tachycardia is a specific type of ventricular tachycardia that occurs in people who have a particular disorder of the heart's electrical activity called a long... read more is a potentially fatal heart rhythm disorder that can be caused by several antipsychotics in both classes. These drugs include thioridazine, haloperidol, olanzapine, risperidone, and ziprasidone.