Psychosis refers to an impairment in an individual's ability to perceive and interact with his environment. Some examples of psychotic features include hallucinations (seeing, hearing, or feeling things that aren't there) and delusions (believing in things that aren't true despite evidence to the contrary). Diseases that may include psychotic features such as schizophrenia, depression with psychosis, and bipolar disorder have long been feared and misunderstood. It is only in recent decades that scientists have begun to understand what causes psychosis and how it can be treated.
Research on the physiological basis of psychosis really only began to progress once it was realized that hallucinogens such as LSD and mescaline are serotonin agonists. What this means is that these drugs activate the same receptors in the brain that are activated by one of many neurochemical signaling molecules (or neurotransmitters) called serotonin. Serotonin normally functions in the brain to regulate arousal. In other words, it controls how awake or asleep you are.
Working under the hypothesis that patients with psychosis might have some internal hallucinogen in their bodies due to the similarities between the drugs' effects and the diseases symptoms, researchers searched for such substances in the blood, urine and brains of psychiatric patients. They were unable to find anything, but they did discover which serotonin receptor specifically caused the drugs' effects (called 5-HT2A). They realized that blocking this specific receptor would stop a psychotic patient's hallucinations and delusions in the same way that blocking it would stop LSD or mescaline from working.
Researchers also discovered that some drugs they already used to treat psychosis acted on the dopamine system, another neurotransmitter. One of the functions of dopamine is to inhibit areas of the brain. For example, people with Parkinson's disease lose the inhibitory function of dopamine in certain areas, and this leads to the characteristic tremor. The anti-psychotic drugs being used blocked dopamine. This did help some symptoms, but what is apparent now is that blocking dopamine too strongly has several negative side effects, such as problems with movement similar to a patient with Parkinson's.
New drugs were discovered that blocked the serotonin system (to stop psychotic symptoms) and left the dopamine system relatively alone (so there were less Parkisonian side effects). These were called "atypical antipsychotics" because of their unusual properties, but they are now the most commonly used antipsychotic medications.
Seroquel (or Quetiapine) is an atypical antipsychotic that blocks the 5-HT2A serotonin system. Therefore, it blocks the excess arousal that characterizes both psychotic hallucinations and LSD intoxication. It also blocks dopamine (as do most atypicals), but to a lesser degree. By blocking dopamine, it improves the so-called "negative" symptoms of schizophrenia such as blunted emotional responses and withdrawal from society. Unfortunately, no drug is perfect, and Seroquel blocks many other receptors in the brain. For example, it blocks histamine receptors that may cause excessive sleepiness. It also blocks alpha-1 receptors that may cause low blood pressure.
The search for a perfect antipsychotic drug continues, but in the meantime atypical antipsychotics such as Seroquel have drastically improved the outlook for patients. with psychosis.
- "Goodman & Gilman's The Pharmacological Basis of Therapeutics, 11e;" Laurence L. Brunton, editor-in-chief ; 2006
- "Basic & Clinical Pharmacology, 11e;" Bertram G. Katzung, Susan B. Masters, Anthony J. Trevor; 2009
- "Adams & Victor’s Principles of Neurology, 9e;" Allan H. Ropper, Martin A. Samuels; 2009