Antipsychotics Medication

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Though antipsychotics (also called neuroleptics) are commonly thought to treat only schizophrenia, they can be used in other “psychosis” such as mania, bipolar disease and mood disorders. Schizophrenia is psychiatric disease that affects almost 1 % of the population worldwide and is characterized by hallucinations (illusions), delusions (unusual thinking) and social isolation.  These symptoms can be subdivided into positive symptoms (hallucinations, delusions) and negative symptoms (blunted affect, lack of pleasure).  The general treatment regimen is to prescribe antipsychotics medication first and possibly but not always give psychological intervention in conjunction.

The foundation for treating schizophrenia mainly revolves around the dopamine hypothesis.  This theory draws from:
•    evidence that abuse of stimulants, especially cocaine and amphetamine which bind dopamine receptors, exhibit “schizophrenia-like” symptoms. 
•    evidence includes PET brain scans of schizophrenic vs. normal patients where schizophrenic patients have increased dopamine receptor density (more receptors) indicating overactivation. 
•    Lastly, some of the early antipsychotics, such as reserpine and chlorpromazine (Thorazine), that helped to alleviate symptoms of schizophrenia showed an ability to block (antagonize) dopamine receptors, specifically the D2 receptor subtype.  It is proposed that schizophrenia is a brain abnormality caused by overactivity of dopamine neurons.

The antipsychotic drugs that treat schizophrenia are separated into two classes, the typical or “first generation” antipsychotics, and the atypical or “second generation” antipsychotics, which have less effect on D2 receptors indicating the dopamine hypothesis is not entirely true.

Typical Antipsychotics

The typical antipsychotics medication are divided into three groups based on their structure.  They are generally effective for binding the D2 receptor subtype.  Some popular drugs of this group include chlorpromazine, thioridazine (Mellaril) and haloperidol (Haldol).  Despite the effectiveness of typical antipsychotics, some are being replaced with atypical antipsychotics due to the side effects that typical antipsychotics generally harbor.  Some of these effects are so adverse that they can cause the patient to stop medication use.  These adverse effects are usually the result of these drugs’ affinity for dopamine receptors outside the area where the brain implicates in schizophrenia.   The most pervasive effect is tardive dyskinesia, or involuntary, un-purposeful repetitive movements.  This can be exhibited as rapid eye movements, puckering of lips and tongue protrusion (i.e. showing of the tongue outside of the mouth).  Tardive dyskinesia is the result of long-term antipsychotic use.

Parkinsonism or Parkinson’s syndrome may also result from long term antipsychotic use and is characterized by tremor, posture instability and rigidity of the body.  Patients want to initiate movement, but are unable too.  This effect probably arises from supersensitivity of dopamine neurons, again outside of the area in the brain thought to mediate schizophrenia.  Other typical antipsychotics side effects may include seizures, hypotension, impotence, and lethargy.

Atypical Antipsychotics

The newer, atypical antipsychotics medication were developed in response to side effects, focusing on getting rid of tardive dyskinesia. These drugs do not resemble any of the older typical antipsychotics nor do they resemble each other.   Some popular drugs include clozapine (Clozaril), olanzepine (Zyprexa), respiradone (Risperdal), sertindole (Serlect) and quetiapine (Seroquel).  Their mechanisms of action are not well characterized, but what is known for sure is that these drugs have less effect at dopamine D2 receptors.  Some bind serotonin receptors (5-HT2A subtype).  This certainly goes against the dopamine hypothesis of schizophrenia indicating that the theory is incomplete, possibly implying a role for serotonin receptors.  Glutamate receptors might also be implicated because abuse of PCP and ketamine (psychedelics) induces symptoms that are very similar to ones in schizophrenia, maybe even more so than stimulants do.   The involvement of other receptors makes for a murky picture in the diagnosis and treatment of schizophrenia.  More research is needed for clarification and this may result in more effective drugs.

Aside from that however, the side affect of atypicals antipsychotics are less then the older typical antipsychotics because.  Some of these though may include stroke in the elderly, minor tardive dyskinesia (over long decades of use) and diabetes.  Metabolic disorders, especially diabetes, seem to be prevalent with atypical antipsychotics, but the mechanism is not clear.  Clozapine may produce a severe and grave condition known as angranulocytosis (white blood cell loss) in 1-2 % of users.  This condition has a quick onset and may result in death due to invasion by harmful bacteria and viruses that are no countered by the missing white blood cells.  Therefore, white blood cell counts are mandatory for patients on this drug.

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