Antipsychotic Medication: A User's Guide - Part II
(Column: Ask the Doctor)
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Dr. Goldfinger discusses medications that are currently available by prescription.
I'm going to alter the usual format of this column and instead of responding to questions from the readership, take on a task I was asked to pursue by the New York City Voices' Editorial Board. I would like to discuss antipsychotic medications -- what they are, what they do, how they affect one's body and how each one differs from the others. Naturally, by trying to squeeze all of this information into two columns, I won't be able to talk about each medication in any great detail. However, as usual, if you send your questions via E-mail askdoc@newyorkcityvoices.org or by mail, I will be happy to address them individually in future columns.

"Atypical" antipsychotics -- These atypical medications all work on different chemical messages in the brain than the older drugs. This has a number of advantages. Many of the newer drugs are more effective against certain symptoms of psychosis than the older drugs were. In addition, they tend to have different and often fewer side effects. Many people find it much easier to keep taking these atypical medications than they did the traditional neuroleptics.

Atypical antipsychotics also seem to be effective for more symptoms than the older drugs. The symptoms of schizophrenia, for example, have often been divided into positive symptoms and negative symptoms. Positive symptoms can be seen as adding something to your behavior such as hallucinations, delusions, or intrusive thoughts. Negative symptoms take something away from your behavior. Classical negative symptoms are feelings of apathy (not caring about what goes on), withdrawal, a loss of interest or enjoyment, a lack of energy or a feeling that one would just as soon stay in bed, sit around or not be bothered by what is going on around you. The older medications work best for positive symptoms. Many of the atypical antipsychotics work well for negative symptoms in addition to being effective for positive symptoms. Therefore, in addition to being less likely to cause Tardive Dyskinesia and other movement disorders, the newer medications also are more likely to improve your energy level, interest, and ability to return to functioning.

Clozapine was the first of the atypical antipsychotics to be developed. Clozapine remains a unique medication, the most effective ever to be discovered and often helpful when no other medications work. Clozapine is helpful for both positive and negative symptoms, and in fact can arrest or even reverse Tardive Dyskinesia. However, Clozapine also has a series of quite serious side effects, which make it inconvenient to use. Approximately 1% of those who take clozapine develop a problem with their white blood cells called agranulocytosis, which can lead to infections or even death. However, if caught early, this condition reverses itself if clozapine is stopped. Therefore, people taking clozapine must get a white blood cell count every week for the first six months of treatment and every two weeks thereafter. At the first signs that your white blood cell count is too low, your doctor will discontinue clozapine. However, do keep in mind that this is a relatively rare event and that for most individuals, clozapine is a safe and highly effective medication.

Clozapine can cause seizures and those with a history of seizure disorder can be at a higher risk. Many people on clozapine gain a significant amount of weight, have problems with orthostatic hypertension (dizziness when standing up quickly) and may notice dramatic increases in the amount of saliva they produce. Like any of the newer medications, clozapine is also associated with sexual side effects in some individuals. Usually, clozapine is only considered when other medications have failed.

Risperdal was the second atypical medication to be discovered. Risperdal has been shown to be more effective than haldol both in inpatient treatment of positive and negative symptoms and for relapse prevention. Risperdal can cause sedation in some people and is also associated with weight gain, though not as much clozapine or Olanzapine. Risperdal sometimes raises the level of a hormone named prolactin, and because of this can be associated with amenhorrhea (missing one's periods) in some women. In high doses, Risperdal can cause extrapyramidal side effects (like stiffness and "restless legs") just like the traditional antipsychotics. However, this usually does not happen at doses at or below 4mgs/day, the amount most commonly prescribed.

Zyprexa was the third atypical antipsychotic medication to be introduced. It is as effective as Haldol for treating positive symptoms and more effective in the acute treatment of negative symptoms. People who continue taking Zyprexa as outpatients after discharge are less likely to be rehospitalized in the following year than those who take Haldol. In addition, Zyprexa seems to be particularly effective for symptoms of mania and expansive mood.

Weight gain and sedation are the most common side effects with Zyprexa. Weight gain is the side effect that most people find most troublesome on olanzapine. Usually, it begins within six weeks of starting the medication, so if you are worried about weight gain, this will let you know early on if you are likely to gain weight on the medication. In addition, people often feel particularly sedated and sleepy in the morning, though this side effect (unlike the weight gain) does go away after the first few weeks of treatment in most cases.

Seroquel is an atypical antipsychotic with a quite good side effect profile. It is one of the least potent per milligram, so sometimes doses as high as 800mg per day are needed. Common side effects include sedation, dizziness and weight gain, but it is very unlikely to cause either Extrapyramidal (movement) symptoms or sexual side effects in women. Although in early studies Seroquel was found to cause cataracts in one species of dogs, many clinicians and most researchers agree that there is no risk to humans. One problem with Seroquel is that it usually needs to be taken twice a day, which is harder to remember to do.

Geodon is the newest atypical antipsychotic available. Like Seroquel it is shorter acting and needs to be taken twice a day. It is the least studied of the medications, since it has only been approved for general prescribing for about four months. Those who have treated individuals with Geodon say that it has remarkably few side effects, and unique among the new meds, on average it is not associated with any weight gain. Geodon has been shown to cause prolongation of the electrical conduction activity of the heart, called QT prolongation. This is not likely to be a problem for most people, but means that it should not be used in people with heart problems, and your doctor may want to take some tests of your heart rhythm before beginning you on this medication. Geodon does seem to have long term helpful effects on negative symptoms.

Overall, it is impossible to say which medication will be the best one for you. All have different side effects and different pluses and minuses. As I say so often here, the important thing is for you and your doctor to have an open dialog about what you want and need, and which side effects you personally think you will find hardest and easiest to live with.

Please feel free to continue to write to me with medication and other questions, which I will answer in future columns. Meanwhile, I would like, once again, to thank my close friend and colleague, Peter Weiden MD, for his help with my understanding of medications and for his guidance. He and several others have written a wonderful book, Breakthroughs in Antipsychotic Medications: A Guide for consumers, families and clinicians which I have consulted extensively in preparing this column.
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