Recent advances in Schizophrenia treatment

I recently attended a professional seminar on effective new treatments for psychotic disorders. I particularly enjoyed the presentation given by Dr. Daniel E Casey, from the Oregon Health and Sciences University, in Portland. Dr. Casey has served as chairman of the Food and Drug Administration (FDA) advisory committee on psychopharmacology and is a noted psychiatric researcher and clinician.

I spoke with Dr. Casey about aripiprazole, the most recently FDA approved medication for schizophrenia. Marketed under the name Abilify ®. Dr. Casey told me, “The novelty the uniqueness of Abilify is that it has a different mechanism of action. It is called a dopamine partial agonist.” In previous studies, it was found that medications that effectively treat psychosis had some effects on the neurotransmitter, dopamine. What became known as the “dopamine hypothesis of schizophrenia,” postulates that these patients have a hyperactivity of dopamine, especially in the areas connecting the emotional and reasoning centers in the brain (the mesocortical system). Current thinking among researchers is that there’s more to schizophrenia than dopamine hyperactivity and there is a lot more needed in the treatment of the majority of schizophrenic patients than a simple blockade of the neuronal dopamine receptors.

With the success of a variety of new drugs, now called “atypical antipsychotics,” we have seem beneficial changes in a wider number of disabling symptoms than ever before. One of the significant result breakthroughs made possible by the atypicals is their effectiveness in treating both positive and negative symptoms. I asked Dr. Casey to clarify the difference between these two groups of symptoms. “The positive symptoms are called positive because they are added to the normal personality,” he said, (positive symptoms include hallucinations, delusions, and incoherent speech, for example) “and the negative symptoms are missing or minus from the normal personality.”

Finding a drug that will treat both hallucinations and relieve extreme apathy, while not at the same time causing severe weight gain, hormonal changes or other health risk issues is the Holy Grail of schizophrenia treatment. Dr. Casey notes, “So often families say, “I’m glad the voices are gone, but what can we do to get them out of bed to get them motivated to go to work or school or stop watching TV all day long?” These are the toughest symptoms to work with – that’s why the negative symptoms are so debilitating over the long time for these patients.”

Explaining the mechanisms of aripiprazole, Dr. Casey notes, “A partial agonist acts as a modulator of a system so that when the drug is in an environment where the dopamine system is hyper or over-active, such as we think it is in the mesolimbic system where we think the positive symptoms of schizophrenia derive, this drug will act as an antagonist, to tone down or decrease the activity in the system.” What’s very new here is a second property of this compound. “When the same drug finds itself in an environment where it is under functioning the drug will act as an agonist, to increase the activity in that brain area. For example, in the prefrontal cortex of the brain, where we think negative symptoms, such as the lack of energy, apathy, decreased ability to feel and express enjoyment and pleasure, emanate.”

One final caveat – most of the effective antipsychotic medications are about equally effective, in terms of measures of improvement in drug studies. What has made the atypicals more desirable in recent years are the substantial differences between their side effect profiles and that of the older compounds. To cover this area adequately I will present another Your Mind Matters specifically on this subject.

One of the distinct advantages of aripiprazole, according to Dr. Casey, is that it seems to be the antipsychotic medication with the lowest additional health or discomfort burden. He told me, “What is nice about Abilify is that it doesn’t make people gain weight - and it doesn’t have the undesirable metabolic side effects - silent medical risk factors that can cause them to gain weight or that can make insulin go up, as ell as raising the cholesterol and triglycerides levels – these are associated with heart disease – but people don’t have any symptoms of these until they have had these elevation for a long time, or unless they are tested by their physician.

There are a lot of factors that must be considered when choosing an antipsychotic medication. Physicians, patients and families need to measure the benefits of each medication and assess the risks of side effects and medical complications uniquely, for each patient. Not everyone responds to any one drug – often patients will have to take a different drug or a combination of drugs to achieve optimal benefit. Patients and families who keep informed about new methods and findings that bear on their health and well being take an important step in assuring that they will receive the best care possible.

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