Changing our Understanding of Antipsychotic Medications

It started off as a search for chemical receptors in the brain that drugs can act on. It has ultimately led to changing our understanding of how quickly antipsychotic medications work.

Several years ago, Dr. Shitij Kapur and his colleagues at the Centre for Addiction and Mental Health (CAMH) and the University of Toronto used brain imaging technology to demonstrate where antipsychotics act in the brain and how fast they get there. They were surprised to find that the medications reached targeted areas of the brain and established sufficient levels to start relieving symptoms of schizophrenia within several hours. The researchers also discovered that the medication stayed in the brain much longer than blood levels would predict. Yet, the current clinical dogma supported the delayed onset hypothesis, which suggests that there is a long delay before antipsychotic medications become effective. This led the group to a series of further studies.

In a recent article published in the Journal of Psychiatry and Neuroscience, Drs. Agid, Kapur and Seeman reviewed data from a number of trials to question the delayed onset hypothesis. They reviewed data from 42 clinical trials involving 7,450 patients. The researchers showed that the effects of antipsychotic medications, used to treat schizophrenia, are evident within the very first week. This means there was no delayed onset of effectiveness.

To further identify precisely when within the first week the effects began, the researchers reviewed data from studies using injectable antipsychotics. They showed that improvements occurred within the very first day. The paper also reviewed data from a German study by Leucht et al., which studied subjects for an entire year. This studied showed that more than half the improvement that researchers observed with the first year was evident with the first two weeks of treatment.

While these data challenge current dogma, the results do not mean that an individual experiencing psychosis would be treated with medication and immediately released from hospital.

Said Dr. Phillip Seeman, “ the patient has the fire stopped by medication, but the smoke lingers on. The origin of the psychosis is blocked by medication, but the memory of these psychotic thoughts lingers and takes a few weeks to calm down.”

This work could also impact how clinical trials in new medications should be designed for the future. According to Dr. Kapur, “Because we all thought that antipsychotic effect took a few weeks to begin, clinical trials are usually of 6-8 weeks duration. The new ideas question that premise. We could see shorter and more efficient trials. This could reduce the exposure and expense of drug development.”

Challenging and changing psychiatric dogma does not immediately relate to changes in treatment for individuals with schizophrenia. This kind of fundamental shift in thinking does take time to implement. But, the data from this review, along with recent findings from other groups around the world, seriously questions the dogma that has been at the heart of clinical psychiatry for years. It challenges the delay onset hypothesis and may ultimately lead to improved schizophrenia treatment.

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