Saturday 24 February 2018

The case for personalised medication in psychiatry

Stock photo: PA
Stock photo: PA

Patricia Casey

The world's leading oncologists recently gathered in Chicago for the American Society of Clinical Oncology meeting. Recent developments in cancer treatments were discussed. And the buzz words that emanated from the presentations were "precision medicine" and "personalised medicine".

The two terms are used interchangeably and are now also beginning to appear in psychiatry. These are not merely fashionable terms but represent a sea change in the way cancer and its treatment are approached. If they find application in psychiatry they will revolutionise treatment.

The thinking behind personalised medicine is that even similar tumours in two people behave differently because the make up of individuals impacts on the disease process.

At present, everybody with the same histological cancer and at the same stage receives a similar treatment protocol. So for example, everybody with, say, an adenocarcinoma of the bowel that has some spread will receive the same chemotherapy. But there is a growing recognition that one size doesn't fit all.

While the histology may be the same, the tumours themselves may respond differently to the same treatment. This is because the genes underlying the person's own biology may be different and so a seemingly similar tumour may respond differently to the same chemotherapy.

A further aspect is that the side effects of various treatments impact on people differently. One person may experience significant nausea while another on the same treatment may not, but experience extreme tiredness.

It is sometimes mistakenly believed that personalised medicine involves developing drugs specifically to take account of each person's genetic and biological profile. This is an incorrect interpretation. Rather personalised medicine applies the differences between broadly similar drugs to take account of unique differences between patients that are identified by genetic and imaging studies. So the medication fits the patient.

In relation to psychiatry, some take it to refer to the practice of "holistic" psychiatry without recourse to medication - this is also a misunderstanding of the word "personalised".

The psychiatry sector is working on several disorders, on several fronts. Conditions such as schizophrenia, bipolar disorder, major depression and post-traumatic stress disorder are the subject of examination.

Risk factors, so that early intervention could prevent the transition to a full disorder, are being explored, as are the optimum treatments taking account of the person's biological profile.

Finally the risk of side effects is becoming a productive area of research so that these can be minimised.

All of these advances require that we have a detailed knowledge of the genetics that determine the person's biological profile, an understanding of their brain functioning at a cellular level from imaging techniques and that the speed at which individuals break down drugs once they are absorbed is known to us.

In respect of the latter, slow and rapid metabolisers can be administered different dosages taking account of this pattern. For example a person who breaks down a drug rapidly is likely to need a higher dose than one whose enzymes act more slowly. At present all are given the same dose.

A detailed understanding of the person's genetic status and how this affects the brain receptors, onto which various neurochemicals bind, has implications for the drugs that should be used to treat various conditions. Those that target the specific biological deficits found in an individual would be favoured.

Take major depression - the symptoms that the term major depression describes is most likely not a single condition but a group of conditions, all with similar symptoms but with different biological underpinnings. That may explain why some drugs work on some people but not on others.

If we could identify which biological markers were dysfunctional, say using PET scanning, we could personalise the treatment so that the drug was matched to their biological need.

But this approach is not just concerned with medication but can also be applied to talking therapies. Again, using the example of major depression: a sample of people with this condition had PET scans to measure cellular activity in various parts of the brain. They were then given either an antidepressant or cognitive therapy and the investigators tried to identify if there was a pattern that indicated which group did and didn't get better with each treatment.

Patterns emerged suggesting that talking therapy was superior when abnormalities were found in certain brain areas, while antidepressants were shown to have greater benefit when dysfunction was identified in other areas. The study was published in JAMA Psychiatry in 2013.

It is still too early to make specific recommendations about genetic testing for various abnormalities linked to cellular or neurochemical activity. But as the cost of the tests, PET and gene studies, reduces - as is already happening - the dawn of personalised psychiatry will arrive and will transform the lives of many.

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