Personalized Treatment-at Neuropsychiatry Pharmacogenetics

NPISTANBUL Neuropsychiatry Hospital is the first hospital in Turkey to have it's own pharmacogenetic laboratory. Thus, being able to provide patients with 'Genetic Counseling in Psychiatry' and help them understand more about their illness. The pharmacogenetics laboratory is equipped with highly advanced, modern technology which speeds up the therapeutic process by providing test results about the patient's blood-medication levels and genetic background.

Clinical Pharmacogenetics Laboratory

Genotyping studies have been conducted to determine pharmacogenetic profiles of individuals in Laboratory of Molecular Biology and Genetics at University of Üsküdar . Our laboratory designed in accordance with studies to moleculer level and carried into effect with the necessary machinery and equipment was the formation of a molecular laboratory.

Our laboratory to perform genotyping, blood or any tissue samples from patients with DNA / RNA isolation are carried out. Then these samples are promptly taken for genotyping or identification of expression levels. Conventional PCR (polymerase chain reaction, PCR), restriction enzyme cutting fragment analysis (RFLP), sequence analysis of the work carried out for genotyping. Also in our laboratory, Real-time PCR with a more sensitive analysis is carried out.

Genotyping phenotypically complement the work in some cases, has become a leader in some cases. A treatment program is applied in patients with a more effective, and side effects are minimized in a short time with the provision of Genotype-Phenotype correlation. Genotype CYP2A, CYP2C, CYP2D6, CYP3A4 analyzes of groups, 5HTT polymorphism the main genotyping genes.

Psychiatric Genetic Counseling

People with personal or family history of psychiatric or mental health conditions can apply for genetic counseling. After specialists gather information about the person's history and analyze the person's family members, our staff of highly-educated genetic specialists begin their search for the causes and reasons of any psychiatric or mental health condition that the person might have. This method can also determine problems that may be expected to occur in the future and help understand the person's situation better.

Information about the Future of Your Child

Also with help of the genetic counseling service, if you plan on becoming pregnant or already are, you may learn about whether or not your child is at any risk for having a certain illness or psychiatric disorder.

"Personalized Treatment"

What is the use of the Pharmacogenetic Laboratory and TDM?

The method of 'Personalized Treatment'analyzes the various responses a patient's body may give to medications because of certain genetic variations s/he may possess. Differences that take place in genetic structures during the metabolization of each medication may decrease the effect of the medication. With the method of therapeutic drug-monitoring (TDM), unnecessary conditions or high risk of side-effects that may be caused by certain medications are found with the genetic tests performed. This way, our medical staff can know from advance what medications will be effective for the treatment of each patient.

Pharmacogenetics

Major depressive disorder, schizophrenia and related disorders are among the greatest causes of disability and death all over the world. These disorders which have many effects on public health are fairly common, chronicle and recurrent. Antidepressants are standard treatment for clinical depression likewise antipsychotics are standard treatment for schizophrenia.

Despite the wide variety of drugs, without considering initial psychiatric drug choice, 30-50% of the patient doesn't response to acute treatment. In the case of major psychiatric disorders, need for clinical accomplishment is quite increased. Defining genetic factors that lies under the drug response become one of the most promising research area of molecular biology and genetics. According to the randomized and controlled researches, only 35-45% of patients treated with standard dose of widely used antidepressants could be reached to the premorbid functionality level without any important depression symptom after 6 – 8 weeks.

Concerning drug metabolism, wide genetic variety was defined in the genetic modulators of drug effectiveness and drug treatment response. Beside that, it's not possible yet to detect possibility of the drug response of the patient and choose and modify the best drug and dosage via genetic techniques. While developing more faster and effective ways of genetic test, guidance of the pharmacogenetics to whole treatment can be possible after acquired reliable prediction power of clinical results. It seams that this can be possible by using pharmacogenetics accompanied with drug blood level monitoring.

Therapeutic Drug Monitoring (TDM)

During the last three decades, Therapeutic Drug Monitoring (TDM) was defined for many drugs as a branch of clinical chemistry. Today, TDM is coupled with Pharmacogenetic tests. Despite the fact that TDM has obvious benefits for psychiatry, clinical applications have been applied for limited number of patients and cases. For this reason, clinical and scientific organizations published atlases and guidelines in which psychiatric pharmacotherapy is used as a practice for the acute or long term treatment of psychiatric patients. These guidelines published by American Psychiatric Association (2000), World Health Organization 'World Journal of Biological Psychiatry' (2001-2003), German Association for Psychiatry and Nervous System Disorders (1998), German Drug Commition of the Medical Association (1997). Algorithms (treatment procedures) that are used in psychiatric pharmacotherapy were defined in these publications, and also the aim of them is to deal with psychopathology, comorbidity existence, sex, age and personal biological factors.

TDM indications for psychoactive drugs were defined as follows:

1. Obligatory for the drugs that have a possibility of drug intoxication (lithium, valproic acid)
2. Insufficient clinical response despite the appropriate duration and dosage of the drug
3. Unexpected side effects despite the appropriate dosage of the drug
4. Possible drug-drug interactions.
5. In order to prevent relapse
6. For the children and adolescents
7. For the patients over 65 years old
8. Comorbidity existance (affecting kidney, liver)
9. For patients with genotypic changes
10. Detection of the decremental or incremental effects at multible drug treatment
11. In spite of sufficient drug dosage and adequate clinical response when the disease relapses
12. Problems when switching from a brand name drug (produced by the company holding the patent) to a generic drug (produced by the domestic companies).

Pharmacogenetics Laboratory at NPİSTANBUL Neuropsychiatry Hospital was founded to monitor drug blood level by TDM (Therapeutic Drug Monitoring) and identify genetic profiles of patients correlated to the drugs that are used.

In this laboratory, validated methods were developed for quantitative measurement of risperidone, escitalopram, fluoxetin, paroxetin, mirtazapine, quetiapine, venlafaxine, amisulpiride, olanzapine, carbamazepine and many other drugs by using citrated human plasma. Measurements are made using LC-MS/MS. Desipramine is used as an internal standard solution while the precision and accuracy are in the acceptable range defined by FDA Guidance 2001. This technique is used just for new born check-up in the hospitals of Turkey. This is the first time use of a high tech system for quantitative drug analysis in the clinical routine.

The technique that was developed is an appropriate phenotyping procedure for tracing unexpected toxicity during normal rates of the drug dosage. It could detect metabolized drug levels which might be fast or slow, in order to prevent unnecessary drug use. It allows us to detect the patients with gen polymorphism by means of drug blood concentration differences. Additionally, need for genotyping which is a long lasting procedure is decreased.

Psychiatric Genetic Counseling (Assessment Of The Risk For an Inherited Disorder)

The genetic counseling session will probably last about an hour, and what is covered during the session will be different for each person. But here are some general things that are likely to occur:
- A detailed family history will be taken by the counselor. The more information you can gather the better the counselor can study and share the type and pattern of psychiatric conditions that may run in your family.
- Using the family history information, the counselor will talk about the likely cause of the illness in your family. Some people are interested in talking about risks for themselves, their children or other family members to develop the condition or related conditions.
- Education about the cause and symptoms of the condition(s)
- While genetic testing is not yet available for most psychiatric conditions, the genetic counselor will explore with you how likely it is that other family members might become ill.
- The genetic counselor may also discuss environmental risk factors in and outside of the home, what to look for in a young person at risk for the condition and when to seek treatment.
- The genetic counselor can help you develop strategies for dealing emotionally with the risk in your family and the uncertainty related to whether a family member will or will not become ill.

Why see a psychiatric genetic counselor?

If you have a personal or family history of a psychiatric or mental health condition, the psychiatric genetic counselor will help to answer questions you have about the cause of the condition and the chance it can happen again in your family. These types of conditions may include depression, bipolar disorder, schizophrenia and others. If you are pregnant or considering pregnancy, the risk to your children based on your personal or family history of a psychiatric disorder will be discussed.

In general, there is no genetic testing offered during psychiatric genetic counseling sessions, but during genetic counseling session you can get information about actual genetic research results.

What should I do prior to appointment?

To get the most out of the appointment, try to provide as much information as possible about the psychiatric conditions in your family. Try to find out about:

- Your own mental health history and current status
- Who in your family has mental health conditions
- The names of the condition(s) that run in your family, if known
- Ages that people in your family began having symptoms and were diagnosed