Investigation of Genetic Predictors of the Response to Selective Serotonin Re-uptake Inhibitors (SSRI) Treatment

The antidepressant medications are among the most commonly prescribed pharmacological agents in patients with mood and anxiety disorder. Despite recent advances in antidepressant pharmacotherapy, there is a pressing need for substantial optimization and improvment of outcome of pharmacotherapy of psychiatric disorders by providing individualized and science-based treatment guidelines. Besides it is rather difficult in clinical practice to predict, which patient will response to a certain pharmacological treatment well and which one less so. Putative predictors of response to antidepressant include demographic and clinical characteristics, personality traits, biological markers and psychophysiological features. Recently the research studies shown that divergences in antidepressant efficacy may be related to genetic variations of patients. The pharmacogenetic studies have multiplied in recent decade due to the impact that such studies may have in everyday clinical practice once reliable predictors could be identified. The pharmacogenetic research using new DNA microarray-based technology can reasonably be expected to contribute to the prediction of likelihood of treatment response and risk of development of adverse side effects in individual patients in case of antidepressant treatment. By reducing costly treatment failures and the likelihood of serious adverse events, pharmacogenetic testing may help to improve the treatment possibilities for chronic diseases, reduce the burden prescription drug costs, and lower the costs of drug development. The further detailed investigation of peripheral gene expression profiles may help to identify responsible genes that underlie the process of development of affective disorders and open novel horizons for understanding molecular mechanisms of psychopharmacological treatment.

To participate in the study the subjects must be at least 18 years old and give a written informed consent after an oral and written explanation of the study aims and methods. The study sample will include the female and male patients with panic disorder or major depression diagnosis according to DSM-IV criteria. Patients will be recruited from the out- and inpatients services of the Psychiatric Clinic of the Tartu University Hospital. For the detailed assessment of clinical severity of specific disorder and treatment effects the disorder-specific rating scales: Montgomery-Asberg's Depression Rating Scale (MADRS), Clinical Global Impression scale (CGI) will be used. The adverse effects will be evaluated by letting the patients to fill the checklist of side-symptoms. In both patient groups (with panic disorder and major depression) an SSRI escitalopram (Cipralex) will be administrated for 12 weeks in flexible dose ranging between 10 - 20 mg/per day. At the end of week 12 the patients will defined as responders if the decrease in MADRS scores is at least 50% and score on the CGI improvement scale is 2 or less. The remitters will defined if the scores are less than 12 on the MADRS. Patients who do not meet these criteria will defined as non-responders and non-remitters respectively. Depressive patients, showing non-response to escitalopram monotherapy will given the combination of 20 mg of escitalopram and 150-300 mg of bupropion (Wellbutrin SR) for 6 weeks.

Eligibility Criteria:
Inclusion Criteria:

* Both genders
* Diagnosis according to DSM-IV criteria
* At severity of depression of at least moderate as indicated by a Montgomery-Asberg's Depression Rating Scale (MADRS) total score of 22 or higher
* Only secondary current comorbid anxiety disorder

Exclusion Criteria:

* Bipolar disorder
* Psychotic disorder or features
* Current eating disorders
* Mental retardation
* Any pervasive developmental disorder or cognitive disorder
* Alcohol or drug abuse-related disorders within 12 months prior to baseline
* Acute infections, neurological or any other unstable general disorders, serious suicide risk, formal behaviour therapy, or systematic psychotherapy, pregnancy or breastfeeding
* A history of hypersensitivity or non-response to escitalopram or bupropion