Sex influence on the clinical improvement of major depressive disorder in patients treated with Venlafaxine: a prospective cohort study

Abstract

BACKGROUND Major Depressive Disorder (MDD) is a common severe disorder which consists of symptoms conditioning important disability and causes difficulties in the functioning areas such as social life or occupation. MDD has a very high prevalence being the most frequent mental disorder in Spain, and its prevalence is of 6,7%. It is as twice as prevalent in women as in men being 9,2% against 4%. This disorder has a multifactorial aetiology being genetic factors, stressful life events and socioeconomic factors the most relevant. There are some biological, social and psychological factors that may explain the difference in the prevalence between men and women. Those are hormonal factors, exposition to sexual abuse, being exposed to caretaker responsibilities and emotion-focused roles. To diagnose a patient of MDD the DSM-5 criteria are used. These criteria include all the symptomatology related to this disorder. Apart from the diagnostic criteria, there are some scales to assess the severity of the MDD episode. The most used is the Hamilton Depression Rating Scale (HDRS). There are three main strategies that have proven to be effective to treat an MDD episode: antidepressant drugs, psychotherapy and electroconvulsive therapy. Venlafaxine is a dual antidepressant drug; it is a 5-HT and

Noradrenaline reuptake inhibitor. It is metabolised in the liver to its active metabolite O- desmethylvenlafaxine, and to a less active metabolite N-desmethylvenlafaxine by the enzyme

CYP3A4. This enzyme has a higher expression in women than in men. OBJECTIVE The main objective of this study is to assess if the patient’s sex influences the clinical improvement of depression in patients treated with Venlafaxine, and therefore if there is a relationship between the patient's sex and the clinical improvement. DESIGN The study is designed as a multicentre prospective observational cohort study that will be carried out in all the Adult Mental Health Centres (AMHC) of Girona province, in total seven centres will participate in this study. PARTICIPANTS In this study will participate all MDD patients of Girona province treated with Venlafaxine 225mg and aged between 30-50 years at the beginning of the study. This population will be divided into two groups: men and women. The two groups will be as equal as possible. METHODS Information will be recorded directly from the patient. To assess the clinical improvement a psychiatrist will perform the HDRS and will give punctuation to patients at the beginning of the study and every three months until they reach their first year of follow-up. After answering the HDRS, patients will be transferred to the nursery where a blood draw will be done to measure the blood levels of N-desmethylvenlafaxine. All these data will be analysed posteriorly