Serotonin pathway polymorphisms and the treatment of major depressive disorder and anxiety disorders

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Date: Apr. 2015
From: Pharmacogenomics(Vol. 16, Issue 5)
Publisher: Future Medicine Ltd.
Document Type: Report
Length: 11,310 words
Lexile Measure: 1860L

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Author(s): Sarah G Helton aff1 , Falk W Lohoff [*] aff1


antidepressants; anxiety disorders; biomarker; genetics; pharmacogenetics; serotonin; treatment response

Antidepressant drugs are often prescribed for the treatment of major depressive disorder (MDD) and anxiety disorders. However, in general only a third of patients treated with antidepressants show a positive therapeutic response [1 ]. Treatment response and side effects for the same drug, and even at the same dose, often differ between patients, with some patients responding favorably to one treatment but not another. There are several factors that influence drug response rates, such as clinical, environmental and social factors, as well as genetic factors. Isolating variables that could predict a more beneficial therapeutic response to a particular drug would allow the potential to use a medication with greater certainty and efficiency. Pharmacogenetics, a predictive tool used to identify and develop genetic biomarkers that can predict a patient's therapeutic response and risk of side effects, will help the practitioners choose effective and safe treatment for patients suffering from psychiatric disorders.

Serotonergic drugs for the treatment of MDD & anxiety disorders

According to The Diagnostic and Statistical Manual of Mental Disorders (5th edition; DSM-5; American Psychiatric Association, 2013), MDD is characterized by exhibiting a depressed mood most of the day for nearly every day for a 2-week period and/or having a diminished interest or pleasure in almost all activities nearly every day for the same 2-week period. However, individual symptoms can vary across patients substantially. Risk factors for an MDD diagnosis include genetic, environmental and social factors, as well as having a history of a major depressive episode. In the United States, MDD has a lifetime prevalence of approximately 16% in the adult population [ 2 ].

Anxiety disorders comprise a heterogeneous group of illnesses that have in common heightened and excessive levels of 'fear,' which often leads to functional impairment and adverse physical symptoms. The most common disorders include generalized anxiety disorder (GAD), panic disorder (PD), social anxiety disorder (SAD) and now reorganized for DSM-5 as separate categories post-traumatic stress disorder (PTSD) and obsessive-compulsive disorder (OCD). As a group, anxiety disorders represent the most common psychiatric disorder, affecting about 18% of the general population 18 years and older in a given year [3 ]. Anxiety disorders are highly comorbid among themselves and with major depression [3 ]. It is thus not surprising that antidepressant drugs are effective in the treatment of both disorders, which might actually reflect some shared biological mechanisms for depression and anxiety.

Treatments for MDD and anxiety disorders usually span the spectrum from cognitive, behavioral and pharmacological interventions, often resulting in combinations. In general, treatment involves a sequential process that focuses first on remission of symptoms and long-term on maintaining suppression of depression and anxiety symptoms and functional recovery. Initially, monoamine oxidase inhibitors and tricyclic antidepressants were used to treat depression, while benzodiazepines were prescribed for the treatment of anxiety disorders. However, benzodiazepines did not treat comorbid depression and often caused unwanted side effects and dependence when used...

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Gale Document Number: GALE|A411315287