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Depression and anxiety disorders are the most common mental illnesses, each affecting in excess of 15% of the population at some point in the life span. With the advent of more selective and safer drugs, the use of antidepressants and anxiolytics has moved from the exclusive domain of psychiatry to primary care and other medical specialties. The relative safety of the majority of commonly used antidepressants and anxiolytics notwithstanding, their optimal use requires a clear understanding of their mechanisms of action, pharmacokinetics, adverse effects, potential drug interactions, and the differential diagnosis of psychiatric illnesses (Thronson and Pagalilauan, 2014).

Both depression and anxiety can affect an individual patient simultaneously; some of the drugs discussed here are effective in treating both types of disorders, suggesting common underlying mechanisms of pathophysiology and responses to pharmacotherapy. In large measure, our current understanding of pathophysiological mechanisms underlying depression and anxiety has been inferred from the mechanisms of action of psychopharmacological compounds, notably their actions on neurotransmission involving serotonin (5HT, 5-hydroxytryptamine), norepinephrine (NE), and γ-aminobutyric acid (GABA) (see Chapter 16). While depression and anxiety disorders comprise a wide range of symptoms, including changes in mood, behavior, somatic function, and cognition, progress has been made in developing animal models that respond with some sensitivity and selectivity to antidepressant or anxiolytic drugs (Cryan and Holmes, 2005; Xu et al., 2012). The last half-century has seen notable advances in the discovery and development of drugs for treating depression and anxiety (Hillhouse and Porter, 2015).



ADHD: attention-deficit/hyperactivity disorder

AMPA: α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, an exogenous ligand for the GluA subtype of glutamate receptors

BDNF: brain-derived neurotrophic factor

CREB: cyclic AMP response element binding protein

CYP: cytochrome P450

DA: dopamine

DAT: dopamine transporter

GABA: γ-aminobutyric acid

GI: gastrointestinal

MAO: monoamine oxidase

MAOI: monoamine oxidase inhibitor

NE: norepinephrine

NET: neuronal NE transporter

NMDA: N-methyl-D-aspartate

PTSD: posttraumatic stress disorder

SERT: neuronal serotonin/5HT transporter

SNRI: serotonin-norepinephrine reuptake inhibitor

SSRI: selective serotonin reuptake inhibitor

TCA: tricyclic antidepressant


Symptoms of Depression

Depression can occur in major depressive disorder (i.e., unipolar depression), persistent depressive disorder (dysthymia), or bipolar I and II disorders (i.e., manic-depressive illness). Bipolar depression and its treatment are discussed in Chapter 19. Lifetime risk of unipolar major depression is approximately 15%. Females are affected with major depression twice as frequently as males (Brody et al., 2018). There also is some evidence for sex-based, differential response to pharmacotherapy. Depressive episodes are characterized by sad mood, pessimistic worry, diminished interest in normal activities, mental slowing and poor concentration, insomnia or increased sleep, significant weight loss or gain due to altered eating and activity patterns, psychomotor agitation or retardation, feelings of guilt and worthlessness, decreased energy and libido, and suicidal ideation. In depressive episodes, ...

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