Augmentation Strategies Combinations of Antidepressants

Some clinicians make a distinction between combination and augmentation therapies, with the former referring to the use of antidepressants in combination, and the latter referring to the use of drugs that are not antidepressants to augment-approved antidepressants. In our view, this is an artificial distinction, and prefer the term augmentation to refer to any combination of medications used to enhance antidepressant response. We recognize that a growing segment of clinical pharmacologists are...

Cns

Both tension headaches and migraines have been reported to worsen when SSRIs are started (33), although improvement has also been noted. In some cases, headaches tend to increase in frequency over time (69). Sedation or activation with insomnia is known to occur, especially at the initiation of treatment, although this is somewhat variable depending on the SSRI. Some patients report increased dreaming, vivid dreams, and nightmares. Some authorities believe that fluoxetine has the highest...

Other Antidepressants

A number of antidepressants were introduced after SSRIs. Venlafaxine is a nonselective serotonin and norepinephrine reuptake inhibitor. Desvenlafaxine, the primary metabolite of venlafaxine, has a similar profile to its parent compound, but dosing may be easier. Duloxetine is also a nonselective serotonin and norepineph-rine reuptake inhibitor, but has greater potency than venlafaxine (181). Neither compound has significant anticholinergic or antihistaminic effects. Mirtazapine is a...

SSRIs History

The first selective serotonin reuptake inhibitor (SSRI), fluoxetine, was introduced to the American market in 1988 (30). Other SSRIs, sertraline, paroxetine, and flu-voxamine, followed closely. Although widely used in Europe for some time, it was not until the late 1990s that another SSRI, citalopram, became available to American clinicians and later, its enantiomer, escitalopram, was introduced. By the early 1990s, the SSRIs became first-line antidepressants in clinical practice and accounted...

The Role of Mixed Action Antidepressants in Therapeutics

Recently marketed non-SSRI antidepressants are considered by most clinicians as second-line therapeutic options for treatment refractory patients or as augmenting agents. Since these antidepressant medications act on different neuronal systems, they are a rational choice in non-responders (182). They are also used as adjunctive agents to augment SSRIs in partial responders. Their overall efficacy as antidepres-sants is comparable to that of the standard antidepressant classes such as SSRIs,...

Hypothalamic Pituitary Adrenal HPA Axis in Depression CRF

The HPA axis is the primary neuroendocrine system mediating the stress response and includes the hormones and structures mediating the production of glucocorticoids. Corticotrophin-releasing hormone (CRH), also known as corticotrophin-releasing factor (CRF), is produced in the paraventricular nucleus of the hypothalamus. It acts on CRF1 and CRF2 receptors in the central nervous system and anterior pituitary (34). The CRF1 receptor mediates anxiety and depression behaviors and the stress...

Other Neuromodulators Cytokines Substance P Glutamate yAminobutyric Acid and Enkephalins

Cytokines are chemical mediators of the inflammatory response. Several studies have found that patients with major depression have increased levels of inflammatory markers in CSF and blood. There is substantial inconsistency in reports identifying specific markers, although some evidence supports increased interleu-kin (IL)-1, IL-6, tumor necrosis factor (TNF)-alpha and increases in acute phase proteins such as C-reactive protein and chemokines. A meta-analysis (151) found that levels of...