Selective serotonin reuptake inhibitors, SSRIs

SSRIs are the initial antidepressants of choice for uncomplicated depression because of their minimal anticholinergic effects.

They have the advantage of ease of dosing and low toxicity in overdose. SSRIs are greatly preferred over the other classes of antidepressants for the treatment of children and adolescents, and these agents are also the first-line medications for late-onset depression, due to their superior tolerability and comparatively more benign safety profile.

The SSRIs are not thought to be as worrisome in patients with cardiac disease, as they do not appear to exert any effect on blood pressure, heart rate, cardiac conduction, or cardiac rhythm; however, dose-dependent QT prolongation has been reported with citalopram. Because of the risk for QT prolongation, citalopram is contraindicated in individuals with congenital long QT syndrome.

Because the adverse-effect profile of SSRIs is less prominent than other agents, improved compliance is promoted. Common adverse effects of SSRIs include gastrointestinal upset, sexual dysfunction, bleeding, emotional blunting, cognitive dysfunction, and changes in energy level (ie, fatigue, restlessness).

The US Food and Drug Administration issued a safety information update in December 2011 concluding that it is unclear whether the use of SSRIs during pregnancy causes persistent pulmonary hypertension in the newborn. The FDA currently recommends that health care professionals and patients weigh the small potential risk of persistent pulmonary hypertension against the substantial risks of untreated depression during pregnancy.

Citalopram (Celexa)

Citalopram enhances serotonin activity as a result of selective reuptake inhibition at the presynaptic neuronal membrane. It has minimal effects on norepinephrine and dopamine.

Although it has FDA approval only for depression, citalopram is commonly prescribed for other psychiatric disorders, including obsessive-compulsive disorder, generalized anxiety disorder, panic disorder, and premenstrual dysphoric disorder.

The FDA advises that the dose of citalopram not exceed 40 mg/day because of the risk of potentially fatal QT prolongation. Furthermore, higher doses have not been shown to be more effective in treating depression.

Escitalopram (Lexapro)

Escitalopram is an SSRI and S-enantiomer of citalopram used for the treatment of depression. The mechanism of action is thought to be potentiation of serotonergic activity in the central nervous system resulting from inhibition of CNS neuronal reuptake of serotonin. Escitalopram has little or no effect on norepinephrine and dopamine reuptake.

Onset of depression relief may occur after 1-2 wk, but individual responses vary, and a full effect may not be seen until 8-12 weeks.

Fluoxetine (Prozac)

Fluoxetine is a commonly used SSRI and was the first of the SSRIs to become available in the United States. It selectively inhibits presynaptic serotonin reuptake with minimal or no effect on reuptake of norepinephrine or dopamine. It is commonly prescribed for many indications that are not FDA approved, including fibromyalgia, posttraumatic stress disorder, Raynaud phenomenon, social anxiety disorder, and selective mutism.

Fluvoxamine (Luvox)

Fluvoxamine enhances serotonin activity due to selective reuptake inhibition at the neuronal membrane. It does not significantly bind to alpha-adrenergic, histamine, or cholinergic receptors and thus has fewer side effects than tricyclic antidepressants. Fluvoxamine is a strong inhibitor of cytochrome P-450. Although fluvoxamine is FDA approved only for obsessive-compulsive disorder, it is commonly prescribed for other psychiatric disorders, including social anxiety disorder, posttraumatic stress disorder, pain disorder, and major depression.

Paroxetine (Paxil)

Paroxetine is a potent selective inhibitor of neuronal serotonin reuptake and also has a weak effect on norepinephrine and dopamine neuronal reuptake. It has slight anticholinergic effects and may cause more weight gain than other SSRIs. Paroxetine is sometimes prescribed for indications that are not FDA approved, such as eating disorders and the relief of vasomotor symptoms of menopause.

Sertraline (Zoloft)

Sertraline selectively inhibits presynaptic serotonin reuptake. It has very minimal effects on norepinephrine and dopamine neuronal uptake. Sertraline is sometimes prescribed for indications that are not FDA approved, such as eating disorders, generalized anxiety disorder, and panic disorder.

Vilazodone (Viibryd)

Vilazodone's mechanism of antidepressant effect is related to serotonergic activity in the CNS through selective inhibition of serotonin reuptake. This agent is also a partial agonist at serotonergic 5-HT1A receptors, although the contribution of this activity to the drug's antidepressant effect is unknown.

Vilazodone is indicated for major depressive disorder. The dose should be adjusted when this agent is given with moderate or strong CYP3A4 inhibitors.

Vortioxetine (Brintellix)

Vortioxetine enhances serotonergic activity through 5-HT reuptake inhibition. It also modulates serotonin receptor activity through 5-HT1A receptor agonism and 5-HT3 receptor antagonism, although the contribution of these activities to the antidepressant effect is not fully understood. It is approved to treat major depressive disorder in adults.

Дата добавления: 2015-07-12