Agents Used for Depression

From a pathophysiologic perspective, a decrease in certain neurotransmitters (serotonin, norepinephrine and possibly dopamine) have been causally associated with depression through the indirect evidence that all approved antidepressants will increase the activity of one or more of these chemical messengers. 

All of the current antidepressants agents are equally effective in the general depressed population, generating a therapeutic response in 60% to 70% of patients given a therapeutic trial. Generally, symptoms begin to improve within the first 2 weeks of treatment, and 4 weeks (or more) are required to observe optimal treatment outcomes. 

Selective serotonin reuptake inhibitors (SSRIs) are the most popular treatment option due to safety in overdose situations, low side effect burden, and ease of administration (i.e., once-daily dosing with minimal titration required). SSRIs are also effective treatment for the management of anxiety disorders, a common psychiatric comorbidity among the depressed. 

Because 25% of patients will stop SSRIs due to side effects and an additional 30% to 40% will fail to achieve a therapeutic response, other antidepressant alternatives are of great importance. Venlafaxine is a dual-action antidepressant that enhances serotonin activity at low doses and norepinephrine at higher doses. Preliminary evidence suggests that these multiple actions on neurotransmitters may confer therapeutic superiority over SSRIs for the management of severe or melancholic depression, but the risk of HTN with high-dose venlafaxine should not be overlooked. 

Bupropion is another second-line agent, particularly for patients who are wary of the SSRIs negative impact on sexual dysfunction. Because it appears to relieve depression through a completely different mechanism than SSRIs, enhancing norepinephrine or dopamine, it is often administered to patients who fail SSRIs or exhibit a partial response. The most common side effects encountered with bupropion are insomnia, jitteriness, and nausea. Bupropion is contraindicated in patients with a history of seizures or eating disorders. 

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