Which antidepressant, such as Selective Serotonin Reuptake Inhibitors (SSRIs) or Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs), has the least side effects in long-term use?

From the Guidelines

Escitalopram is generally considered to have the most favorable long-term side effect profile among commonly prescribed antidepressants, including SSRIs and SNRIs, due to its relatively low propensity for drug interactions and discontinuation syndrome. When considering the long-term use of antidepressants, it's crucial to weigh the benefits against the potential risks and side effects. According to the clinical practice guideline for the assessment and treatment of children and adolescents with anxiety disorders 1, SSRIs vary in their potential for drug-drug interactions, with citalopram/escitalopram having the least effect on CYP450 isoenzymes compared to other SSRIs.

Key considerations for long-term antidepressant use include:

• The potential for discontinuation syndrome, which is more commonly associated with paroxetine, fluvoxamine, and sertraline 1
• Drug-drug interactions, particularly with monoamine oxidase inhibitors (MAOIs) and drugs that prolong the QT interval 1
• The risk of suicidal thinking or behavior, which has been associated with paroxetine compared to other SSRIs 1
• Common long-term side effects, such as sexual dysfunction, weight changes, and emotional blunting, which can vary significantly between individuals

Given these considerations, escitalopram stands out as a preferable option for long-term use due to its pharmacological profile and lower risk of adverse effects. Regular follow-up with a healthcare provider is essential to monitor for side effects and adjust treatment as needed, especially during the first few months of therapy and when changing dosages.

From the FDA Drug Label

The FDA drug label does not answer the question.

From the Research

Antidepressants with the Least Side Effects in Long-term Use

• The antidepressant with the least side effects in long-term use is not explicitly stated in the provided studies, but some comparisons can be made between different classes of antidepressants, such as Selective Serotonin Reuptake Inhibitors (SSRIs) and Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs) 2, 3.
• Fluoxetine, an SSRI, has been compared to other antidepressants in terms of side effects, and it was found that fluoxetine has a better tolerability profile than tricyclic antidepressants (TCAs), but not significantly different from other SSRIs 2.
• In terms of individual side effects, fluoxetine was found to have more activating and gastrointestinal adverse effects compared to other antidepressants, which may require additional management strategies 2.
• SNRIs, such as venlafaxine, milnacipran, and duloxetine, have also been studied in terms of their tolerability, and it was found that duloxetine and milnacipran appear to be better tolerated than venlafaxine, with less cardiovascular toxicity 3.
• Long-term use of fluoxetine has been associated with some late-onset side effects, such as restlessness, tension, agitation, and sleep disturbances, which may be related to the development of supersensitivity of serotonin-related receptors 4.
• However, another study found that common adverse events associated with initiating fluoxetine treatment, such as nausea, insomnia, nervousness, and somnolence, resolve in the majority of patients and become significantly less frequent with continued treatment over a 6-month period 5.

Comparison of SSRIs and SNRIs

• SSRIs, such as fluoxetine, have a more favorable short-term side-effect profile compared to TCAs, but their long-term effects are not as well understood 2, 4.
• SNRIs, such as duloxetine and milnacipran, may have a better tolerability profile than some SSRIs, such as venlafaxine, but more studies are needed to confirm this 3.
• The choice of antidepressant should be based on individual patient needs and medical history, as well as the potential for drug interactions and side effects 6.