From the Guidelines
Selective serotonin reuptake inhibitors (SSRIs) that tend to be more activating and less likely to cause drowsiness include Prozac (fluoxetine) and sertraline, as they have been associated with weight loss with short-term use and weight neutrality with long-term use 1. When considering the treatment of depression, it's essential to choose an SSRI that minimizes sedation and promotes alertness.
- Fluoxetine (Prozac) is often considered the most energizing of the traditional SSRIs, typically started at 10-20mg daily in the morning, due to its longer half-life and effects on norepinephrine at higher doses 1.
- Sertraline (Zoloft) is also a well-tolerated SSRI with less effect on metabolism of other medications, and it has been associated with weight loss with short-term use and weight neutrality with long-term use 1. It's crucial to note that individual responses to these medications can vary significantly, and finding the right medication often requires trial and adjustment with healthcare provider guidance. The choice of agent must still be guided by best practice for the individual patient’s circumstance, taking into account the potential for weight gain or loss, as well as other side effects such as sexual dysfunction or increased risk for nonfatal suicide attempts 1.
From the FDA Drug Label
The mechanism of action of sertraline is presumed to be linked to its inhibition of CNS neuronal uptake of serotonin (5HT). In vitro studies in animals also suggest that sertraline is a potent and selective inhibitor of neuronal serotonin reuptake and has only very weak effects on norepinephrine and dopamine neuronal reuptake In vitro studies have shown that sertraline has no significant affinity for adrenergic (alpha1, alpha2, beta), cholinergic, GABA, dopaminergic, histaminergic, serotonergic (5HT1A, 5HT1B, 5HT2), or benzodiazepine receptors; antagonism of such receptors has been hypothesized to be associated with various anticholinergic, sedative, and cardiovascular effects for other psychotropic drugs
The more activating SSRI that does not cause drowsiness is sertraline.
- Key points:
- Sertraline is a potent and selective inhibitor of neuronal serotonin reuptake.
- It has no significant affinity for receptors associated with sedative effects.
- The provided information does not directly compare the activating effects of different SSRIs, but sertraline's mechanism of action suggests it may be less sedating than other options like paroxetine, which has a higher incidence of somnolence reported in its label 2.
From the Research
More Activating SSRIs
The following SSRIs are considered to be more activating and less likely to cause drowsiness:
- Fluoxetine 3, 4, 5: known for its activating properties, with common side effects including insomnia, nervousness, and agitation
- Sertraline 6, 5, 7: has a similar side effect profile to fluoxetine, with activating properties and common side effects including insomnia and headache
- Paroxetine 6, 5, 7: can be activating, but may also cause sedation in some patients, with common side effects including headache, tremor, and sweating
Comparison of SSRIs
A meta-analysis of 20 short-term comparative studies of 5 SSRIs (citalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline) showed no difference in efficacy between individual compounds, but a slower onset of action of fluoxetine 7. The study also found that fluoxetine caused more agitation, weight loss, and dermatological reactions than the other SSRIs.
Side Effects
Common side effects of SSRIs include:
- Gastrointestinal disturbances (e.g. nausea) 5, 7
- Headache 5, 7
- Insomnia 3, 4, 5
- Activation (e.g. agitation, nervousness) 3, 4, 5
- Sedation (e.g. drowsiness) 5, 7
- Sexual dysfunction 5, 7
Selection of SSRIs
Guidelines for the selection of individual SSRIs in clinical practice propose that:
- Citalopram should be avoided in patients likely to take overdoses 7
- Fluoxetine may not be the drug of first choice for patients in whom a rapid antidepressant effect is important or for those who are agitated, but it may have advantages over other SSRIs in patients who are poorly compliant with treatment and those who have previously had troublesome discontinuation symptoms 7
- Fluvoxamine, and possibly paroxetine, should not be used as first choice in patients especially prone to SSRI-related adverse reactions 7
- When in doubt about the risks of drug interactions, citalopram or sertraline should be considered given the lower theoretical risk of interactions 7