From the Guidelines
Selective Serotonin Reuptake Inhibitors (SSRIs) like escitalopram (Lexapro) are generally considered the anxiety medications with the fewest side effects and lowest risk profiles. According to the most recent evidence 1, escitalopram may have the least effect on CYP450 isoenzymes compared with other SSRIs, resulting in a lower propensity for drug interactions. Typically, escitalopram is started at 5-10mg daily and can be increased gradually. These medications work by increasing serotonin levels in the brain, which helps regulate mood and anxiety.
Some key points to consider when prescribing SSRIs include:
- Starting with a subtherapeutic dose as a “test” dose to assess for initial adverse effects such as anxiety or agitation 1
- Gradually increasing the dose as tolerated, with faster up-titration potentially indicated for more severe anxiety presentations 1
- Monitoring for symptoms, especially in the first 24 to 48 hours after dosage changes, when concomitantly administering SSRIs with other serotonergic drugs 1
- Avoiding concomitant administration of SSRIs with monoamine oxidase inhibitors (MAOIs) due to the increased risk of serotonin syndrome 1
Side effects, when they occur, are usually mild and temporary, including initial nausea, headaches, or sleep changes that often resolve within 1-2 weeks. SSRIs are non-addictive and don't cause the dependence issues seen with benzodiazepines like Xanax. They're safer for long-term use and don't have the sedation, cognitive impairment, or withdrawal concerns associated with other anxiety medications. However, these medications take 2-6 weeks to reach full effectiveness, so patience is important. It's essential to consult with a healthcare provider before starting any medication, as individual factors like medical history and other medications can affect which option is best for you.
From the FDA Drug Label
Incidence in Placebo-Controlled Trials Table 2 enumerates the most common treatment-emergent adverse events associated with the use of sertraline Table 3 enumerates treatment-emergent adverse events that occurred in 2% or more of adult patients treated with sertraline and with incidence greater than placebo Table 4 lists the adverse events associated with discontinuation of sertraline hydrochloride treatment (incidence at least twice that for placebo and at least 1% for sertraline in clinical trials) Table 5 below displays the incidence of sexual side effects reported by at least 2% of patients taking sertraline in placebo-controlled trials
The FDA drug label does not answer the question.
From the Research
Anxiolytic Medications with Least Adverse Effects
- The serotonin-noradrenaline reuptake inhibitors (SNRIs), such as venlafaxine, milnacipran, and duloxetine, have been found to be efficacious in relieving anxiety symptoms within depression, and some have proven efficacy in certain anxiety disorders 2.
- Venlafaxine has a favorable drug-drug interaction profile, with low protein binding and no inhibition of CYP enzymes, making it a potential option if drug-drug interactions are a concern 3.
- Sertraline, a selective serotonin reuptake inhibitor (SSRI), has been found to be safe and well-tolerated in numerous patient populations, with a good tolerability profile and low fatal toxicity 4.
- A qualitative review of SNRIs in anxiety found that venlafaxine is as efficacious as selective serotonin reuptake inhibitors in treating anxiety, with comparable tolerability 5.
Comparison of Anxiolytic Medications
- SSRIs, such as sertraline, have been found to be as effective as tricyclic antidepressants in treatment of major depression with less significant side effects 6.
- SNRIs, such as venlafaxine, may have an advantage over selective reuptake inhibitors in certain anxiety disorders, such as post-traumatic stress disorder (PTSD), and in patients with comorbid anxiety and depression 2.
- The relative safety of SSRIs in overdose, despite the occurrence of serotonin syndrome, makes them more desirable than other antidepressants 6.
Safety and Tolerability
- Venlafaxine has a clear dose progression, with low doses predominantly binding to the 5-HT transporter and more binding of the NE transporter as the dose ascends, which may contribute to its favorable safety and tolerability profile 3.
- Sertraline has been found to have a good tolerability profile, with low fatal toxicity, and is effective for acute treatment and longer-term management of social anxiety disorder, posttraumatic stress disorder, panic disorder, and generalized anxiety disorder 4.
- The prognosis in animals that receive treatment for SSRI poisoning is excellent, with no deaths reported in a retrospective study of 313 SSRI-poisoned dogs 6.