What are the key points to know about Selective Serotonin Reuptake Inhibitors (SSRIs) and Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs)?

From the Guidelines

SSRIs and SNRIs are two important classes of antidepressant medications commonly prescribed for depression, anxiety disorders, and other mental health conditions, with SSRIs often being first-line treatments due to better tolerability, while SNRIs may be more effective for pain conditions or depression with significant fatigue. The key points to know about Selective Serotonin Reuptake Inhibitors (SSRIs) and Serotonin-Norepinephrine Reuptake Inhibors (SNRIs) include:

• Common SSRIs include fluoxetine (Prozac, 20-80mg daily), sertraline (Zoloft, 50-200mg daily), escitalopram (Lexapro, 10-20mg daily), and citalopram (Celexa, 20-40mg daily) 1.
• Popular SNRIs include venlafaxine (Effexor XR, 75-225mg daily), duloxetine (Cymbalta, 30-120mg daily), and desvenlafaxine (Pristiq, 50-100mg daily) 1.
• These medications work by increasing levels of serotonin (SSRIs) or both serotonin and norepinephrine (SNRIs) in the brain by blocking their reabsorption.
• Treatment typically requires 2-4 weeks before benefits appear, and therapy should continue for at least 6-12 months after symptom improvement.
• Common side effects include nausea, headache, sleep disturbances, sexual dysfunction, and initial anxiety.
• SNRIs may additionally cause increased blood pressure and heart rate due to norepinephrine effects.
• Both medication types require gradual tapering when discontinuing to avoid withdrawal symptoms.
• They should not be combined with MAOIs, and caution is needed with other serotonergic medications to prevent serotonin syndrome.
• According to the most recent guideline, SSRIs are suggested for social anxiety disorder, with a weak recommendation and low certainty of evidence 1. Some other points to consider:
• The Japanese Society of Anxiety and Related Disorders/Japanese Society of Neuropsychopharmacology suggests SSRIs and venlafaxine, a SNRI, for social anxiety disorder, with a weak recommendation and low certainty of evidence 1.
• The American Academy of Child and Adolescent Psychiatry suggests SNRIs for patients 6 to 18 years old with social anxiety, generalized anxiety, separation anxiety, or panic disorder, with a 2C recommendation 1.
• The American College of Physicians recommends using second-generation antidepressants, including SSRIs and SNRIs, to treat depressive disorders, with moderate-quality evidence 1.

From the FDA Drug Label

All patients being treated with antidepressants for any indication should be monitored appropriately and observed closely for clinical worsening, suicidality, and unusual changes in behavior, especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases The following symptoms, anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, and mania, have been reported in adult and pediatric patients being treated with antidepressants for major depressive disorder as well as for other indications, both psychiatric and nonpsychiatric The development of a potentially life-threatening serotonin syndrome has been reported with SNRIs and SSRIs, alone but particularly with concomitant use of other serotonergic drugs Patients should be monitored for the emergence of serotonin syndrome.

The key points to know about Selective Serotonin Reuptake Inhibitors (SSRIs) and Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs) are:

• Patients should be monitored for clinical worsening, suicidality, and unusual changes in behavior
• Symptoms such as anxiety, agitation, and panic attacks have been reported in patients treated with antidepressants
• There is a risk of serotonin syndrome, particularly with concomitant use of other serotonergic drugs
• Patients should be screened for bipolar disorder before initiating treatment with an antidepressant 2 3
• Concomitant use of SSRIs or SNRIs with MAOIs is contraindicated
• Treatment should be discontinued if serotonin syndrome occurs, and supportive symptomatic treatment should be initiated

From the Research

Overview of SSRIs and SNRIs

• Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) are widely used to treat mood and anxiety disorders 4.
• SSRIs and SNRIs have different pharmacologic characteristics, dosing, and administration 4.

Efficacy and Tolerability

• A study comparing the efficacy of SSRIs, SNRIs, and novel agents found that all groups showed notable declines in depression severity, with the novel agents group showing the largest mean reduction 5.
• The same study found that the novel agents group had the highest mean rise in quality of life (QoL) ratings and the lowest incidence of side effects 5.
• SNRIs have been found to be efficacious in treating anxiety disorders, with no major differences in efficacy compared to SSRIs 6.
• SNRIs have also been found to be helpful in relieving chronic pain associated with and independent of depression, whereas SSRIs are generally ineffective in treating chronic pain 6.

Adverse Effects

• SSRIs have been found to have a range of adverse effects, including gastrointestinal disturbances, headache, sedation, insomnia, activation, weight gain, impaired memory, excessive perspiration, paresthesia, and sexual dysfunction 7, 8.
• One of the more controversial adverse effects of SSRIs is the increased risk of suicidality in children and young adults aged 18-24, although this risk is not found in adults without certain risk factors 7.
• A risk-benefit analysis must be considered when prescribing SSRIs, taking into account the potential treatment effects, adverse effects, and dangers of the illness to be treated 7.

Pharmacology and Mechanism of Action

• SSRIs work by inhibiting presynaptic reuptake of serotonin at the serotonin transporter, increasing serotonin at the postsynaptic membrane in the serotonergic synapse 7.
• SNRIs block the reuptake of both serotonin and norepinephrine, with differing selectivity between the two neurotransmitters 6.
• The six major SSRIs marketed in the USA have unique pharmacokinetics, pharmacodynamics, and side effect profiles despite sharing a similar mechanism of action 7.