From the Guidelines
Desvenlafaxine is generally considered the most tolerable SNRI with the lowest risk of adverse effects for most patients. This recommendation is based on the fact that desvenlafaxine has a more predictable pharmacokinetic profile and fewer drug interactions compared to other SNRIs, such as venlafaxine and duloxetine 1.
Key Points to Consider
- Desvenlafaxine has minimal effects on the CYP450 system, which reduces the risk of drug interactions 1.
- Common side effects of desvenlafaxine include nausea, dizziness, headache, and sweating, but these are usually mild and temporary 1.
- Desvenlafaxine's favorable tolerability profile stems from its direct metabolism to its active form without requiring liver enzyme conversion, unlike venlafaxine which must be converted to its active metabolite 1.
Important Considerations for Prescribing Desvenlafaxine
- The typical starting dose of desvenlafaxine is 50 mg once daily, which is also the recommended therapeutic dose, making it simpler to use without the need for titration in most cases.
- The medication should be taken at the same time each day, with or without food.
- When discontinuing, a gradual taper is recommended to avoid withdrawal symptoms.
Comparison with Other SNRIs
- Venlafaxine may be associated with greater suicide risk than the other SNRIs, and both venlafaxine and desvenlafaxine have been associated with overdose fatalities 1.
- Duloxetine has been associated with hepatic failure and severe skin reactions, including erythema multiforme and Stevens-Johnson syndrome 1. Overall, desvenlafaxine's favorable pharmacokinetic profile, minimal drug interactions, and lower risk of adverse effects make it the most tolerable SNRI for most patients 1.
From the FDA Drug Label
The most commonly observed adverse reactions in duloxetine delayed-release capsules-treated patients (as defined above) were: Diabetic Peripheral Neuropathic Pain: nausea, somnolence, decreased appetite, constipation, hyperhidrosis, and dry mouth Fibromyalgia: nausea, dry mouth, constipation, somnolence, decreased appetite, hyperhidrosis, and agitation. Chronic Pain due to Osteoarthritis: nausea, fatigue, constipation, dry mouth, insomnia, somnolence, and dizziness. Chronic Low Back Pain: nausea, dry mouth, insomnia, somnolence, constipation, dizziness, and fatigue The most commonly observed adverse reactions in duloxetine delayed-release capsules-treated patients in all the pooled adult populations (i.e., MDD, GAD, DPNP, FM, OA, and CLBP) (incidence of at least 5% and at least twice the incidence in placebo-treated patients) were nausea, dry mouth, somnolence, constipation, decreased appetite, and hyperhidrosis.
Most Tolerable SNRI:
- The provided drug labels do not directly compare the tolerability of different SNRIs.
- However, based on the adverse reaction profiles, venlafaxine and duloxetine have similar side effect profiles, with nausea, dry mouth, somnolence, constipation, decreased appetite, and hyperhidrosis being common adverse reactions.
- Venlafaxine may have a slightly lower risk of certain adverse effects, such as nausea (6% vs 23% for duloxetine) and somnolence (9% vs 10% for duloxetine), but the difference is not significant enough to conclude that one is more tolerable than the other.
- It is essential to note that the tolerability of an SNRI can vary depending on individual patient factors, and the decision to prescribe a particular SNRI should be based on a thorough evaluation of the patient's medical history, current medications, and potential risks and benefits. 2, 2, 3
From the Research
SNRI Tolerability
The tolerability of Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs) can vary depending on the specific medication and individual patient factors. Some SNRIs are considered to be better tolerated than others, with fewer adverse effects and a lower risk of discontinuation symptoms.
Comparison of SNRIs
- Venlafaxine: has a dose-dependent adverse effect profile, with nausea, diarrhea, fatigue, and sexual side effects at low doses, and mild increases in blood pressure, diaphoresis, tachycardia, tremors, and anxiety at higher doses 4
- Desvenlafaxine: has a favorable safety and tolerability profile, with common side effects including insomnia, somnolence, dizziness, and nausea, and a low risk of discontinuation symptoms 5, 6, 7
- Duloxetine: has a more balanced profile of binding, with common side effects including nausea, dry mouth, dizziness, constipation, insomnia, asthenia, and hypertension 4
- Milnacipran: has few pharmacokinetic and pharmacodynamic interactions with other drugs, but can cause dysuria, blood pressure, and pulse elevations, particularly at high doses 4
Most Tolerable SNRI
Based on the available evidence, desvenlafaxine appears to be one of the most tolerable SNRIs, with a favorable safety and tolerability profile, and a low risk of discontinuation symptoms 5, 6, 7. Additionally, desvenlafaxine has been found to have a low risk of drug-drug interactions, making it a potential option for patients with complex medication regimens 4, 7. However, it is essential to note that individual patient factors and medical history should be considered when selecting an SNRI, and the most tolerable option may vary depending on the specific patient.