What are the potential side effects of switching from Selective Serotonin Reuptake Inhibitor (SSRI) to Serotonin-Norepinephrine Reuptake Inhibitor (SNRI)?

From the Guidelines

When switching from an SSRI to an SNRI, patients should be informed about potential side effects including nausea, headache, dizziness, increased sweating, dry mouth, insomnia, anxiety, and constipation, and a gradual cross-taper approach is recommended to minimize these effects. These side effects typically occur during the first few weeks of treatment and often diminish over time 1. Patients may also experience discontinuation symptoms if the SSRI is stopped abruptly, including dizziness, flu-like symptoms, irritability, and sensory disturbances.

Key Considerations

• A gradual cross-taper approach is recommended, slowly decreasing the SSRI while introducing the SNRI at a low dose and gradually increasing it 1.
• Blood pressure monitoring is important as SNRIs can cause hypertension, particularly at higher doses 1.
• Sexual side effects may persist or change, and some patients report increased energy or activation compared to SSRIs.
• SNRIs like venlafaxine (Effexor), duloxetine (Cymbalta), and desvenlafaxine (Pristiq) work by inhibiting both serotonin and norepinephrine reuptake, which can provide additional benefit for pain conditions and treatment-resistant depression but may cause more noradrenergic side effects than SSRIs 1.

Potential Adverse Effects

• Diaphoresis, dry mouth, abdominal discomfort, nausea, vomiting, diarrhea, dizziness, headache, tremor, insomnia, somnolence, decreased appetite, and weight loss 1.
• Sustained clinical hypertension, increased blood pressure, and increased pulse 1.
• Uncommon but potentially serious adverse effects include suicidal thinking and behavior, behavioral activation/agitation, hypomania, mania, sexual dysfunction, seizures, abnormal bleeding, and serotonin syndrome 1.

From the FDA Drug Label

During marketing of venlafaxine HCl, other SNRIs (Serotonin and Norepinephrine Reuptake Inhibitors), and SSRIs (Selective Serotonin Reuptake Inhibitors), there have been spontaneous reports of adverse events occurring upon discontinuation of these drugs, particularly when abrupt, including the following: dysphoric mood, irritability, agitation, dizziness, sensory disturbances (e. g. paresthesias such as electric shock sensations), anxiety, confusion, headache, lethargy, emotional lability, insomnia, hypomania, tinnitus, and seizures.

The potential side effects of switching from SSRI to SNRI may include:

• Dysphoric mood
• Irritability
• Agitation
• Dizziness
• Sensory disturbances (such as electric shock sensations)
• Anxiety
• Confusion
• Headache
• Lethargy
• Emotional lability
• Insomnia
• Hypomania
• Tinnitus
• Seizures 2

From the Research

Potential Side Effects of Switching from SSRI to SNRI

• The potential side effects of switching from Selective Serotonin Reuptake Inhibitor (SSRI) to Serotonin-Norepinephrine Reuptake Inhibitor (SNRI) are not explicitly stated in the provided studies, but some information can be inferred from the available data 3, 4, 5, 6, 7.
• A study from 2002 found that adverse effects are the most frequent reason for discontinuing or switching SSRIs within the first 3 months of treatment, with drowsiness/fatigue, anxiety, headache, and nausea being the most commonly reported side effects 3.
• Another study from 2006 compared switching strategies after a first SSRI and found that response rates after switching to any class of antidepressants varied between 12% and 86%, and remission rates varied between 7% and 82% 4.
• A 2014 study compared the efficacy and tolerability of vortioxetine and agomelatine in patients with major depressive disorder who had an inadequate response to SSRI/SNRI monotherapy, and found that vortioxetine was superior to agomelatine in terms of response and remission rates, and had a lower rate of withdrawal due to adverse events 6.
• The most common adverse events reported in this study were nausea, headache, dizziness, and somnolence 6.
• A survey of psychiatrists found that the majority of clinicians opted to switch agents rather than add a specific medication to the existing SSRI to manage most SSRI-associated side effects, except for sexual dysfunction and insomnia 7.

Switching Strategies

• The available evidence suggests that switching from SSRI to SNRI may be a viable option for patients who do not respond to SSRI treatment, but the potential side effects and benefits of this switch should be carefully considered 4, 6.
• The choice of switching strategy may depend on the individual patient's response to treatment and the presence of any side effects 4, 7.
• Further research is needed to fully understand the potential side effects and benefits of switching from SSRI to SNRI, and to determine the most effective switching strategies 4.