From the Guidelines
High-dose Selective Serotonin Reuptake Inhibitors (SSRIs) can cause significant side effects, including increased risk of suicidal thinking and behavior, serotonin syndrome, and other severe adverse events, as reported in a 2020 study 1. When considering the use of high-dose SSRIs, it is essential to weigh the potential benefits against the risks of adverse effects. Common side effects of high-dose SSRIs include:
- Nausea and vomiting
- Diarrhea
- Headaches
- Insomnia
- Sexual dysfunction, including decreased libido and delayed orgasm
- Excessive sweating More concerning effects may include:
- Increased anxiety and agitation
- Tremors and akathisia (restlessness and inability to remain still)
- Serotonin syndrome, a potentially life-threatening condition characterized by confusion, rapid heart rate, high blood pressure, dilated pupils, muscle rigidity, hyperthermia, and seizures, as described in a study from 2020 1. It is crucial to note that the risk of suicidal thinking and behavior is a significant concern, particularly in children and adolescents, with a pooled absolute rate of 1% for youths treated with an antidepressant and 0.2% for youths treated with a placebo, as reported in a 2020 study 1. The use of high-dose SSRIs should be carefully monitored, and patients should be educated about the potential risks and side effects, as well as the importance of seeking immediate medical attention if symptoms occur, as recommended in a study from 2008 1.
From the FDA Drug Label
The FDA drug label does not answer the question about the side effects of high-dose Selective Serotonin Reuptake Inhibitors (SSRIs).
From the Research
Side Effects of High-Dose SSRIs
The side effects of high-dose Selective Serotonin Reuptake Inhibitors (SSRIs) can be severe and potentially life-threatening. Some of the possible side effects include:
- Serotonin syndrome, a condition characterized by excessive levels of serotonin in the body, which can cause symptoms such as agitation, confusion, rapid heart rate, and changes in blood pressure 2, 3, 4
- Increased risk of bleeding and thrombotic events, particularly in patients with a history of stroke or myocardial infarction 5
- QT prolongation, a condition that can increase the risk of abnormal heart rhythms 5
- Nausea, vomiting, mydriasis, hypersalivation, and hyperthermia, which can occur as a result of excessive serotonin levels in the central nervous system 3
- Ataxia, tremors, muscle rigidity, diarrhea, and seizures, which can occur at higher doses of SSRIs 3
Risk Factors for Side Effects
Certain patients may be at increased risk for side effects from high-dose SSRIs, including:
- Patients with a history of stroke or myocardial infarction, who may be at increased risk of bleeding and thrombotic events 5
- Patients taking other medications that can interact with SSRIs, such as certain antibiotics or antifungals, which can increase the risk of serotonin syndrome 2, 4
- Patients with certain medical conditions, such as liver or kidney disease, which can affect the metabolism and excretion of SSRIs 6
Importance of Monitoring and Dose Adjustment
It is essential to closely monitor patients taking high-dose SSRIs for signs of side effects and to adjust the dose as needed to minimize the risk of adverse events. This may involve regular check-ups with a healthcare provider, monitoring of vital signs and laboratory tests, and adjustment of the dose or discontinuation of the medication if side effects occur 6, 5