What is discontinuation syndrome in Selective Serotonin Reuptake Inhibitors (SSRI)?

From the Guidelines

Discontinuation syndrome in SSRI is a condition characterized by various symptoms, including dizziness, fatigue, lethargy, and anxiety, that occur when a person suddenly stops taking or rapidly reduces their SSRI dose, particularly with shorter-acting SSRIs like paroxetine, fluvoxamine, and sertraline. According to the clinical practice guideline for the assessment and treatment of children and adolescents with anxiety disorders 1, a discontinuation syndrome has been reported following missed doses or acute discontinuation of shorter-acting SSRIs. The symptoms of discontinuation syndrome can include dizziness, fatigue, lethargy, general malaise, myalgias, chills, headaches, nausea, vomiting, diarrhea, insomnia, imbalance, vertigo, sensory disturbances, paresthesias, anxiety, irritability, and agitation 1.

Key Considerations

• The risk of discontinuation syndrome is higher with shorter-acting SSRIs, such as paroxetine, fluvoxamine, and sertraline 1.
• To prevent discontinuation syndrome, SSRIs should be tapered gradually over weeks or months under medical supervision 1.
• A conservative medication trial for mild to moderate anxiety presentations may entail increasing the dose as tolerated within the therapeutic dosage range in the smallest available increments at approximately 1- to 2-week intervals when prescribing shorter half-life SSRIs 1.

Prevention and Management

• Medical education, training, and experience are necessary to safely and effectively prescribe antidepressant medications and manage discontinuation syndrome 1.
• Systematic assessment of treatment response using standardized symptom rating scales can be considered as a supplement to prevent and manage discontinuation syndrome 1.
• If discontinuation symptoms occur, resuming the medication at a lower dose and tapering more slowly can help manage symptoms.

From the FDA Drug Label

Discontinuation of Treatment With PAXIL Recent clinical trials supporting the various approved indications for PAXIL employed a taper-phase regimen, rather than an abrupt discontinuation of treatment. During marketing of PAXIL and other SSRIs and SNRIs, there have been spontaneous reports of adverse events occurring upon the 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 and tinnitus), anxiety, confusion, headache, lethargy, emotional lability, insomnia, and hypomania. While these events are generally self-limiting, there have been reports of serious discontinuation symptoms.

Discontinuation syndrome in SSRI refers to the symptoms that occur when treatment with an SSRI, such as paroxetine, is stopped or the dose is reduced. These symptoms can include:

• Dysphoric mood
• Irritability
• Agitation
• Dizziness
• Sensory disturbances
• Anxiety
• Confusion
• Headache
• Lethargy
• Emotional lability
• Insomnia
• Hypomania It is recommended to gradually reduce the dose rather than stopping abruptly to minimize the risk of discontinuation syndrome 2.

From the Research

Definition and Characteristics of Discontinuation Syndrome in SSRI

• Discontinuation syndrome in SSRI refers to a set of symptoms that occur when an SSRI is suddenly stopped or the dosage is significantly reduced after at least one month of use 3.
• The symptoms can cause clinically significant distress or impairment and are not due to a general medical condition or recurrence of a mental disorder 3.
• Common symptoms include dizziness, nausea or emesis, fatigue, headache, gait instability, insomnia, and irritability 3, 4.

Factors Influencing the Occurrence of Discontinuation Syndrome

• The method of drug withdrawal is a significant factor, with abrupt discontinuation leading to a higher frequency of discontinuation syndrome 5.
• Age may also be a factor, with younger patients more likely to experience discontinuation syndrome, possibly due to a higher tendency to stop taking the medication abruptly 5.
• Patients who experience adverse reactions in the early phase of treatment with paroxetine are more likely to develop discontinuation syndrome 5.
• The duration of treatment with SSRI and the maintenance dosage do not appear to be correlated with the occurrence of discontinuation syndrome 5.

Prevention and Treatment of Discontinuation Syndrome

• Gradually tapering the dosage of the SSRI when treatment is withdrawn can help prevent discontinuation syndrome 6, 4, 5.
• If symptoms occur, reinstating the SSRI and then gradually withdrawing it can lead to symptom resolution 3, 6.
• Switching to a different SSRI, such as fluoxetine, may also be considered as a strategy to prevent or treat discontinuation syndrome 6.