Is Zoloft sedating or activating? (+3 possibilities)

In this short article, we shall discuss whether Zoloft is sedating or activating. We shall also discuss the mechanisms through which the drug elicits these side effects and how to manage them.

Is Zoloft sedating or activating?

Zoloft is both sedating and activating. Zoloft (Sertraline) has a stimulatory activity in some patients that manifests as anxiety, jitteriness, insomnia and irritability (1,2,3). However, it may also cause sedation which manifests as daytime somnolence, fatigue and sleepiness in other patients (1,2,3). The effects usually occur at the onset of therapy, but may also occur at any time during treatment.

The drug is therefore administered in the morning and evening to cater for both groups (1). Patients who experience activation symptoms are recommended to take the drug in the morning, whereas those who experience sedating effects are recommended to take the drug in the evening to minimize the adverse effects.

Consult your doctor or pharmacist if you experience any of these effects and feel that they are becoming bothersome. Your doctor will advise you on the best time to take the medication to reduce the adverse effects.

Zoloft is a widely used antidepressant that is classified as a selective serotonin reuptake inhibitor (SSRI). It works by increasing the reuptake of serotonin in the brain synapses thereby increasing its levels in the brain (1,2). This improves depressive symptoms since serotonin regulates mood and behaviour (1,2).

The activation by Zoloft manifests as anxiety, agitation, jitteriness, insomnia and irritability (1,3). It usually starts at the onset of treatment and subsides within the first few weeks, or at discontinuation of treatment. It may be distressing to some patients and may delay the treatment (4).

The Zoloft-induced sedation presents with daytime fatigue, somnolence and sleepiness (1,2). It may also occur at the onset of treatment, or within the first few weeks. It usually subsides after a short while, by may persist for some time (1). Switching to bedtime dosing usually resolves the adverse effect (1).

How does Zoloft induce activation?

The mechanism through which Zoloft induces activation is not well understood. Its delayed onset of action is thought to partly contribute (4). Sertraline usually takes between 2 to 4 weeks before it begins to act. During this period, the rise in serotonin levels is thought to inhibit the production of more serotonin by the receptors, leading to low serotonin levels. This may trigger the activation symptoms (4).

Other researchers have attributed the activation to Zoloft’s inhibition of catecholamine reuptake, particularly dopamine. This raises the dopamine levels, which may induce activation symptoms (1).

How does Zoloft cause sedation?

Zoloft’s mechanism of sedation is thought to involve antagonism of sigma-1 receptors which induce sedation by increasing opioid signalling (1). The sedation effect has also been postulated to arise from polymorphism of the hypocretin type 2 receptor gene which is thought to regulate the sleep-wake cycle, or circadian rhythm (1). Researchers have attributed this to patients being either sensitive or resistant to Zoloft-induced sedation (1).

How frequent are these effects?

Research has shown that 7% or more of the patients who take Zoloft develop activation symptoms, with insomnia being the most prevalent (4,5,6,7). Indeed, some researchers have even reported prevalence as high as 65% (5). The wide range has largely been attributed to inaccurate reporting since patients with neuropsychiatric disorders such as akathisia may present with features similar to activation symptoms (5,7). They may therefore have been inadvertently reported as activation symptoms. Sedation has been reported to occur in 11% of those who take Zoloft (6).

What factors influence Zoloft’s activation or sedation?

Several factors have been touted to influence Zoloft’s peculiar ability to elicit opposing effects. These include genomic predisposition, drug dose, patient age, and disease severity (1,7). The polymorphism of the serotonin transporter promoter gene has been described to influence the development of activation symptoms, whereas polymorphism of the hypocretin type 2 receptor is thought to elicit the development of sedation symptoms (1,4,7).

Sertraline-induced sedation has been reported to be more common at doses exceeding 100mg per day, whereas activation appears to be independent of the dose. Both are reported to occur early in treatment or following an increase in the dose (1,3,4,7).

Activation has been reported to be more prevalent in children than adults and in patients with a history of bipolar disorder (4,7).

How can Zoloft’s activating or sedating effects be managed?

The management of Zoloft-induced activation or sedation depends on the severity of the adverse effect. Activation symptoms may be reduced by taking the drug in the morning (1,2). Additionally, lowering the dose may be considered if the symptoms persist, and the drug may be discontinued in severe cases (3,4). The sedating effects may be managed by taking the drug at bedtime (1).

Please contact your doctor if you experience activating or sedating side effects. Your doctor will assess your condition and recommend morning or bedtime dosing, or any other intervention depending on your presenting symptoms.

Understanding Zoloft’s activating or sedating effects

Zoloft can induce activating symptoms in some people, and sedating effects in others. The activating symptoms may present as anxiety, jitteriness or insomnia, whereas sedation usually manifests as daytime fatigue and drowsiness. Both effects can occur at any time during your treatment but usually subside after some time. They may however persist in a few people and become bothersome.

I would strongly urge you to contact your doctor if you experience any of these symptoms, especially if they become bothersome as they require different management strategies depending on the presenting conditions.

References