A Guide to Zoloft Side Effects

An overview of Zoloft

If you're prescribing antidepressants, you've likely reached for Zoloft many times. This widely used medication has earned its place as a go-to option for good reason. It's practical, generally well-tolerated, and versatile enough to treat multiple conditions.

Zoloft, the brand name for sertraline, belongs to the selective serotonin reuptake inhibitor class, which means it blocks serotonin from being reabsorbed back into nerve cells. This increases serotonin availability in the brain, helping to stabilize mood and reduce symptoms across various mental health conditions.

Clinicians turn to Zoloft to treat depression and for managing a broad range of disorders (Medscape, 2020). This also includes bipolar disorder, obsessive-compulsive disorder (OCD), panic disorder, social anxiety disorder (SAD), posttraumatic stress disorder (PTSD), panic attacks, and premenstrual dysphoric disorder (PMDD). While most indications are for adults, Zoloft is also approved for treating OCD in children and adolescents aged 6 to 17.

When starting patients on Zoloft, it's crucial to prepare them for the timeline. Therapeutic effects typically take several weeks to kick in, so patience is key. Zoloft is often preferred over other antidepressants for its generally favorable tolerability profile (Halverson, 2019).

Clinicians note that it tends to cause fewer sedative or cognitive side effects of sertraline. However, patients should still be monitored for increased risk of allergic reactions, high blood pressure, memory problems, bleeding problems, and trouble sleeping. Special caution is advised when prescribing to young adults, and clinicians should carefully review how the medication affects those taking other medicines or with pre-existing liver problems.

Zoloft abuse

For context, approximately 5.3 million Americans misused benzodiazepines in the past year (Maust et. al., 2019)—highlighting the broader scope of prescription drug misuse that includes SSRIs like Zoloft.

While Zoloft (sertraline) is generally considered safe and not traditionally addictive, it is not immune to misuse. In fact, it ranks among the more commonly abused antidepressants in the United States, though far less frequently than prescription drugs such as benzodiazepines (Food and Drug Administration, n.d.). For context, approximately 5.3 million Americans misused benzodiazepines in the past year (Maust et. al., 2019)—highlighting the broader scope of prescription drug misuse that includes SSRIs like Zoloft.

Clinicians who prescribe sertraline should be aware that Zoloft abuse doesn’t typically stem from a pursuit of euphoria. Unlike substances that trigger a “high,” Zoloft primarily alters serotonin levels in the brain, and other factors more often drive misuse. Individuals may exceed prescribed doses, combine it with other substances, or use it for longer than recommended. Though not physically addictive in the classical sense, such patterns can foster psychological dependence and, in some cases, physical withdrawal symptoms.

Individuals may also experience withdrawal effects—sometimes called SSRI discontinuation syndrome—if they suddenly stop taking sertraline. This signals that, despite its therapeutic profile, Zoloft can contribute to dependence when misused.

Common motivations for Zoloft abuse include:

• Self-medication: Some individuals self-adjust their dose to seek greater relief from anxiety or untreated depression, often underestimating the risks.
• Polysubstance use: In certain cases, people combine Zoloft with other substances to alter or prolong effects, especially during periods of medication shortages or when interacting with other medications.
• Psychological dependence: The belief that higher doses equate to better outcomes can lead patients down a path of unintended misuse, especially when coping with mental illnesses such as high or low mood states or post-traumatic stress disorder.

There are rare anecdotal reports of alternative routes of administration (such as snorting) or extremely high doses producing altered sensations. However, this is neither well-documented nor consistent. Patients should be reminded not to take double or extra doses if they miss a dose, as this can increase the risk of adverse reactions.

In summary, while Zoloft abuse is relatively rare, it does occur, primarily driven by attempts to self-medicate or manage withdrawal. Clinicians should monitor for signs of misuse and advise patients to seek immediate care for symptoms such as trouble breathing or muscle weakness, which can signal serious complications or dangerous drug interactions.

Individuals may also experience withdrawal effects—sometimes called SSRI discontinuation syndrome—if they suddenly stop taking sertraline.

Common side effects

Like many SSRIs, Zoloft (sertraline) is generally well tolerated, but it does come with potential side effects that clinicians should monitor. Most are mild to moderate and may lessen as the body adjusts to treatment.

• Gastrointestinal symptoms are among the most frequently reported. These include nausea (26%), diarrhea (20%), dry mouth (14%), acid reflux (8%), constipation (6%), and vomiting (4%) (Anderson, 2018).
• Nervous system effects can also occur, with patients reporting dizziness (12%), drowsiness or somnolence (11%), and tremors (9%) (Cunha, 2018).
• A potential for increased suicidal thoughts in patients under 24, especially early in treatment or after dose adjustments (Zoloft.com, n.d.). Close monitoring is essential during these periods.

If side effects persist or become bothersome, patients should consult their healthcare provider rather than discontinuing Zoloft abruptly.

Serious side effects

While Zoloft is generally well tolerated, it can occasionally cause serious side effects that require immediate medical attention. These are rare but important to monitor, especially in patients with pre-existing conditions or those on interacting medications.

Angle closure glaucoma, seizures, and hyponatremia

Some patients may experience closed-angle glaucoma, resulting in eye pain or vision changes (Kirkham & Seitz, 2016). Seizures can occur, though infrequently. Clinicians should also be aware of low sodium levels (hyponatremia), particularly in older adults or those on diuretics.

Cardiac risks and arrhythmias

Zoloft may affect heart rhythm in rare cases, potentially triggering long QT syndrome or other arrhythmias (Gutlapalli et. al., 2022) such as AV block or ventricular tachycardia. Symptoms like fainting, chest pain, or a slow/irregular heartbeat require prompt evaluation.

Psychiatric effects and serotonin syndrome

Clinicians should remain alert for manic episodes, increased bleeding risk, and the serious potential of serotonin syndrome. Key signs include confusion, high fever, muscle rigidity, tremors, rapid heartbeat, and vomiting.

Suicidal thoughts and behaviors

Zoloft carries a black box warning for the potential increase in suicidal thoughts and behaviors, particularly in patients under 24, especially during the first weeks of treatment or after dosage adjustments.

Long-term side effects

While many patients tolerate Zoloft (sertraline) well, long-term use can lead to persistent side effects that clinicians should be prepared to discuss and monitor. Understanding these effects helps guide treatment planning and patient counseling.

• Sexual problems: Sexual dysfunction, including decreased libido, delayed ejaculation, and the inability to reach orgasm, has been reported in up to 72% of people taking antidepressants long-term (Higgins, 2010).
• Weight gain: Weight gain is a commonly reported side effect, affecting up to 65% of long-term antidepressant users (Salamon, 2024).
• Emotional numbness: About 65% of people on long-term antidepressant treatment report feeling emotionally numb (Cartwright et. al., 2016).

How to manage and mitigate side effects

Proactively managing Zoloft (sertraline) side effects helps patients stay comfortable and maintain adherence to treatment. Here are practical strategies clinicians can share:

Managing gastrointestinal issues

Taking Zoloft with bland foods (like crackers) may reduce nausea (MedlinePlus, 2016). Ginger tea or supplements can also help. If diarrhea or constipation becomes troublesome, a clinician-guided solution may be needed.

Addressing sexual side effects

If sexual side effects arise, patients should consult their clinician—dosage adjustments or alternative treatments may help. It’s important not to self-adjust medication.

Managing sleep disturbances

Consider shifting Zoloft to nighttime dosing to reduce daytime sleepiness. Persistent sleep issues warrant provider discussion.

Handling dizziness, tremors, and sweating

These effects often improve with time. Recommend patients avoid sudden movements to limit dizziness.

Safety measures and precautions to take

Clinicians should counsel patients on key safety measures when prescribing Zoloft (sertraline) to help prevent serious complications.

First, review the patient’s medical history and current medications. Zoloft can interact with other drugs, including MAOIs, pimozide, and disulfiram. Patients with liver or kidney disease may require dose adjustments to ensure optimal treatment.

Advise patients to take Zoloft exactly as prescribed and to avoid sudden discontinuation—gradual tapering helps prevent withdrawal symptoms like agitation or electric shock sensations. For liquid forms, they should use a proper measuring device.

Encourage close monitoring for side effects such as increased bleeding, manic episodes, or symptoms of serotonin syndrome. Promptly report any mood changes, suicidal thoughts, or vision problems to a healthcare provider.

References

Anderson, L. A. (2018). Sertraline side effects. Drugs.com. https://www.drugs.com/sfx/sertraline-side-effects.html

Cartwright, C., Gibson, K., Read, J., Cowan, O., & Dehar, T. (2016). Long-term antidepressant use: Patient perspectives of benefits and adverse effects. Patient Preference and Adherence, 10(1), 1401–1407. https://doi.org/10.2147/PPA.S110632

Cunha, J. (2018). Zoloft (Sertraline HCl): Side effects, interactions, warning, dosage & uses. RxList. https://www.rxlist.com/zoloft-drug.htm

Food and Drug Administration USA. (n.d.). Highlights of prescribing information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/019839S74S86S87_20990S35S44S45lbl.pdf

Gutlapalli, S. D., Prakash, K., Swarnakari, K. M., Bai, M., Manoharan, M. P., Raja, R., Jamil, A., Csendes, D., Desai, A., Desai, D. M., & Alfonso, M. (2022). The risk of fatal arrhythmias associated with sertraline in patients with post-myocardial infarction depression. Cureus, 14(9). https://doi.org/10.7759/cureus.28946

Halverson, J. (2019, November 27). Depression medication: Antidepressants, SSRIs, antidepressants, SNRIs, antidepressants, TCAs, antidepressants, MAO inhibitors, augmenting agents, serotonin-dopamine activity modulators, antidepressants, other, stimulants, thyroid products, neurology & psychiatry, herbals, NMDA antagonists. Medscape. https://emedicine.medscape.com/article/286759-medication

Higgins, A. (2010). Antidepressant-associated sexual dysfunction: Impact, effects, and treatment. Drug, Healthcare and Patient Safety, 2, 141. https://doi.org/10.2147/dhps.s7634

Kirkham, J., & Seitz, D. (2016). Evidence of ocular side effects of SSRIs and new warnings. Evidence Based Mental Health, 20(1), 27. https://doi.org/10.1136/eb-2016-102528

Maust, D. T., Lin, L. A., & Blow, F. C. (2019). Benzodiazepine use and misuse among adults in the United States. Psychiatric Services, 70(2), 97–106. https://doi.org/10.1176/appi.ps.201800321

MedlinePlus. (2016). Bland diet: MedlinePlus medical encyclopedia. https://medlineplus.gov/ency/patientinstructions/000068.htm

Medscape. (2020, September 28). Zoloft (sertraline) dosing, indications, interactions, adverse effects, and more. https://reference.medscape.com/drug/zoloft-sertraline-342962

Salamon, M. (2024, August 2). Weighing in on weight gain from antidepressants. Harvard Health. https://www.health.harvard.edu/blog/weighing-in-on-weight-gain-from-antidepressants-202408023063

Zoloft. (n.d.). Important safety information. https://www.zoloft.com/en/Safety-Info

Common FAQs

How long until the side effects should stop?

Many common side effects, such as nausea, fatigue, or dizziness, tend to improve within the first few weeks of treatment. If side effects persist beyond four to six weeks, it’s worth consulting your healthcare provider for further guidance.

What side effects disappear when the medication is stopped?

Once Zoloft is discontinued, side effects like nausea, diarrhea, insomnia, sweating, and dizziness often resolve as the medication clears from your system. However, some effects—such as sexual dysfunction or weight changes—may take longer to improve and should be monitored.

Is it better to take Zoloft in the morning or at night?

The timing of Zoloft dosing depends on how the individual tolerates it; those experiencing drowsiness may prefer to take it at night, while others dealing with insomnia might benefit from taking it in the morning. A clinician can help tailor the dosing schedule based on each patient’s experience.

What should you avoid when taking sertraline?

Patients should avoid alcohol, which can worsen side effects and impair judgment, and be cautious with NSAIDs or blood thinners, which may increase bleeding risk. It’s also wise to avoid driving or operating heavy machinery until they know how Zoloft affects their concentration and coordination.