Sertraline side effects: what to expect during treatment

Sertraline is a selective serotonin reuptake inhibitor (SSRI) prescribed for depression, generalised anxiety disorder, obsessive-compulsive disorder, panic disorder and PTSD.

Its side effects are primarily related to increased serotonin activity throughout the body.

Very common (affecting more than 1 in 10 people):

• Nausea: the most frequently reported early side effect, affecting approximately 25% of patients. It is usually worst in the first 1 to 2 weeks and often settles by week 3 to 4
• Diarrhoea: loose stools occur more commonly with sertraline than with other SSRIs, due to serotonin's role in gut motility
• Headache: typically mild and self-limiting
• Insomnia or sleep disturbance: difficulty falling or staying asleep, often most prominent early in treatment

Common (affecting 1 in 10 to 1 in 100 people):

• Dizziness
• Fatigue or drowsiness: some patients feel tired rather than alert, particularly at higher doses
• Dry mouth
• Increased sweating: including night sweats
• Tremor: fine hand tremor
• Reduced appetite or increased appetite: weight effects vary between individuals
• Sexual dysfunction: reduced libido, delayed ejaculation or difficulty reaching orgasm. This affects an estimated 30 to 60% of patients and is often underreported

The BNF notes that many of these effects are transient and improve within the first 2 to 4 weeks. Taking sertraline with food can reduce nausea.

The first 1 to 2 weeks of sertraline treatment can be challenging, as side effects often emerge before the therapeutic benefits are felt.

Typical timeline:

• Days 1 to 3: nausea, headache and a feeling of restlessness or "jitteriness" are most common. Some patients feel more anxious initially, which is a recognised paradoxical effect of SSRIs
• Days 4 to 7: nausea usually begins to improve. Sleep disturbance may persist. Some patients notice loose stools
• Week 2: most acute side effects are settling. Appetite may be affected (increased or decreased). Sweating may become noticeable
• Weeks 3 to 4: mood and anxiety should begin to improve. This is when sertraline's therapeutic effects start to emerge
• Weeks 4 to 6: the full therapeutic effect is usually established. If there is no improvement by 6 to 8 weeks, the dose may be increased

Why the early period is difficult:

Sertraline increases serotonin levels in the brain from the first dose, but the brain takes time to adapt its receptors.

The side effects reflect the sudden increase in serotonin activity, while the therapeutic benefits require downstream receptor changes that take longer to develop.

Key advice for the first two weeks:

• Persist with treatment unless side effects are intolerable or concerning
• Take the tablet with food (preferably breakfast or lunch) to reduce nausea
• Avoid starting sertraline before an important event where side effects could be problematic
• Contact your prescriber if anxiety worsens significantly, as the starting dose may be reduced to 25 mg

NICE advises that patients should be reviewed within 2 weeks of starting an SSRI, especially if under 30 years of age.

Sexual dysfunction is one of the most significant long-term side effects of sertraline and all SSRIs. It is also one of the most common reasons patients consider stopping treatment.

Types of sexual dysfunction:

• Reduced libido: decreased interest in sexual activity
• Erectile dysfunction in men
• Delayed ejaculation or inability to ejaculate in men
• Anorgasmia: difficulty reaching orgasm in both men and women
• Reduced genital sensitivity
• Vaginal dryness in women

How common is it?

Clinical trials report rates of 10 to 20%, but dedicated sexual function studies suggest the true prevalence is 30 to 60% of patients.

The discrepancy arises because patients often do not volunteer this information unless specifically asked.

Management strategies:

• Dose reduction: sexual side effects are often dose-dependent. Reducing to the lowest effective dose may help
• Timing adjustments: taking sertraline after sexual activity rather than before may provide a short window of reduced effect
• Drug holidays: some clinicians allow a brief pause (e.g. skipping 1 to 2 days before a weekend) for medicines with shorter half-lives, though this is not standard practice for sertraline
• Switching SSRI: mirtazapine and bupropion are associated with lower rates of sexual dysfunction
• Adding a second medicine: in some cases, low-dose bupropion or sildenafil may be considered

The BNF lists sexual dysfunction as a recognised effect of all SSRIs. Open discussion with your prescriber is essential.

While sertraline is generally well tolerated, there are serious risks that patients and prescribers must be aware of.

Suicidal thoughts in young adults:

The MHRA has issued warnings that SSRIs, including sertraline, may increase the risk of suicidal thoughts and self-harm in patients under 25, particularly in the early weeks of treatment or during dose changes.

• Reviewing patients under 30 within 1 week of starting treatment
• Weekly reviews for the first month
• Clear safety netting advice for patients and their families

Serotonin syndrome:

A rare but potentially life-threatening condition caused by excessive serotonin activity. It can occur when sertraline is combined with other serotonergic medicines (e.g.

tramadol, triptans, MAOIs, St John's Wort).

• Agitation, confusion and restlessness
• Rapid heart rate and high blood pressure
• Dilated pupils and muscle twitching
• High temperature and sweating
• Diarrhoea

Seek emergency help immediately if these symptoms develop.

Bleeding risk:

SSRIs reduce platelet aggregation and may increase the risk of gastrointestinal bleeding, particularly when combined with NSAIDs (e.g. ibuprofen) or anticoagulants.

The BNF advises caution and consideration of gastroprotection.

Hyponatraemia:

Low sodium levels, particularly in elderly patients, can cause confusion, drowsiness and seizures. This is more common in the first few weeks and in patients taking diuretics.

QT prolongation:

At high doses, sertraline may prolong the QT interval on an ECG, increasing the risk of cardiac arrhythmias.

Weight changes with sertraline are a common concern and can go in either direction.

Short-term effects (first 1 to 3 months):

• Many patients experience reduced appetite and mild weight loss during the first few weeks, partly due to nausea and partly due to sertraline's mild appetite-suppressing effect
• Some patients notice no change in weight at all

Long-term effects (beyond 6 months):

• Weight gain becomes more common with prolonged use. A large observational study found that SSRI users gained an average of 1.5 kg more than non-users over 10 years
• The mechanism is not fully understood but may involve changes in appetite regulation, metabolic rate and food preferences as the depression or anxiety improves
• Weight gain varies considerably between individuals; some patients gain nothing while others gain several kilograms

Comparison with other antidepressants:

• Sertraline is considered weight-neutral to mildly weight-gaining
• Mirtazapine and amitriptyline are associated with more significant weight gain
• Bupropion is the antidepressant most consistently associated with weight loss or weight neutrality
• Among SSRIs, fluoxetine may cause less weight gain than sertraline or paroxetine

Management:

• Monitor weight from the start of treatment
• Maintain a balanced diet and regular physical activity
• Discuss concerns with your prescriber, who may consider switching to an alternative if weight gain becomes significant

The BNF lists both weight gain and weight loss as possible effects of sertraline.

Stopping sertraline abruptly or reducing the dose too quickly can cause discontinuation symptoms. These are sometimes called SSRI withdrawal or discontinuation syndrome.

Common withdrawal symptoms:

• Dizziness and vertigo: often described as a "spinning" sensation
• Electric shock sensations ("brain zaps"): brief, sudden jolts often triggered by eye movement
• Nausea and vomiting
• Irritability and mood swings
• Anxiety and agitation: which can be confused with a relapse of the original condition
• Insomnia and vivid dreams
• Flu-like symptoms: sweating, chills, fatigue
• Paraesthesia: tingling or numbness

How common are withdrawal symptoms?

Estimates vary, but approximately 20 to 50% of patients who stop an SSRI abruptly experience some degree of discontinuation symptoms.

They are usually mild and self-limiting, lasting 1 to 3 weeks, but can occasionally persist for months.

How to stop safely:

• Always taper gradually under medical supervision
• NICE recommends reducing the dose in steps over at least 4 weeks, and sometimes over several months for patients on long-term treatment
• Common taper schedules: 100 mg to 50 mg for 2 to 4 weeks, then 50 mg to 25 mg for 2 to 4 weeks, then stop
• Liquid formulations are available if smaller dose reductions are needed

When to seek advice:

• If withdrawal symptoms are severe or do not improve after 2 weeks
• If you are unsure whether symptoms represent withdrawal or relapse
• If you want to stop sertraline, always discuss this with your prescriber before making any changes