What is the recommended tapering schedule for an adult patient with a history of depression or anxiety taking Zoloft (sertraline) 25 mg to discontinue the medication?

How to Wean from Zoloft 25 mg

For an adult discontinuing Zoloft (sertraline) 25 mg, use a slow hyperbolic taper over several months, reducing by approximately 10% of the current dose every 2-4 weeks, reaching doses far below the standard 25 mg minimum before complete cessation. 1, 2

Why Slow Tapering is Critical

• Abrupt discontinuation or rapid tapers (≤4 weeks) significantly increase relapse risk compared to slow tapering (>4 weeks), with relapse rates approximately doubled 2
• Standard guideline recommendations of 2-4 week tapers down to therapeutic minimum doses show minimal benefit over abrupt discontinuation and are often poorly tolerated 1
• Withdrawal symptoms from SSRIs like sertraline can be severe and are frequently mistaken for relapse, leading to unnecessary resumption of medication 3, 1

Recommended Tapering Schedule for Sertraline 25 mg

Since you're already at a low dose (25 mg is the minimum therapeutic dose), you need an extended taper with very small reductions:

Weeks 1-2: Reduce to 22.5 mg daily

• This represents a 10% reduction from current dose 2
• Monitor for withdrawal symptoms: dizziness, nausea, fatigue, anxiety, irritability, sensory disturbances 3

Weeks 3-4: Reduce to 20 mg daily

• Another 10% reduction of the 22.5 mg dose 2

Weeks 5-6: Reduce to 18 mg daily

• Continue 10% reductions of current dose 2

Weeks 7-8: Reduce to 16 mg daily

Weeks 9-10: Reduce to 14 mg daily

Weeks 11-12: Reduce to 12.5 mg daily

Continue this pattern, reducing by 10% of the current dose every 2 weeks until reaching very small doses (2-3 mg) before complete cessation 1, 2

Total expected duration: 3-6 months minimum 1, 2

Why Hyperbolic (Not Linear) Tapering

• PET imaging data shows that SSRI effects on serotonin transporters follow a hyperbolic curve, meaning equal dose reductions have increasingly larger biological effects at lower doses 1
• Reducing from 50 mg to 25 mg has far less biological impact than reducing from 25 mg to 12.5 mg, even though both are 25 mg reductions 1
• This explains why standard tapers fail—they create disproportionately large biological changes at the end of the taper 1

Practical Implementation

Since sertraline is not available in liquid form or doses below 25 mg tablets:

• Use a pill cutter for precise splitting of 25 mg tablets
• For doses below 12.5 mg, you may need to alternate doses (e.g., for 10 mg average, take 12.5 mg one day and 7.5 mg the next)
• Some patients dissolve tablets in water for more precise dosing, though this is off-label 1

Adding Psychological Support Dramatically Improves Success

Slow tapering combined with cognitive behavioral therapy (CBT) is as effective as continuing the antidepressant for preventing relapse (relapse risk ratio 0.52 vs abrupt discontinuation) and superior to tapering alone 2

• CBT during tapering increases successful discontinuation rates to 40-75% 4
• Even minimal psychological support (counseling, support groups) improves outcomes 5
• Without psychological support, slow tapering alone shows uncertain benefit (low certainty evidence) 2

Monitoring and Managing Withdrawal Symptoms

Common SSRI withdrawal symptoms include: 3

• Somatic: Dizziness, light-headedness, nausea, fatigue, myalgia, flu-like symptoms, sensory disturbances, sleep problems
• Psychological: Anxiety, agitation, crying spells, irritability

If withdrawal symptoms emerge:

• Pause the taper at the current dose for 1-2 weeks until symptoms resolve 2
• If symptoms are severe, return to the previous dose and slow the taper rate further 3
• Reassure that symptoms are typically transient and self-limiting 3

Critical Pitfalls to Avoid

• Never taper by fixed amounts (e.g., reducing by 5 mg every week)—this creates disproportionately large biological effects at lower doses 1
• Do not confuse withdrawal symptoms with depression relapse—withdrawal typically includes physical symptoms (dizziness, nausea) that depression does not 3, 1
• Avoid tapering faster than 10% of current dose every 2 weeks, as faster tapers show minimal benefit over abrupt discontinuation 1, 2
• Do not assume that because 25 mg is a "low dose" that discontinuation will be easy—the biological impact of stopping from 25 mg can be substantial 1

When to Seek Specialist Help

Consider psychiatric consultation if: 4

• Severe withdrawal symptoms emerge despite slow tapering
• Clear signs of depression relapse occur (persistent low mood for >2 weeks, loss of interest, suicidal thoughts)
• Previous unsuccessful tapering attempts
• Co-occurring substance use disorders or unstable psychiatric conditions

Expected Timeline and Outcomes

• Minimum tapering duration: 3-6 months from 25 mg to zero 1, 2
• Successful discontinuation rates with slow taper plus psychological support: 40-75% 2
• Improved cognitive and psychomotor functioning typically follows successful withdrawal 5
• Most withdrawal symptoms resolve within days to weeks after stabilizing at a given dose 3

Alternative: Dose Reduction Instead of Complete Cessation

If complete discontinuation proves difficult, maintaining at 50% of the minimal effective dose (approximately 12.5 mg) reduces relapse risk compared to abrupt stopping (RR 0.62) while avoiding full-dose continuation 2

6, 7, 8, 3, 1, 2