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Antidepressants

MHRA Guidance Selective serotonin reuptake inhibitors (SSRIs) and serotonin and noradrenaline reuptake inhibitors (SNRIs): use and safety. Published Dec 2014.

NICE BNF Drugs: Sertraline, Paroxetine

NICE Clinical Guideline [CG192] Antenatal and postnatal mental health: clinical management and service guidance. Last updated: Fed 2020.

NICE BNF Treatment summaries Depression.

NICE CKS Depression – antenatal and postnatal. Last revised: Nov 2023.

NICE CKS Depression. Last revised Feb 2025.

NICE BNF Treatment summaries Antidepressant drugs.

Guidelines

Patient Counselling / Prescription Information

A few important aspects that are important and common in exams:

Onset of Action

Antidepressants generally take up to 4 weeks of initiation for clinically noticeable improvement.

Monitoring and Follow-up

All patients:

  • Review 2-4 weeks after initiation

Patients 18-25 y/o or those at risk of suicide:

  • Review 1 week after initiation or increasing the dose (due to the initial increased risk of suicidal ideation)

Duration of Treatment

Only consider stopping after symptom remission:

  • Continue for at least 6 months after remission (same dose) (~12 months in elderly)
    • If antidepressants are used for anxiety disorders (including GAD) / OCD  → continue at least 12 months (as relapse rates are higher)

The dose should preferably be reduced gradually over 4 weeks, or longer if withdrawal symptoms emerge (6 months in patients who have been on long-term maintenance treatment).

  • ExceptionFluoxetine (can be stopped immediately)

Adverse Effects

Important adverse effects:

  • Increase risk of suicidal ideation in the early weeks of treatment (highest in 18-25 y/0)
  • Risk of withdrawal symptoms if abruptly stopped / doses missed (may occur within 5 days)
    • Paroxetine and venlafaxine have the highest risk
  • Hyponatraemia (especially SSRIs)

The FINISH mnemonic can be used to recall common symptoms of antidepressant withdrawal.

F – Flu-like symptoms

I – Insomnia

N – Nausea (& other symptoms of GI upset: vomiting, diarrhoea, abdominal cramping)

I – Imbalance (& dizziness)

S – Sensory disturbances (‘electric shock’ sensations or tingling)

H – Hyperarousal (irritability, anxiety)

Switching Between Antidepressants

Switching Antidepressants Recommendations [Ref]

Most antidepressants can be switched directly (with no cross-tapering or drug-free period needed):

  • SSRI (caution with fluoxetine – see below) → other SSRI OR SNRI
  • SNRI → SSRI OR other SNRI
  • TCA ↔ other TCA

 

Exceptions / Cautions (to prevent interactions & serotonin syndrome)

  • Fluoxetine → any SSRI/SNRI/TCA
    • Gradually taper down & discontinue fluoxetine → 4-7 days drug-free period → start new antidepressant (from low-dose).
  • SSRI/SNRI ↔ TCA
    • Cross-taper: taper the initial antidepressant down whilst simultaneously starting a low dose of the new antidepressant (slowly uptitrated); works vice-versa
    • No need for a drug-free period
    • Further detail: fluvoxamine/paroxetine, clomipramine 
  • SSRI/SNRI/TCA ↔ irreversible MOA inhibitors
    • Gradually taper down & discontinue initial antidepressant → ≥ 2 weeks drug-free period (5 weeks after fluoxetine) → then start new antidepressant; works vice-versa

Pregnancy and Breastfeeding

Pregnancy

SSRIs and SNRIs can cross the placenta and have a potential effect on the fetus.

Choice of antidepressant in pregnancy: SSRIs (have the most safety data in pregnancy)

  • If patient plans to breastfeed, sertraline and paroxetine might be preferred
  • If patient is already stable on current treatment, that is not an SSRI, risk of destabilisation must be taken into account (i.e., factoring the potential risk of exacerbation of the psychiatric disorder)

Recognised risks outlined by MHRA and NICE CKS:

  • Persistent pulmonary hypertension in the newborn (PPHN)
  • Neonatal withdrawal and serotonergic effects 
  • Postpartum haemorrhage (if used in the month before delivery)
  • Some studies show an association between SSRI use in pregnancy and an increased risk of miscarriage

No antidepressant has been consistently proven to cause birth defects. NICE CKS says that although some have been associated with a specific increased risk of adverse pregnancy outcomes, the absolute risk of fetal harm is low.

Breastfeeding

Sertraline and paroxetine are generally the SSRIs of choice for treatment initiated in breastfeeding women.

References






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