Antidepressants

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

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)

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)Generalised anxiety disorder/ OCDObsessive-compulsive disorder  → 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).

• Exception → Fluoxetine

  Can be stopped abruptly without causing significant withdrawal symptoms or discontinuation syndrome, due to its long half-life and active metabolite, which provide a self-tapering effect and minimize the risk of withdrawal phenomena (lowest risk among SSRIs and SNRIs).

   (can be stopped immediately)

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)

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)

• FluoxetineFluoxetine has a long half-life and inhibits CYP2D6, which results in risk of interaction or serotonin syndrome if there is a direct switch. → 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

    fluvoxamine/paroxetine (potent CYP inhibitors with higher risk of interaction) are exceptions in the SSRI => TCA conversion. It is not advised for them to be cross tapered with a TCA. Instead taper and stop first → 4–7-day drug-free period → then start low-dose TCA.

    , clomipramineClomipramine is a potent inhibitor of serotonin reuptake, and serotonin syndrome is more likely if co-administered with an SSRI or SNRI - cross-tapering is not recommended except under specialist supervision.

• SSRI/SNRI/TCA ↔ irreversible MOA inhibitorsPhenelzine, Tranylcypromine, Isocarboxazid
  • Gradually taper down & discontinue initial antidepressant → ≥ 2 weeks drug-free period (5 weeks after fluoxetine) → then start new antidepressant; works vice-versa

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)
  • Background risk: 1-2 per 1,000 pregnancies
  • Risk with maternal SSRI use: 5 per 1,000 pregnancies
• Neonatal withdrawal and serotonergic effects

  May occur if SSRIs / SNRIs are used until or shortly before birth:

  • Difficulty in sucking / sleeping 
  • Irritablity
  • Tremor
  • Muscle weakness
  • Persistent crying
   
• 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

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