Key Facts

Antidepressant prescribing is one of the most common prescribing decisions in UK medicine. Approximately 8.3 million adults received an antidepressant prescription in England in 2022-23.

Epidemiology

Antidepressant prescribing has approximately doubled over the last decade. SSRIs account for ~60% of prescriptions. There is ongoing debate about overprescribing vs undertreatment.

Aetiology

Antidepressants work by modulating monoamine neurotransmission (serotonin, noradrenaline, dopamine). The 2-4 week delay in clinical effect suggests downstream neuroplastic changes (BDNF, neurogenesis) are the actual mechanism of action rather than immediate reuptake inhibition.

Pathophysiology

See Psychopharmacology for detailed mechanisms.

Indications

• Moderate-severe depression (NICE NG222)
• Anxiety disorders (GAD, panic, social anxiety, PTSD, OCD)
• Neuropathic pain (amitriptyline, duloxetine)
• Migraine prophylaxis (amitriptyline)
• Premature ejaculation (dapoxetine — short-acting SSRI)
• Nocturnal enuresis (imipramine — rarely used)

Starting Treatment

• Discuss risks, benefits, and alternatives — shared decision-making
• Start at recommended starting dose (not low dose unless elderly/anxious)
• Warn about initial worsening of anxiety/agitation (first 1-2 weeks)
• MHRA: Monitor for suicidality in under-25s in first weeks
• Follow-up at 2 weeks, then 4 weeks to assess tolerance and early response

Red Flags

• Suicidal ideation in first 2-4 weeks of treatment — especially in young adults
• Hyponatraemia (elderly on SSRIs) — confusion, seizures
• QTc prolongation (citalopram, escitalopram, TCAs)
• Serotonin syndrome — medical emergency
• Prescribing TCAs to patients with suicide risk — toxic in overdose

| Scenario | Action | |---|---|---| | No response after 4-6 weeks at adequate dose | Increase dose or switch | | Partial response | Increase to maximum tolerated dose | | Intolerable side effects | Switch to alternative within or between classes | | Treatment-resistant (failed 2 adequate trials) | Augmentation (lithium, quetiapine, aripiprazole) or specialist referral | | Bipolar depression suspected | Avoid SSRI monotherapy — mood stabiliser needed |

Baseline

• PHQ-9: Severity and monitoring
• FBC, U&Es, LFTs, TFTs: Baseline
• ECG: If prescribing citalopram (>20mg), TCAs, or patient has cardiac risk factors
• Pregnancy test: If relevant (discuss teratogenicity)

Ongoing

• U&Es: Check Na⁺ within 4 weeks (hyponatraemia risk, especially elderly)
• PHQ-9: Repeat at 4-6 weeks and regularly thereafter
• Side effect monitoring: Sexual dysfunction, GI symptoms, sleep, weight
• ECG: If dose-related QTc concern

Choosing an Antidepressant (NICE NG222)

• First-line: SSRI — sertraline 50mg OD (most evidence, safe in cardiac disease)
• Alternatives: Fluoxetine 20mg, citalopram 20mg, escitalopram 10mg
• If SSRI not tolerated/ineffective: Mirtazapine 15-45mg ON, venlafaxine 75-225mg, duloxetine 60-120mg
• If insomnia/appetite loss prominent: Mirtazapine
• If pain component: Duloxetine or amitriptyline
• In pregnancy: Sertraline (most data for safety)
• In elderly: Start low (half starting dose), check Na⁺, avoid TCAs (falls, anticholinergic burden)

Duration

• Continue for ≥6 months after remission (first episode)
• ≥2 years if ≥2 previous episodes
• Consider indefinite treatment if ≥3 episodes or severe episodes

Discontinuation

• Taper over ≥4 weeks (longer if on treatment >6 months or high dose)
• Fluoxetine may need less gradual taper (long half-life)
• Paroxetine and venlafaxine have highest discontinuation symptom rates
• If symptoms return during taper — restart at previous effective dose

Referral Criteria

• Failed 2 adequate antidepressant trials — specialist referral
• Bipolar depression suspected — psychiatry
• Pregnancy or planned pregnancy — specialist advice
• Severe side effects or drug interactions — specialist/pharmacy

• NNT for antidepressants in moderate-severe depression: ~7
• ~50% respond to first antidepressant trial; ~70% respond by second trial
• Combined antidepressant + psychological therapy is most effective for moderate-severe depression
• Long-term antidepressant use significantly reduces relapse (NNT ~4 for prevention over 12 months)
• Discontinuation symptoms are common but self-limiting (usually resolve within 1-2 weeks with slow taper)

SSRI Comparison

Serotonin Syndrome vs NMS