A closer look · For clinicians
Prescribing, safety and the science.
Considerations before treatment, adverse effects, urgent red flags, mechanism and evidence.
01Clinician note
Before prescribing: indications and contraindications
Inspected Australian Lexapro PI (sponsor revision 23 August 2023) indications: major depression, generalised anxiety disorder (GAD), social anxiety disorder and OCD (OCD is outside this guide). Panic disorder is off-label in Australia despite RCT evidence and UK licensing: document the rationale and shared decision. Depression-associated anxiety is not interchangeable with a separate anxiety-disorder diagnosis. Confirm the dispensed brand's current PI.
Australian contraindications: hypersensitivity to escitalopram, citalopram or excipients; coadministration with an MAOI or within the prohibited washout; pimozide. Washout: 14 days after an irreversible MAOI and at least one day after moclobemide before starting; at least 14 days after stopping escitalopram before an MAOI/RIMA. Linezolid is an MAOI and is not an ordinary co-prescription. QT prolongation is described in the Australian warnings without a separate QT-specific entry in §4.3; do not import overseas contraindication lists.
Establish diagnosis, severity, functional goals, previous response, preference, psychotherapy access and risk. NICE NG222 advises against routinely offering antidepressants first line for less severe depression unless the patient prefers this; that is UK decision support, not an Australian regulatory restriction.
02Clinician note
Cautions, baseline assessment and monitoring
Baseline: assess suicidal ideation/intent, previous mania/hypomania or bipolarity, seizures, bleeding history, narrow-angle glaucoma risk, cardiac disease/bradycardia, renal/hepatic function and pregnancy/lactation plans. Review prescription, OTC and herbal medicines and record baseline sexual function. Consider baseline sodium in at-risk patients (older adults, diuretics, volume depletion) and ECG/electrolytes when cardiac/QT risks are present; these are risk-directed, not universal label-mandated tests.
Dosing: 10 mg once daily, increasing to 20 mg/day by response and tolerability. Over 65 years: maximum maintenance 10 mg/day; a lower starting dose for frailty is clinical judgement, not a fixed §4.2 rule. Hepatic impairment or known CYP2C19 poor metaboliser: 5 mg/day for two weeks, then consider 10 mg/day. No routine adjustment in mild/moderate renal impairment; caution if CrCl <30 mL/min.
Pregnancy: Australian category C (not a safety ranking). Weigh untreated illness against neonatal adaptation/withdrawal, PPHN association and postpartum haemorrhage, especially with late-pregnancy exposure. Excreted in breast milk; individualise maternal/infant assessment. Avoid abrupt cessation when pregnancy is recognised.
Monitoring: early review of mood, suicide risk and activation (NICE: one week for ages 18–25 or suicide concern; generally within two weeks otherwise), then symptoms, function, adherence and adverse effects, after each dose change and during taper. Repeat sodium when indicated; monitor glucose in diabetes, bleeding, falls, sexual function and cardiac symptoms. Improved questionnaire scores do not remove suicide risk.
03Clinician note
Interactions and switching
Serotonergic drugs, including tramadol and certain other opioids, triptans, lithium and St John's wort, increase serotonin-toxicity risk. NSAIDs, aspirin and anticoagulants increase bleeding risk. Other QT-prolonging medicines compound arrhythmic risk.
CYP2C19 inhibitors, including esomeprazole/omeprazole, fluconazole and fluvoxamine, can raise escitalopram exposure: review dose and ECG risk rather than automatically combining maximal doses. Escitalopram also affects some CYP2D6 substrates.
MAOIs/RIMA (including moclobemide and linezolid) and pimozide are contraindicated as above. Complex switches need medicine-specific advice; washout rules differ between SSRIs (Zoloft, for example, specifies 14 days in each direction around an MAOI). Counsel about alcohol and avoiding driving when dizzy, drowsy or visually impaired.
04Clinician note
Adverse effects: technical overview
Adult placebo-controlled pools (historical US label, Tables 2–3) show nausea, insomnia, somnolence, diarrhoea, fatigue, dry mouth and decreased libido. MDD (n=715) and GAD (n=429) pools are separate; do not merge them or apply them to panic or social anxiety. Sex-specific events use sex-specific denominators: ejaculatory disorder MDD 9% vs <1% (225/188 men), GAD 14% vs 2% (182/195 men); anorgasmia MDD 2% vs <1% (490/404 women), GAD 6% vs <1% (247/232 women). Sexual dysfunction is under-reported; ask directly. Early GI effects, sleep disturbance and activation warrant review of timing, food and titration; persistent or severe effects warrant reassessment.
Persistent sexual dysfunction after cessation is recognised by the TGA (May 2024); prevalence is unknown. Serotonin syndrome, SIADH/hyponatraemia, QT prolongation/arrhythmia, abnormal bleeding, mania, seizures, angle-closure glaucoma and severe hypersensitivity are communicated qualitatively here; no rates are given, and reports do not establish causation in an individual.
Discontinuation symptoms (dizziness, electric-shock sensations, anxiety, insomnia, flu-like or GI symptoms) may mimic relapse. The older PI one-to-two-week minimum is not a universal safe taper: NICE supports symptom-led stepwise reductions, smaller decrements at lower doses, over weeks or months. Severe withdrawal may warrant reinstating the last tolerated dose and tapering more slowly.
05Clinician note
Urgent red flags and clinical action
Suicidality, severe activation/akathisia or mania: urgent risk assessment and safety plan. Imminent intent, inability to remain safe, psychosis or dangerous mania warrants emergency mental-health care (000 if in immediate danger). Akathisia is a treatment complication; do not reflexively increase the dose.
Serotonin toxicity: rapidly evolving agitation or confusion, hyperreflexia/clonus, tremor, diaphoresis, fever and autonomic instability, especially after an interacting drug or escalation. Stop implicated serotonergic drugs and arrange urgent emergency assessment and supportive management.
Symptomatic hyponatraemia/SIADH: new confusion, marked weakness, unsteadiness or seizures. Assess sodium urgently and withhold/reassess escitalopram; seizure or reduced consciousness is an emergency.
Arrhythmia/QT concern: syncope, sustained palpitations or seizure-like collapse requires ECG and electrolyte assessment and urgent escalation. Major GI bleeding, anaphylaxis, an acute painful red eye or visual loss, or a new seizure also require urgent assessment.
06Clinician note
Serotonin transporter inhibition
Escitalopram is the S-enantiomer of citalopram and a selective serotonin reuptake inhibitor. It inhibits the serotonin transporter (SERT), reducing presynaptic reuptake and increasing serotonergic neurotransmission.
Transporter inhibition occurs before clinical response, which develops over weeks. This time course does not establish that depression or anxiety is caused by a proven serotonin deficiency; patient explanations should avoid a simple “chemical imbalance” claim and should not promise immediate relief.
07Clinician note
Read the outcomes in context
MDD: Burke et al. (2002) randomised 491 outpatients to escitalopram 10 mg, 20 mg, citalopram 40 mg or placebo for eight weeks; escitalopram improved validated depression scores versus placebo. Do not extrapolate a universal responder rate or assume 20 mg is needed for everyone.
GAD: Bose et al. (2008) randomised escitalopram 10–20 mg/day (n=127), venlafaxine XR (n=129) and placebo (n=136) over eight weeks, supporting symptom improvement. Social anxiety: Kasper et al. (2005) supports symptom and functional improvement over 12 weeks; exact response estimates were not extracted. Panic disorder (off-label in Australia): Stahl et al. (2003) provides ten-week RCT evidence.
These selected short trials were inspected mainly as abstracts or indexed reports. They do not resolve comparative superiority, long-term individual prognosis or treatment-resistant disease. Continuation after depression remission is commonly at least six months, adjusted for recurrence risk; anxiety maintenance is indication- and response-specific.
08Clinician note
How it compares with sertraline
Both are approved in Australia for MDD, but anxiety approvals differ. Inspected Lexapro: GAD and social anxiety approved; panic disorder off-label. Inspected Zoloft: panic and social anxiety (including relapse prevention) approved; GAD off-label. Escitalopram starts at 10 mg daily (maximum 20 mg/day; 10 mg/day maintenance maximum over 65 years). Sertraline starts at 50 mg for MDD, or 25 mg for one week for panic/social anxiety, up to 200 mg/day, with no fixed age-only lower maximum.
Distinctive considerations: escitalopram has a specified hepatic regimen and CYP2C19-inhibitor interactions (e.g. esomeprazole/omeprazole); sertraline needs review of CYP2D6 substrates, phenytoin and warfarin. MAOI washout rules and CMI missed-dose wording differ.
These are not head-to-head rankings. No verified head-to-head superiority finding was identified, and separate trial side-effect pools should not be compared as a safety league table. Choose by diagnosis, past response, preference, comorbidity, interactions and tolerability, with psychotherapy considered.
09Clinician note
Labelling, overseas guidance and uncertainty
The inspected Australian PI is the sponsor revision of 23 August 2023 (displayed MIMS revision 1 October 2023); no later revision was verified and the TGA ARTG copy was not accessible. Recheck the current PI/CMI for the dispensed brand. The side-effect figures come from historical US label trial pools, not the Australian PI: they are rounded reported events, without one stated trial duration, and are not attributable risk.
UK NICE guidance (NG222, CG113) informs review intervals, continuation and tapering, but is not Australian labelling; UK panic-disorder licensing does not transfer to Australia. Persistent sexual dysfunction appears in Australian labelling and the 2024 TGA update, with unknown prevalence. The PI and oral-solution CMI differ on mixing the solution with other liquids; check before counselling.