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← Psychiatry indexChapter sections
Purpose and principlesIndications, selection and cautionsAssessment before treatmentTreatment approachRegimens, contraindications and interactionsComplications, monitoring and follow-upSpecial situationsCommon pitfallsQuestionsSources
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Educational draft · awaiting clinical reviewThe full textbook explains uncertainty but does not replace live national or local guidance, specialist advice, or current prescribing information.

SSRI, SNRI and other antidepressant adverse effects

Psychiatry · UK scope · Sources checked 7 Sept 2026 · Clinical review pending

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Toxicity needs immediate assessment

Clonus with fever and agitation, syncope with palpitations, seizure, major bleeding, severe confusion or emergent suicidal intent can represent serious antidepressant harm.

Action: Arrange emergency assessment for physiological instability or immediate self-harm risk; stop suspected serotonergic agents in serotonin toxicity, obtain ECG and electrolytes when indicated, and involve acute medicine and psychiatry.

Purpose and principles

Identify antidepressant adverse effects early, separate tolerable adjustment symptoms from time-critical toxicity, and adapt prescribing without overlooking depression, withdrawal, interactions or the person's treatment priorities.

Adverse-effect assessment starts with a timeline: the pretreatment symptom, medicine and formulation, dose changes, actual doses taken, and new prescribed or non-prescribed substances. Depression itself may cause insomnia, low libido, appetite change and impaired concentration. A symptom beginning after treatment increases suspicion of an adverse effect, but temporal association alone does not establish causation. Ask what the person finds most intrusive and how it affects work, driving, relationships and willingness to continue.

Serotonergic effects commonly produce nausea, diarrhoea, sweating, headache and altered sleep during initiation. Mild symptoms may improve with time, whereas persistent sexual dysfunction or emotional blunting deserves an active discussion. Avoid presenting all adverse effects as transient. Activation may manifest as anxiety or restlessness; reduced need for sleep, expansive mood, disinhibition or grandiosity suggests a manic switch and changes the diagnostic and treatment plan.

Indications, selection and cautions

Activation and suicidality

Explore new pacing, panic, inability to remain still, impulsivity and suicidal thoughts directly, including access to medicines and immediate safety.

Bleeding signal

Ask about melaena, haematemesis, bruising and concurrent ibuprofen, aspirin or anticoagulation; normal routine coagulation tests do not exclude platelet-mediated bleeding.

Hyponatraemic illness

Headache, nausea, confusion and unsteadiness can progress to seizure; risk rises with older age, diuretics and previous low sodium.

Sexual and functional burden

Distinguish loss of desire, delayed orgasm, erectile difficulty and reduced genital sensation from relationship stress and persisting depressive symptoms.

Red flags requiring action

  • New agitation with inducible or spontaneous clonus, hyperreflexia and autonomic disturbance after a serotonergic addition requires urgent assessment for serotonin syndrome.
  • Confusion, falls or seizure after initiation, particularly with a thiazide or in an older adult, warrants urgent sodium measurement.
  • Jaundice, dark urine or sustained unexplained fatigue during agomelatine treatment requires immediate cessation and liver assessment.

Assessment before treatment

  1. 01
    Medication reconciliationFirst step
    Why
    Identify pharmacological contributors and the chronology of new symptoms.
    Interpretation and limitations
    Include over-the-counter analgesics, St John's wort, tramadol, recreational drugs and missed doses; several modest risks can combine into a serious interaction.
  2. 02
    Blood pressure and pulse
    Why
    Assess noradrenergic stimulation and postural symptoms in context.
    Interpretation and limitations
    Repeated sustained elevation on venlafaxine warrants dose and treatment review; severe headache, chest pain or neurological signs require an urgent pathway.
  3. 03
    Sodium, renal function and electrolytes
    Why
    Investigate confusion, seizure, falls or susceptibility to arrhythmia.
    Interpretation and limitations
    Acute symptomatic hyponatraemia needs hospital management and assessment of drug contribution; potassium and magnesium deficiencies amplify QT risk.
  4. 04
    ECG with QT assessment
    Why
    Investigate palpitations, syncope or relevant cardiac and interaction risks.
    Interpretation and limitations
    For citalopram or escitalopram, QTc above 500 milliseconds requires gradual withdrawal and clinical risk management; 480–500 milliseconds requires benefit-risk review with dose reduction or withdrawal considered.
  5. 05

Treatment approach

01TolerabilityManage non-urgent adverse effectsFirst stepSymptoms are troublesome but there are no physiological or psychiatric emergency features.+
  1. 1Check onset, severity, benefit so far and the patient's priorities before changing the prescription.
  2. 2Discuss a practical timing adjustment, slower titration or dose review appropriate to the actual medicine.
  3. 3Agree when to reassess and consider a planned switch if the burden persists despite an adequate management attempt.
02EscalationInvestigate serious suspected toxicityEscalationNeuromuscular excitation, syncope, seizure, major bleeding or marked confusion develops.+
  1. 1Assess ABCDE, observations and immediate safety while identifying all recently added serotonergic or QT-prolonging medicines.
  2. 2

Regimens, contraindications and interactions

An SSRI option whose dose should reflect response and tolerability rather than automatic escalation.

Sertraline for adult depression

A licensed starting regimen is 50 mg orally once daily; if needed increase by 50 mg at intervals of at least one week, to a maximum 200 mg daily.

Use lower or less frequent dosing in hepatic impairment; avoid severe hepatic impairment, contraindicated MAOI combinations and unexamined serotonergic interactions.

A distinct antidepressant option requiring a reliable liver-monitoring arrangement throughout treatment.

Agomelatine for major depression

Give 25 mg orally at bedtime; after two weeks consider 50 mg nightly if symptoms have not improved and the benefit-risk assessment supports escalation.

Contraindicated in hepatic impairment and with potent CYP1A2 inhibitors such as fluvoxamine or ciprofloxacin; do not use at age 75 or over.

Complications, monitoring and follow-up

  • At early review record mood, suicidality, activation, adherence and the specific adverse effects discussed at baseline, then set the next appointment according to risk.
  • Measure venlafaxine blood pressure periodically and after dose increases; reassess cardiovascular risk rather than assuming a single baseline result remains sufficient.
  • For agomelatine test liver function at approximately 3, 6, 12 and 24 weeks, restarting that schedule after a dose increase and testing thereafter when indicated.
  • If new agomelatine transaminase elevation appears, repeat liver tests within forty-eight hours; after discontinuation for liver injury, follow tests until they return to normal.
  • Track weight, sleep, falls and anticholinergic burden when the selected antidepressant makes these outcomes clinically relevant.

Special situations

A normal platelet count

Serotonergic bleeding relates partly to platelet function, so a normal count does not invalidate a convincing gastrointestinal bleeding history.

Withdrawal mimics intolerance

Short half-life medicines can cause dizziness and electric-shock sensations after missed doses, even while the prescription appears unchanged.

Suicide risk and supply

The toxicity of the medicine in overdose and the amount supplied should be discussed when planning treatment for someone at increased self-harm risk.

Persistent sexual symptoms

Sexual dysfunction can occasionally persist after SSRI or SNRI discontinuation; acknowledge the report, investigate other causes and arrange follow-up rather than promising immediate resolution.

Common pitfalls

  1. 01

    Increasing the antidepressant dose to treat medication-induced akathisia without first reassessing the source of distress.

  2. 02

    Combining a serotonergic antidepressant with tramadol or a herbal serotonergic product without considering toxicity.

  3. 03

    Continuing agomelatine despite jaundice while waiting for a routine scheduled blood test.

  4. 04

    Stopping a tolerated effective antidepressant abruptly for a manageable symptom without discussing withdrawal and relapse.

  5. 05

    Assuming an older person with confusion has worsening depression before checking sodium and other causes of delirium.

Practice

Two practice questions

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PsychiatryOriginal SBA

Falls after initiation

A 79-year-old taking bendroflumethiazide becomes confused and unsteady twelve days after starting sertraline. There is no focal neurological deficit. Which investigation is most directly relevant to the suspected medicine complication?

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Sources and review status5 sources · checked 7 Sept 2026 · clinical review pending+
Sources

Sources and review status

National guidance is shown before implementation-dependent detail. Typical adult dose examples remain subject to patient factors, contraindications and the live BNF or specialist protocol. Source check completed 7 Sept 2026; clinical approval remains outstanding.

  • NICE NG222 depression recommendationsEarly review, antidepressant selection and withdrawal.
  • Sertraline 50 mg tablets SmPCLicensed dosing, sodium, bleeding and serotonin toxicity.
  • Venlafaxine XL 75 mg SmPCBlood pressure and dose-related adverse effects.
  • MHRA citalopram and escitalopram QT warningDose restrictions, contraindications and QTc action thresholds.
  • Valdoxan 25 mg SmPCAgomelatine dosing, contraindications and liver monitoring.

Editorial contact: Doctor’s Passport editorial team. Source-check date is separate from clinical approval. Report a content problem · Content changes

Authoring stateComplete draftClinical stateAwaiting reviewJurisdictionUnited Kingdom
Class labels are useful starting points but conceal important differences. Noradrenergic activity can raise pulse and blood pressure. Histamine blockade contributes to sedation and appetite increase. Muscarinic blockade may cause dry mouth, constipation, urinary retention and blurred vision. Cardiac conduction effects matter particularly in overdose and with interacting medicines. Selective serotonin reuptake inhibition also affects platelet serotonin uptake, explaining why bleeding risk is not limited to people with abnormal platelet counts.

The objective is to preserve effective depression treatment while reducing harm. Options include explanation and practical adjustment, a slower titration, dose reduction when clinically appropriate, changing the medicine, or treating a separate medical cause. An abrupt stop can add withdrawal symptoms and obscure the original problem. Serious toxicity is an exception: immediate withdrawal of the causative medicine and urgent treatment take priority. Document the alternative depression plan and who will review deterioration.

Key points

  • Ask about nausea, bowel change, sleep, sweating, sexual function and agitation before attributing poor adherence to lack of motivation.
  • SSRIs can impair platelet aggregation; NSAIDs, antiplatelets and anticoagulants increase the clinical importance of gastrointestinal bleeding risk.
  • Citalopram and escitalopram have dose-related QT risk; contraindicated combinations and electrolyte abnormalities must be checked explicitly.
  • Venlafaxine can raise blood pressure and produces troublesome withdrawal when doses are missed; check pressure before treatment and after increases.
  • Mirtazapine often increases appetite and sedation, whereas tricyclic medicines add anticholinergic, postural and overdose hazards.
  • Agomelatine requires baseline and scheduled liver testing, including renewed testing after dose escalation.
  • Review after one week when starting an antidepressant in people aged 18–25 or when suicide risk is a particular concern; otherwise the first review is usually within two weeks.
Agomelatine liver tests
Why
Detect hepatocellular injury before and during exposure.
Interpretation and limitations
Do not start with transaminases above three times the upper limit of normal; stop if this threshold is exceeded or liver-injury symptoms develop.
Obtain targeted ECG and blood investigations and arrange emergency transfer when toxicity or serious instability is suspected.
  • 3Communicate the withheld medicines and subsequent psychiatric follow-up plan so treatment is not inadvertently restarted without review.
    • 03Treatment changeBalance benefit against continuing harmPersistent adverse effects undermine adherence or outweigh the antidepressant's benefit.+
    1. 1Reassess diagnosis, response, relapse history and whether a separate physical or sexual-health disorder explains symptoms.
    2. 2Choose a medicine with a more acceptable adverse-effect profile and check its specific switching requirements.
    3. 3Write a taper or washout schedule with early review, recognising that a direct switch is appropriate only for specified medicine pairs.