SN2 SHORT NOTE 5M ★ High-yield

Classify antidepressants. Compare SSRIs with tricyclic antidepressants.

Pharmacology · 2nd Professional — Para-Clinical

Classification

Class	Drugs	Mechanism
SSRIs — first-line	Fluoxetine, sertraline, escitalopram, paroxetine, fluvoxamine	Selective serotonin reuptake inhibition
SNRIs	Venlafaxine, duloxetine	Serotonin and noradrenaline reuptake inhibition; duloxetine also for neuropathic pain
Tricyclics	Amitriptyline, imipramine, nortriptyline, clomipramine	Reuptake inhibition plus antimuscarinic, antihistaminic and alpha-blocking actions — hence the side effects and the danger in overdose
MAO inhibitors	Phenelzine, tranylcypromine (irreversible); moclobemide (reversible, MAO-A selective)	Block monoamine breakdown; the cheese reaction with tyramine
Atypical	Mirtazapine (increases appetite and sleep — useful in the wasted or insomniac patient), bupropion, trazodone, vortioxetine	—

Comparison of Ssris and Tricyclics

Feature	SSRIs	Tricyclics
Efficacy	Comparable	Comparable, perhaps better in severe depression
Antimuscarinic effects	Minimal	Marked — dry mouth, blurred vision, constipation, retention
Cardiac	Minimal (some QT effect with citalopram)	Postural hypotension, tachycardia, arrhythmia
Weight	Little change or slight gain	Weight gain
Sedation	Minimal	Marked
Overdose	Relatively safe	Dangerous — sodium channel blockade causes broad QRS, arrhythmia, seizures, coma; treated with sodium bicarbonate. A week’s supply can be lethal, which matters greatly in a suicidal patient
Characteristic effects	Nausea, insomnia, sexual dysfunction, hyponatraemia in the elderly, increased bleeding risk	Sedation, anticholinergic burden

CLINICAL PEARL

The decisive advantage of the SSRIs is not efficacy but safety in overdose. They are no more effective than tricyclics; they are simply far harder to die from — which matters when prescribing to people at risk of suicide. That single consideration, not any superior antidepressant action, is what made them first-line.

Principles of Use

Response takes 2 to 4 weeks, and full benefit 6 to 8 weeks; the patient must be told this clearly, or they will stop when nothing happens in the first week
Continue for at least 6 to 9 months after remission of a first episode, and longer for recurrent depression — stopping early is the commonest cause of relapse
Suicide risk may rise in the first weeks, as energy and initiative recover before mood does; close follow-up is essential in this period, particularly in adolescents
Discontinuation syndrome — dizziness, paraesthesiae, "electric shock" sensations, flu-like symptoms and anxiety; worst with paroxetine and venlafaxine (short half-lives), least with fluoxetine. Taper rather than stop abruptly
Serotonin syndrome if combined with an MAO inhibitor, tramadol, linezolid, triptans or St John wort

Other Uses

Anxiety disorders, panic, obsessive-compulsive disorder (clomipramine and SSRIs), post-traumatic stress disorder
Neuropathic pain — amitriptyline, duloxetine; effective at doses lower than those used for depression
Nocturnal enuresis in children (imipramine); migraine prophylaxis (amitriptyline); chronic fatigue and fibromyalgia
Bupropion for smoking cessation

Applied Aspects

Explain the delay in onset and the need to continue — poor adherence from unmet expectations is the commonest reason treatment appears to fail
Avoid tricyclics where suicide risk is significant, or dispense small quantities; in India, where deliberate self-poisoning is common, this is an important practical consideration
Check sodium in elderly patients on SSRIs, in whom hyponatraemia from SIADH is common and easily missed
Ask about sexual dysfunction directly; it affects a substantial proportion, is rarely volunteered, and is a frequent unreported reason for stopping
Allow a washout before switching to or from an MAO inhibitor — at least 2 weeks, and 5 weeks after fluoxetine
Psychological therapy is at least as effective as medication in mild to moderate depression, and the combination is better than either alone in severe illness

All questions in Central Nervous System Drugs

Every Pharmacology chapter →