Antidepressant Weaning & Cross-Tapering

Blocks serotonin reuptake in the presynaptic neuron, increasing synaptic serotonin availability. First-line agents for most depression and anxiety.

Examples: Sertraline, Paroxetine, Fluoxetine, Citalopram, Escitalopram.

Withdrawal risk: Moderate (paroxetine higher). Can cause discontinuation syndrome within 1-7 days if stopped abruptly.

Notes: Generally well-tolerated. Half-lives vary (fluoxetine ~48 h; others ~20-30 h).

Blocks reuptake of both serotonin and noradrenaline, increasing both neurotransmitters. Used for depression, anxiety, and chronic pain.

Examples: Venlafaxine, Duloxetine.

Withdrawal risk: High (especially venlafaxine). Discontinuation syndrome can be severe and prolonged (dizziness, paraesthesia, flu-like symptoms).

Notes: Dose-dependent; noradrenergic effects emerge at higher doses. Requires slower tapering than SSRIs.

Blocks α₂-adrenergic autoreceptors and antagonises 5-HT₂ and 5-HT₃ receptors. Enhances both noradrenaline and serotonin signalling via receptor antagonism.

Examples: Mirtazapine.

Withdrawal risk: Low to moderate. Generally well-tolerated discontinuation.

Notes: Sedating (especially at lower doses); activating at higher doses. Weight gain and metabolic effects common.

Blocks reuptake of serotonin and noradrenaline non-selectively; anticholinergic and antihistamine effects at therapeutic doses. Older agents, less commonly used for depression but still used for neuropathic pain and migraine.

Examples: Amitriptyline, Nortriptyline.

Withdrawal risk: Moderate. Anticholinergic rebound (sweating, palpitations, agitation) possible.

Notes: Narrow therapeutic index; cardiac conduction effects at high doses. Requires baseline ECG.