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Overview of Antidepressants
- 1. Antidepressants Antidepressants can take between 10-20 days to begin making an effect. After symptoms have improved they should be continued for at least 6 months at the same dose. 1. Serotonin-selective reuptake inhibitors (SSRIs) 2. Tricyclics (TCAs) 3. Monoamine oxidase inhibitors (MAOIs) 4. Other SSRIs E.g. Fluoxetine, paroxetine & sertraline 1st line Treatment Safer in overdose than other antidepressants Mechanism: Block serotonin (5-HT) reuptake at pre-synaptic membranes Resulting in increased synaptic 5-HT Pharmokinetics: Well absorbed orally ½ life varies between 15-24 hrs Fluoxetine ½ life – 24-96 hrs Paroxetine & Fluoxetine increase TCA toxicity don’t use in combination Side Effects: Dry mouth Nausea Vomiting & diarrhoea Dizziness Sedation Sexual dysfunction Agitation Akathisia Parkinsonism & convulsions (both rare)
- 2. TCAs E.g. Imipramine, clomipramine & amitriptyline Possibly better than SSRIs in severe depression, however are much more toxic in overdose! Mechanism They block the reuptake of 2 things: 1. 5-HT (clomipramine more 5-HT selective) 2. Noradrenaline (lofepramine more selective) Pharmokinetics Rapidly absorbed orally – 90% bound to albumin Metabolized in the Liver Side Effects Anticholinergic dry mouth, blurred vision, constipation & urinary retention (strong with amitriptyline) Postural hypotension & sedation due to being an adrenergic α receptor antagonist Weight ↑ & sexual dysfunction 5HT blockade Day time drowsiness & difficulty concentrating Caution in patients with: Close angle glaucoma Prostatism Epilepsy Hepatic Impairment Cardiac disease SSRI Discontinuation Syndrome Occurs most frequently if paroxetine is suddenly stopped. Symptoms include: Headache Dizziness Shock-like sensations Paraesthesia GI symptoms Lethargy Insomnia Changes in mood Serotonin Syndrome Rare Potentially fatal Due to increased 5-HT activity Symptoms: Psychological – agitation, confusion Neuro – nystagmus, myoclonus, tremor, seizures Other – hyperpyrexia, autonomic instability
- 3. MAOIs E.g. Phenelzine & isocarboxacid Not widely used only in resistant depression or atypical depression Mechanism Increase 5HT & Noradrenaline due to blocking there metabolism. Side Effects Anticholinergic (see above) Weight-gain Insomnia Postural hypotension Tremor Limb parasthesia Peripheral oedema Useful things to remember: 1. In pregnancy fluoxetine or the TCAs, nortriptyline, amitriptyline & imipramine 2. If breast-feeding SSRIs either paroxetine or sertraline 3. If a chronic health problem is present citalopram or sertraline as they cause fewer interactions 4. In children fluoxetine (after psychological input e.g. CBT) Tyramine Reaction Causes: Foods containing tyramine e.g. cheese, game, yeast & some alcoholic drinks Sympathomimetic drugs e.g. non-prescription cold remedies Results in a severe hypertensive reaction which can cause a subarachnoid bleed.