<p> Neuroscience 18c - Antidepressant Drugs Anil Chopra</p><p>1. Definitions & classification 2. Monoamine theory of depression 3. Types of antidepressant drugs a. Tricyclic antidepressants (TCAs) b. Monoamine oxidase inhibitors (MAOIs) c. Selective 5-HT re-uptake inhibitors (SSRIs) d. ‘Atypical’ antidepressants 4. Lithium 5. Electroconvulsive therapy (ECT)</p><p>Unipolar Depression  Characterised by mood swings in the same direction.  Is late in onset.  Reactive Depression o Related to a stressful event o Non familial.  Endogenous depression o Not related to a stressful event o Familial.</p><p>Bipolar Depression  Also known as manic depression  Characterised by oscillating depression.  Early adult onset  Strong hereditary tendency</p><p>Monoamine theory of Depression: this is the theory that depression is caused by deficits in monoamine production (dopamine, noradrenaline, serotonin). The theory is supported by the fact that: - Monoamine oxidase inhibitors (reduce catabolism of monoamines) improve mood. - Tri-cyclic antidepressants (block uptake of noradrenaline) improve mood. - Reserpine (depletes amines) causes depression in animals. - Methyldopa (reduces noradrenaline synthesis) causes depression. It does not however explain why: - Amphetamines, cocaine, and L-dopa (all increase monoamines) do not affect mood - Atypical antidepressants (iprindole) work without affecting monoamine systems. - There is a delay of 2 weeks between when therapy starts and when the effects take place. Tricyclic Antidepressants Names Amitriptyline, desipramine, imipramine, protriptyline, clomipramine.</p><p>Usage Chronic & bipolar depression. Neuropathic pain Nocturnal eneuresis ADHD</p><p>Mode of Action They block monoamine uptake (mainly noradrenaline and serotonin) from the synaptic cleft hence increase transmission.</p><p>Side Effects - Orally administered - Metabolised by liver and excreted in kidney - Long duration of action (1-3 days) They also have actions at muscarinic receptors: (anti-muscarinic effects) . Dry mouth and nose (salivary secretion is affected) . Blurred vision (accommodation in the eye is affected) . Decreased gastro-intestinal motility and secretion. This may lead to constipation . Urinary retention or difficulty with urination . Hyperthermia . Sedation . Postural hypotension . DANGER IF OVERSOSE  Seizures  Cardiac dysrhythmias.  Coma  Respiratory depression . Drug interactions  Increased action by aspirin, phenytoin, neuroleptic, OCP. Also reacts with CNS depressants and antihypertensive drugs. Monoamine Oxidase Inhibitors</p><p>Names Iproniazid, toloxatine, deprenyl</p><p>Usage Depression</p><p>Mode of Action Irreversibly block the action of mono-amine oxidase which causes decrease in breakdown of: - Noradrenaline (Monoamine oxidase A) - serotonin (Monoamine oxidase A) - dopamine (Monoamine oxidase B) Most are non-selective so will inhibit both of them and cause an increase in cytoplasmic NA and 5-HT (serotonin).</p><p>Side Effects and Pharmacokinetics - Orally administered - Long duration of action (2 weeks) - Metabolised in the liver and excreted in the urine. Side effects include:  Postural hypotension  Tremors  Insomnia  Siezures  Sedation  Weight gain  Liver damage  Has many drug interactions o ‘Cheese reaction’: Tyramine-containing foods + MAOI causes hypertensive crisis (throbbing headache, increase in blood pressure and risk of intracranial haemorrhage) o With TCA’s can cause hypertension o Can react with Pethidine to produce hyperpyrexia, restlessness, coma & hypotension</p><p>Selective Serotonin Reuptake Inhibitor</p><p>Name Fluoxetine (Prozac)</p><p>Usage Clinical depression</p><p>Mode of Action Works in the same way as MAOI – inhibits the uptake of serotonin only resulting in a less pronounced effect than MAOIs. Side Effects and Pharmacokinetics - Orally administered - Long duration of action (1-3 days) - Delayed onset of action (2 weeks) Interacts with tri-cyclic antidepressants. Side effects include:  Nausea,  Anorexia,  Insomnia  Loss of libido</p><p>Atypical Antidepressants</p><p>Names – maprotiline, venlafaxine, trazodone, mianserin, bupropion</p><p>Usage – Clinical depression</p><p>Mode of Action – generally unknown although some act as MAOIs.</p><p>Side Effects – rare.</p><p>Name – lithium</p><p>Usage – clinical depression & mania/bipolar depression</p><p>Mode of Action – inorganic ion taken as lithium carbonate. Not properly understood but has numerous effects on neurotransmitter systems such as interference with IP3 an cAMP formation (secondary messenger in dopamine receptors)</p><p>Side Effects and Pharmacokinetics - Taken orally as lithium carbonate. - Long plasma halflife and narrow therapeutic window. Interacts with diuretics (enhances action) Side effects include:  Nausea  Headache  Hypothyroidism  Tremor  Weakness  Mental confusion  Polyuria  Thirst  Acute overdose can lead to confusions, convulsions and dysrhythmias Electroconvulsive Therapy ECT</p><p>This is a treatment in which seizures are electrically induced in anesthetized patients for therapeutic effect. It is used as a treatment for severe major depression which has not responded to other treatment, and is also used in the treatment of mania (often in bipolar disorder), catatonia, schizophrenia and other disorders.</p>