Antidepressant Agents

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Overview
Treat for depression Heterocyclic antidepressants (tricyclic & tetracyclic) Selective serotonin reuptake inhibitors (SSRIs) Monoamine oxidase inhibitors (MAOIs) Atypical antidepressants Serotonin Norepinephrine reuptake inhibitors (SNRIs)

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While heterocyclics were once the mainstay of treatment, because of their more positive side effect profile, SSRIs are now use as first-line agents All antidepressants take about 3-6 weeks to work & all have equal efficacy Antidepressant agents do not elevate mood in nondepressed people & have no abuse potential

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Stimulants, such as methylphenidate or dextroamphetamine, may also be useful in treating depression. They work quickly, & thus may help to improve mood in terminally ill or elderly patients. They are also useful in patients with depression refractory to other treatments & in those at risk for development of adverse effects of other agents for depression. Disadvantages include their addiction potential

Heterocyclic Agents
Block reuptake of norepinephrine & serotonin Increasing the availability of these neurotransmitters & improving mood Also block muscarinic acetylcholine receptors Histamine receptors are also blocked Other adverse effects include precipitation of manic episodes in potentially bipolar patients, cardiovascular effects such as orthostatic hypotension, neurologic effects such as tremor, weight gain & sexual dysfunction Dangerous in overdose

SSRIs
SSRIs little effect on dopamin, norepinephrine, acetylcholine or histamine systems Because of this selectivity, SSRIs cause fewer side effects & are safer in overdose than heterocyclic or MAOIs e.g. Fluoxetine Paroxetine Sertraline Fluvoxamine

MAOIs
Inhibit the breakdown of neurotransmitters by monoamine oxidase (MAO) in the brain in an irreversible reaction, thereby increasing norepinephrine & serotonin availability in the synapse & improving mood
Particularly useful treatment resistence to other agents A major drawback of use of MAOIs is a potentially fatal reaction when they are taken in conjuction with certain food

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This reaction occurs because a. MAO metabolizes tyramine, a pressor, in the gastrointestinal tract

b. If MAO is inhibited, ingestion of tyrammine-rich foods (e.g., aged chesse, beer, wine, broad beans, beef or chicken liver, & smoked or pickled meats or fish) or sympathomimetic drugs (e.g., ephedrine, methylphenidate, phenylephrine, pseudoephedrine can tyramine level cause blood pressure, sweating, headache & vomiting (i.e., hypertensi crisis), which in turn can lead to stroke & death

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MAOIs & SSRIs the serotonin syndrome marked by: autonomic instability, hyperthermia convulsions coma death Other adverse effects of MAOIs are similar to those of the heterocyclics, including danger in overdose e.g., Moclobemide

Atypical antidepressants

e.g., Trazodone Mirtazapine

SNRI

e.g., Venlafaxine (Effexor) Duloexetine (Cymbalta)