Antidepressant Agents Affective Disorder (Terminology) Affect Peoples feelings in response to their environment Affective disorder A persons mood

mood goes far beyond the usual, normal ups and downs Depression Severe and long-lasting feelings of sadness beyond what was the precipitating event Signs and Symptoms of Depression Low energy level Sleep disturbances Lack of appetite Limited libido Inability to perform activities of daily living Overwhelming feelings of sadness, despair, hopelessness, and disorganization Biogenic Amine Theory of Depression Depression results from a deficiency of norepinephrine (NE), dopamine, or serotonin (5HT) Monoamine oxidase (MAO) may break them down to be recycled or restored in the neuron Rapid fire of the neurons may lead to their depletion The number or sensitivity of postsynaptic receptors may increase, depleting neurotransmitter levels Three Actions of Antidepressant Agents 1. Inhibit the effects of MAO, leading to increased NE or 5HT in the synaptic cleft 2. Block reuptake by the releasing nerve, leading to increased neurotransmitter levels in the synaptic cleft 3. Regulate receptor sites and breakdown of neurotransmitters, leading to an accumulation of neurotransmitters in the synaptic cleft Classifications of Antidepressants Tricyclic antidepressants (TCAs) MAO inhibitors (MAOIs) Selective serotonin reuptake inhibitors (SSRIs)

Sites of Action for Selected Antidepressants

Tricyclic Antidepressants ( TCAs ) Types Amines, secondary amines, and tetracyclics Action Reduce the reuptake of 5HT and NE into nerves Usage All TCAs are similar Choice depends on individual response to the drug and tolerance of adverse effects Focus on the Prototype Antidepressant: Imipramine (Tofranil) Indications: Relief of symptoms of depression; enuresis in children >6 years of age; unlabeled consideration control of chronic pain Actions: Inhibits presynaptic reuptake of norepinephrine and serotonin; anticholinergic at CNS and peripheral receptors; sedating Oral route: Onset varies; peak 24 hours T: 816 hours, metabolized in the liver, excretion in the urine

Monoamine Oxidase Inhibitors (MAOIs) Isocarboxazid (Marplan) Used for patients who did not respond to or could not take newer, safer antidepressants Phenelzine (Nardil) Used for some patients who did not respond to newer, safer antidepressants Tranylcypromine (Parnate) Used for adult outpatients with reactive depression Focus on the MAOI Prototype: Phenelzine Indications: Treatment of patients with depression who are unresponsive to, or unable to take other antidepressive therapy Actions: Irreversibly inhibits MAO, allowing norepinephrine, serotonin, and dopamine to accumulate in the synaptic cleft Oral route: Onset slow; duration 4896 hours T: Unknown; metabolized in the liver, excreted in the urine Selective Serotonin Reuptake Inhibitors (SSRIs) The newest group of antidepressant drugs Specifically block the reuptake of 5HT, with little to no known effect on NE Do not have the many adverse effects associated with TCAs and MAOIs Indications for SSRIs Depression OCDs ( Obsessive Compulsive Disorder ) Panic attacks Bulimia PMDD ( Premenstrual Dysphoric Disorder ) Posttraumatic stress disorders Social phobias Social anxiety disorders Focus on the Prototype SSRI: Fluoxetine (Prozac) Indications: Treatment of depression, OCDs, bulimia, PMDD, panic disorders; unlabeled uses include chronic pain, alcoholism, neuropathies, obesity Actions: Inhibits CNS neuronal reuptake of serotonin with little effect on norepinephrine and little affinity for cholinergic, histaminic, or alphaadrenergic sites Oral route: Onset slow; peak 68 hours T: 24 weeks; metabolized in the liver, excreted in the urine and feces

Fluoxetine ( Prozac ) 3

= the 1st SSRI = Indications : OCDs, bulimia and PMDD ( premenstrual dysphoric disorder ) Fluvoxamine ( Luvox ) = OCD ( Obsessive Compulsive Disorder ) Paroxetine ( Paxil ) = Indications : depression, panic disorders, posttraumatic stress reaction, social disorders & OCDS Sertraline ( Zoloft ) = Indications : depression & OCDS, posttraumatic disorder & panic disorder Citalopram ( Celexa ) = newest SSRI = Indication : depression Full therapeutic effect is up to 4 weeks Other Antidepressants Bupropion (Wellbutrin, Zyban) = depression = dose, smoking cessation Trazodone (Desyrel) = depression Mirtazapine (Remeron) = depression Venlafaxine (Effexor) = has fewer adverse CNS effects = depression Nefazodone (Serzone) = depression