Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Chapter 32 Antidepressants

2 Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Antidepressants  Primarily used to relieve symptoms of depression  Can also help patients with anxiety disorders  Not indicated for uncomplicated bereavement

3 Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Depression  Most common psychiatric disorder  30% of the U.S. population will experience some form during their lifetime  Approximately 5% of adult population is depressed  Incidence in women twice as high as in men  Risk of suicide is high in depression  Often untreated

4 Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Clinical Features  Depressed mood  Loss of pleasure or interest  Insomnia (or sometimes hypersomnia)  Anorexia (or sometimes hyperphagia)  Mental slowing and loss of concentration  Feelings of guilt, worthlessness, helplessness  Thoughts of death and suicide  Overt suicidal behavior (patient with plan or serious intent should be hospitalized for therapy)  Symptoms must be present most of the day, nearly every day, for at least 2 weeks

5 Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Pathogenesis  Complex and incomplete  Possible contributing factors  Genetic heritage  Difficult childhood  Chronic low self-esteem  Monoamine hypothesis of depression  Depression is caused by functional insufficiency of monoamine neurotransmitters

6 Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Treatment Modalities  Pharmacotherapy  Primary therapy  Depression-specific psychotherapy (eg, cognitive behavioral therapy)  The two together are better than either one alone, consider psychotherapy/counseling while waiting for antidepressants to work, which may be 4-8 weeks

7 Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Suicide Risk with Antidepressants  May increase suicidal tendency early in the treatment  Patients should be observed closely for:  Suicidality  Worsening mood  Changes in behavior  Precautions  Prescriptions should be written for the smallest number of doses consistent with good patient management  Dosing of inpatients should be directly observed

8 Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Selective Serotonin Reuptake Inhibitors (SSRIs)  Introduced in 1987  Most commonly prescribed antidepressants  As effective as TCAs, but do not cause hypotension, sedation, or anticholinergic effects  Overdose does not cause cardiac toxicity  Death by overdose is extremely rare

9 Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Selective Serotonin Reuptake Inhibitors (SSRIs)  Fluoxetine (Prozac, Sarafem)  Most widely prescribed SSRI in the United States  Other SSRIs

10 Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Mechanism of Action  Produce selective inhibition of serotonin reuptake  Produce CNS excitation

11 Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Therapeutic Uses   Primarily used to treat major depression   Other uses   Obsessive-compulsive disorder   Bulimia nervosa   Premenstrual dysphoric disorder

12 Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Adverse Effects   Serotonin syndrome (agitation, sweating, hyperreflexia)   2–72 hours after treatment   Withdrawal syndrome – therapy is generally continued for a months, but withdraw from meds gradually)   Neonatal effects when used in pregnancy   Teratogenesis   Extrapyramidal side effects   Bruxism   Bleeding disorders   Sexual dysfunction- drug holiday Friday/Saturday may be prescribed   Weight gain

13 Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Drug Interactions  Monoamine oxidase inhibitors  Risk of serotonin syndrome- discontinue MAOI 2 weeks prior to starting SSRI  Warfarin  Tricyclic antidepressants and lithium  Can elevate levels of these drugs

14 Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Other SSRIs  Sertraline (Zoloft)  Paroxetine (Paxil)  Citalopram (Celexa)  Escitalopram (Lexapro)  Fluvoxamine (Luvox)

15 Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Serotonin/Norepinephrine Reuptake Inhibitors (SNRIs)  Venlafaxine (Effexor)  Duloxetine (Cymbalta)

16 Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Venlafaxine (Effexor)  Indications  Major depression  Generalized anxiety disorder  Social anxiety disorder (social phobia)  Blocks NE and serotonin uptake  Does not block cholinergic, histaminergic, or alpha 1 -adrenergic receptors  Serious reactions if combined with MAOIs

17 Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Venlafaxine (Effexor)  Side effects  Nausea  Headache  Anorexia  Nervousness  Sweating  Somnolence  Insomnia  Weight loss/anorexia  Diastolic hypertension  Sexual dysfunction  Hyponatremia (in older adult patients)  Neonatal withdrawal syndrome

18 Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Tricyclic Antidepressants (Imipramine, amitriptyline)  Drugs of first choice for many patients with major depression  Most common adverse effects: sedation, orthostatic hypotension, and anticholinergic effects  Most dangerous adverse effect: cardiac toxicity  May increase risk of suicide early in treatment

19 Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Chemistry  Nucleus of the tricyclic antidepressants has three rings  Similar to phenothiazine antipsychotics  Produce varying degrees of:  Sedation  Orthostatic hypotension  Anticholinergic effects

20 Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Mechanism of Action  Block neuronal reuptake of two monoamine transmitters  Norepinephrine (NE)  Serotonin

21 Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Fig. 32–2. Mechanism of action of tricyclic antidepressants.

22 Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Adverse Effects  Orthostatic hypotension  Anticholinergic effects  Diaphoresis  Sedation  Cardiac toxicity  Seizures  Hypomania  “Yawngasm”

23 Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Drug Interactions  Monoamine oxidase inhibitors  Direct-acting sympathomimetic drugs  Indirect-acting sympathomimetic drugs  Anticholinergic agents  CNS depressants

24 Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Toxicity  Clinical manifestations  Primarily from anticholinergic and cardiotoxic actions Dysrhythmias Dysrhythmias Tachycardia Tachycardia Intraventricular blocks Intraventricular blocks Complete atrioventricular block Complete atrioventricular block Ventricular tachycardia Ventricular tachycardia Ventricular fibrillation Ventricular fibrillation

25 Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Toxicity  Treatment  Gastric lavage  Ingestion of activated charcoal  Physostigmine  Propranolol, lidocaine, or phenytoin

26 Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Monoamine Oxidase Inhibitors (phenelzine, isocarboxacid)  2nd- or 3rd-choice antidepressants for most patients  As effective as TCAs or SSRIs, but more dangerous  Risk of triggering hypertensive crisis if patient eats foods rich in tyramine (see page 32-6)  Drug of choice for atypical depression

27 Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Monoamine Oxidase Inhibitors  Mechanism of action  Block MOA, the enzyme that converts monoamine neurotransmitters (NE, serotonin, and dopamine) into inactive products  Inactivate tyramine and other biogenic amines

28 Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Fig. 32–3. Mechanism of action of monoamine oxidase inhibitors.

29 Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Monoamine Oxidase Inhibitors  Therapeutic uses  Depression  Other uses Bulimia nervosa Bulimia nervosa Obsessive-compulsive disorder Obsessive-compulsive disorder Panic attacks Panic attacks  Adverse effects  CNS stimulation  Orthostatic hypotension  Hypertensive crisis from dietary tyramine

30 Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Monoamine Oxidase Inhibitors  Drug interactions  Sympathomimetic agents  Interactions secondary to inhibition of hepatic MAO  Antidepressants: TCAs (risk of hypertensive episodes) and SSRIs (increased risk of serotonin syndrome)  Meperidine- hyperpyrexia

31 Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Fig. 32–4. Interaction between dietary tyramine and MAOIs.