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

2. 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. 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. 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. 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. 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. 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. 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. 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. 10 Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Mechanism of Action  Produce selective inhibition of serotonin reuptake  Produce CNS excitation

11. 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. 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 9- 12 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. 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. 14 Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Other SSRIs  Sertraline (Zoloft)  Paroxetine (Paxil)  Citalopram (Celexa)  Escitalopram (Lexapro)  Fluvoxamine (Luvox)

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

16. 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. 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. 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. 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. 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. 21 Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Fig. 32–2. Mechanism of action of tricyclic antidepressants.

22. 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. 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. 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. 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. 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. 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. 28 Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Fig. 32–3. Mechanism of action of monoamine oxidase inhibitors.

29. 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. 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. 31 Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Fig. 32–4. Interaction between dietary tyramine and MAOIs.