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

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

Chapter 32

Antidepressants

2Copyright © 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

3Copyright © 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

4Copyright © 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

5Copyright © 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

6Copyright © 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

7Copyright © 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

8Copyright © 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

9Copyright © 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

10Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.

Mechanism of Action Produce selective inhibition of serotonin

reuptake Produce CNS excitation

11Copyright © 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

12Copyright © 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

13Copyright © 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

14Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.

Other SSRIs Sertraline (Zoloft) Paroxetine (Paxil) Citalopram (Celexa) Escitalopram (Lexapro) Fluvoxamine (Luvox)

15Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.

Serotonin/Norepinephrine Reuptake Inhibitors (SNRIs)

Venlafaxine (Effexor) Duloxetine (Cymbalta)

16Copyright © 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

alpha1-adrenergic receptors Serious reactions if combined with MAOIs

17Copyright © 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

18Copyright © 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

19Copyright © 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

20Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.

Mechanism of Action Block neuronal reuptake of two monoamine

transmitters Norepinephrine (NE) Serotonin

21Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.

Fig. 32–2. Mechanism of action of tricyclic antidepressants.

22Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.

Adverse Effects Orthostatic hypotension Anticholinergic effects Diaphoresis Sedation Cardiac toxicity Seizures Hypomania “Yawngasm”

23Copyright © 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

24Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.

Toxicity Clinical manifestations

Primarily from anticholinergic and cardiotoxic actions• Dysrhythmias• Tachycardia• Intraventricular blocks• Complete atrioventricular block• Ventricular tachycardia• Ventricular fibrillation

25Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.

Toxicity Treatment

Gastric lavage Ingestion of activated charcoal Physostigmine Propranolol, lidocaine, or phenytoin

26Copyright © 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

27Copyright © 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

28Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.

Fig. 32–3. Mechanism of action of monoamine oxidase inhibitors.

29Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.

Monoamine Oxidase Inhibitors

Therapeutic uses Depression Other uses

• Bulimia nervosa• Obsessive-compulsive disorder• Panic attacks

Adverse effects CNS stimulation Orthostatic hypotension Hypertensive crisis from dietary tyramine

30Copyright © 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

31Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.

Fig. 32–4. Interaction between dietary tyramine and MAOIs.