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


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


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


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


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


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


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


Selective Serotonin Reuptake Inhibitors (SSRIs)

Fluoxetine (Prozac, Sarafem) Most widely prescribed SSRI in the United States

Other SSRIs


Mechanism of Action Produce selective inhibition of serotonin

reuptake Produce CNS excitation


Therapeutic Uses Primarily used to treat major depression Other uses

Obsessive-compulsive disorder Bulimia nervosa Premenstrual dysphoric disorder


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


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


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


Serotonin/Norepinephrine Reuptake Inhibitors (SNRIs)

Venlafaxine (Effexor) Duloxetine (Cymbalta)


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


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


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


Chemistry Nucleus of the tricyclic antidepressants has

three rings Similar to phenothiazine antipsychotics Produce varying degrees of:

Sedation Orthostatic hypotension Anticholinergic effects


Mechanism of Action Block neuronal reuptake of two monoamine

transmitters Norepinephrine (NE) Serotonin


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


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


Drug Interactions Monoamine oxidase inhibitors Direct-acting sympathomimetic drugs Indirect-acting sympathomimetic drugs Anticholinergic agents CNS depressants


Toxicity Clinical manifestations

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


Toxicity Treatment

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


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


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


Fig. 32–3. Mechanism of action of 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



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


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

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

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