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Chapter 32

Chapter 32. Antidepressants. 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

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Chapter 32

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  1. Chapter 32 Antidepressants

  2. Antidepressants • Primarily used to relieve symptoms of depression • Can also help patients with anxiety disorders • Not indicated for uncomplicated bereavement

  3. 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. 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. 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. 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. 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. 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. Selective Serotonin Reuptake Inhibitors (SSRIs) • Fluoxetine (Prozac, Sarafem) • Most widely prescribed SSRI in the United States • Other SSRIs

  10. Mechanism of Action • Produce selective inhibition of serotonin reuptake • Produce CNS excitation

  11. Therapeutic Uses • Primarily used to treat major depression • Other uses • Obsessive-compulsive disorder • Bulimia nervosa • Premenstrual dysphoric disorder

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

  15. Serotonin/Norepinephrine Reuptake Inhibitors (SNRIs) • Venlafaxine (Effexor) • Duloxetine (Cymbalta)

  16. 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

  17. 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. TricyclicAntidepressants (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. Chemistry • Nucleus of the tricyclic antidepressants has three rings • Similar to phenothiazine antipsychotics • Produce varying degrees of: • Sedation • Orthostatic hypotension • Anticholinergic effects

  20. Mechanism of Action • Block neuronal reuptake of two monoamine transmitters • Norepinephrine (NE) • Serotonin

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

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

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

  24. Toxicity • Clinical manifestations • Primarily from anticholinergic and cardiotoxic actions • Dysrhythmias • Tachycardia • Intraventricular blocks • Complete atrioventricular block • Ventricular tachycardia • Ventricular fibrillation

  25. Toxicity • Treatment • Gastric lavage • Ingestion of activated charcoal • Physostigmine • Propranolol, lidocaine, or phenytoin

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

  29. 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

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

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