Antidepressants Flashcards
Electroconvulsive therapy
When drugs and psychotherapy have not worked
– When a rapid response is needed
– For severely depressed patients
– For suicidal patients
– For elderly patients at risk of starving
Suicide Risk with Antidepressants
May increase suicidal tendencies during early treatment
■ Patients should be observed closely for the following:
– 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
As effective as tricyclic antidepressants (TCAs) but do not cause hypotension, sedation, or anticholinergic effects
Overdose does not cause cardiac toxicity
■ Death by overdose is extremely rare
Fluoxetine [Prozac, Sarafem]
– Most widely prescribed SSRI in the world
– Bipolar disorder
– Obsessive-compulsive disorder
– Panic disorder
– Bulimia nervosa
– Premenstrual dysphoric disorder
– Off-label uses: Posttraumatic stress disorder, social phobia, alcoholism, attention-deficit/hyperactivity disorder, Tourette syndrome, and obesity
■ Produce selective inhibition of serotonin reuptake
■ Produce central nervous system (CNS) excitation
Adverse Effects
■ Serotonin syndrome
– Begins 2 to 72 hours after treatment
– Altered mental status (e.g., agitation, confusion, disorientation, anxiety, hallucinations, and poor concentration)
– Incoordination, myoclonus, hyperreflexia, excessive sweating, tremor, and fever
– Deaths have occurred
– Syndrome resolves spontaneously after discontinuing
the drug
– Risk increased by concurrent use of MAOIs and other drugs
■ Withdrawal syndrome ■ Neonatal effects when used during pregnancy ■ Teratogenesis ■ Extrapyramidal side effects ■ Bruxism ■ Bleeding disorders ■ Sexual dysfunction ■ Weight gain
Drug Interactions ■ Monoamine oxidase inhibitors
– Risk of serotonin syndrome
■ Antiplatelet drugs and anticoagulants
■ Aspirin and nonsteroidal antiinflammatory drugs
■ Warfarin
■ TCAs and lithium
– Can elevate levels of these drugs
Sertraline [Zoloft]
Blocks uptake of serotonin and dopamine – CNS stimulation – Minimal effects on seizure threshold – Therapeutic uses ■ Major depression ■ Panic disorder ■ Obsessive-compulsive disorder ■ Posttraumatic stress disorder ■ Premenstrual dysphoric disorder ■ Social anxiety disorder Drug interactions ■ MAOIs ■ Pimozide
Fluvoxamine [Luvox]
– Inhibition of serotonin reuptake – Used for obsessive-compulsive disorder – Rapidly absorbed from the gastrointestinal tract – Half-life: About 15 hours – Interacts adversely with MAOIs
side effects.
■ Abnormal liver function
■ Sedative effects
Paroxetine [Paxil, Paxil CR, Pexeva]
Inhibition of serotonin uptake – Indications ■ Major depression ■ Obsessive-compulsive disorder ■ Social phobia ■ Panic disorder ■ Generalized anxiety disorder ■ Posttraumatic stress disorder ■ Premenstrual dysphoric disorder ■ Postmenopausal vasomotor symptoms
Citalopram [Celexa]
Does not block receptors for serotonin, acetylcholine, norepinephrine (NE), or histamine
Used for major depression – Half-life: About 35 hours – Side effects (most common) ■ Nausea ■ Somnolence ■ Dry mouth ■ Sexual dysfunction – Can cause neonatal abstinence syndrome – Interacts with MAOIs
Escitalopram [Lexapro]
S-isomer of citalopram – Better tolerated than citalopram – Side effects ■ Nausea ■ Insomnia ■ Somnolence ■ Sweating ■ Fatigue – Interacts with MAOIs
Serotonin/Norepinephrine Reuptake Inhibitors
Venlafaxine [Effexor]
ndications
– 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
side effects – Nausea – Headache – Anorexia – Nervousness – Sweating – Somnolence – Insomnia – Weight loss/anorexia – Diastolic hypertension – Sexual dysfunction – Hyponatremia (in older adult patients) – Neonatal withdrawal syndrome
Desvenlafaxine [Pristiq]
Mechanism of action
– Strong inhibitor of 5-hydroxytryptamine and NE reuptake
– Does not block cholinergic, histaminergic, or alpha1- adrenergic receptors
Side effects – Nausea – Headache – Dizziness – Insomnia – Diarrhea – Dry mouth – Sweating – Constipation – Sexual effects, including erectile dysfunction – Decreased libido
Duloxetine [Cymbalta]
■ Mechanism of action and therapeutic use
– Inhibits serotonin and NE reuptake
– Weakly inhibits dopamine reuptake
– Does not inhibit monoamine oxidase (MAO)
– Relieves depression
– Relieves pain of diabetic peripheral neuropathy
■ Pharmacokinetics
– Well absorbed after oral administration
– Food reduces rate of absorption
– Highly bound to albumin in the blood
– Half-life: 12 hours
Drug interactions – Alcohol – MAOIs – Drugs that inhibit CYP1A2 or CYP2D6 ■ Preparations, dosage, and administration
Levomilnacipran [Fetzima]
New serotonin/norepinephrine reuptake inhibitor approved for major depressive disorder
■ Adverse effects
– Erectile dysfunction – Constipation
– Nausea
Tricyclic antidepressants
Drug Interactions ■ MAOIs ■ Direct-acting sympathomimetic drugs ■ Indirect-acting sympathomimetic drugs ■ Anticholinergic agents ■ CNS depressants
Clinical manifestations – Primarily from anticholinergic and cardiotoxic actions ■ Dysrhythmias ■ Tachycardia ■ Intraventricular blocks ■ Complete atrioventricular block ■ Ventricular tachycardia ■ Ventricular fibrillation
Treatment – Gastric lavage – Ingestion of activated charcoal – Intravenous sodium bicarbonate to treat cardiac dysrhythmias caused by cardiotoxicity
Monoamine Oxidase Inhibitors
Second or third choice antidepressants for most patients
■ As effective as TCAs and SSRIs but more hazardous
■ Risk of triggering hypertensive crisis if patient eats foods rich in tyramine
■ Drug of choice for atypical depression
■ Isocarboxazid [Marplan]
■ Phenelzine [Nardil]
■ Tranylcypromine [Parnate
Mechanism of action
– Convert monoamine neurotransmitters (NE, serotonin,
and dopamine) into inactive products
– Inactivate tyramine and other biogenic amines
– Two forms of MAO in the body:
■ MAO-A ■ MAO-B]
Therapeutic uses – Depression – Other uses ■ Bulimia nervosa ■ Agoraphobia ■ Attention-deficit/hyperactivity disorder ■ Obsessive-compulsive disorder ■ Panic attacks ■ Adverse effects – CNS stimulation – Orthostatic hypotension – Hypertensive crisis from dietary tyramine
Hypertensive crisis/dietary tyramine – Tyramine: Promotes the release of NE from sympathetic neurons – Hypertensive crisis ■ Severe headache ■ Tachycardia ■ Hypertension ■ Nausea and vomiting ■ Confusion ■ Profuse sweating ■ Stroke ■ Death
Treatment: Intravenous vasodilator
■ ■ ■
Sodium nitroprusside (a nitric oxide donor) Phentolamine (an alpha-adrenergic antagonist)
Labetalol (an alpha-adrenergic and beta-adrenergic antagonist)
Drug interactions
– Indirect-acting sympathomimetic agents
– Interactions secondary to the inhibition of hepatic MAO
– Antidepressants: TCAs and SSRIs
– Antihypertensive drugs
– Meperidine
