Chapter 27: Antidepressants Flashcards
depression
Most common psychiatric disorder
30% of the U.S. population will experience some form during their lifetime
Approximately one in every eight adults in the United States is depressed
Incidence in women twice as high as that in men
Risk of suicide is high with depression
Often untreated
~ 15 mil adults. 1 in every 8 in US
Only ~ 35% of people get treated
clinical features of depression
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, and helplessness
Thoughts of death and suicide
Overt suicidal behavior
Symptoms must be present most of the day, nearly every day, for at least 2 weeks
Grief and sadness are different that depression
Grief and sadness are normal responses to stressors and will resolve spontaneous
depression pathogenesis
Complex and incomplete
Possible contributing factors:
Genetic heritage
Difficult childhood
Chronic low self-esteem
Monoamine hypothesis of depression
Depression is caused by the functional insufficiency of monoamine neurotransmitters
tx for depression
Pharmacotherapy
Primary therapy
Depression-specific psychotherapy (e.g., cognitive behavioral therapy and interpersonal psychotherapy)
Electroconvulsive therapy (somatic 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
Transcranial magnetic stimulation
basic considerations for depression tx
Time course of response
Symptoms resolve slowly
Initial responses develop after 1 to 3 weeks
takes at least 4-8 wk to assess efficacy
Maximal responses may not be seen for 12 weeks
Failure when taken 1 month without success
Drug selection
Antidepressants have nearly equal efficacy
Selection
Managing treatment
Start low dose and gradually increase
Ineffective- increase dose, if still ineffective can switch to mother med in same class, switch to a drug in different class, add TCA
After depression is treated, cont tx for 4-9 months to prevent relapse
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
When meds start to work, get more motivation to suicide
Admin in inpatient setting should be directly observed
AD across lifespan
Infants
Children
Pregnant women
Breastfeeding women
Older adults
SSRI
Introduced in 1987
Most commonly prescribed antidepressants
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] uses
SSRI -first avail
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
fluox MOA
Produce selective inhibition of serotonin reuptake
Produce central nervous system (CNS) excitation
fluox pharmacokinetics
Well absorbed with PO
Half life of 2 days –fluco
Neurofloctine 7 day half life
SE sexul dysfunction and weight gain
fluox 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
fluox drug interactions
Monoamine oxidase inhibitors
Risk of serotonin syndrome
Antiplatelet drugs and anticoagulants
Aspirin and nonsteroidal antiinflammatory drugs
Increase r/o bleeding
Warfarin
Watch INR
TCAs and lithium
Can elevate levels of these drugs
Fluoxetine is highly bond plasma protien and compete with other drugs
sertraline [zoloft]
Blocks uptake of serotonin and dopamine
CNS stimulation
Minimal effects on seizure threshold
SSRI
If SE with one, try another. Remember to withdrawal slowly
sertraline uses
Major depression
Panic disorder
Obsessive-compulsive disorder
Posttraumatic stress disorder
Premenstrual dysphoric disorder
Social anxiety disorder
sertraline SE
Headache
Nausea
Tremor
Diarrhea
Insomnia
Weight gain
Agitation
Sexual dysfunction
Neonatal abstinence syndrome and persistent pulmonary hypertension of the newborn when used during late pregnancy
Nervousness
sertraline drug interactions
MAOIs
Pimozide
Fluvoxamine [Luvox]
Inhibition of serotonin reuptake SSRI
Used for obsessive-compulsive disorder
Rapidly absorbed from the gastrointestinal tract
Half-life: About 15 hours
Interacts adversely with MAOIs
Fluvoxamine [Luvox] SE
Nausea
Vomiting
Constipation
Weight gain
Dry mouth
Headache
Sexual dysfunction
Abnormal liver function
Sedative effects
Paroxetine [Paxil, Paxil CR, Pexeva] uses
Inhibition of serotonin uptake SSRI
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
SNRI
Venlafaxine [Effexor]
Duloxetine [Cymbalta]
Block neural uptake of serotonin and NE. Min effects on those other transmitters
Similar effects to SSRIs
SSRI typicaly better tolerated
Venlafaxine [Effexor]
Blocks NE and serotonin uptake
Does not block cholinergic, histaminergic, or alpha1-adrenergic receptors
Serious reactions if combined with MAOIs
First available
Well absorbed with or without food
Half life of 5h
11h for active metabolite
Venlafaxine uses
Major depression
Generalized anxiety disorder
Social anxiety disorder (social phobia)
effexor SE and drug interactions
Nausea -30-50% will get nausea
Headache
Anorexia -dose depend
Nervousness
Sweating
Somnolence
Insomnia
Weight loss/anorexia
Diastolic hypertension
Sexual dysfunction
Hyponatremia (in older adult patients)
Neonatal withdrawal syndrome (late in preg)
Don’t use in glaucoma pt bc of sustained mydrasis, increased r/o eye injury
Don’t stop abruptly
Don’t use with MAOI or other sertogenic drugs
use in combo carefully with SSRI
MOAI should be stopped 14 days before starting effector an if switching from Effexor to MOAI –stop 7 days before
Desvenlafaxine [Pristiq] MOA
Strong inhibitor of 5-hydroxytryptamine and NE reuptake
Does not block cholinergic, histaminergic, or alpha1-adrenergic receptors
pristiq SE
Nausea
Headache
Dizziness
Insomnia
Diarrhea
Dry mouth
Sweating
Constipation
Sexual effects, including erectile dysfunction
Decreased libido
Duloxetine [Cymbalta] MOA and uses
Inhibits serotonin and NE reuptake
Weakly inhibits dopamine reuptake
Does not inhibit monoamine oxidase (MAO)
Relieves depression
Relieves pain of diabetic peripheral neuropathy
Duloxetine [Cymbalta] pharakinetics
Well absorbed after oral administration
Food reduces rate of absorption
Highly bound to albumin in the blood
Half-life: 12 hours
Duloxetine [Cymbalta] SE
Nausea
Somnolence
Dry mouth
Sweating
Insomnia
Blurred vision
Effects in pregnancy and lactation
Duloxetine [Cymbalta] drug interactions
Alcohol
MAOIs
Drugs that inhibit CYP1A2 or CYP2D6
Levomilnacipran [Fetzima]
New serotonin/norepinephrine reuptake inhibitor approved for major depressive disorder
Adverse effects
Erectile dysfunction
Constipation
Nausea
TCA
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 during early treatment
est 1950s
TCA chemistry
Nuclei of the TCAs have three rings
Similar to phenothiazine antipsychotics
Produce varying degrees of the following:
Sedation
Orthostatic hypotension
Anticholinergic effects
TCA MOA
Block neuronal reuptake of two monoamine transmitters
NE
Serotonin
pharmacokinetics TCA
Long and variable half-lives
Usually single daily dose
Requires individualization of dosage
TCA uses
Depression
Bipolar disorder
Fibromyalgia syndrome
Other uses
Neuropathic pain
Chronic insomnia
Attention-deficit/hyperactivity disorder
Panic disorder
Obsessive-compulsive disorder
TCA ADRS
Orthostatic hypotension
Anticholinergic effects
Diaphoresis
Sedation
Cardiac toxicity –blocks vagel influences, slows conduction at bundle of his
Seizures
Hypomania
suicide risk early in tx
TCA drug interactions
MAOIs –r/o hypertensive crisis
Direct-acting sympathomimetic drugs
poteniate
Indirect-acting sympathomimetic drugs
Decrease response
Anticholinergic agents
CNS depressants
TCA toxicity
Primarily from anticholinergic and cardiotoxic actions
Dysrhythmias
Tachycardia
Intraventricular blocks
Complete atrioventricular block
Ventricular tachycardia
Ventricular fibrillation
TCA tox tx
Gastric lavage
Ingestion of activated charcoal
Intravenous sodium bicarbonate to treat cardiac dysrhythmias caused by cardiotoxicity
TCA dosage and routes
Dosage
Initial doses should be low
Routes of administration
All can be administered by mouth
TCA prep and drug selection
All TCAs considered to be equally effective
Selection based on side effects
TCA considerations
Baseline ekg –esp of they have baseline dysrhythmias and over 40y and periodicallu
Edu on ortho hypo and anticholinergic
MAOI
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]
takes several weeks to peak activity
MAOI MOA
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
Inactivate NE
MAO-B
Inactivate dopamine
Affected by antidepressants
Act on MAO in two ways: reversible and irreversible
Reversible: Lasts 3 to 5 days
Irreversible: Lasts about 2 weeks
All of the MAOIs in current use cause irreversible inhibition
MAOI uses
Depression
Other uses
Bulimia nervosa
Agoraphobia
Attention-deficit/hyperactivity disorder
Obsessive-compulsive disorder
Panic attacks
MAOI ADR
CNS stimulation
Orthostatic hypotension
Hypertensive crisis from dietary tyramine
MAOI 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
tyramine foods to avoid
Aged cheesed (cheddar, Swiss, parm, blue cheese, Gorgonzola), cured meats (suausages, pepperoni, salami), smoked or processed meats (hot dogs, corned beef, smoked fish) pickled foods (sourkrut), sauces (soy, shrimp, teriyaki), soybean products, snow pea, dried or over ripe fruits (raisins or prunes), meat tenderizers, alc (beer, red wine, sherry lqiers)
MAOI HTN crisis tx
Sodium nitroprusside (a nitric oxide donor)
Phentolamine (an alpha-adrenergic antagonist)
Labetalol (an alpha-adrenergic and beta-adrenergic antagonist)
MAOI drug interactions and route
Drug interactions
Indirect-acting sympathomimetic agents
Interactions secondary to the inhibition of hepatic MAO
Antidepressants: TCAs and SSRIs
Antihypertensive drugs
Meperidine
Preparations, dosage, and administration
All MAOIs administered orally
Selegiline [Emsam]
First transdermal treatment for depression
Much lower risk of hypertensive crisis with transdermal route as compared with oral route
Enters the system without going through the gastrointestinal tract
Adverse effects still occur when used with sympathomimetic drugs
Avoid carbamazepine [Tegretol] and oxcarbazepine [Trileptal]
Bupropion [Wellbutrin]
Actions and uses
Acts as stimulant and suppresses appetite
Antidepressant effects begin in 1 to 3 weeks
Does not affect serotonergic, cholinergic, or histaminergic transmission
Does not cause weight gain
may increase sex drive
MDD and SAD
Marked as sybaritic and burden to aid in smokin cessation
Unlabeled uses: neuropathic pain, depressive episodes in BPD, manage ADHD
wellbutrin ADR
Seizures
Agitation
Tremor
Tachycardia
Blurred vision
Dizziness
Headache
Insomnia
Dry mouth
Gastrointestinal upset
Constipation
Weight loss
well butrin drug interactions
MAOIs can increase the risk of bupropion toxicity
wellbutrin admin
Immediate-release, sustained-release, and extended-release tablets
other atyial AD
Mirtazapine [Remeron]
Salmonella’s weight gain, elevated cholesterol levels ADR
Well tolerated
Nefazodone [Serzone]
Trazodone [Oleptro]
Vilazodone [Viibryd]
Amoxapine
nonconventional drugs for depression
St. John’s wort (Hypericum perforatum)
S-adenosylmethionine
ECT
Outside the realm of pharmacology
Valuable treatment for depression
Two desirable characteristics
Effectiveness
Rapid response (relative to antidepressant drugs)
Two primary types of patients
Those who have failed to respond to drugs
Those who are severely depressed and suicidal
Can terminate ongoing depressive episode
Adverse effect
Some loss of memory for events immediately surrounding treatment
TMS
Outside the realm of pharmacology
Reserved for severe refractory depression
Employs an insulated magnetic coil placed against the scalp to deliver pulsed magnetic fields to the left dorsolateral prefrontal cortex
Daily 40-minute sessions for 6 weeks
Adverse effects
Transient headaches, scalp discomfort, eye pain, toothache, muscle twitching, and seizures; cognitive changes have not been reported
VNS
For long-term therapy of treatment-resistant depression
When at least four antidepressant drugs have failed
Mechanism of action
An implanted device
Delivers electrical pulses to the vagus nerve
Side effects
Hoarseness
Voice alteration
Cough
Dyspnea
light therapy
Exposure to bright light
Effective treatment for seasonal affective disorder and nonseasonal major depression
May enhance serotonergic neurotransmission
The more intense the light, the greater the response
