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ADPY 7500 > Antidepressants > Flashcards

Antidepressants Flashcards

1
Q

How do you give a patient an adequate trial of an antidepressant?

A

Usually between 1 and 2 months at full dose, before considering changing medications

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2
Q

What are the major categories of antidepressants?

A

SSRIs (selective serotonin reuptake inhibitors), Heterocyclic antidepressants, including TCAs and tetracyclic antidepressants, Monoamine oxidase inhibitors (MAOIs), Miscellaneous antidepressants

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3
Q

Response rates of antidepressants

A

All have similar response rates in treating major depression but differ in safety and side effect profiles.

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4
Q

How many patients will respond to antidepressants?

A

About 70 percent of patients with major depression. About 30 percent of this is placebo response.

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5
Q

How long do antidepressants need to work?

A

Most require a trial of at least 3-4 weeks for effect, with some people requiring as little as 1-2 weeks and some 6-8 weeks for noticeable effects.

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6
Q

Withdrawal phenomenon:

A

Most antidepressants have this. Characterized by dizziness, headaches, nausea, insomnia and malaise. Depending on dose and half-life, they may need to be tapered.

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7
Q

SSRIs and related antidepressants:

A

Because of safety and tolerability, they have become the most common agents used to treat major depression.

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8
Q

The choice of a particular medication used for a given patient should be based on:

A
  • Patient’s symptoms
  • Previous treatment responses by the patient or a family member to a particular drug
  • Medication side effect profile
  • Comorbid conditions
  • Risk of suicide
  • Cost
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9
Q

SSRIs Mechanism:

A

Inhibit presynaptic serotonin pumps that take up serotonin, leads to increased availability of serotonin in synaptic clefts. However, research indicates that the mechanism of action may be more complex.

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10
Q

Response to SSRIs:

A

Although structural differences are minimal, patients often respond differently in terms of both efficacy and side effects to different SSRIs.

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11
Q

Dosing of SSRIs:

A

Based on their half lives, most are dosed daily, Fluoxetine also has a weekly dosing form available.

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12
Q

SSRI Plasma Levels:

A

There is no correlation between plasma levels and efficacy or side effects.

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13
Q

SSRIs are most commonly prescribed antidepressants due to several distinct advantages:

A
  • Low incidence of side effects, most of which resolve with time
  • No food restrictions
  • Much safer in overdose
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14
Q

6 Examples of SSRIs:

A

Fluoxetine (Prozac), Sertraline (Zoloft), Paroxetine (Paxil), Fluvoxamine (Luvox), Citalopram (Celexa), Escitalopram (Lexapro)

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15
Q

Fluoxetine (Prozac)

A
  • Longest half-life with active metabolites; therefore, no need to taper
  • Safe in pregnancy, approved for use in children
  • More common sleep changes and anxiety
  • Can elevate levels of neuroleptics, leading to Inc. side effects
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16
Q

Sertraline (Zoloft)

A
  • Highest risk for GI disturbances
  • Very few drug interactions
  • More common sleep changes
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17
Q

Paroxetine (Paxil)

A
  • Highly protein bound leads to several drug interactions
  • More anticholinergic effects like sedation, constipation, weight gain
  • Short half-life leading to withdrawal phenomena if not taken consistently
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18
Q

Fluvoxamine (Luvox)

A
  • Currently approved only for use in obsessive-compulsive disorder (OCD)
  • Nausea and vomiting more common
  • Lots of drug interactions
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19
Q

Citalopram (Celexa)

A
  • Fewest drug-drug interactions

- Possibly fewer sexual side effects

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20
Q

Escitalopram (Lexapro)

A
  • Levo-Enantiomer of citalopram; similar efficacy, possibly fewer side effects
  • More expensive than citalopram
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21
Q

Comparative Side Effects SSRIs

A

SSRIs have significantly fewer side effects than TCAs and MAOIs due to serotonin selectivity (they do not act on histamine, adrenergic, or muscarinic receptors)

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22
Q

SSRIs in Overdose

A

SSRIs are much safer in overdose. Most side effects occur because of the extensive number of serotonin receptors throughout the body, including the GI tract.

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23
Q

When do SSRI side effects usually resolve?

A

Mostly resolve within a few weeks.

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24
Q

What are the SSRI side effects?

A
  • Sexual dysfunction (25-30 percent), decreased interest, anorgasmia, delayed ejaculation. These typically do not resolve in a few weeks.
  • GI disturbance: Mostly nausea and diarrhea, giving with food can help
  • Insomnia: also vivid dreams, often resolves over time
  • Headache
  • Anorexia, weight loss
  • Restlessness: an akathisia-like state has been reported at initiation and termination of SSRIs
  • Seizures: Rate of 0.2%, slightly lower than TCAs
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25
Q

OTC drugs that increase serotonin:

A

Drugs that inc. serotonin may be found in OTC cold remedies, possibly leading to serotonin syndrome. A classic example is someone on a high-dose antidepressant taking cough medicine.

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26
Q

How do you treat the sexual side effects of SSRIs?

A

Augment the regimen with buproprion, change to a non-SSRI antidepressant, or add medications like sildenafil for men

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27
Q

FDA Black Box Warning against all SSRIs for…

A

“increased suicidal thinking and behavior.” This is most documented in children and adolescents, but may be accurate for adults as well.

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28
Q

Serotonin Syndrome

A

Caused by taking two drugs, both of which increase serotonin and lead to too much serotonin in the brain. An example is triptans used with SSRIs. This is characterized by fever, diaphoresis, shivering, tachycardia, hypertension, delirium and neuromuscular excitability (especially hyperreflexia and “electric jolt” limb movements), potentially leads to death.

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29
Q

In what cases is Serotonin Syndrome common?

A

When serotonergic drugs are used with MAOIs. SSRIs should not be used for at least 2 weeks before or after use of an MAOI.

30
Q

What are two Serotonin-Norepinephrine Reuptake Inhibitors?

A

Venlafaxine (Effexor), Duloxetine (Cymbalta)

31
Q

How do SSRIs affect Warfarin?

A

SSRIs can lead to increased levels of warfarin, requiring increased monitoring when starting and stopping these medications

32
Q

Venlafaxine (Effexor):

A
  • Often used for depression, anxiety disorders like generalized anxiety disorder (GAD), and may have some use in attention deficit/hyperactivity disorder (ADHD)
  • Low drug interaction potential
  • Extended release (XR form) allow for once-daily dosing
  • Side effect profiles similar to SSRIs
  • Can Inc. blood pressure (BP); do not use in patients with untreated or labile BP
  • New form, desvenlafaxine (Pristiq) is the active metabolite of venlafaxine and is expensive
33
Q

Duloxetine (Cymbalta):

A
  • Often used for people with depression and neuropathic pain or in fibromyalgia
  • Side effects are similar to SSRIs, but more dry mouth and constipation relating to its norepinephrine effects
  • There may be more liver side effects in patients with liver disease or heavy alcohol use
  • Expensive
34
Q

Bupropion (Wellbutrin):

A
  • Norepinephrine Dopamine Reuptake Inhibitors
  • Relative lack of sexual side effects as compared to the SSRIs
  • Some efficacy in treatment of adult ADHD
  • Side effects include inc. risk of seizures and psychosis at high doses and inc. anxiety in some
  • Contraindicated in patients with patients with seizure or active eating disorders and in those currently on an MAOI
35
Q

Why should you be careful with bupropion?

A

Bupropion can lower seizure threshold. Use it with caution in patients with epilepsy and eating disorders.

36
Q

What is a well known side effect of Trazodone?

A

Priapism (trazodone will raise the bone)

37
Q

Trazodone (Desyrel) and Nefazodone (Serzone):

A
  • Serotonin receptor antagonists and agonists
  • Useful in treatment of refractory depression, major depression with anxiety, and insomnia (secondary to its sedative effects)
  • The do not have the sexual side effects of SSRIs and do not affect rapid eye movement (REM) sleep
38
Q

What is Nefazodone’s Black Box Warning?

A

For rare but serious liver failure (1 per 250,000-300,000 people)

39
Q

What are the side effects of Trazodone and Nefazodone?

A

Nausea, dizziness, orthostatic hypotension, cardiac arrhythmias, sedation and priapism (especially with trazodone)

40
Q

Mirtazapine (Remeron):

A
  • Alpha2-adrenergic receptor antagonists
  • Useful in treatment of refractory major depression, especially in patients who need to gain weight
  • Side effects include sedation, weight gain, dizziness, somnolence, tremor, dry mouth, constipation, and rare agranulocytosis
  • No sexual side effects and few drug interactions
41
Q

What is Mirtazapine (Remeron) often used for?

A

Depression in elderly - helps with sleep and appetite.

42
Q

What are Heterocyclic Antidepressants?

A

TCAs

43
Q

What is the mechanism for TCAs?

A

They inhibit reuptake of norepinephrine and serotonin, increasing availability of monoamines in the synapse.

44
Q

How often are TCAs dosed?

A

Because of long half-lives, most are dosed once daily.

45
Q

Why are TCAs rarely used as first-line agents?

A

Because they have a higher incidence of side effects, require greater monitoring of dosing, and can be lethal in overdose.

46
Q

What are the two types of Tricyclic Antidepressants?

A

Tertiary amines and Secondary amines

47
Q

What are the traits of tertiary amines?

A

Highly anticholinergic, more sedating, greater lethality in overdose.

48
Q

What are the four types of tertiary amines?

A
  1. Amitriptyline (Elavil)
  2. Imipramine (Tofranil)
  3. Clomipramine (Anafranil)
  4. Doxepin (Sinequan)
49
Q

Amitriptyline (Elavil)

A

Useful in chronic pain, migraines, and insomnia

50
Q

Imipramine (Tofranil)

A
  • Has intramuscular form

- Useful in enuresis and panic disorder

51
Q

Clomipramine (Anafranil)

A

Most serotonin specific, useful in treatment of OCD

52
Q

Doxepin (Sinequan)

A
  • Useful in treating chronic pain

- Emerging use as a sleep aid in low doses

53
Q

What are the two types of secondary amines?

A

Nortriptyline (Pamelor, Aventyl) and Desipramine (Norpramin)

54
Q

Traits of secondary amines:

A

Metabolites of tertiary amines (less anticholinergic, less sedating)

55
Q

Nortriptyline (Pamelor, Aventyl)

A
  • Least likely to cause orthostatic hypotension
  • Useful therapeutic blood levels
  • Useful in treating chronic pain
56
Q

Desipramine (Norpramin)

A
  • More activating; least sedating

- Least anticholinergic

57
Q

What is the mainstay of treatment for TCA overdose?

A

IV sodium bicarbonate

58
Q

What supply of TCAs can be lethal in overdose?

A

As little as 1-2 g.

59
Q

What are the two Tetracyclic Antidepressants?

A

Amoxapine (Asendin) and Maprotiline (Ludiomil)

60
Q

Amoxapine (Asendin)

A
  • Metabolite of antipsychotic loxapine

- May cause EPS and has similar side effect profile to typical antipsychotics

61
Q

Maprotiline (Ludiomil)

A

Higher rates of seizure, arrhythmia, and fatality on overdose

62
Q

What are the major complications of TCAs?

A

3 Cs:

  • Cardiotoxicity
  • Convulsions
  • Coma
63
Q

What are the traits of TCAs?

A

Highly protein bound and lipid soluble, and therefore can interact with other medication that have high protein binding.

64
Q

What is the cause of most TCA side effects?

A

Side effects are mostly due to lack of specificity and interaction with other receptors.

65
Q

What are the antihistamine side effects of TCAs?

A

Sedation

66
Q

What are the antiadrenergic properties of TCAs?

A

(Cardiovascular side effects): Orthostatic hypotension, dizziness, reflex tachycardia, arrhythmias, and electrocardiographic (ECG) changes (widening QRS, QT and PR intervals)

67
Q

In what patients should you avoid TCAs?

A

Patients with preexisting conduction abnormalities or recent MI.

68
Q

What are the antimuscarinic/anticholinergic effects of TCAs?

A

Dry mouth, constipation, urinary retention, blurred vision, tachycardia, exacerbation of narrow angle glaucoma

69
Q

What do TCAs do to weight?

A

Cause weight gain

70
Q

How often do seizures occur with TCAs?

A

Occur at a rate of about 0.3 percent, more common at higher plasma levels and with clomipramine and tetracyclics.

71
Q

Why must you assess suicide risk with patients on TCAs?

A

TCAs are lethal in overdose! Agitation, tremors, ataxia, delirium, hypoventilation from central nervous system (CNS) depression, myoclonus, hyperreflexia, seizures, and coma are signs of overdose.

72
Q

What are the serotonergic effects of TCAs?

A

Erectile/ejaculatory dysfunction in males, anorgasmia in females

ADPY 7500 (11 decks)

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