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Pharmacology > Depression > Flashcards

Depression Flashcards

1
Q

Major depression diagnostic criteria?

A

At least 5 of the following (and 1 must include depressed mood or loss of interest) for more than two weeks.

  • Sleep - increased or decreased
  • Interest or lack thereof
  • Guilt (seen more in elderly, may feel worthless)
  • Energy - low
  • Cognition (confusion, concentration)
  • Appetite (less or more)
  • Psychomotor (lethargic, heaviness)
  • Suicidal ideation
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2
Q

Define persistent depressive disorder.

A

If you have depression that lasts for 2 years or longer, it’s called persistent depressive disorder. It does not have to meet as many criteria as for major depressive disorder.

This term is used to describe two conditions previously known as dysthymia (low-grade persistent depression) and chronic major depression.

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3
Q

What is the major mood stabilizer for bipolar?

A

Lithium

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4
Q

Describe the difference between bipolar I and II.

A

Bipolar I is characterized by extreme manic highs and extreme lows that meet criteria for major depression.

Bipolar II is characterized by these swings but less extreme.

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5
Q

Define seasonal affective disorder. What is the treatment?

A
  • Seasonal affective disorder is a period of major depression that most often happens during the winter months, when the days grow short and you get less and less sunlight. It typically goes away in the spring and summer.
  • If you have SAD, antidepressants can help. So can light therapy. You’ll need to sit in front of a special bright light box for about 15-30 minutes each day.
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6
Q

Define psychotic depression.

A

People with psychotic depression have the symptoms of major depression along with “psychotic” symptoms, such as:

  • Hallucinations (seeing or hearing things that aren’t there)
  • Delusions (false beliefs)
  • Paranoia (wrongly believing that others are trying to harm you)
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7
Q

Define peri or post partum depression. Treatment?

A

Women who have major depression in the weeks and months after childbirth may have peripartum depression.

Approximately 1 in 10 men also experience depression in the peripartum period.

Antidepressant drugs can help similarly to treating major depression that is unrelated to childbirth

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8
Q

Define premenstrual dysphoric disorder (PMDD). Treatment?

A

Women with PMDD have depression and other symptoms at the start of their period.

Besides feeling depressed, you may also have:

  • Mood swings
  • Irritability
  • Anxiety
  • Trouble concentrating
  • Fatigue
  • Change in appetite or sleep habits
  • Feelings of being overwhelmed

Treatment: Antidepressant medication or sometimes oral contraceptives can treat PMDD.

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9
Q

Define “situational depression”.

A

This isn’t a technical term in psychiatry. But you can have a depressed mood when you’re having trouble managing a stressful event in your life, such as a death in your family, a divorce, or losing your job. Your doctor may call this “stress response syndrome.”

Psychotherapy can often help you get through a period of depression that’s related to a stressful situation.

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10
Q

Define atypical depression.

A

This type is different than the persistent sadness of typical depression. It is considered to be a “specifier” that describes a pattern of depressive symptoms. If you have atypical depression, a positive event can temporarily improve your mood.

Other symptoms of atypical depression include:

  • Increased appetite
  • Sleeping more than usual
  • Feeling of heaviness in your arms and legs
  • Oversensitive to criticism
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11
Q

Treatment for atypical depression?

A

Antidepressants can help. Your doctor may suggest a type called an SSRI (selective serotonin reuptake inhibitor) as the first-line treatment.

They may also sometimes recommend an older type of antidepressant called an MAOI (monoamine oxidase inhibitor), which is a class of antidepressants that has been well-studied in treating atypical depression

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12
Q

What are the main neurotransmitters involved in mood regulation?

A
  1. Dopamine
  2. Norepenephrine
  3. Serotonin
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13
Q

What are the rates of depression each year in the U.S.? Lifetime prevalence?

A

Depression is a serious disorder that afflicts approximately 14 million adults in the United States each year.

The lifetime prevalence rate of depression in the United States has been estimated to include 16 percent of adults (21 percent of women, 13 percent of men), or more than 32 million people.

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14
Q

Most clinically useful antidepressant drugs potentiate, either directly or indirectly, the actions of which neurotransmitter(s)?

A

norepinephrine and/or serotonin

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15
Q

What is the biogenic amine theory?

A

It proposes that depression is due to a deficiency of monoamines, such as norepinephrine and serotonin (5HT), at certain key sites in the brain.

Conversely, the theory envisions that mania is caused by an overproduction of these neurotransmitters.

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16
Q

What are SSRI’s?

A

Selective Serotonin Reuptake Inhibitors: A group of chemically diverse antiepressant drugs that specifically inhibit serotonin reuptake, having 300- to 3000-fold greater selectivity for the serotonin transporter as compared to the norepinephrine transporter.

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17
Q

Why have SSRI’s larglye replaced TCA’s and MOA’s in treating depression?

A

They have fewer adverse effects and are safer even in overdose. Orthostatic hypotension, sedation, dry mouth and blurred vision are seen with TCA’s but not SSRI’s.

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18
Q

What are the common SSRI’s?

A
  1. Citalopram
  2. Escitalopram
  3. Fluoxetine
  4. Fluvoxamine
  5. Paroxetine
  6. Sertraline
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19
Q

How long do antidepressants, including SSRI’s, take before they are effective?

A

Two weeks to produce significant improvement. Maximum benefit may require up to 12 weeks or more.

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20
Q

What percentage of depressed patients do not respond to the first antidepressant they try?

A

40%

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21
Q

What percentage of people will respond to at least one antidepressant drug?

A

80%

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22
Q

Other than depression, what other psychiatric disorders respond to SSRI’s?

A
  • Bulimia nervosa (only fluoxetine)
  • Generalized anxiety disorder, social anxiety
  • Obsessive Compulsive Disorder (only fluvoxamine)
  • Panic Disorder, PTSD
  • PMDD premenstrual dysphoric dysorder
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23
Q

What are the common health problems caused by anorexia nervosa? What medication is contraindicated?

A
  • Amenorrhea
  • Infertility
  • Low BMI
  • Osteoporosis

Bupropion contraindicated

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24
Q

What are common health conditions from bulimia nervosa? What is the best medication? What are some common signs to help diagnose bulimia?

A
  • Esophageal and tooth damage
  • Heart failure
  • normal or high BMI

SSRI’s are best for this

Bupropion is contraindicated

Signs: Enamel erosion, Parotitis, Russell sign (callouses on knuckles)

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25
Q

Do people purge when they have a binge eating disorder? What medication is best?

A

No. Purging is associated with bulimia. Binge eating is its own disorder. It responds best to stimulants and orlistat.

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26
Q

How well are SSRI’s absorbed with oral administration? How long until peak level? What is the average half life?

A

SSRI’s are well absorbed and food has little effect on absorption (except for sertraline which is increased)

Peak levels occur around 8 hours.

Most SSRI’s have a half life of 16-36 hours.

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27
Q

How is fluoxetine (Prozac) different from other SSRI’s?

A
  1. Much longer half life of 50 hours. Available as once weekly sustained release
  2. The metabolite is as potent as the parent compound and half life of metabolite is 10 days.
28
Q

How are SSRI’s primarily excreted? Exceptions? What should you do for a patient with hepatic impairment?

A

Primarily excreted through kidneys.

Exception: Paroxetine and sertraline also undergo fecal excretion (35% P, 50% S)

Dosages of all SSRI’s should be adjusted DOWN for people with hepatic impairment.

29
Q

What are some common adverse effects of SSRI’s?

A
  • Anxiety/agitation
  • Fatigue
  • GI effects
  • Headaches
  • Sexual dysfunction
  • Sleep disturbance
  • Sweating
  • Weakness
  • Weight change
30
Q

Which SSRI’s are more sedating than activating, good for people with insomnia?

A

Paroxetine and Fluvoxamine

Remember: Fluvoxamine best for OCD, thinking too much, sedate

Paroxetine, think par, para, parasympathetic, sedate

31
Q

Which SSRI’s are more activating, good for patients with fatigue or somnolence?

A

Fluoxetine or Sertraline

Think: Fluoxetine (prozac) hyper, long half life, working for days, activate

Sertraline, easily absorbed, go getter, activator

32
Q

Although uncommon, sexual dysfunction (loss of libido, delayed ejaculation, anorgasmia) can occur with SSRI’s. What is an option for managing this?

A

Replace the offending antidepressant with an atypical one having few sexual side effects such as Bupropion or Mirtazapine.

Think: Bu - boo, love, sex, Prop - sex toys

Mirt, mirth, girth, increase appetite for sex (and food)

33
Q

Some men experience erectile dysfunction along with depression. What might be the best treatment? Caution?

A

Vasodilators (Sildenafil, Tadalafil, Vardenafil)

Caution: do not co-administer with nitrates. Risk of life threatening hypotension!

34
Q

What is serotonin syndrome? What are the symptoms?

A

Serotonin syndrome is a cluster of autonomic, motor and mental status changes resulting from excess serotonin.

Symptoms include

  • Agitation
  • Clonus muscle twitching
  • Diaphoresis
  • Hyperthermia
  • Hypertensive
  • Muscle rigidity
  • Mental status changes
  • Mydriasis
  • Sweating
  • Tachycardia
  • Tremor
35
Q

Interactions of which drugs are likely to cause serotonin syndrome?

  • MAOI’s
  • SSRI’s
  • TCA’s
  • Antibiotics
  • Anti nausea
  • Cough medicine
  • Drugs of abuse
  • Opiates
  • Triptans
A
36
Q

How do SNRI’s work? When are they chosen?

A

Serotonin-Norepinephrine Reuptake Inhibitors

These selectively inhibit reuptake of both 5HT and NE.

Second line antidepressants. They may be effective in treating depression in patients in whom SSRI’s are ineffective.

They are also helpful to treat chronic painful symptoms like backache and muscle aches, which SSRI’s cannot help with.

37
Q

Name two common SNRI’s.

A

Duloxetine (think dual, 5HT and NE)

Venlafaxine (think Venn diagriam, overlap of two or three, sometimes dopamine)

38
Q

Can SSRI’s cause cardiac problems or seizures?

A

Large intake of SSRI’s does not usually cause cardiac problems (copmared to the risk from TCA’s) but seizures are a possibility.

39
Q

All SSRI’s have the potential to cause serotonin-related discontinuation syndrome. What are the symptoms of this? Which agents have the lowest risk of this problem?

A
  • Agitation
  • Flu like symptoms
  • Headache
  • Malaise
  • Sleep problems

The drugs with shorter half lives and inactive metabolites have a higher risk.

Fluoxetine with the longest half life and active metabolites has teh LOWEST risk.

40
Q

Diabetic neuropathy is best treated with which drugs?

A

SNRI’s first, TCA’s second

41
Q

What are the neurotransmitter interactions of Venlafaxine? Side effects?

A

Potent inhibitor of serotonin reuptake. Inhibitor of NE reuptake at medium to high doses. Mild inhibitor of dopamine at high doses.

Venn diagram - reuptake inhibitor of three NT

At high doses there my be increased heart rate and blood pressure.

More common side effects are more benign like constipation, headache, insomnia and sexual dysfunction.

42
Q

Describe the neurotransmitter interactions of Duloxetine? Contraindications?

A

Inhibits serotonin and norepinephrine at ALL doses.

Contraindicated for patients with hepatic insufficiency as it is extensively metabolized in the liver.

Metabolites excreted in uring, not recommended for end stage renal disease patients.

43
Q

What is the half life of Duloxetine? Side effects?

A

Half life approximately 12 hours. Food delays.

Most common side effects are GI problems like dry mouth, nausea, constipaiton.

Diarrhea and vomiting, insomnia and sweating less common.

Most bothersom are sexual dysfunciton, increase BP and HR.

44
Q

What are the atypical antidepressants? Why would they be used?

A

Mixed group of agents with with actions at several different sites. Not any more efficacious than others but side effect profiles are different.

  • Bupropion
  • Mirtazapine
  • Nefazadone
  • Trazadone
45
Q

How does Bupropion work? When would it be chosen?

A

Weak dopamine and norepinephrine reuptake inhibitor. Short half life means more than once a day dosing.

Unique in that it decreases craving and withdrawal symptoms for nicotine in smokers.

Similar side effects to other antidepressants except it has a very low incidence of sexual dysfunction

46
Q

How does Mirtazapine work? When would it be chosen?

A

Enhances serotonin and norepinephrine neurotransmission due to ability to blcok presynaptic receptors.

Sedative effects because of potent antihistaminic activity, but does not cause antimuscarinic side effects.

Does not interfere with sexual functioning!

Increased appetite and weight gain frequently occur. Good choice for elderly who are not sleeping or eating properly.

47
Q

How do Nefazodone and Trazadone work? What medical problem is Trazadone associated with causing?

A

Both are weak inhibitors of serotonin reuptake. They block postsynaptic receptors. Increase serotonin release over time.

Trazadone has been associated with priapism.

48
Q

How do TCA’s work?-

A

TCA’s block norepinephrine and serotonin reuptake into presynaptic nerve terminals. This causes increased concentrations of monoamines in the synaptic cleft, ultimately resulting in antidepressant effects. They are not as selective for it as SNRI’s as they also block serotonergic, adrenergic, histaminic and muscarinic receptors.

49
Q

What are the names of the most important TCA’s?

A
  • Amitriptyline
  • Clomipramine
  • Desipramine (selective only to NE)
  • Doxepin
  • Imipramine
  • Nortriptyline
  • Protriptyline
  • Trimipramine

Amoxapine is a tetracyclic though generally included as well.

50
Q

What are the major actions of TCA’s?

A

Elevate mood, improve mental alertness, increase physical activity and reduce morbid preoccupation in 50-70 percent of indivduals with major depression. Some TCA’s can also treat panic disorder or more specific issues.

51
Q

Other than depression, what is imipramine used for? Caution?

A

Used to control bed wetting in children (older than six years) by causing contraction of the internal sphincter of the bladder. Cautiously used as it can cause cardiac arrhythmias and other cardiovascular issues.

52
Q

What is amitryptyline commonly used for?

A

Migraine headache and chronic neuropathic pain syndromes in a number of conditions for which the cause of pain is unclear.

53
Q

What are some of the adverse effects of TCA’s and why?

A

Weight gain is common. Sexual dysfunction is possible though lower than SSRI’s.

Blockade of histamine receptors leads to sedative effects.

Blockade of muscarinic receptors leads to:

  • Blurred vision
  • Constipation
  • Dry mouth (xerostomia)
  • Glaucoma
  • Urinary retention

Blockade of adrenergic receptors:

  • Dizziness
  • Orthostatic hypotension
  • Reflex tachycardia
54
Q

Describe the therapeutic index for TCA’s.

A

They have a narrow therapeutic index. For example, five to six fold the maximal daily dose of imipramine can be lethal. Depressed patients who are suicidal should be given limited quantities and monitored.

55
Q

Why should TCA’s (and all antidepressants) be used cautiously in bipolar patients?

A

They may cause a switch to manic behaviour.

56
Q

What is monoamine oxidase? What does it do?

A

MAO is a mitochondrial enzyme found in nerve and other tissues, such as the gut and liver.

In the neuron, MAO functions as a safety valve to oxidatively deaminate and inactivate any excess NT molecules (NE, 5HT, Dopamine) that may leak out of synaptic vesicles when the neuron is at rest.

57
Q

How do MAO inhibitors work?

A

They form stable complexes with the enzyme MOA, causing irreversible (or sometimes reversible) inactivation. This results in increased stores of norepinephrine, serotonin and dopamine within the neuron and subsequent diffusion of excess NT in the synaptic cleft.

58
Q

What are the three MAO inhbitors currently available for the treatmeent of depression?

A

Phenelzine

Tranylcypromine

Selegiline (approved for Parkinson’s as well, available transdermally)

59
Q

Why are the use of MAO inhibitors now limited?

A

Patients require complicated dietary restrictions. These drugs inhibit not only MAO in the brain but also MAO in the liver and gut that catalyze oxidative deamination of drugs and potentially toxic substancces, such as tyramine, which is found in certain foods. Individuals on MAOI’s are unabel to degrade tyramine in food and my experience hypertensive crisis!

60
Q

How long does it take for MAO inhibitors to work?

A

MAO is fully inhibited after several days however the antidepressant action is delayed several weeks.

61
Q

What side effects do selegiline and tranylcypromine have?

A

They have an amphetamine-like stimulant effect that may produce agitation or insomnia.

62
Q

Although MAOI’s are considered last line agents owing to their risk for drug-drug and drug-food interactions, they are used in specific cases. When would they be chosen?

A
  • Depressed patients who are unresponsive or allergic to TCA’s
  • Patients with low psychomotor activity
  • Useful in high anxiety or treatment of phobic states
  • Atypical depression characterized by labile mood, appetite disorder and rejection sensitivity
63
Q

What is the first line treatment for people with manic-depressive states? How does it work? What perecent of patients benefit?

A

Lithium salts

Uncertain how it works

60-80% of bipolar patients

64
Q

What is the therapeutic index of lithium salts? What are some adverse effects?

A

Therapeutic index is extremely low, comparable to digitalis.

Common adverse effects:

  • dizziness
  • dry mouth
  • fatigue
  • GI disorder
  • hand tremor
  • polydipsia
  • polyuria
  • polyphagia
  • sedation

More serious effects:

  • ataxia
  • confusion
  • convulsions
  • course tremors
  • hypothyroidism
  • slurred speech
65
Q

What other medications have been approved for bipolar disorder?

A
  • Antiepileptic drugs: carbamazepine, valproate, lamotrigine
  • Antipsychotics
  • Atypical antipsychotics (risperidone, olanzapine, quetiapine)
  • Benzodiazepines for acute stabilization

Pharmacology (5 decks)

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