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HSHD 2 Block 3 > Antidepressants and Mood Stabilizers > Flashcards

Antidepressants and Mood Stabilizers Flashcards

1
Q

Types of antidepressant medications

A

•Selective serotonin reuptake inhibitors (SSRIs)

First line in treatment of MDD and Anxiety disorders

  • Serotonin-norepinephrine reuptake inhibitors (SNRIs)
  • Tricyclic antidepressants
  • Monoamine oxidase inhibitors (MAOIs)
  • Atypical antidepressants
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2
Q

How is serotonin synthesized and stored

A

Serotonin = 5-hydroxytryptamine (5HT)

Synthesized from tryptophan in the presynaptic neuron by 2 enzymes:

Tryptophan hydroxylase (TRY-OH) converts tryptophan to 5-hydroxytryptophan (5-HTP)

Aromatic amino acid decarboxylase (AAADC) coverts 5-HTP to 5HT

After synthesis, 5HT is taken up into synaptic vesicles by vesicular monoamine transporter (VMAT2) and stored there until it is needed in neurotransmission

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3
Q

How are the effects of serotonin terminated

A

5HT action is terminated by:

Monoamine oxidase (MAO) – converts into inactive metabolites. There are MAO-A and MAO-B

Serotonin transporter (SERT) – presynaptic transport pump. Clears 5HT out of synapse and back into presynaptic neuron

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4
Q

Black box warning for antidepressants

A

increased risk of suicidal thoughts and behaviors among children and adolescents taking antidepressant medications

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5
Q

MOA of SSRIs

A

Inhibition of serotonin reuptake transporter (SERT)

Increases available 5HT in synapse

Will inhibit SERT everywhere that it is found

  • GI tract – GI side effects
  • Platelets – GI bleeding
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6
Q

Indications for SSRIs

A
  • Major depressive disorder
  • Anxiety disorder – generalized anxiety disorder, social phobia, panic disorder
  • PTSD
  • OCD – at higher doses than used to treat mood or anxiety disorders
  • Premenstrual dysphoric disorder
  • Bulimia
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7
Q

Side effects of SSRIs

A
  • Most common: GI distress – nausea, abdominal pain
  • Most common side effect causing discontinuation: sexual dysfunction
  • GI bleeding
  • Serotonin Syndrome
  • Black Box Warning: Increased risk for suicidal ideation and behaviors in children and adolescents (under the age of 24)
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8
Q

Clinical considerations for SSRIs

A
  • Take 4-6 weeks to become effective
  • Relatively safe and well tolerated
  • Taper when discontinuing to prevent discontinuation syndrome
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9
Q

Examples of SSRIs and characteristics

A

Fluoxetine (Prozac)

Sertraline (Zoloft)

Citalopram (Celexa)

Escitalopram(Lexapro)

Paroxetine(Paxil)

Fluvoxamine(Luvox)

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10
Q

MOA of Serotonin-Norepinephrine Reuptake Inhibitors (SNRI)

A

Inhibition of serotonin reuptake transporter (SERT) and norepinephrine transporter (NET)

Increases available 5HT and NE in synapse

Nonspecific

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11
Q

Indications for SNRIs

A
  • Major depressive disorder
  • Bipolar depression
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12
Q

Side effects of SNRIs

A

Most common: hypertension, sweating, GI symptoms

  • Associated with sexual dysfunction, but much less than SSRI
  • GI bleeding
  • Serotonin Syndrome
  • Black Box Warning: Increased risk for suicidal ideation and behaviors in children and adolescents (under the age of 24)
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13
Q

Special populations for SNRIs

A
  • Contraindicated in patients with uncontrolled hypertension
  • Caution in patients with hepatic impairment
  • Contraindicated in patients with eating disorders (anorexia and bulimia)
  • Pregnancy – use with extreme caution, SSRI preferred
  • Elderly – use with caution, SSRI preferred
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14
Q

Clinical considerations for SNRIs

A

Due to noradrenergic activity, can exacerbate anxiety and PTSD symptoms

Discontinuation syndrome is significant, taper slowly

Onset of action is faster than with SSRIs, usually within 2-4 weeks

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15
Q

Examples of SNRIs and characteristics

A

Venlafaxine (Effexor)

Duloxetine (Cymbalta)

Others

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16
Q

MOA of Tricyclic Antidepressants (TCA)

A

Inhibition of serotonin reuptake transporter (SERT) and norepinephrine transporter (NET)

Inhibition of H1-histaminic receptors

Inhibition of M1-muscarinic cholinergic receptors

Inhibition of α1-adrenergic receptors

Inhibition of voltage-gated sodium channels is problematic in overdose

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17
Q

Signs of TCA

A

Can be lethal in overdose – usually requires ICU admission

“Triple C” of TCA overdose

•Convulsions

•Coma

•Cardiotoxicity – wide QRS complex tachycardia

•Dry mouth, nausea, vomiting, urinary retention, headache

•Can cause hypotension

•Apnea

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18
Q

Indications for TCAs

A
  • Major depressive disorder
  • Bipolar depression
  • Anxiety disorders
  • Fibromyalgia, neuropathic pain
  • See individual drugs for additional indications
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19
Q

Side effects of TCAs

A

•Sedation, weight gain, orthostatic hypotension

•Anticholinergic side effects – dry mouth, constipation, urinary retention, blurred vision

  • Arrhythmias – it is recommended to check an EKG prior to initiation, monitor QTc interval
  • Seizures
  • Sexual dysfunction, GI bleeding
  • Serotonin Syndrome
  • Black Box Warning: Increased risk for suicidal ideation and behaviors in children and adolescents (under the age of 24)
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20
Q

Special populations of TCAs

A

Pregnancy – all category C, use with caution

Epilepsy – can decrease seizure threshold, use with caution

Elderly – use with extreme caution due to anticholinergic side effects and increased risk for falls

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21
Q

Examples of TCAs and

A

Amitriptyline

Imipramine

Clomipramine

Doxepin

22
Q

What is serotonin syndrome

A

Confusion, agitation, fever, autonomic instability, hyperreflexia, myoclonus, nausea, diarrhea

Typical onset within hours of extra serotonin administration

Due to excess of serotonin in the CNS

23
Q

TX for serotonin syndrome

A
  • Supportive
  • Benzodiazepines for agitation
  • Cyproheptadine – 5HT2 receptor antagonist (serotonin antagonist)
24
Q

Monoamine Oxidase

A

Enzyme responsible for breakdown of monoamine neurotransmitters as well as monoamines ingested in food

  • Located on the outer membrane of mitochondria
  • Two forms
  • MAO-A
  • MAO-B
25
Q

Differences between MAO-A and MAO-B

A
26
Q

MOA of MAOIs

A

Inhibit action of monoamine oxidase, preventing breakdown of monoamine neurotransmitters

Inhibition of both MAO-A and MAO-B causes increase in dopamine, serotonin, and norepinephrine

  • MAOIs are one of the only therapeutic strategies to increase dopamine in depression
  • Can be reversible, irreversible, selective or nonselective
27
Q

Function of Tyramine and caution

A

Tyramine increases the release of norepinephrine

Under normal circumstances, MAO-A readily destroys the excess norepinephrine

In the presence of MAOI, NE destruction is inhibited, leading to accumulation of NE and excessive stimulation of postsynaptic adrenergic receptors –> vasoconstriction and hypertension –> hypertensive emergency

28
Q

Dietary restrictions with MAOIs

A
  • Patients must be advised of adherence to a specific diet to avoid foods high in tyramine
  • Aged cheese

•Tap/unpasteurized beer

•Certain wines

•Soy products

29
Q

Drug interactions with MAOIs

A
  • Sympathomimetic drugs – increase in norepinephrine
  • Decongestants (phenylephrine, pseudoephedrine)
  • Stimulants (amphetamine, methylphenidate, modafinil,armodafinil)

Antidepressants with NE reuptake inhibition (TCAs, NRIs, SNRIs, NDRIs)

Phentermine

Local anesthetics containing vasoconstrictors

Tramadol

Cocaine, methamphetamine

Anesthetics – risk of vasoconstriction

Wash out MAOI for 10 days prior to surgery

30
Q

MAOI contraindications

A

SSRIs, SNRIs, clomipramine, St. John’s Wort

MDMA, cocaine, methamphetamine

Opioids: meperidine, tramadol, methadone, fentanyl

Others: dextromethorphan

2 week washout period for most drugs (3 weeks for fluoxetine

This is all due to serotonin syndrome

31
Q

Examples of MAOIs and characteristics

A

PHENELZINE, TRANYLCYPROMINE, ISOCARBOXAZID

SELEGELINE

32
Q

What are the atypical antidepressants

A

Buproprion (wellbutrin)

Mirtazapine (Remeron)

Trazodone, Nefazodone

33
Q

Burproprion MOA

A

Inhibition of reuptake of dopamine and norepinephrine (NDRI)

34
Q

Buproprion indications

A

Major depressive disorder

Bipolar depression

Non-stimulant treatment of adult ADHD

Smoking cessation (Chantix)

Obesity

35
Q

Buproprion side effects

A
  • Seizures
  • Headache
  • Increased anxiety
  • Black Box Warning: Increased risk for suicidal ideation and behaviors in children and adolescents (under the age of 24)
36
Q

Buproprion special indications and considerations

A
  • Contraindicated in patients with epilepsy
  • Contraindicated in patients with eating disorders
  • Contraindicated in patients with active severe alcohol use disorder / alcohol withdrawal
  • Not associated with sexual dysfunction – used to treat patient that have intolerable sexual dysfunction with other antidepressants
  • Faster onset of action
37
Q

Mirtazapine (Remeron) MOA

A

•α2-receptor antagonist – increases release of serotonin and norepinephrine

•5HT3 receptor antagonist – protects against serotonin induced GI side effects

•H1 (histamine) receptor antagonist – sedation, weight gain

38
Q

Mirtazapine indications

A
  • Major depressive disorder
  • Bipolar depression
  • Anxiety disorder – generalized anxiety disorder, social phobia, panic disorder
  • PTSD
  • Appetite stimulation
39
Q

Mirtazapine side effects

A
  • Sedation
  • Weight gain
  • Orthostatic hypotension
  • Constipation
  • Black Box Warning: Increased risk for suicidal ideation and behaviors in children and adolescents (under the age of 24)
40
Q

Mirtazapine special populations and considerations

A
  • Use with caution in elderly – sedation can increase risk for falls
  • Less sexual side effects than other antidepressant medications
  • Faster onset of action
  • Useful as sleep aid and to stimulate appetite
41
Q

Trazodone, Nefazodone MOA

A
  • Antagonist at 5HT2A – sedation
  • Antagonist of H1 (histamine) receptor – sedation
  • Antagonist of α1-adrenergic receptor – sedation
  • At very high doses SERT antagonist – antidepressant
42
Q

Trazodone, Nefazodone indication and side effects

A

Used as hypnotic agent due to extreme sedation at doses required to treat depression

  • Black Box Warning: Increased risk for suicidal ideation and behaviors in children and adolescents (under the age of 24)
  • Sedation

•Priapism

43
Q

Lithium MOA and clearance

A

MOA is unknown

•Cleared from the body through glomerular filtration, some reabsorbed with sodium through proximal tubule

44
Q

Lithium indications

A
  • Acute treatment of mania
  • Maintenance therapy in bipolar disorder
  • Bipolar depression
  • Adjunctive agent for treatment of unipolar depression
  • Prevent suicide in patients with mood disorders
45
Q

Lithium side effects

A
  • GI side effects: dyspepsia, nausea, vomiting, diarrhea
  • Weight gain, hair loss
  • Tremor
  • Polydipsia, polyuria
  • Nephrogenic diabetes insipidus (due to ADH antagonism)
  • Long term side effects: adverse effects on thyroid (hypothyroidism) and kidney (acute and/or chronic kidney failure)
46
Q

Lithium special populations and monitoring

A
  • Pregnancy – contraindicated, causes Ebstein’s anomaly
  • Contraindicated in patients with kidney disease

Prior to initiating therapy AND periodically must check:

•Renal function

•TSH

  • Narrow therapeutic window: 0.6-1.2
  • Monitor EKG – can prolong QTc
47
Q

Lithium toxicity (acute v chronic)

A

Acute toxicity – think GI

  • Vomiting, diarrhea
  • Volume depletion

Chronic toxicity – think neurologic symptoms

  • Tremor, ataxia, hyperreflexia
  • Altered mental status
48
Q

Lithium drug interactions

A

Lithium concentration is increased by:

  • Loop diuretics (furosemide)
  • Thiazide diuretics
  • ACE inhibitors
  • NSAIDs
49
Q

Valproate info

A
50
Q

carbamazapeme info

A
51
Q

Oxcarbazepine (Trileptal) info

A
52
Q

Lamotrigine info

A

HSHD 2 Block 3 (15 decks)

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