PSYCH - Anxiety, Depression, Mania Flashcards
What is the monoamine deficiency hypothesis of depression?
depression caused by under-activity or underproduction of monoamines (dopamine, serotonin, and norepinephrine) in the brain
What functions do anti-depressant drugs modulate?
initially thought to modulate monoamine neurotransmission, but now speculated to enhance synaptic plasticity, dendritic morphology, and neurogenesis (by modulating transcriptional activity)
Where are Serotonin, NE, and Dopamine produced in the brain? Where do these NT-producing cells project to?
Serotonin - raphe nucleus –> projects to amygdala/hippocampus (fear/anxiety, learning/memory)
NE - locus coeruleus –> various sites, but does NOT project to the amygdala/hippocampus
Dopamine - VTA–> projects to frontal lobes (executive functions, decision making)
Different classes of antidepressents exert their effects on different neurotransmitters. What NTs do these classes work on:
SSRI SNRI MAOi NDRI TCA SARI NaSSA
SSRI - Serotonin SNRI - NE NDRI - dopamine MAO - ALL TCA, SARI, NaSSA - Serotonin + NE
MAO Inhibitors can cause Serotonin syndrome and/or Hypertensive crisis. How does it do this?
What are the symptoms of each one?
MAO inhibitors blocks MAO from metabolizing serotonin, NE, and dopamine.
Serotonin syndrome and/or Hypertensive crisis occurs when patients are taking a MAOi + another anti-depressant (SSRI, SNRI or tyramine containing products - wine/cheese)
Serotonin Syndrome
- musculoskeletal changes (rigidity, myoclonus)
- autonomic instability (hyperthermia, cardiovascular instability)
- Neuromuscular signs - seizures
Hypertensive Crisis
- NE binds a1 receptors on vascular system, which causes vasoconstriction.
Why do patients have to be weaned on/off MAOi?
Long-term use of MAOi can lead to downregulation of beta-receptors; an abrupt stop in MAOi use can result in a rebound effect.
Which two antidepressants result in suicidal ideation in patients up to 25 years old?
What is an alternative for these patient populations?
SSRI (Citalopram) and SNRI (Venlafaxine)
Alternative: TCA (Nortriptyline)
Citalopram
Class:
Clinical use:
Major side effects:
Contraindications:
Class: SSRI
Clinical use: Depression + OCD
Major side effects: GI DISTURBANCES, QT prolongation, decreased sexual drive, MANIA, weight LOSS, but suicidal ideation in patients up to 25yo
Contraindications: MAOi, TCA, NSAIDs, St. John’s wort, or any drug that inhibits/enhances CYP450, and any drugs that induce QT prolongations (Class IA and Class III anti-arrhythmic drugs)
Which three antidepressants decrease sexual drive?
What is an alternative for these patient populations?
SSRI (Citalopram) and SNRI (Venlafaxine), TCAs (Nortriptyline)
Alternative: Bupropion (NDRI)
Which antidepressant decrease sexual drive?
What is an alternative for these patient populations?
TCAs
Alternative: Bupropion
Why is it that Citalopram causes GI disturbances?
Citalopram = SSRI
most serotonin receptors are present in the gut, so SSRIs tend to increase diarrhea and loose stools, but these tend to resolve quickly
Why is that Citalopram can cause mania?
Citalopram = SSRI
most patients with depression also have a comorbidity with bipolar disorder, thus SSRIs can induce mania in these patients, although the onset takes many years
Of the SSRIs, which one inhibits cytochrome P450 (thereby enhancing the effect of several drugs metabolized by this enzyme (ie TCAs, haloperidol, anti-arrhythmics)
Fluoxetine
Venlafexaine
Class:
Clinical use:
Major side effects:
Contraindications:
Class: SNRI
Clinical use: depression
Major side effects: increase BP, weight gain, sedation, suicidal ideation in patients up to 25yo
Contraindications: Hypertensive patients, MAOi, TCAs, NSAIDs,
Nortriptyline
Class:
Clinical use:
Major side effects:
Contraindications:
Class: TCA
Clinical use: depression + enuresis + pain
Major side effects: weight gain, sedation, decreased sexual drive, 3 C’s (coma, convulsions, cardiotoxicity), but NO suicidal ideation
Contraindications: patients in the acute post-MI phase
Tertiary TCAs are processed by the body ot produce Secondary TCAs. Give an example of how this changes the function.
Imipramine (3˚) –> desipramine (2˚)
blocks 5HT –> blocks NE
or
amitriptyline –> Nortriptyline
Bupropion
Class:
Clinical use:
Major side effects:
Contraindications:
Class: NDRI
Clinical use: depression + ADHD, smoking cessation, SAD
Major side effects: insomnia, tremors, seizures, but NO weight gain or decreased sexual drive
Contraindications: MAOi, TCA, NSAIDs, Levodopa, Tramadol, patients with eating disorders or patients with SEIZURES/EPILEPTIC DISORDERS because it increases the risk of seizures by lowering the seizure threshold.
Why is it that patients on MAOi can’t eat cheese, wine, or smoked meats?
MAO metabolizes tyramine, which is found in these products. MAOi prevent the metabolism of tyramine, which results in its accumulation in the gut.
High levels of tyramine stimulates the release of Epi + NE from the nervous tissue, thereby leading to a HTN crisis
Phenelizine
Tranylcypromine
Class:
Clinical use:
Major side effects:
Contraindications:
Class: MAOi
Clinical use: Atypical depression, Anxiety (patients with anxiety, phobic features, or hypochondriasis)
Major side effects: Serotonin Syndrome, HTN crisis
Contraindications: anti-depressants, smoked meats, wine, cheese
Mirtazapine
Class:
Clinical use:
Major side effects:
Contraindications:
Class: NaSSA
Clinical use: Depression
Major side effects: sedation, weight gain
Contraindications:MAOi or meds that are metabolized by CYP450 because Mirtazapine is a POTENT INHIBITOR of CYP450
Nefazodone, Trazodone
Class:
Clinical use:
Major side effects:
Contraindications:
Class: SARI
Clinical use: Depression
Major side effects: sedation, weight gain
Contraindications: meds that are metabolized by CYP450 because Nefazodone, Trazodone are POTENT INHIBITORS of CYP450
Diazepam
Class:
Clinical use:
Major side effects:
Contraindications:
Class: Benzodiazepines (binds to GABA receptor with alpha 1, 2, 3, 5 subunits)
Clinical use: anxiety, seizures/status epilepticus, OH withdrawal, anestheisa
Major side effects: sedation, altered mental status, ataxia
Contraindications: patients with liver dz or patients who use OH, barbiturates or other CNS depressants (ie opiates, cimetidine)
What is the mechanism of benzodiazepines?
binds to a site on the GABA receptor and enhances its activity (inhibitory effects), thereby leading to hyperpolarization and decreased activity in neurons of the limbic, thalamic, and hypothalamic regions of the CNS
Zolpidem
Class:
Clinical use:
Major side effects:
Contraindications:
Class: Benzodiazepines (binds to GABA receptor with alpha 1 subunit only)
Clinical use: insomnia only
Major side effects: anterograde amnesia, hallucinations, sleep walking+eating (esp. with bacon)
Contraindications: patients with liver dz or patients who use OH, barbiturates or other CNS depressants (ie opiates, cimetidine)
Buspirone
Class:
Clinical use:
Major side effects:
Contraindications:
Class: 5HT partial agonist
Clinical use: generalized anxiety disorder
Major side effects: dizziness, insomnia, nausea,
Contraindications: MAOi’s or patients with severely compromised liver/renal function
*can use with OH
