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Flashcards in Antidepressants Deck (32):

What is reactive (secondary) depression?

- temporary reaction to real stimuli such as grief or illness
- tx is mostly by psychotherapy


What is considered major depression?

- one or more major depressive episodes free of manic, mixed or hypomanic episodes


What is the lifetime prevalence of depression? When foes it usually onset?

9.6% in males and 20.4% in females
- onset is frequently 25-44 years of age


What are the emotional sx of major depression?

- inability to experience pleasure
- loss of interest in usual activities
- pessimistic outlook
- anxiety


What are the physical sx of depression?

- chronic fatigue, terminal insomnia, appetite disturbances


What are the cognitive symptoms of depression?

poor concentration, slow thinking, poor short term memory
- confusion


What are the psychomotor sx of depression?

- slowed physical movements and speech


What are the common non-pharm therapies for depression?

psychotherapy and ECT


What is the amine hypothesis?

-- depression is related to reduces synaptic levels of NE and 5HT
- autopsy showed reduced NE and 5HT metabolism in depressed suicide victims
--- this predicts that the amine NT are not being synthesized sufficiently
- most antidepressant drugs work by enhancing synaptic monoamines - do this by blocking normal neurotransmitter reuptake processes


What are the 2 phases of drug action in the synapse?

Phase 1- amine enhancement
- short term (min-hours); uptake inhibition
Phase 2- amine enhancement
- long term (weeks) effects of phase 1 enhancement - produces further enhances amine levels to reach therapeutic significance

--- longer term effects cause presynaptic auto-receptor down regulation


Understanding phase 2..

- normal scenario: presynaptic receptors feedback inhibit to stop the release of amines
- phase 1 causes homeostatic down regulation of these receptors to maintain "normal" agonist: receptor interaction levels- you have fewer inhibitory auto receptors here
- results in negative feedback and phase 2 amine release


What is the cellular feature that can be seem to correlate with improved mood?

presynaptic receptor down regulation directly correlates with improved mood
- down regulation occurs on a timescale that is quite common to the time that you get improvement in mood


What are the different classes of antidepressants?

-MAO inhibitors
- TCAs
-SNRIs and atypicals


Tricyclic Antidepressants

examples: amitriptyline, Imipramine, clomipramine, doxepin, protriptylline, desipramine
- Mechanism: mixed NE and 5HT reuptake inhibitors
- great variation in relative NE:5HT reuptake blockade potencies
-also used in neuropathic pain(NET effect)
- ALSO blocks cholinergic, histaminergic, a1 adrenergic receptors


What are the adverse effects of TCAs?

- antimuscarinic, cardiovascular (orthostatic hypotension, conduction defects), sedation, sympathomimetic (tremor, insomnia), neurologic (seizures), metabolic (weight gain, sexual disturbances), overdose (dangerous cardiac arrhythmias)


What are the drug interactions associated with TCAs?

- pharmacokinetic: CYP 2D6 inhibitors, highly protein bound
- pharmacodynamic: sedatives, sympathomimetics, antimuscarinics


What are the drug interactions associated with SSRIs?

- ex: fluoxetine, paroxetine, sertraline, citalopram
- MOA: block serotonin reuptake more effectively than NE
- no more effective than TCAs
- fluoxetine was used first - paroxetine and sertraline have shorter half lives- citalopram is the most SERT selective
- also drug interaction differences


What are the adverse effects of SSRIs?

- much less cholinergic, histaminergic, adrenergic receptor blockade than TCAs- more tolerable side effect profile
- safer than o/d
- associate with mild, short lived GI symptoms, headache
- sexual dysfunction, fatigue, insomnia can be problems
- paroxetine withdrawal - dizziness, nausea, tremor, anxiety
- platelet inhibition


What are the drug interactions associated with SSRIs?

Pharmacokinetic: strong CYP 2D6 inhibitors, TCAs, antipsychotics, beta blockers interfere with metabolism.
Pharmacodynamic: low non SERT interactions


What is the advantage of using SSRIs over TCAs?

- have equal efficacy with milder side effect profile
- much more favourable TI
- smaller chance of having additive drug interactions



- examples: venlafaxine, duloxetine, desvenlafaxine
-MOA: inhibits both serotonin and NE reuptake, but NOT TCA
- also weak dopamine reuptake inhibitors
- no affinity for muscarinic, a1 adrenergic or histaminergic receptors


What are the adverse effects of SNRIs?

- much lower incidence than TCAs, similar to SSRIs
- can include nausea, sweating, dizziness, anxiety, sexual dysfunction, hypertension


What are the drug interactions?

- limited pharmacodynamic
- protein binding varies: venlafaxine 30%, duloxetine >90%
- CYP 2D6 substrate


What is the advantage of SNRIs over SSRIs/TCAs?

- have a milder side effect profile over SSRIs?
- may be useful for depression with neuropathic pain
- fewer drug interactions
- potentially lower safety margin than SSRIs in O/D


Mirtazapine is considered what?

atypical antidepressants


What is the mechanism of action of mirtazapine?

- structurally a tetracyclic compound
- blocks a2 adrenergic receptors, thus increasing NE release
- low affinity for muscarinic, a1 adrenergic receptors
- potent blocker of histamine receptors


What are the adverse effects of mirtazepine?

-sedation, weight gain
- no anticholinergic effects
- less propensity for sexual side effects than SSRIs and TCAs


What are the advantages of mirtazapine?

- as tolerable as SSRIs
- anxiolytic/sedative effects can be useful (antihistamine)
- minimal cholinergic/ adrenergic drug interactions
- weight gain is a major drawback
-- this is a good drug to use when someone is concerned about sexual dysfunction!


What is the MOA of buproprion?

- does not inhibit NE or serotonin reuptake
- blocks DA reuptake weakly
-mild stimulant - treat comorbid fatigue/poor concentration, ADHD
- low affinity or muscarinic, a1 adrenergic or histaminergic receptors


What are the adverse effects of buproprion?

- much lower incidence than TCAs
- can include nausea, headache, dizziness, seizures.. no sexual dysfunction, weight gain and sedation


What drug interactions are involved with buproprion?

- meds that lower seizure threshold, L-dopa
- CYP 2D6 inhibitor

---- good option for a drug for people experiencing sexual dysfunction and also don't want weight gain


What are the first line therapies for treating depression?