Term
| Theraputic effects are delayed due to: |
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Definition
| the time required for 5HT1A autoreceptors to downregulate/desensitize. |
|
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Term
| Side Effects Appear When: |
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Definition
As soon as postsynaptic receptors (especially 5HT2) are activated by the increase in 5HT caused by antagonism of transporter
Dissipate when postsynaptic receptors have downregulated or desensitized |
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Term
| Acute/excessive activation 5-HT2A/2C in amygdala, VMPFC |
|
Definition
| can lead to mental agitation, anxiety, panic |
|
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Term
| Acute/excessive activation 5HT2A in basal ganglia |
|
Definition
| leads to decreased DA and akathisia, psychomotor retardation, mild parkinsonism, dystonia |
|
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Term
| Acute/excessive activation 5HT2C in mesolimbic pathway |
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Definition
| lead to decreased DA and apathy, anhedonia, and decreased libido |
|
|
Term
| Acute/excessive activation 5HT2C/2A in VTA & locus coeruleus |
|
Definition
| lead to decreased DA & NE, respectively, in prefrontal cortex and deficits in attention, cognition |
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Term
| Acute/excessive activation 5HT2A in brainstem sleep areas |
|
Definition
| lead to nocturnal myoclonus (perhaps by disinhibition of cholinergic neurons), disruption of slow-wave sleep, awakenings |
|
|
Term
| Acute/excessive activation 5HT3 in hypothalamus, area postrema |
|
Definition
|
|
Term
| Acute/excessive activation 5HT2A/2C in lower spinal cord |
|
Definition
| lead to delayed organism, anorgasmia |
|
|
Term
| Acute/excessive activation 5HT3/4 in GI |
|
Definition
| lead to motility (cramps, diarrhea) |
|
|
Term
| Increased activation of 5-HT1A receptors |
|
Definition
| lead to decreased negative affect (dysphoria, rumination, guilt/disgust, worthlessness, loneliness, fear/anxiety, irritability, hostility, suicidality) |
|
|
Term
| Noradrenergic ascending system |
|
Definition
| soma of neurons located in locus coeruleus & projecting widely to cortex, cerebellum |
|
|
Term
| From locus coeruleus to Prefrontal cortex |
|
Definition
| regulates mood, attention |
|
|
Term
| From locus coeruleus to Limbic cortex |
|
Definition
| regulates emotions as well as energy, fatigue, psychomotor agitation/retardation |
|
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Term
| From locus coeruleus to Cerebellum |
|
Definition
| Inhibits pain regulates motor movements, especially tremor |
|
|
Term
| From NE neurons in lower brainstem to spinal cord |
|
Definition
|
|
Term
|
Definition
binds NE on NE neuron
On dendrites/soma, inhibits firing leads to decreased release of NE
On terminal, inhibits release of NE |
|
|
Term
|
Definition
binds NE on 5-HT terminal
Inhibits release of 5-HT |
|
|
Term
|
Definition
binds NE on soma/dendrites of 5-HT neuron (in raphe nuclei)
Facilitates firing leading to increased release of 5-HT |
|
|
Term
|
Definition
| decrease in “positive affect” and increase in “negative affect” |
|
|
Term
| Antagonizing NE re-uptake |
|
Definition
| increase positive affect and decreasing negative affect |
|
|
Term
| serotonin norepinephrine reuptake inhibitors |
|
Definition
Somewhat more activating because of NE
May be more likely to induce mania in bipolar pts
If NE is increased, activation is not usually excessive due to blunting by 5-HT.
-also increases DA in prefrontal cortex.
-Good for very severe depression or highly recurrent depression, which don’t respond well to SSRI’s |
|
|
Term
| Why does NRI also increases DA in prefrontal cortex |
|
Definition
| DA in PFC normally taken up by NE reuptake mechanisms |
|
|
Term
| norepinephrine dopamine reuptake inhibitor |
|
Definition
|
|
Term
|
Definition
Used when increased activation/stimulation is advantageous to treat “reduced positive affect”
Switch to or augment w/ buproprion when SSRI or SNRI fails to treat these sx’s or causes them |
|
|
Term
|
Definition
| restlessness, anxiety, tremor, insomnia, psychosis, generalized seizures (very rare w/ extended-release forms), panic in susceptible pts, switch to mania. |
|
|
Term
| Drugs that have Alpha 2 antagonism properties |
|
Definition
| antidepressant, anxiolytic effects. |
|
|
Term
|
Definition
| decreases dopamine (reward center) and thus SSRI's decrease libido, and Martazapine corrects because it antagonizes this receptor |
|
|
Term
|
Definition
Effective for decreasing anxiety
Often used for insomnia
Sleep induction (at doses lower than 15 mg due to H1 antagonism)
Restorative sleep due to 5HT2A antagonism
Wt gain is common.
Such wt gain may be beneficial for elderly, pts w/ wasting diseases or pts w/ anorexia. |
|
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Term
| SARIs (serotonin 2A antagonist/reuptake inhibitors |
|
Definition
Know this line: Used mainly for sleep (at low dose)
Very sedating (blocks H1, 1 receptors)
Hypnosis is main use due to small antidepressant effect at tolerable doses.
Used as adjunct to antidepressants by blocking some SEs associated w/ stimulation of 5HT2A receptors (anxiety, agitation, insomnia, sexual dysfunction)
Orthostasis and dizziness are common; priapism may rarely occur.
trazodone and nefazodone |
|
|
Term
|
Definition
Inhibit reuptake of 5HT & NE to varying degrees, depending on exact drug
Currently used to augment newer AD’s or for pain
Demonstrated efficacy in adults but not in youth
No abuse potential (no effect on DA)
Antagonism of voltage-gated Na+ channels leading to seizures, coma, arrhythmia, death in overdose.
Antagonism of numerous receptors (M1, H1, alpha1) causes many side effects (SEs). |
|
|
Term
| Tricyclics (TCA) half-lives |
|
Definition
Long, 22-95 hours, Especially critical for elderly (cognitive impairment,
falls, constipation, urinary retention) |
|
|
Term
|
Definition
| metabolizes 5-HT, DA, NE, EP |
|
|
Term
| MAOI’s (monoamine oxidase inhibitors) |
|
Definition
Considered “gold standard” of drugs for MDD
Can decrease “negative affect” and increase “positive affect”
Can cause hypertensive crisis & fatal strokes (the “cheese effect”) if taken with foods that contain tyramine
Tyramine potently releases NE. |
|
|
Term
| MAO inhibitors are used when |
|
Definition
Other ADs or combinations have failed
Atypical depression, depression in the elderly, dysthymia, panic disorder, phobia, anorexia nervosa, bulimia, or hypochondriasis |
|
|
Term
|
Definition
With a drug that can cause serotonin syndrome
If pt has cardiovascular or cerebrovascular disease, pheochromocytoma, frequent or severe headaches, or will have elective surgery requiring general anesthesia |
|
|
Term
| When switching to of from a MAOI |
|
Definition
Must wait for 5 weeks after D/C of a serotonergic drug before initiating MAOI.
Must wait for 2 weeks after D/C of MAOI before initiating another antidepressant. |
|
|
Term
| SPAs (5-HT1A partial agonists) |
|
Definition
| property have antidepressant & anxiolytic effects. Ex: buspirone (BuSpar)and vilazodone (Viibryd®) |
|
|
Term
| SEs of TCAs and antidepressants in general: |
|
Definition
Vary w/ drug, patient, DDI’s
Most usually occur early (within 2 wks) and then dissipate to various degrees. |
|
|
Term
|
Definition
Nausea
Anxiety/activation
Sleep disturbance
Akathisia (restlessness)
Sexual dysfunction
Least likely w/ bupropion (Wellbutrin®) |
|
|
Term
| Catecholaminergic (DA, NE) |
|
Definition
Activation
Sympathomimetic (jacked up Sympathetic nervous system) |
|
|
Term
| One of the general ADs SEs: behavioral activation (irritability, hypomanic sx’s) |
|
Definition
Primarily due to 5-HT2 (Increased Glu activity) May occur within hrs of starting or increasing dose; usually gone in 10 days. May signal switching to mania in bipolar
Usually during first 2-3 wks, but as late as 2 months later
Can increase suicidality/suicide risk |
|
|
Term
|
Definition
Risk of increased suicidality in pts < 24 yrs of age on ADs:
All AD’s have black box warning.
Sometimes, vegetative sxs (appetite, sleep, energy) improve before mood sxs.
Highest risk for completed suicides with increased energy but still depressed
One study indicated highest risk in first 9 days |
|
|
Term
| Greatest risk of suicidality |
|
Definition
| First 9 days (Pt's getting more energy and motivation to actually follow through with ideation) |
|
|
Term
|
Definition
Worsening of depression
Gradual cognitive & affect blunting
Occurs w/ most AD’s
Seizure risk (all AD’s lower seizure threshold)
Hypertension
Most seen w/ Effexor
Allergies
Most common sx’s are hives/rash
Orthostasis (blocking alpha1 receptor)
Rare w/ newer generation AD’s
Mainly w/ trazodone |
|
|
Term
| Hypertensive crisis when MAOI’s added to |
|
Definition
Drugs that stimulate alpha1 postsynaptic vascular receptors, such as the decongestants (phenylephrine & pseudoephedrine)
Stimulants (amphetamines, methylphenidate) |
|
|
Term
MAO’s added to:
ADD’s with NRI
NRI’s
SNRI’s
NDRI’s
TCA’s |
|
Definition
| DDI’s more common & can be more lethal than MAOI’s-tyramine |
|
|
Term
|
Definition
| Confusion, psychosis, fever, sweating, diarrhea, restlessness, agitation, hyper-reflexia, tremor/myoclonus, migraines, seizures, brain damage, coma, death |
|
|
Term
|
Definition
60% of pts; within several days, persisting 3-4 wks
“FINISH” sxs |
|
|
Term
|
Definition
Flulike sxs (lethargy, myalgias, chills, headache)
Insomnia (including vivid dreams)
Nausea (nausea, vomiting, diarrhea)
Imbalance (dizziness, vertigo, ataxia)
Sensory sxs (paresthesia sensation of electric shocks in limbs or head)
Hyperarousal (anxiety, agitation)
Hyperactivity, depersonalization, dysphoria, cognitive dysfunction may occur. |
|
|
Term
| Antihistaminic (blocking H1 receptor) |
|
Definition
Sedation
Especially w/ Luvox, Remeron (at doses lower than 15 mg), trazodone (at lower doses of 25-50 mg)
Weight gain
Especially w/ Remeron
Wellbutrin is only one that does not. |
|
|
Term
| All SSRI’s except citalopram (Celexa®) and escitalopram (Lexapro®) |
|
Definition
| inhibit all 4 major families of isoenzymes. |
|
|
Term
| Choosing an Antidepressant (KNOW) |
|
Definition
| diagnose properly and go beyond dxs and treat sxs & problems of that unique person |
|
|
Term
| Most common reason for lack of response |
|
Definition
-Inadequate standard treatment
-Other reeasons: permanent neurologic impairment, naddressed psychological issues, and toxic living environment |
|
|
Term
|
Definition
Improve adherence if necessary
Psychotherapy can be invaluable
Check DDIs, including drug abuse
Increase Dose
Increase Time |
|
|
Term
|
Definition
2nd antidepressant from a different class
Add NDRI or 5-HT1A partial agonist to SSRI
T3 (Cytomel) or T4 (e.g., Synthroid)
lithium
Other agents as sxs require
Psychotherapy may:
Increase or prolong therapeutic effects
Decrease probability of relapse or recurrence
If no remission, try Remeron + Effexor = “California rocket fuel” or MAOI |
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