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Psychopharm 4
Antipsychotics continued and Mood Stabilizers
56
Psychology
Professional
05/23/2012

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Term
Theraputic effects are delayed due to:
Definition
the time required for 5HT1A autoreceptors to downregulate/desensitize.
Term
Side Effects Appear When:
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
Term
Acute/excessive activation 5-HT2A/2C in amygdala, VMPFC
Definition
can lead to mental agitation, anxiety, panic
Term
Acute/excessive activation 5HT2A in basal ganglia
Definition
leads to decreased DA and akathisia, psychomotor retardation, mild parkinsonism, dystonia
Term
Acute/excessive activation 5HT2C in mesolimbic pathway
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
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
lead to nausea, vomiting
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
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
Inhibits pain
Term
a2 autoreceptor
Definition
binds NE on NE neuron
On dendrites/soma, inhibits firing leads to decreased release of NE
On terminal, inhibits release of NE
Term
a2 heteroreceptor
Definition
binds NE on 5-HT terminal
Inhibits release of 5-HT
Term
a1 receptor
Definition
binds NE on soma/dendrites of 5-HT neuron (in raphe nuclei)
Facilitates firing leading to increased release of 5-HT
Term
NE deficiency
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
bupropion
Term
NDRI
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
SE of NDRI
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
5HT2A
Definition
decreases dopamine (reward center) and thus SSRI's decrease libido, and Martazapine corrects because it antagonizes this receptor
Term
Mirtazapine
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.
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
Tricyclics (TCAs)
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
MAO (monoamine oxidase)
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
Do not use an MAOI
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
Serotonergic SEs
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
Another AD general SE
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
Other AD SEs
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
Serotonin syndrome
Definition
Confusion, psychosis, fever, sweating, diarrhea, restlessness, agitation, hyper-reflexia, tremor/myoclonus, migraines, seizures, brain damage, coma, death
Term
SSRI withdrawal syndrome
Definition
60% of pts; within several days, persisting 3-4 wks
“FINISH” sxs
Term
FINISH
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
Optimizing
Definition
Improve adherence if necessary
Psychotherapy can be invaluable
Check DDIs, including drug abuse
Increase Dose
Increase Time
Term
Augmenting:
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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