Mood stabilizers Flashcards
Considerations w/ depakote & lamictal together
- Concurrent dosing Depakote and Lamictal (CYP 450 strong inducers and inhibitors) = Lamictal dose must be halved when taken with Depakote
- Depakote is a mild-moderate CYP-450 inhibitor
- Depakote inhibits Lamictal ===== Slows metabolism of Lamictal
=====Increased levels of Lamictal in blood ====Risk of toxicity====Cut
dose in half
Lamictal- dose, indication, SE
Lamotrigine (Lamictal)
*100-200mg
* Efficacy for bipolar depression
* No blood monitoring
* S/E: dizziness, ataxia, headache somnolence, nausea, diplopia
* Can cause idiosyncratic liver injury
RARE: Steven Johnson Syndrome (life threatening rash involving the
skin and mucus membranes)
**Start low and go slow
*Teratogenic risks with mood stabilizers
Carbamazepine (Tegretol): Neural tube defects
Lithium(Eskalith): Epstein anomaly
Divalproex sodium (Depakote): Neural tube deficits- specifically spina bifida, atrial septal defects, cleft palate and possible long-term developmental deficits
*Good prognostic indicator for Lithium
episode pattern of mania, depression and euthymia
*Good prognostic indicator for Carbamazepine
rapid cycling mania
*Family hx r/t rx choices
When medications are or have been effective for family members, it is best to trial it
*Considerations with antidepressants in bipolar disorder
Caution using antidepressants in Bipolar patients – it may trigger a rapid switch in polarity (patients may go rapidly from depressed to mania
What is the only med has indications for all 3 phases of bipolar disorder? (acute mania, acute bipolar depression, or maintenance)
quetiapine
Other than meds, what can also be considered as appropriate monotherapy for depression?
The treatment of depression has a more streamlined treatment algorithm. Psychotherapy has been shown to be as effective as medication for patients and can be considered for monotherapy in mild to moderate depression cases or for those patients who are wary of starting medication
What antidepressant is superior in efficacy?
There are no antidepressants that are superior in efficacy so it is generally accepted to trial several of the second-generation antidepressants (SSRIs, SNRIs, etc.) as monotherapy or in combination before moving on to the first-generation antidepressants (TCAs, MAOIs).
What are two newer second generation antipsychotics that can also be indicated for mood disorders?
Cariprazine (Vraylar) is indicated for the acute treatment of manic or mixed episodes associated with bipolar I disorder (monotherapy) and brexpiprazole (Rexulti) for adjunctive treatment of MDD.
3 of the most common sx of depression w/ mixed features (DMX) that are NOT DSM-5 dx criteria & why?
irritability, distractibility, and psychomotor agitation are among the most common symptoms of DMX, they are excluded from DSM-5 mixed features criteria due to the overlap of these symptoms with other disorders (e.g., anxiety disorders) and between mania and depression
What’s one of the most important question to ask EVERY patient with depression EVERY time?
Any manic/hypomanic symptoms
and/or
family history of bipolar disorder?
Required sx to be present for dx major depressive episode
Must be at least one:
depressed mood or apathy/loss of interest
Must be 4 of these:
weight/appetite change
sleep disturbances
psychomotor agitation/ retardation
fatigue
guilt/worthlessness
executive dysfunction
SI
Required sx to be present for dx manic episode
Must be at least one:
elevated/expansive mood or irritable mood
Must be 4 of these:
inflated self esteem/grandiosity
increased goal directed activity or agitation
risk taking
decreased need for sleep
distractible/concentration
more talkative pressure speech
flight of ideas/racing thoughts
Bipolar I
full blown manic episodes usually followed by depressive episodes
Bipolar II
at least one hypomanic episode and one major depressive episode
can depression and mania occur together
yes can occur at same time= mixed mood state or mixed features
it’s a spectrum
criteria for manic/hypomanic episode with mixed features
full criteria for manic/hypomanic episode
AND
at least 3:
depressed mood
loss of interest/pleasure
psychomotor retardation
fatigue/loss of energy
feelings of worthlessness/excessive/inappropriate guilt
recurrent thoughts of death or SI/actions
criteria for depressive episode with mixed features
full criteria for major depressive episode AND at least 3:
elevated/expansive mood (feeling high, excited, hyper)
inflated self esteem/grandiosity
more talkative than usual/feeling pressured to keep talking
flight of ideas/subjective experience that thoughts are racing
increase in energy or goal directed activity
increased/excessive involvement in activities that have bad consequences
decreased need for sleep
*(NOT included: psychomotor agitation, irritability, distractibility)
why do you want to make early accurate dx for dipolar disorder?
unipolar vs bipolar depression cannot be readily distinguished on basis of patient’s current sx, there are hints that can raise suspicion of bipolar depressive episode
*missing dx bipolar depression early may lead to worse quality of life d/t giving the wrong tx which= ineffective or dangerous. Increases risk mood cycling, relapse, suicide, decreased chance of responding to correct bipolar med later on
Key indicators that patient has bipolar over depression
family hx & get hx of patient from someone close to them like mother or spouse
sx more common in bipolar:
family hx bipolar
family hx substance abuse
comorbid substance abuse
suicide attempts
early age onset < 25 y/o
irritability
psychotic sx
mood reactivity
restlessness
psychomotor agitation
psychomotor retardation
shorter depressive episodes
more previous depressive episodes
guilty
melancholia
how much more likely is it for pt to have bipolar disorder instead of depression if first degree relative with bipolar
8-10 fold greater risk of developing bipolar depression vs general population
what neurotransmitters are associated w/ mood disorders
classically: monomaine transmission of norepinephrine, dopamine, & serotonin
recently: glutamate and GABE w/ associated ion channels
Norepinephrine
noradrenergic neuron utilizes
produced from tyrosine which then becomes dopamine which then becomes norepinephrine (NE)
what enzymes terminates norepinephrine
monoamine oxidase (MAO) or catechol-O-methyltransferase (COMT)
or by transport pump for NE that removes but doesn’t destroy (NE reuptake pump)
what do presynaptic alpha 2 autoreceptors do for NE
act like stepping on a brake- turn off further release of NE
drugs can mimic action
GABA (y-aminobutyric acid)
principle inhibitory neurotransmitter in brain, reduces activity of many neurons
produced by glutamate
GABA a/b/c are the 3 major types of receptors
what’s important determination of the function of GABA a
depends upon which isoform subunits present, receptor action can vary quite a bit
monoamine hypothesis of depression
classic theory, depression is d/t deficiency of monoamine neurotransmission. Simplistic “chemical imbalance”, more complicated than that
lacking evidence
monoamine receptor hypothesis and neurotrophic factors (of depression)
abnormality in monoamine receptors trigger downstream molecular events including regulation of gene expression and production of growth factors; compensatory upregulation of postsynaptic neurotransmitter receptors; lowers levels of monoamine neurotransmitters
all leading to depression
no solid evidence for this hypothesis either
Neuroplasticity and neuroprogression hypothesis of depression
depression not simply monoamine deficiency- classic drugs for depression raise monoamine level immediately but clinical improvements take weeks
Molecular events:
evidence of delayed down regulation of neurotransmitter receptors following immediate elevation of monoamines after antidepressant drugs
downstream synthesis of growth factors like BDNF
**environmental factors (stress, inflammation, adversity, microbiome, illness, etc) = loss growth factors = neuro progression starting with lack of synaptic maintenance > loss of synapses and dendritic arborization > loss of neurons
also theory of hypothalamic-pituitary-adrenal axis dysregulation in depression = neurodegeneration. High levels of glucocorticoids with chronic stress could contribute to atrophy of neurons
neuroinflammation may cause depression- chronic stress, obesity, illness, adversity, etc.
circadian rhythm disorder could cause depression
what else is an important factor related to impaired functioning in mood disorders (especially depression) other than sadness?
cognitive symptoms
hippocampal decline in depression
memory worsens with increasing depressive episodes
cognitive dysfunction r/t # passed episodes not severity of current presentation
cognitive sx can endure longer than mood sx in MDD
In mood disorders, what can different symptoms be linked to in brain?
each of 9 sx listed for dx depression or mania can be mapped onto brain circuits whose inefficient information processing theoretically mediates these sx
what innervates brain circuits that are linked to sx of mood disorders
the 3 monoamine neurotransmitter systems: norepinephrine, dopamine, serotonin
*glutamate & GABA are found everywhere (ubiquitous) throughout every area of brain
List each monoamine neurotransmitter & if dysfunction associated with increase/decrease in positive/negative affect
dopamine dysfunction= reduction of positive affect
serotonin dysfunction= increase in neg affect
norepinephrine dysfunction= both reduction of positive affect and increase in neg affect
sx reduced positive affect
(dopamine dysfunction & maybe norepinephrine dysfunction)
depressed mood, loss of joy, loss of interest/pleasure, loss of energy/enthusiasm, decreased alertness, decreased self-confidence
sx of increased negative affect
(serotonin dysfunction & maybe norepinephrine dysfunction)
depressed mood, guilt/disgust, fear/anxiety, hostility, irritability, loneliness
what symptoms of depression and mania are linked with prefrontal cortex brain circuit?
DEPRESSION
mood
guilt, suicidality, worthlessness
psychomotor (mental) fatigue
concentration, interest/pleasure
MANIA
racing thoughts
grandiosity
distractibility
talkative/pressured speech
mood
risks
what symptoms of depression and mania are linked with basal forebrain brain circuit?
DEPRESSION
0
MANIA
decreased sleep/arousal
what symptoms of depression and mania are linked with striatum brain circuit?
DEPRESSION
pleasure
interests
fatigue/energy
physical/psychomotor fatigue
MANIA
racing thoughts
goal-directed
grandiosity
motor/agitation
what symptoms of depression and mania are linked with thalamus brain circuit?
DEPRESSION
0
MANIA
decreased sleep/arousal
what symptoms of depression and mania are linked with hypothalamus brain circuit?
DEPRESSION
sleep
appetite
MANIA
decreased sleep/arousal
what symptoms of depression and mania are linked with amygdala brain circuit?
DEPRESSION
guilt
suicidality
worthlessness
mood
MANIA
mood
what symptoms of depression and mania are linked with spinal cord brain circuit?
DEPRESSION
physical fatigue
MANIA
0
what symptoms of depression and mania are linked with cerebellum brain circuit?
DEPRESSION
psychomotor
MANIA
0
neurotransmitters to target for sleep sx in depression
Need to block: 5HT & histamine
Boost: GABA
neurotransmitters to target for concentration sx in depression
boost norepinephrine or dopamine
neurotransmitters to target for fatigue sx in depression
boost norepinephrine or dopamine
What are the classes of antidepressants
- selective serotonin reuptake inhibitors (SSRIs)
- serotonin-norepinephrine reuptake inhibitors (SNRIs)
- tricyclic antidepressants (TCAs)
- monoamine oxidase inhibitors (MAOIs)
- norepinephrine-dopamine reuptake inhibitors (NDRIs)
- mixed serotonin receptor agonists/antagonists (SRAs)
- alpha-2 adrenergic receptor antagonists
