Mood stabilizers Flashcards by Britney N

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

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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

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*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

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*Good prognostic indicator for Lithium

episode pattern of mania, depression and euthymia

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*Good prognostic indicator for Carbamazepine

rapid cycling mania

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*Family hx r/t rx choices

When medications are or have been effective for family members, it is best to trial it

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*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

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What is the only med has indications for all 3 phases of bipolar disorder? (acute mania, acute bipolar depression, or maintenance)

quetiapine

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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

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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).

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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.

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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

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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?

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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

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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

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Bipolar I

full blown manic episodes usually followed by depressive episodes

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Bipolar II

at least one hypomanic episode and one major depressive episode

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can depression and mania occur together

yes can occur at same time= mixed mood state or mixed features

it’s a spectrum

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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

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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)

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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