Neuro Pt 3 Depression, Schizophrenia, Bipolar Disorder Flashcards
Depression
- Definition:
- Depressed mood most of the time for > __ weeks and/or loss of ____ or _____ in most activities
- DSM V Criteria: __ or more (must include the first 2)
- _____
- _____
- Change in w____ or a____
- I____ or hyper_____
- Psychomotor r_____ or a______
- Loss of e____ or f_____
- ___lessness or g____
- Impaired con_____ or in______
- Thought of d____ or ______ ideation or suicide _____
- Definition
- 2, interest, pleasure
- 5
- Depressed mood
- Loss of interest or pleasure
- weight, appetite
- insomnia, hypersomnia
- retardation, agitation
- energy, fatigue
- worthlessness, guilt
- concentration, indecisiveness
- death, SI, attempt
Pathophysiology of Depression
- Hypotheses
- Neurotrophic - brain derived neurotrophic factor (BDNF) _____
- Neurotransmitters - deficiency of (3)
- Neuroendocrine - hormonal imbalances of (2)
- Genetic factors account for up to 50% of depression
- Treatment
- _____ amount of neurotransmitter available at the synaptic clef (noradrenergic, serotoninergic)
- _____ rate at which neurotransmitter is taken back up into presynaptic neuron
- _______ neurotransmitter’s metabolic degradation
- _____ amount of neurotransmitter available at the synaptic clef (noradrenergic, serotoninergic)
- Hypothesis
- Deficiency
- Serotonin (5HT), Norepinephrine (NE), Dopamine (DA)
- Estrogen, Testosterone
- Tx
- Increase
- Decrease
- Inhibit
- Increase
BDNF is a protein in our brain that helps the growth of neurons
Treatment for Depression
(5)
- Tricyclic Antidepressants (TCAs)
- Monamine oxidase Inhibitors (MAOIs)
- Selective-serotonin reuptake inhibitors (SSRIs)
- Selective-norepinephrine reuptake inhibitors (SNRIs)
- Others (miscellaneous)
- Buproprion (Wellbutrin)
List in order of discovery, worked on AE when making new drugs
Time of Onset
- How long does it take to reach full effect of medication?
- 1-2 wks
- Improved ____
- Reduced _____
- 1-3 wks
- Improved ____, _____
- Increased ____ level, ____ level
- 2-4 wks
- Improved ____
- Reduced ____
- 4-6 weeks (counselling!!)
- 1-2 wks
- sleep
- anxiety
- 1-3 wks
- self-care, concentration
- energy, activity
- 2-4 wks
- mood
- suicidal ideation
Tricyclic Antidepressants (TCA)
Indication
- _____ available (prior to 1980s and discovery of SSRIs)
- Today reserved for _____ disease
- earliest
- refractory
TCA
MOA
- ________ inhibition of ______ and _____ ______ (allows for increased NE to bind to receptors at synaptic cleft)
- Secondary amines more ____ for ___ (potency)
- Other receptor effects:
- a1-adrenergic blockade - (1)
- Histamine 1 receptor (1)
- Anticholinergic (2)
- Sodium and calcium channel blockade (1)
- Non-selective inhibition of norepinephrine (NE) and serotonin (5HT) reuptake
- selective for NE
- orthostatic hypotension
- sedation
- dry mouth, constipation
- cardiotoxicity
TCA
Tertiary Amines (2)
Secondary Amines (1)
Prevalence of use?
- Tertiary Amines
- Amitriptyline (Elavil)
- Doxepin (Sinequan)
- Secondary Amines -> Lack active metabolites and have linear kinetics (wide therapeutic window)
- Nortriptyline (Pamelor)
- First class of antidepressant medications available, however, side effects have limited their use
Secondary amines are the newer group
TCA
AE (5)
- Antihistamine (sedation, weakness, fatigue)
- Anticholinergic (dry mouth, blurred vision, constipation, urinary retention)
- a1-receptor blockade (hypotension)
- Sodium channel blockade (arrhythmias, QTc prolongation)
- Other (sexual dysfunction, seizure potential, weight gain, photosensitivity, hepatotoxicity, withdrawal if stopped abruptly (titrate slowly))
- BC its SO NONSELECTIVE - it causes all these AE*
TCA
Drug Interactions (3)
-
MAOI
- MAOIs inhibit the breakdown of neurotransmitters (dopamine, serotonin, norepinephrine)
- HTN, tachycardia, confusion, seizures
- Serotonin syndrome
- MAOIs inhibit the breakdown of neurotransmitters (dopamine, serotonin, norepinephrine)
- SSRIs - may lead to Serotonin Syndrome
-
Alcohol and other CNS depressants
- Additive effects (drowsiness, diziness)
- Worsen depression
Almost never given with any other antidepressant - don’t really see combinations
Monamine Oxidase Inhibitors (MAOIs)
Indication
Due to potential serious adverse effects from drug and food interactions, NOT used as first line therapy (more for refractory)
MAOI
MOA
Irreversible inhibition of monamine oxidase (1-2 wks to restore)
Responsible for metabolism of NE, 5HT, Dopamine within the neuronal synapse
MAO-A - nonselective (NE, 5HT)
MAO-B - selective for dopamine
In depression, we do the opposite of PD where we use lower doses - we want higher doses to target the NE and 5HT
MAOI
Agents
Selegiline (Emsam)
(non-selective inhibits both MAO-A and B)
MAOI
Significant AE
- Postural Hypotension
- Hypertensive Crisis (food interaction)
- Sleep disturbances
- Weight gain
MAOI
Significant Drug Interactions
Drug-Food Interactions
- TCAs
- SSRIs
- Sympathomimetic agents (cocaine)
- Linezolid (abx) - also has MAOI properties so you can see additive effects of blocking those
- MAO inhibition may persist up to 10-14 days following discontinuation (remember irreversibly binds)
- Tyramine content (aged cheeses, meats, yeast extract, red wine) Bananas, dried fruits
Selective Serotonin Reuptake Inhibitors (SSRIs)
Indication
Targeted the results of TCAs without the histamine/cholinergic/adrenoceptor properties
GOLD STANDARD DRUG OF CHOICE*
SSRI
MOA
Blocks serotonin transporter (SERT)
- Blocking reuptake of 5HT into presynaptic neuron = increased circulating 5HT for post synaptic uptake
SSRI
Agents
Late 1980s
Fluoxetine (Prozac, Prozac weekly)
Paroxetine (Paxil, Paxil CR)
Sertraline (Zoloft)
Fluvoxamine (Luvox)
Citalopram (Celexa)
Escitalopram (Lexapro)
SSRI
Fluoxetine
Half life?
Active Metabolites?
- ~5 days (requires 5 week washout)
- YES
Remember, takes about 5 half lives for drug to be eliminated
SSRI
AE
- CNS
- CV
- Hematologic
- GI
- Sexual Dysfunction
- Weight gain
- Withdrawal syndrome (4)
- Incidence of orthosatic hypotension, sedation, anitcholinergic SE, and CV effects are significantly less than ____
- Fluoxetine - activating (insomnia) take in the morning, Paroxetine - sedating take at night so not tired all the time
- QT prolongation with citalopram and escitalopram
- Increased risk for bleeding (esp w ASA, NSAIDs, anticoag)
- N/V, diarrhea (GI effects more early on esp if started with high dose thats why we start slow and titrate up)
- SSRIs have highest incidence
- Paroxetine > all others
- GI complaints, flu-like symptoms, anxiety, insomnia (if abruptly dc’d)
- TCAs
SSRI
Drug Interactions (3)
- Timing if converting between SSRIs and MAOIs
- *fewest drug interactions with (3)
MAOIs, TCAs, Linezolid (has MAO inhibition)
- Wait up to 5 weeks after stopping (Fluoxetine) SSRI before starting MAO
- Wait 2 weeks after stopping MAOI before starting SSRI
- citalopram, escitalopram, sertraline
- ex) if pt on SSRI and admitted for infection and given linezolid = given together can cause hypertensive crisis/serotonin syndrome*
- UP to 5 weeks since other ones take shorter to clear*
AB is a 33 yo F started on fluoxetine (Prozac) for depression. Fluoxetine has a half life of ________, should be taken in the ______, and is known to cause _____ side effects when compared to amitriptyline
- 24 hrs, morning, less
- 24 hrs, evening, less
- 5 days, morning, less
- 5 days, evening, less
- 5 days, morning, more
5 days, morning, less
Serotonin Syndrome
Life threatening central excitatory syndrome rd INCREASE serotonin
- Hyperthermia, confusion, agitation, autonomic hyperactivity, myoclonus, hyperreflexia, diaphoresis, tremor, diarrhea, neuromuscular abnormalities, ocular clonus
- Tx: stop + supportive care
- Non antidepressant meds associated (anti-emetics, dextromethorphan, fentanyl, linezolid, meperidine, serotonin agonists sumatriptan, tramadol, valproic acid)
Buproprion (Wellbutrin)
Indications
MOA
Route
Pharmacokinetics
Significant AE (3)
- Adjunctive tx for depression
- Blocks reuptake of dopamine and norepinephrine
- PO only
- Hepatically metabolized through CYP2D6
- Lowers seizure threshold (high doses/abrupt withdrawal), Activating (tremor, insomnia), No sexual dysf/weight gain
- The newer the drugs the MOA gets shmancy*
- Doesn’t touch serotonin - also used off label for smoking cessation so if pt has both can help both*
- However if pt suffers from epilepsy don’t want to use bc lowers seizure threshold*
- Just know its a SUBSTRATE of CYP - so if given with inducer may lower serum levels*
Selective Norepinephrine Reuptake Inhibitors (SNRIs)
MOA
Bind to serotonin (SERT) and norepinephrine (NET) transporters
- prevents reuptake of both 5HT and NE (selective for NE)
SNRI
Route
All PO
SNRI
Agents
Venlafaxine (Effexor) - Immediate and ER
Desvenlafaxine (Pristiq)- ER
Duloxetine (Cymbalta)
Miilnacipran (Savella)
SNRI
Significant AE
- Hypertension (NE)
- Sexual Dysfunction
- Insomnia (take in morning)
- Nausea
- NOREPI-so all flight or flight AE- take in morning*
- Sexual dysfunction bc again too much 5HT effects release of some hormones*
Boxed Warning for All Antidepressants
- Important to monitor pts for failure to ____ or ____ sx of depression when these drugs are ___ or dose is _____
Antidepressants increase risk of SUICIDAL THINKING and BEHAVIOR in children, adolescents, and young adults (18-24yo) with major depressive disorder and other psychiatric disorders
- respond, worsening, started, increased
- Bc takes time to work and they are stimulating, gives ppl the strength to commit suicide while suicidal ideation not yet gone away*
Management of Depression
- Antidepressant pharmacotherapy initiated, follow up in __ weeks
- For partial or no response what do you do?
- For full response what do you do?
- Assess response __-__ weeks
- For partial or no response what do you do?
- For full response what do you do?
-
2 weeks
- Assess adherance-Increase doseif clinically indicated and no issues with tolerability -Consider ECT for severe symptoms
- Maintain treatment if no issues with tolerability
-
4-6 weeks
- Increase dose OR Change to alternative antidepressant in same class OR Change/Augment psychotherapy OR Consider ECT
- Move to continuation phase
Assessing adherence = always first step - esp in neuropsych disorders ppl more prone to noncompliance - may have negative attitudes toward med/too expensive
Depression in Pregnancy
- Reported in __-__% of pregnant women
- Mild to moderate depression
- _____ pharmacotherapy unless ____ hx
- _____/_____ FIRST LINE
- Severe depression
- _____/____ pharmacotherapy
- Which drug is safest? Less likely to cross into breast milk?
- Which drugs to for sure avoid bc causes birth defects?
- If previously failed multiple therapies, okay to continue
- _____/____ pharmacotherapy
- 14-23%
- discontinue, severe
- CBT/interpersonal psychotherapy
- Initiate/continue
- Sertraline
- Paroxetine/Fluoxetine
Really try not to use antidep bc teratogenic
Which of the following is an MAOI used to treat depression?
- Sertraline (Zoloft)
- Notriptyline (Pamelor)
- Seligiline (Emsam)
- Fluvoxamine (Luvox)
Seligiline (Emsam)
Schizophrenia
“to split” “mind”
- _____ characterized by a clear sensorium but a marked thinking disturbance
- Typical onset:
- Diagnosis
- Reduced _____ + __ of any _____ or ____ symptoms
- Persistent for at least ___ months
- Not necessarily ______
- Psychosis
- Late adolescence, early adulthood
- functioning, 2 of positive or negative
- 6
- violent
Schizophrenia Positive Symptoms
Definition
- D_______
- H_______
- Disorganized ____
- Unusual _____
- Ho_____
- Ex_____
- G_____
Acute episodes of psychosis “positive symptoms”, often accompanied by a decline in overall functioning over time secondary to “negative symptoms”
- Delusions
- Hallucinations
- speech
- behavior
- Hostility
- Excitement
- Gradiosity
Schizophrenia Negative Symptoms
- _____ affect
- Lack of m_____ and p_____
- _____ withdrawal
- Un_____ness
- _____ withdrawal
- Poverty of ______
- Blunted
- motivation, pleasure
- Emotional
- Uncooperativeness
- Social
- Speech
Negative = lacking
Neurotransmitter Hypotheses of Schizophrenia
- Pathophysiology remains ________, but thought to be related to complex neurotransmitter alterations
- Dopamine receptor _____
- Dopamine hyperactivity (caudate nucleus)
- _____ symptoms
- Dopamine hypoactivity (frontotemporal regions)
- _____ symptoms and _____ dysfunction
- Dopamine hyperactivity (caudate nucleus)
- Serotonin receptros (5HT-2a)
- Present on dopaminergic axons
- ______ 5HT concentrations found in schizophrenia
- Receptor responsible for regulation of glutamate, NE, DA, stabilizing NMDA receptor, GABA
- unknown
- defect
- positive
- negative, cognitive
- 5HT2
- Higher
In general we treat shiz by blocking dopamine and 5HT (serotonin)
Antipsychotic Drugs
MOA (2)
Which one alleviates positive and which one alleviates negative?
- Dopamine receptor blockers inhibit the release of DA and thereby alleviate positive symptoms
- Serotonin (5HT2) receptor agonist/antagonist** can alleviate **negative symptoms of schizophrenia
Antipsychotic Drug Sx Relief
Counsel on duration to symptom relief
- Initially:
- 2-8 wks:
- Late > 8 wks:
- aggression
- attention, anxiety, socialization
- hallucinations, disturbances
- Initially aggression will subside w the D2 blockers (we dont’ often use 1st gen but in acute phase we use them esp for acute aggression)*
- Takes time to work effectively -> v difficult to treat -> sometimes hospitalizatin if harm to themselves*
Typical Antipsychotics
MOA
D2 receptor antagonists (also block muscarininc, histamine, and a1 receptors) - Positive symptoms only
1st Gen: similar to TCAs they are nonselective -> also have tendency to bind to alot of receptors -> very sedating bc of histamine blockade, orthostatic hypotension nc of a1 receptors, anticholinergic
Typical Antipsychotics
Agents
- Phenothiazines
Chlorpromazine
Fluphenazine
- Butyrophenones
Haloperidolol (Haldol)
We don’t really see typical (1st gens) used chronically, really for decompensated schiz when presenting with positive symptoms - aggression, psychosis, SI
Haloperidol (Haldol)
Routes
Tablet
Injection
Solution
Depot
One time doses at hospital when ppl acting up
Typical Antipsychotics
AE
Anticholinergic SE
Orthostatic hypotension
QTC prolongation
EPS
Hyperprolactinemia
Atypical Antipsychotics
MOA
Block D2 receptors to a lesser extent vs. typicals and block 5HT-2A receptors
All may dissociate rapidly from D2 receptors (less EPS) and 5HT1 agonist (reduce glutamate release)
Atypical Antipsychotics
Agents
Clozapine (Clozaril)
Olanzapine (Zyprexa)
Quetiapine (Seroquel)
Aripiprazole (Abilify)
Risperidone (Risperdal)
Lumateperone (Caplyta)
Atypical Antipsychotics
Advantages (3)
Disadvantages (2)
Less sedation, movement disorders, tardive dyskinesia
More weight gain, metabolic disturbances
Less AE however more weight gain/metabolic dist. - this limitation maybe dt serotonin like phenomonen
Atypical Antipsychotics
Indications
More long term management, more for negative symptoms
(will still help positive sx just to a lesser extent)
In addition to blocking D2 receptors, typical antipsychotics also block muscarinic, histamine, and alpha 1 receptors. Which of the following is a potential SE when starting a typical antipsychotic?
- Insomnia
- Extrapyramidal symptoms
- Hypertension
- Hypersalivation
Extrapyramidal symptoms
Aripiprazole (Abilify)
MOA
Partial D2 agonist, 5HT-1A agonist, 5HT-2A antagonist
What i want you to know is it CAN BE MIXED- partial D2 agonist = partially agonizing - we see a reduction in dopamine just not as pronounced as BLOCKING D2 receptors
Aripiprazole (Abilify)
Routes
- PO
- IM depot Q4-6 wks
-
Aristada (newest formulation, 6 wks)
- Must continue PO tx during first 3 wks of transitioning
-
Aristada (newest formulation, 6 wks)
IM depot useful for patients that are noncompliant
Aripiprazole (Abilify)
Advantages
Can also be used for:
Less EPS and weight gain (may be better tolerated vs. others)
weight gain and QTC safe
BPD
Atypical Antipsychotics
AE
- Cardiovascular (1)
- less common with (1)
- Neurologic effects (1)
- Antcholinergic effects (3)
- Weight ____
- greatest with (2)
- Impaired _____ tolerance
- clear risk of __ __ in pts treated with ______ antipsychotics
- Monitor serum _____
- Hematologic
- (1) drug in particular may cause?
- QT Prolongation
- Aripiprazole
- Sedation
- Dry mouth, urinary retention, constipation
- Gain
- Clozapine, Olanzapine
- Glucose
- DM, atypical
- glucose
- Agranulocytosis
- Clozapine -> need labs
Lumateperone (Caplyta)
- Simultaneously modulates s_____, d_____, and g_____ neurotransmission
- ____ interaction with muscarininc, histamine, and alpha receptors (____ AE)
- Placebo-controlled _____, sign. improvement in change of PANSS score (beginning in just one wk from start)
- Significant imp in CGI-S score w ____ dose
- Somnolence, sedation, constipation
- ___ increase in suicidal ideation, EPS, weight changes, QTC prolongation
- one seizure occured in one with hx of epilepsy (should be monitored closely)
- Limitiations; Very ____ _____/______
- Inclusion: ____ psychosis, previously:
- Exclusion: e____, de_____, _____ disorder, >__yo, ___ history, _ _ _
- serotonin, dopamine, glutamate
- Lacks (less AE)
- trial
- increase
- No
- Specific Inclusion/Exclusion
- Acute psyhocsis, previously responded to antipsychotic meds
- epilepsy, depression, BD, >60yo, CV hx, HIV
“Dream drug” - targets what we want, doesn’t target what we don’t want - seemed promising but the issue is they were so specific with who they treated
Boxed Warning - All Antipsychotics
Dementia: elderly pts with dementia related psychosis treated with antipsychotics increased risk of death
Most deaths appear to be either CV (HF, sudden death) or infectious (PNA)
Bipolar Disorder
- Recurrent episodes of ____, _____, and major ____ with _____ mood in between
- Mania, Hypomania, Depression, Normal
- Mania - distinct period of abnormally and persistently elevated, expansive, or irritable mood and abnormally and persistently increased activity or energy, lasting at least 1 wk
- Hypomania - above, lasting for at least for days
- Depression - major depressive disorder
Lithium
Warnings/Contraindications
Increased risk of what?
- Renal Insufficiency
- Dehydration
- Sodium Depletion
INCREASED RISK OF TOXICITY dt decreased clearance
Lithium is like salt so if body is dehydrated/depleted its going to hold onto it
Lithium
Significant Drug Interactions
- NSAIDS
- ACE Inhibitors and ARBS
- Diuretics (cause sodium depletion -> decreased clearance again)
INCREASED RISK FOR TOXICTY dt INCREASED CONCENTRATIONS
Lithium
Nursing Implication*
With such a narrow therapeutic window, we routinely monitor serum concentrations
ST is a 50 yo male, long time pt of yours, properly managed on lithium for the management of his bipolar disorder. ST contacts you after sudden onset of nausea, vomiting, and impaired memory. What could be the cause of these symptoms?
- ST has recently started taking ibuprofen (NSAID) 4 times/day for the management of new onset back pain
- ST has recently stopped taking his diuretic
- ST has recently replaced his second cup of coffee each day with a glass of water
- All of the above
- ST has recently started taking ibuprofen (NSAID) 4 times/day for management of new onset back pain
If a patient is currently receiving warfarin (a CYP enzyme substrate) and is initiated on phenytoin, what do you expect to happen to pts INR and why?
- The INR is expected to decrease bc phenytoin is an inhibitor of CYP enzymes
- The INR is expected to increase bc phenytoin is an inducer of CYP enzymes
- The INR is expected to remain the same
- The INR is expected to decrease because phenytoin is an inducer of CYP enzymes
- The INR is expected to decrease because phenytoin is an inducer of CYP enzymes
Which of the following is TRUE regarding Carbamazepine?
- Carbamazepine works by inhibiting GABA receptors
- Patients of SE Asian and Chinese decent should be tested for HLA-B 1502 which is associated with an increased risk of hypersensitivity
- Carbamazepine can be given IV
- Carbamazepine can be used for generalized non-motor seizures
- Patients of SE Asian and Chinese decent should be tested for HLA-B 1502 which is associated with an increased risk of hypersensitivity
