Mental Health Review / Bipolar Flashcards
What are the primary differences between “Mental Health Disorders” & “Mental Health Problems”?
MHD: Significant impairments to emotional state, behaviors that hinder one’s ability to function; meets diagnostic criteria.
MHP: Disruptions to function but person can still function; does not meet diagnostic criteria.
T or F: Non mental health medications can be authorized by attending physicians for those whom are admitted as involuntary patients.
False… Only mental health drugs can be forcibly administered to involuntary patients (they can refuse other meds).
What defines “involuntary admission criteria”?
1) Mental disorder & requires inpatient care
2) Not capable of making admission / treatment decisions
3) Likely to harm self or others
What are some issues with the current psychotropic drug nomenclature system?
-Confuses patients
-Stigma contributions
-1st indication descriptors
Define “dysthymia”.
A persistent depressive mood
Define “cyclothymia”.
Mood swings between short periods of mild depression and hypomania
What is Bipolar I Disorder?
Period of one or more weeks with a full manic episode (abnormally & persistently elevated mood / energy)
What is Bipolar II Disorder?
Current or past hypomanic episode INCLUDING a current or past major depressive episode
Who does Bipolar affect more: Men or Women?
Equal
How does Bipolar presentation differ between men and women?
Men: More manic episodes
Women: More depressive or mixed
Is Bipolar curable?
No… Realistic goal is to halt disease progression or put somebody into a maintenance state where disease is well managed.
What are the risk factors for developing Bipolar?
-1st degree relative
-Drug / alc abuse
-High stress
-Traumatic events
What medical conditions can serve as risk factors for Bipolar development?
-Hyperthyroid
-Hormonal changes
-CNS disorders
-Endocrine dysregulation
-CVD
What pharmacologic drug classes can induce mania?
-Antidepressants
-Dopamine Augmenting Agents (ie. Amphetamines, Cocaine)
-Thyroid Preps
-Steroids
-Alc / Marijuana / Caffeine
How does the taper strategy for antidepressants differ in bipolar management as opposed to MDD management?
Abrupt stoppage (rather than a gradual taper in MDD) in cases of extreme mania.
What pneumonic is used to remember the antidepressant withdrawal symptoms?
FINISH
F - Flu-Like Sx
I - Insomnia
N - Nausea
I - Imbalances
S - Sensory Disturbances
H - Hyperarousal
What is the average age of onset for a new bipolar diagnosis?
20 - 25yrs
What is a bipolar patient’s best predictor of functionality levels?
Medication Adherence!!!
Approximately ___ % of bipolar patients discontinue their medications due to adverse effects.
50%
What types of medical conditions may worsen existing bipolar or make it more challenging to treat?
-Anxiety Disorders
-Substance Use Disorders
-ADHD
-PTSD
Death via suicide is up to ___ x higher in bipolar patients than it is other patient subtypes.
20x
What sorts of deviations from normal behavior would indicate somebody is going through a manic episode?
-Inflated self esteem
-Reduced need for sleep
-Racing thoughts
-Increased agitation & pressured speech
-Distractable
-Risky behavior partaking
At least three of these!
Pneumonic to remember manic symptoms?
DIGFAST
D - Distracted
I - Irritable
G - Grandiosity
F - Flight of ideas
A - Activity increases
S - Sleep decreases
T - Talkative
Manic symptoms in Bipolar I last >/= __ days, whereas symptoms in Bipolar II last </= __ days.
BDI: >/= 7 days
BDII: </= 4 days
Are there severe functional impairments in BDI? BDII?
BDI: Yes
BDII: No
Is psychosis present in BDI? BDII?
BDI: Yes
BDII: No
Does BDI warrant hospitalization? BDII?
BDI: Yes
BDII: No
Does one require a history of depression to be diagnosed with BDI? BDII?
BDI: No (can have previous history of it, but not necessary for diagnosis).
BDII: Yes (needed for diagnosis).
Which antidepressant class do we see the highest rates of manic episode development with?
SNRIs (then TCAs, then SSRIs)
Symptomatic improvements during a manic episode should be seen within __ - __ weeks being on therapies, whereas full benefits are often seen within __ - __ weeks.
Improvement: 1-2 wks
Full Benefit: 3-4 wks
What other adjunctive non-pharmacologic interventions should be incorporated into the care plans of bipolar patients?
-Exercise
-Sleep
-Balanced Diet
-Reduced or Eliminate Substance Use
-Reduced Nicotine / Caffeine Intake
What are the most commonly used mood stabilizers in bipolar management?
Lithium
Valproic Acid / Divalproex
Lamotrigine
What important PK parameters should be noted with Lithium?
1) Even Vd within total body water spaces… Reduced Vd in elderly = Increased concentrations.
2) t1/2 = 12-27hrs… Longer in elderly (30-36hrs) due to declining renal function as we age.
Which organ is extensively involved with Lithium elimination?
Kidneys (95%)
Perspiration (4%)
What percentage of Lithium is reabsorbed at the Proximal Tubules?
80%
Is Lithium highly plasma protein bound?
Nope (freely filtered by glomerulus similar to other cations such as K+ and Na+).
What factors may reduce the clearance of Lithium?
-Low Na+
-Dehydration
-Kidney Failure
-Reduced Renal Perfusion
What are the target serum concentrations that we want to aim for with bipolar Lithium treatments?
0.8 - 1.2mmol/L (very narrow TI drug)
0.6 - 0.8mmol/L in elderly
What are the signs of Lithium toxicity?
Drowsiness
Ataxia
Tremors
Slurred Speech
Hypertonia
When should Lithium levels be sampled?
12hrs post-dose (usually AM after an evening dose)
How often should Lithium levels be sampled?
1) 5-7d after starting
2) OW once on stable dose x 2wks
3) Monthly x 3mths
4) q6mths thereafter
How do the therapeutic ranges for Lithium differ for treating an acute manic episode vs. maintenance?
Acute: 1.0 - 1.2mmol / L
Maintenance: 0.6 - 1.0 mmol / L
What advantage does dosing Lithium once daily as opposed to twice daily have?
-Increased compliance
-Decreased renal toxicity
-Slowed renal dysfunction progression
How would you elect to adjust maintenance doses of Lithium if a patient had a reported CrCl of </= 50mL / min?
50 - 75% of normal maintenance dose
If a patient is on a BID Lithium dosing regimen, what must we ensure happens before taking serum levels?
HOLD THE MORNING DOSE!!! Skews serum concentrations…
How might pregnancy or severe burns influence Lithium levels?
Increased Vd (fluid levels increase, which dilutes Lithium concentrations).
How does increased caffeine consumption reduce Lithium levels?
Increases renal activity
What pharmacologic agents might reduce serum concentrations of Lithium?
Theophylline
Acetazolamide
NaHCO3
What pharmacologic agents would increase serum concentrations of Lithium?
NSAIDs
Diuretics
ACEi / ARBs
Primary side effects of Lithium?
Polydipsia / Polyuria
Tremors
GI Upset
Acne Development
Alopecia
Wt Gain
Serious signs of Lithium toxicity?
Arrythmias
Seizures
Myocarditis
Acute Tubular Necrosis
Hypothyroidism
Coma
Death
Which of the following is cleaved into its active drug form within the stomach?
Divalproex
Valproic Acid
Divalproex
What percentage of Valproic Acid is bound to plasma proteins?
85 - 90%
Valproic Acid is extensively eliminated by what organ?
Liver (> 95% hepatically metabolized)
What’s the major metabolic pathway responsible for eliminating Valproic Acid?
UDP-mediated glucuronidation / beta oxidation
Describe Valproic Acid’s potential mechanisms of action.
1) Inhibit Voltage-Gated Na+ Channels
2) Increase GABA actions
3) Modulate signal cascades
4) Effects neuron excitation (mediated by NMDA subtype Glutamate receptors)
5) Serotonin / Dopamine / Aspartate / T-Type Ca2+ Channels
What is the therapeutic range for Valproic Acid?
350 - 700umol / L (total)
-However, range is extrapolated from Seizure treatments (often may need to strive higher, individualized levels).
When should steady state trough levels of Valproic Acid be taken?
3 - 4d after starting therapy
What is the general principle for dose adjusting Valproic Acid in hepatic disease?
Avoid altogether (reduced protein binding & clearance of drug).
Do renally impaired patients require Valproic Acid dose adjustments?
Nope
What enzymes do Valproic Acid inhibit?
CYP2C9
Epoxide Hydroxylase
UDPGT
What important drug classes increase Valproic Acid levels?
Macrolide ABs (ie. Clarithromycin, Erythromycin)
Salicylates (ie. Aspirin, Na+ Salicylate)
What drug classes reduce Valproic Acid levels?
Carbapenem ABs (ie. Meropenem, Ertapenem)
Anti-Convulsants (ie. Phenytoin, Carbamazepine, Phenobarbital)
What drugs show concentration increases when on-board with Valproic Acid?
Lamotrigine (cut dose 1/2 & double the titration period)
Warfarin
TCAs
Anti-Convulsants
Adverse effects of Valproic Acid?
Dose-Related: NVD, Anorexia, Constipation (< Divalproex), Tremor, Sedation, Ataxia, Dizziness, Thrombocytopenia
Chronic: Wt Gain, Balding, Menstrual Disturbances
Should Valproic Acid & derivates be avoided in pregnancy?
Yes… Highly teratogenic (strongly encourage contraception use).
JB is a Bipolar patient on Valproic Acid & comes in for a refill. He complains of unexplained fits of fatigue, confusion & vomiting. What test should he get done?
Ammonia
When should CBCs, Platelets, & LFTs be assessed in a patient starting Valproic Acid?
Baseline
qmthly x 3mths
q4 - 6mths
What are some counseling points you can provide a patient on Valproic Acid with to combat common GI & sedative side effects?
TWF, switch to Divalproex (less upsetting to stomach), H2RAs such as Ranitidine.
Taking higher of the two doses at bedtime.
What indications do Lamotrigine have in treating Bipolar?
Maintenance therapy, acute depressive episodes… NOT (!!!) recommended for acute manic episodes.
Describe Lamotrigine’s MOA.
Binds open conformation of Voltage-Gated Na+ Channels, reduces Glutamate release.
Somewhat of an inhibitory effect on Serotonin Receptor.
What is t1/2 of Lamotrigine? When do peak plasma levels occur?
t1/2: 25 - 33hrs
Peak: 1 - 5hrs
Are dose adjustments of Lamotrigine needed in hepatic impairment? Renal impairment?
Yep to both.
After what length of time (in days of missed doses) must Lamotrigine titrations be restarted from scratch?
5d (as concentrations will be totally eliminated from the body by this point).
Why must Lamotrigine be titrated up slowly?
Risk of SJS Rash (1-2% kids, 0.1% adults but more prevalent in first 8wks of starting)
What are the most common side effects of Lamotrigine?
Sedation, Headaches, Dizziness, GI (to lesser extent)
Is it necessary to obtain serum concentrations of Lamotrigine?
Nope… Routine blood work you do with everything else should still be done though.
What sorts of drugs decrease Lamotrigine levels?
ACs (ie. CBZ, Phenytoin, Phenobarbital, Topiramate)
Oral Contraceptives (primarily the estrogen component)
What drug increases Lamotrigine two-fold (you’ve seen this already don’t get this wrong).
Valproic Acid / Divalproex
Chronic use of what OTC medication induces Lamotrigine metabolism & thus decreases its levels?
Tylenol (4g / day)
Why is it important to taper all of the anti-seizure agents used in Bipolar?
Sudden withdrawal / stoppage can trigger seizures (even in those with no prior history).
Describe Carbamazepine’s MOA.
Blocks Voltage-Dependent Na+ Channels
Blocks NMDA Glutamate Receptor, reduces Ca2+
Modulates Aspartate, Glutamate release
What side effect secondary to increased fluid retention is something to worry about with CBZ?
Hyponatremia… Drug stimulates ADH release, promotes increased water reabsorption.
Primary route of elimination of CBZ?
Hepatic (> 99%, primarily CYP3A4)
Why is it so hard to get CBZ to target therapeutic ranges?
Autoinduction (induces its own metabolism via Epoxide-Diol Pathway)
When does autoinduction of CBZ usually stabilize?
1 - 5wks
Trough concentrations of CBZ should be taken within ___ hr(s) prior to next dose.
1hr
In what disease state would we not recommend using CBZ?
Decompensated Liver Disease (not outright CI but dose decrease with Stable Liver Disease)
Does CBZ require renal dose adjustments?
Nope
A bipolar patient is on a CYP3A4 metabolized drug and the physician elects to discontinue their Carbamazepine. What you expect would happen to the other CYP3A4 metabolized drug’s serum concentrations?
Would go up (as CBZ is a potent CYP Enzyme Inducer)
What highlighted drug class increases CBZ levels?
-Macrolide ABs (ie. Erythromycin, Clarithromycin, Telithromycin)
-“Azole” Antifungals (ie. Ketoconazole)
-Cardiovascular Ca2+ Channel Blockers (ie. Diltiazem, Verapamil)
-Cimetidine & Grapefruit Juice
What highlighted drug classes decrease CBZ levels?
-Other ACs (ie. Phenytoin, Phenobarbital)
-Warfarin
-Other Antipsychotics (ie. Lurasidone, Risperidone, Quetiapine…)
-Antidepressants (ie. Citalopram)
-Methadone
-Antiretrovirals (ie. NNRTIs)
Side effects of CBZ?
-GI
-Dizzy / Sedation / Ataxia (same as others)
-Tremors
-HR increase
-Low BP
-SIADH & Hyponatremia
-“Penias”
-Rash & Hypersensitivity Rxns
Asian patients with a positive test for HLA-B____ & Caucasian patients with a positive HLA-A____ are at an increased risk of suffering from hypersensitivity reactions while on Carbamazepine.
Asian: HLA-B1502
White: HLA-A3101
What conditions are outright CIs to CBZ use?
-Hepatic Disease
-CVD
-Blood Dyscrasias
-Bone Marrow Depression
-Concurrent Clozapine use (due to potential WBC Ct drops)
What monitoring parameters for those on CBZ should be assessed?
-CNS, ongoing
-Ocular Exam, baseline & yearly (due to blurred vision / diplopia)
-ECG, baseline
-CBC / LFT / Renal Function, baseline, mthly x 3mths, then q6-12mths
-Bone Mineral Density (if taking CBZ > 5yrs or risk factors of osteopenia)
-Rash, ongoing
Important counseling point for females on CBZ who are sexually active & on hormonal birth control?
Use of alternative contraception (as CBZ reduced efficacy of contraceptive forms on board).
What is the primary MOA of atypical antipsychotics?
Dopamine Blockade
Of the following antipsychotics, which one(s) would you predict to have higher rates of EPS & hyperprolactinemia symptoms?
Quetiapine
Risperidone
Haloperidol
Aripiprazole
Chlorpromazine
Haloperidol, Chlorpromazine (FGAs)
What are the general adverse effects of atypical antipsychotics?
-EPS (ie. Stiffness, Tremor, Shuffling Gait)
-Sexual Dysfunction
-Wt Gain / Dyslipidemia / Diabetes / CVD (Metabolic Conditions)
-AC (ie. Sedation, Constipation, Dry Mouth, Blurry Vision)
-QT Prolongation
-Seizures
What is the current consensus around using antidepressant monotherapies in the management of Bipolar?
Avoid without antimanic agents onboard!!!
Rank the following ADs from best to worst in terms of safety in treating BDII:
Bupropion
Sertraline
Other SSRIs
Venlafaxine
Same order as shown on other side of the card!
Which of the following SSRIs is NOT recommended for BDII management?
Escitalopram
Citalopram
Fluoxetine
Paroxetine
Paroxetine
Ideally, when should antidepressant use be tapered off in managing bipolar?
Short courses of 3 - 4mths, with a taper good to initiate once asymptomatic for 6 - 12wks.
Which antidepressant classes possess the highest risk of switching a bipolar patient over from a depressive episode to a manic one?
TCAs (number one)
SNRIs (number two)
When would combination therapy for bipolar management be recommended?
-Faster response needed
-Those at risk for harming self or others
-Hx partial response to monotherapy
-Those with severe manic episodes
What are 1st line CANMAT guideline bipolar treatments for acute mania?
Monotherapies: Lithium, DVP, Quetiapine, Aripiprazole, Paliperidone, Risperidone
Combo: Lithium or DVP + Quetiapine, Risperidone, or Asenapine
In cases of mixed feature bipolar, what combination of medications is preferred?
Antipsychotic & DVP
What are considered to be the second line options for acute mania?
Monotherapy: Olanzapine, CBZ, Ziprasidone, Haloperidol
Combo: Lithium or DVP + Olanzapine
What agents suck at treating acute mania?
-Gabapentin
-Lamotrigine
-Omega 3 FAs
-Topiramate
1st line options for treating Bipolar I Depression (according to CANMAT)?
Quetiapine, Lamotrigine, Lithium, Lurasidone, Lurasidone + Li/DVP
The Young et al study in 2010 showed that Lithium was no more effective than placebo in treating acute bipolar depression… What was the study’s caveat?
Mean Lithium levels were only 0.61 mEq/L (needed to be higher to see true effects).
Early improvement within ___ wks is a reasonable predictor of overall response to a treatment in BDI Depression.
2wks (however, may take up to 4 - 6wks to see response)
What should be considered the only 1st line BD maintenance therapy that we recommend to all patients?
Psychoeducation
In cases of mixed episode bipolar, should antidepressants be continued or discontinued?
Discontinued (because of worsening potential)
Which medications should be avoided in pregnancy?
DVP / VPA
CBZ
Lithium (Trimester 1)
Which agent appears to be the least risky for managing bipolar in pregnancy?
Lamotrigine
