Bipolar Flashcards
When do symptoms usually occur in bipolar disorder?
Late adolescence or early adult hood
Median age at onset is 20 y/o
However, some may exhibit first sx during childhood or later in life
What is the frequency of episodes of bipolar disorder correlated with?
Increases with Age
What is bipolar I disorder?
Manic episodes recur in >90%
Spend 3x as long in depressed and manic states
Exhibit higher rate of reckless activity, dristractibility, agitated activity, irritable mood, and increased self-esteem
What is involved with Bipolar II disorder?
Higher lifetime prevalence of depressive episodes High prevalence of Fhx Higher co-morbidity w/ anxiety disorders Shorter inter-episode intervals Faster onset More chronic course of dz
What are the two most common co-morbid anxiety disorders associated w/ bipolar?
Panic Disorder
Obsessive-Compulsive disorder
What are the monamines that are involved with regulation of mood?
Norepinephrine
Seratonine
Dopamine
What does dysregulation of the monoamines (NE, 5-HT, DA) lead to?
Depression or mania
What other neurobiology is involved with mood disorders?
Cholinergic system
GABA
Glutamate
Glucocorticoids
What plays a major role in pathogenesis and pathophysiology of mood disordrs?
Neuroplastic changes in the brain
What are the bipolar treatment challenges?
Acute manic episodes Acute depressive episodes Acute mixed episodes (manic and depressive together) Psychotic freatures Rapid cycling (>4 acute episodes/year) Co-morbid substance abuse Hypomanic episodes Seasonal episodes Chronic management and prophylaxis
What are the reasons for medication non-adherence in bipolar disorder?
Not convinced that meds work Intolerant to side effects Do not want to take antipsychiatric meds Medication cost Inconvenience Lack of insight
When do acute manic episodes start and who do they occur in?
Onset typically before 30 and in men and women equally
What is the course for acute manic episodes?
- Begin suddently
- insomnia and irritability are prominent
- Rapid escalation of sx over a few days
- Episodes last a few days to months.
What are the common sx of manic episodes?
- Lasting period of abnormal behavior
- Increased energy, activity, and restlessness
- Excessive high, overly good, and restlessness
- Extreme irritability
- Racing thoughts/talking fast, jumping from one idea to the next.
- Distracted not able to concentrate
- Needs little sleep
- Unrealistic beliefs in ones ability and powers
- Poor judgement
- Spending sprees
- Increased sex drive
- Religious preoccupation
- Provocative, intrusive, or aggressive behavior
- Denial that anything is wrong
- Abuse of drugs, particularly cocaine, ETOH, and sleeping meds.
What are the hyperactive behavior & mood changes?
Insomnia, irritability, loud, distractable, impulsive, pressured speech, increased motor activity, intrusive, expansive, intense, labile, hypersexual, manipulative, aggressive
What is rapid speech and switching among multiple ideas/topics?
Flight of Ideas
What is a vague relationship between thoughts?
Loose associations
What is involved in the neurobiology of mania?
NE- Relative excess
5-HT- relative deficiency
DA- relative excess
What is involved with stage 1 of mania (Hypomania)?
- Euphoria
- Labile affect (irritability, happy then agry)
- Grandiosity
- Overconfidence
- Excessive risk-taking
- Racing thoughts
- Increase psychomotor acvitivy (energy, activity, restlessness)
- Increase in rate & amount of speech
- Decreased need for sleep
What is involved in mania stage 2?
Increased irritability Hostility Anger Delusions Congnitive disorganization Dysphoria (feeling of extreme discomfort & unrest)
What is involved with mania stage 3?
Panic Terror Bizare behaviors Frenzied activity Hallucinations Progression from disorganized though patterns to incoherence and disorientation
What are the goals of tx of acute mania?
Stabalize- obtain rapid control of agitation, aggression, impulsiveness, insomnia
Achieve remission- return to baseline level of functioning, no functional impairment
What is the non-pharmacologic tx of acute mania?
Reduce over stimulation (calm quiet environment)
Reduce potential for risky behaviors (safe, highly structured environment)
What are the pharmacotherapy tx of acute mania?
Antimanic agents or mood stabilizers
Antisychotics (1st and 2nd gen)
Benzodiazepines (PRN and/or short-term for agitation, anxiety, insomnia)
Antidepressants (discontinue)
What are the 2nd generation antipsychotics used to treat acute mania that are FDA approved?
Aripiprazole Olanzapine Quetiapine Risperidone Ziprasidone
What are the 1st generation antipsychotics used to treat acute mania?
Haloperidol
Chlorpromazine
Do you need to discontinue antidepressants being used to treat acute mania?
Yes
Antidepressants may induce mania or hypomania, increase frequency of recurrence of acute episodes, promote tenancy for course of illness to become continuous.
MUST TAPER
How should treatments be individualized for bipolar disorder?
Treatment should be individualized: clinical presentation, severity, and frequency of episodes vary widely among patients.
What are the three most commonly used drugs for bipolar disorder tx?
Three primary drugs used are lithium, carbamazapine, and valproic acid.
Lithium (Eskalith®, Lithobid®)- Indications
Acute manic episodes
Prophylaxis of affective disorders
Acute depressive episodes
Other psychiatric disorders Schizoaffective disorder/Schizophrenia Aggressive/violent behaviors Impulse control disorders Self-injurious behavior Mania secondary to brain injury
What is involved with the pre-lithium work up?
CBC w/ diff Chem profile (Electrolytes, creatinine, BUN) Thyroid function tests UA FBS ECG VItals Serum pregnancy test
Lithium (Eskalith®, Lithobid®)- Acute side effects
usually transient but may become chronic N,V,D muscle weakness polyuria, polydypsia fine hand tremor edema
What are the sx of acute toxicity of lithium?
persistent vomiting impaired renal function
diarrhea lethargy/confusion
COARSE HAND TREMOR somnolence
dysarthria seizures
muscle weakness coma
hyperactive deep tendon reflexes (DTR)
vertigo
What is the management of lithium toxicity?
-D/C lithium
-Obtain lithium serum concentrations, renal panel, vitals, & EKG
-Supportive Care
-Maintain fluid and electrolyte balance
-Gastric lavage if within 1 hour
No charcoal, doesn’t bind lithium
-Whole bowel irrigation with delayed release preparations
-Hemodialysis
Lithium (Eskalith®, Lithobid®)- LChronic effects
Weight gain Hypothyroidism (monitor function) Diabetes insipidus (tx with amiloride) Leukocytosis Rash (acne, psoriasis exacerbation) ECG changes (T wave flattening, QRS inversion Nephrotoxicity
Lithium (Eskalith®, Lithobid®)- routine therapeutic monitoring
- -Serum lithium concentration obtained 5-7 days after initiation of therapy and with every dose change, then every 3 mo. for 6 mo. and every 6 mo. thereafter.
- -BUN, Scr, electrolytes - every 3 months for 6 mo. and every 6 mo. thereafter.
- -Thyroid function test - every 3 months for 6 mo. and every 6 mo. thereafter.
- -Urinalysis
- -CBC - Q12 mo.
- -Monitor for signs of toxicity; pregnancy test in females (Cat. D)
Lithium (Eskalith®, Lithobid®)- Drug interactions
- Thiazide diuretics
- Osmotic diuretics, acetazolamide
- Aminophylline, Theophylline
- SSRIs, Fluoxetine
- Haloperidol
- clozapine
- Carbamazepine
- Metronidazole - abx
- ACE Inhibitors
- NSAIDS
- Calcium channel blockers, verapamil
What are the advantages of lithium therapy?
- Will control a manic patient without a “drugged effect”
- Will normalize mood
- Very good prophylactically to decrease mood swings
- Relapses, when they occur, are less severe and usually shorter in duration
- Plasma concentration monitoring allows careful titration to therapeutic levels
- Low drug cost
What are the disadvantages of lithium therapy?
-Narrow range of therapeutic blood concentrations, requires close monitoring to prevent toxicity.
-Patient compliance and understanding of the warning signs of toxicity is important.
-Lag period before therapeutic effect in manic patients.
Prophylactic effect may take 6 months to 1 year to maximize.
-Rapid cyclers are poor responders.
-Expense of blood tests
Carbamazepine (Tegretol®)- indications
Acute manic episodes
Usually in patients who are treatment resistant, rapid cyclers, lithium intolerant.
Prophylaxis of affective disorders
Other psychiatric disorders
Impulse control disorders
Schizoaffective disorder/schizophrenia (not first line)
Neuropsychiatric disorders in the mentally retarded/developmentally disabled.
Trigeminal neuralgia
Mania secondary to head injury
Aggressive and violent behaviors/rage reactions
Carbamazepine (Tegretol®)- adverse effects
Neurologic- sedation, ataxia, diplopia, dizziness, fatigue, headache, nystagmus, tingling, tremor
Dermatologic- rash, steven johnson syndrome (Most concerning)
Hematologic- transient leukopenia, THROMBOCYTOPENIA (most common), eisinophilia, aplastic anemia, and agranulocytosis
GI- N/V/D
Other- SIADH, slowed cardiac conduction, hepatotoxic, teratogen
What is the most concerning ADR of carbamazepine?
Steven Johnson’s Syndrome
Is carbamazepine an autoinducer?
Yes
Carbamazepine (Tegretol®)- routine monitoring
-Every 2 weeks for 2 months, then every 3 to 6 months
-Chemistry profile
-CBC w/diff. and platelets (to check for SE)
-Liver profile (check for SE)
-Urinalysis
-Carbamazapine blood levels for:
initial stabilization of a pt
therapy failure, inadequate response, worsening of symptoms
complex drug regimens—dose related side effects, drug interactions
Compliance issues differing plasma levels with stable prescribed doses
Carbamazepine (Tegretol®)- drug interactions
Carbamazepine is a potent liver enzyme inducer which can decrease levels of other drugs:
- Antipsychotics
- Tricyclic antidepressants
- Theophylline
- Steroids
- Warfarin (narrow therapuetic so you risk worsening condition)
- Chloramphenicol
- Isoniazid
- Thyroid Hormones (narrow therapuetic so you risk worsening condition)
- Methadone
What are the drugs that can increase carbamazepine concentrations?
Hint- P450 inhibitors
Erythromycin Fluoxetine Theophylline Cimetidine Verapamil Diltiazem Propoxyphyne (Darvon)
What are the drugs that can decreased carbamazepine concentrations?
Hint- P450 inducers
Phenobarbital
Phenytoin
Primidone
Theophylline
Valproic Acid, Divalproex Sodium (Depakene® and Depakote®)- Indications
Bipolar affective disorder (esp. rapid cyclers and mixed states) Aggression and impulse control disorder Mania secondary to head injury Bulimia Schizoaffective disorder/schizophrenia
What is the gold standard for treating bipolar disorder?
Lithium
Valproic Acid, Divalproex Sodium (Depakene® and Depakote®)- Adverse Effects
--Gastrointestinal N,V, D, stomach cramps Constipation Anorexia, wt. loss/gain Hemorrhagic pancreatitis --Neurologic sedation/drowsiness Tremor Nystagmus/diplopia ---Endocrine Breast enlargement, galactorrhea, irregular menses
What drugs can decrease valproic acid concentrations?
Phenobarbital
Phenytoin
Primidone
Carbamazepine
What drug concentrations are increased with valproic acid?
Phenytoin
Phenobarbital
When combined what have clonazepam and valproate causes?
Absence seizures
What is the presentation of bipolar II with major depression episodes?
Irritability Mood lability Racing thoughts Increased sexuality Distractability Increased risk for suicide
What are the goal treatments for bipolar depression
Remission of sx
Return to normal functioning
Avoid precipitation of mania or hypomania
What are the non-pharmacologic tx goals of bipolar depression?
Interpersonal psychotherapy
Cognitive behavioral therapy
Group psychotherapy
What are the FDA approved drugs used to tx bipolar depression?
Olanzapine + fluoxetine
Quetiapine
When can mood stabilizers be used for bipolar depression?
May be used as montherapy or as add-on therapy for BP depression Lithium Lamotrigine Valproate Carbamazepine
What antipsychotics do you want to use for a patient with bipolar depression?
Olanzapine
Quetiapine
Should antidepressants be used to tx bipolar depression?
None have been approved. The only one is FLX with olanzapine
What are the most commonly used agents for bipolar I?
Lithium Lamotrigine Quetiapine Olanzapine/fluoxetine Valproate Carbamazepine
What are the most commonly used agents for bipolar II?
Lithium Lamotragine Carbamazepine Valproate Antidepressants
How is first line tx for bipolar depression selected?
Sx profile Course of illness Prior hx of response Family hx of response Tolerability issues Optimize first line, if no response augment/switch to another first line. If no response consider second-line tx, if inadequate response consider combos
What are the primary goals after resolution of acute episodes of bipolar?
Prevent re-occurrence Extend intervals b/w episodes Decrease severity of episodes Maximize patient functioning Minimize sub threshold sx Minimize med ADRs Prevent suicide Identify prodromal sx
How do you treat rapid cycling?
Assess and tx medical condition
Discontinue antidepressent
Agents of choice- valproate, lithium, lamotrigine, 2nd gen antipsychotic, ECT
What are the therapies for bipolar?
Medication combinations ECT Sleep deprivation Thyroid supplementation Vagal nerve stimulation Psychotherapy Homeopathy Vitamin supplements Herbs
