Mood Stabilizers (Week 7/8) Flashcards
Cyclothymic Disorder
Hypomanic Episode
Manic episode
Bipolar 1
Bipolar 2
Alterations of brain regions in Bipolar Disorder
Amygdala (mood)
Hypothalamus(decreased sleep)
Basal Forebrain(decrased sleep
Nucleus Accumbens(racing thoughts, goal-directed grandiosity
Prefrontal cortex: racing thoughts, grandiosity, distractability, pressured speech.
Diagnostic Criteria for Bipolar 1
-Must have one or more episodes of mania
-Must have one or more depressive episodes
-manic episode must last for at least 1 week.
-depressive episodes may last for weeks or months
-may have hypomania
-not a result of medical condition or intoxication
Mania mneumonic
D:Distractibility (low concentration, easily distractible)
I:Insomnia
G:Grandiosity (feelings of greatness, superiority, uniqueness)
F:Flight of ideas (multiple ideas expressed together in speech, making it barely understandable)
A: increase in goal-directedActivities (continuous search for pleasurable activities: spending money, hypersexuality, smoking, drinking alcohol, taking drugs,…)
S: pressuredSpeech (rapid speech, talking too much, almost unstoppably)
T:Thoughtlessness (high risk activities: sex, projects, drugs,…)
Diagnostic criteria for bipolar 2 disorder
Major depressive symptoms lasting for 2 weeks
At least one hypomanic episode: less severe than a full blown manic episode
Not a result of drug intoxication or medical condition.
Diagnostic criteria for Cyclothymic disorder
Mood swings between major depressive symptoms and
Hypomanic symptoms episode: less severe than a full blown manic episode
Cycle of symptoms present more than 2 years
Not a result of intoxication or medical condition.
What is the gold standard for Bipolar 1 treatment?
Lithium
Lithium
Natural occurring element, Li+ on the periodic table
FDA Approved to treat bipolar disorder: Acute Manic, Mixed episodes and maintenance therapy
Off label: Augment antidepressants, to treat rage reactions, prophylactic agent for cluster headache, schizoaffective disorder
Mechanism of Action: Unknown. Possibly neuroprotective and neuro-proliferative effects preserve grey matter
Protective benefit against suicide
Lithium Pharmacokinetics
Absorption: GI tract
Excretion: Exclusively in kidneys
Narrow therapeutic index
0.6 to 1.2 mEq/L
Lithium Dosing
Dosing: (300-2,400 mg/day divided in 24 hours)
Increasing lithium dose by 300mg/day should increase lithium level by 0.3mEq/L
Onset of action: 6-10 days in mania, up to 3 weeks in depression
Target level: 0.6-1.0 mEq/L
Baseline serum level and after each dose change or annually
Lithium therapeutic Index
Narrow therapeutic index
0.6 to 1.2 mEq/L
Contraindications for Lithium use
Kidney Failure
Cardiovascular Insufficiency
Untreated hypothyroidism
Pregnancy: Ebstein’s anomaly during first trimester
Long term use can cause kidney changes
Significant fluid loss: increases risk of lithium toxicity
Common Lithium Side effects
Nausea
May improve with food or ER formulation
Dry mouth, thirst
Offer ice chips, sugarless gum or hydration
Acne
Resolves after 1 month of use
Alopecia (usually in women)
Check thyroid function
Mild fine tremor
Avoid caffeine
Treat with propanolol
Polyuria/polydipsia (occur in 70% of patients)
Weight gain (average of 4-6kg)
Behavior modification counseling
Leukocytosis
Usually not treated, benign
Psoriasis (common over 50 y/o)
Order topicals for mild/moderate symptoms
Refer to dermatology for severe symptoms
Mild Lithium Toxicity: 1.5-2.0 mEq/L
Toxic serum level of lithium is greater than 1.5 mEq/L to 2.0 mEq/L
GI: Nausea, Vomiting, Diarrhea
Neuro: Lethargy
Muscular: Coarse hand tremor, muscle weakness
Muscle twitching
T-wave depression noted on EKG
Usually benign and treatable
Moderate Toxicity: 2.0-2.5 mEq/L
Severe nausea, vomiting, diarrhea
Confusion, slurred speech
Ataxia, muscle twitching
EKG Changes
Seizures
Oliguria
Circulatory failure
Coma
Death
Severe Toxicity: >2.5 mEq/L
Impaired level of consciousness, coma
Increased deep tendon reflexes
Syncope
Seizures
Death
Important relationships with Lithium:
Diuretics increase Retention of Li
NSAIDs Increase Retention of Li
Renal disease Increases Half-life
Decreased Doses required
Increased Dietary Na decreases Li levels
Decreased Dietary Na Increases Li levels
Decreased Na in blood via sweating, diarrhea increases Li levels
Causes of lithium toxicity
Intentional or accidental overdose
Decreased lithium renal clearance
Kidney disease, sodium deficiency, water deprivation, or medication interactions
A low or no salt diet, use of diuretics, fever and excessive sweating, vomiting, diarrhea
Failure to regular lithium level checks
Prescription of high doses of lithium
Lithium Drug/Drug interactions
Non Steroidal Anti-Inflammatory Drugs
Increase lithium levels by up to 60%
Angiotensin Converter Enzyme Inhibitors
Increases lithium levels by up to 40%
Angiotensin II Receptor Blockers
Increases lithium levels by up to 20%
Diuretics
Decrease lithium levels by up to 40%
Can cause lithium toxicity
Methylxanthines (Caffeine, theophylline)
Decrease lithium by up to 60%
Lithium Toxicity Treatment
-Discontinue lithium treatment immediately
-If due to an overdose, a gastric lavage or induced emesis should be used
-Hemodialysis may be necessary
-Repeated lithium levels are necessary
Lithium Toxicity prevention strategies
-Educate the patient about side effects and signs of toxicity if lithium levels continue to elevated
-Clear instructions must be provided to patients, coarse tremor
-Identify other medications that could exacerbate lithium toxicity (e.g. diuretics)
-Perform regular lithium levels
-Assess risk factors for lithium toxicity in special populations
Lithium Patient Guidelines
-Take at same time daily.
-Mild side effects are transient.
Report vomiting, coarse hand tremor, sedation, weakness, and vertigo.
-Maintain salt intake and a balanced diet.
-Illness with fever, excessive sweating
Might require dose adjustment
-Lithium level: morning blood draw
8 to 12 hours after last dose
Anticonvulsants for Bipolar
Valproate and derivatives (divalproex sodium - Depakote)
Carbamazepine (Tegretol)
Gabapentin (Neurontin) (least side effects)
Lamotrigine (Lamictal)
Topiramate (Topamax)
Highly protein bound
Metabolized by the cytochrome P-540 system
Side effects: dizziness, drowsiness, tremor, visual disturbance, nausea, & vomiting
Valproic Acid
Off label use: treat acute manic phase of bipolar disorder
Dosing: 250-500mg po tid, Max 60mg/kg/day
Long term use to minimize future manic episodes
It may help prevent future depressive episodes
It can help treat rapid cycling and mixed episodes of mania
Valproic Acid’s characteristics
Inhibition of voltage sodium channels
Boosts GABA actions and regulation of downstream signal transduction cascades
Antimanic actions possibly caused by excessive neurotransmission.
Valproic Acid Recommendations
Monitor Valproic Acid blood levels 50-125 mcg/ml, toxic levels at 150 mcg/ml.
Valproic Acid Common Side Effects
-Weight gain
-Metabolic Complications
-Menstrual disturbances
Valproic Acid Black Box Warning
-may cause hepatotoxicity, fetal injury, pancreatitis
Carbamazepine(tegretol)
Used off label: Manic phase of bipolar disorder
Formulation: ER cap, tab, ER tab, chewable and suspension.
Used when patients have not responded to lithium
Dosing: 800mg-1,600mg po bid-qid
Mechanism of action hypotheses include:
Blockage of voltage-sensitive sodium channels
Pharmacokinetics
Highly protein bound, metabolized by P450 system (potential drug-drug interaction)
Carbamazepine’s characteristic and side effects
Inducer of CYP450 and Self-Inducer
Sedation
Bone marrow suppressor
Fetal toxicity
Tegretol Recommended blood levels
6-12 mg /dl
Tegretol Black Box Warning
Black box warning: 1) Serious and fatal skin reactions increased with persons with HLA-B*1502 allele (primarily Asian patients) and, 2) risk for aplastic anemia or agranulocytosis
Lamotrigine
FDA Approved: Bipolar I Disorder maintenance
Off label: First-line treatment for bipolar depression, Not approved for acute bipolar mania
Formulation: tabs, dose pack
Gradual dosing: Week 1-2, 25mg daily, Week 3-4, 50mg daily, then adjust as needed by 50mg/daily
Lamotrigine’s characteristics and side effects
Binds to the open channel conformation of voltage-sensitive sodium channels (VSSC)
Lower potency at the sodium channels
Reduces the release of excitatory neurotransmitter glutamate
Increased likelihood to cause serious rashes/Stevens Johnson Syndrome
Lamotrigine levels are not required
Lamotrigine Black box Warning
Black box warning: Stephen-Johnson’s syndrome is a medical emergency (life threatening)
Oxycarbazepine (trileptal)
Off label use: bipolar disorder
Formulation: tablets and suspension
Dosing: 600mg-1,200mg po bid
Oxcarbazepine’s characteristics and side effects
MOA: Similar mechanism of action of carbamazepine
Binds open change conformation of the VSSC
Less sedative than carbamazepine
Less bone marrow toxicity
Fewer CYP 3A4 interactions
May cause Stevens-Johnson syndrome
Gabapentin(Neurontin), Pregabalin(lyrica)
Used as an adjunctive agent for bipolar disorder
Very limited action as mood stabilizers
Formulation: Caps and solution
Gabapentin Dosing: 300mg-600mg po tid
Off label use: neuropathic pain, fibromyalgia, alcohol dependence and anxiety disorders
Blocks VSCCs, which can help improve seizures, pain, and anxiety
Pregabalin is considered a schedule V drug
Gabapentin may be considered a scheduled drug in some states
Topiramate (Topamax)
FDA Approved: Anticonvulsant, Migraine headache prophylaxis, and in combination with Phentermine for weight loss for obese patients
Off label use: alcohol dependence, bulimia
Formulation: tablets and capsules
Dosing: 100-150mg po bid alcohol dependence
Topiramate’s characteristics and side effects
Potentiates the inhibition of GABA
Effects as a mood stabilizer have been limited
Used as an adjunctive agent for bipolar disorder to manage weight gain, insomnia, anxiety
Atypical Antipsychotics for bipolar disorder
D2 antagonistic actions
Mechanism of action to manage mania is unknown
Used as an adjunctive agent in bipolar disorder
Believed to reduce glutamate hyperactivity via antagonistic actions of 5HT2A leading to reduction of
manic and depressive symptoms
Used to manage psychotic symptoms associated with mania
Used to prevent recurrence of mania
Benzodiazepine use in Bipolar disorder
Not formally approved as mood stabilizers
Used as a calming agent
Used as need for agitation, insomnia, and to attempt to halt manic symptoms
Used intermittently with mood stabilizers to prevent more severe symptoms
They need to be used with caution
Wakefulness Drugs in bipolar disorder
Modafinil and Armodafinil
Off label use: bipolar depression
Used as adjunctive agent to atypical antipsychotics
Hormones and natural products in bipolar disorder
Omega 3 fatty acid
Believed to have mood-stabilizing properties
Inositol used as an augmenting agent
Vitamin folate is used with a mood stabilizing anticonvulsants
Antidepressants in bipolar disorder
Used in case by case basis
Monotherapy is not recommended
May be used in combination with mood stabilizers
Wellbutrin the most recommended antidepressant and TCAs the least recommended
Choosing the right treatment for the patient for Bipolar disorder.
Prudent assessment of patient’s symptoms
Avoid antidepressant monotherapy
A combination of mood stabilizers is a recommended approach to manage
symptoms
Best evidence-based combinations include:
Lithium and an antipsychotic agent
Valproic Acid and an antipsychotic agent
Practice-based evidence combinations include:
Lithium and Valproic Acid
Lamotrigine and Valproic Acid (use with caution)
Lamotrigine, Lithium, and Valproic Acid (use with caution)
Lamotrigine and Seroquel
Gender considerations in Bipolar
Gender considerations
Women with bipolar disorder are more prone to experience depression compared to men
Women are more likely than men to report atypical or vegetative symptoms (e.g. increased appetitive and weight gain)
Anxiety and eating disorders are more frequent in women with bipolar disorder
A postpartum period is a critical period for women to experience depressive, manic, mixed, or psychotic symptoms associated with bipolar disorder
Antipsychotic drugs
Chlorpromazine-Thorazine
Clozapine—Clozaril
Lurasidone-Latuda
Olanzapine—Zyprexa
Quetiapine—Seroquel
Risperidone—Risperdal
Ziprasidone—Geodon
Aripiprazole—Abilify
Chlorpromazine (Thorazine):
Typical, 1st generation antipsychotic
FDA Approved for bipolar mania in adults, severe behavioral problems in children
Available in tabs and IM injection
Weight gain
Erectile dysfunction, retrograde ejaculation, loss of libido and anorgasmia in men and women
Seizures - generalized grand mal
Chlorpromazine Adverse Effects
Neuroleptic malignant syndrome: combination of motor rigidity, hyperthermia, and autonomic dysregulation of blood pressure and heart rate (both go up)
Can be fatal if untreated
Drug collects in skin and sunlight causes pigmentation changes – grayish-purple splotching like bruising)
Can also occur in eye and cause brown in cornea
Agranulocytosis
Chlorpromazine Black Box/Beers Criteria
Black box warning and Beers Criteria list: Avoid in patients with dementia
Clozapine (clozaril)
Atypical Antipsychotic
Used when other antipsychotics have failed
Reduces the risk of suicide in patients with schizophrenia
Neutropenia (WBC <3,000/mcL and Agranulocytosis <500/mcL may occur
Major side effects include seizures in high doses, increased weight gain, increased cardiovascular risks
Strict ANC monitoring must be adhered to
Lurasidone(Latuda)
Atypical, 2nd Generation Antipsychotic
FDA Approved: Bipolar I Disorder acute depression
Less risk for sedation, lesser risk of weight gain and dyslipidemia
Moderate EPS, recommended to be given at night
Asenaphine (Saphris)
Atypical, 2nd generation Antipsychotic
FDA Approved: Bipolar I Disorder, acute manic or mixed presentation
Antagonist to D2 and 5-HT2A receptors
Usual dose 5mg to 10mg bid
Given sublingually as an oral disintegrating tab to enhance absorption. May be used as a rapid PRN agent
Major side effects include sedation, lower risk of EPS, weight gain, dyslipidemia, mouth numbing and foul taste
Do not eat or drink for 10 minutes after administration
Quetiapine(Seroquel)
Atypical, 2nd Generation Antipsychotic
Multipleformulations
FDA Approved: Bipolar depression, maintenance and bipolar adjunctive therapy
Higher potency on D2 receptor
Available in tabs and ER
Major side effects include weight gain, increased triglycerides, insulin resistance
Risperidone (Risperdal)
Atypical, 2nd Generation Antipsychotics
Used to treat bipolar mania
Also used to treat irritability in children and adolescents with autistic disorder
Available in tablets, dissolvable tablets, liquid, and depot injectable formulations
Major side effects include sedation, lower risk of EPS, weight gain, dyslipidemia
Ziprasidone(Geodon)
Atypical 2nd Generation Antipsychotic
It may have antidepressant actions
Given with at least 500 calories of food
Available in tablets and intramuscular forms
Less risk of weight gain, less risk of triglyceride elevation, insulin resistance, dyslipidemia
Olanzapine(Zyprexa)
Atypical, 2nd Generation Antipsychotic
Widely prescribed and used in combination with other agents (e.g. antidepressants)
Can help improve mood
Major side effects include significant weight gain, cardiometabolic risks, increased triglycerides, and insulin resistance may occur
Available in tablets, disintegrating tablets, and injection
