Bipolar Disorders

Types of Bipolar Disorders (6)

1. Bipolar 1 disorder

2. Bipolar 2 disorder

3. Cyclothymic disorder

4. Substance/medication-induced bipolar and related disorder

5. Bipolar and related disorder due to another medical condition

6. Other

Bipolar disorders Specifiers

1. With anxious distress

2. With mixed features

(at least 3 criteria for the opposite pole mood episode have been met)

3. With mood-congruent or mood-incongruent psychotic features

4. With melancholic features

5. With atypical features

6. With rapid cycling

(4 ore more mood episodes in 1 year)

7. With catatonia

8. With peripartum onset

With seasonal pattern

Graph of Bipolar disorders

1. Bipolar 1 --> hits depression and mania

2. Bipolar 2--> hits depression and hypomania

3. Cyclothymia--> hit hypomania

Bipolar disorder (definition)

- Bridge between schizophrenia and depression disorder in terms of sx, family hx, and genetics

Time is takes to for proper bipolar disorder dx?

- Average length of time from start of symptoms to proper diagnosis 6 years

Manic episode criteria (2)

A.

.A distinct period of abnormally and persistently elevated, expansive, or irritable mood and abnormally and persistently increased goal-directed activity or energy, lasting at least 1 week and present most of the day, nearly every day (or any duration if hospitalization)

B

During the period of mood disturbance and increased energy or activity, 3 or more of the following symptoms (4 if the mood is only irritable) are present to a significant degree and represent a noticeable change in behavior.

Symptoms of Criteria B for manic disorder (7)

Must have 3 or more of the following (4 if mood is only irritable)

DIG FAST

1. Distractibility and easy frustration

2. Indiscretion (excessive pleasurable activities)

3. Grandiosity

4. Flight of ideas

5. Activity increased

6. Sleep deficit

7. Talkativeness

Diagnostic features of Manic episode (6)

1. During manic episodes, individuals have poor insight (do not perceive that they are ill or need of treatment, and resist efforts to be treated)

2. May change dress, makeup, or appearance to be more sexually suggestive or flamboyant

3. Gambling and antisocial behaviors may accompany manic episode

4. Some become hostile and physically threatening to others, and when delusional, physically assaultive, or suicidal

5. Episodes often result in involuntary hospitalization, difficulties with the law, and serious financial difficulties

6. Mood may shift very rapidly to anger or depression.

Bipolar 1 criteria (6)

A. 3 ore more symptoms of mania (4 if mood is only irritable), of DIGFAST sx

B. 7 or more consecutive days and present nearly most of the day every day

C. Hospitalization to prevent harm to self or others

D. Psychotic features-ideas of reference

E. Include depressive episode

F. Mania may have been preceded by and may be followed by hypomania and MDD episodes

Bipolar 1 consequences (3)

1. High rates of serious and/or untreated medical conditions, most commonly metabolic syndrome and migraine headaches

2. Impairment in occupational function in euthymic state, resulting in lower SES despite equivalent levels of education.

3. Cognitive impairments often persist through the lifespan, even euthymic periods

Bipolar 1 comorbidities (3)

1. 75% have anxiety disorder

2. Higher risk for ADHD, ODD, IED, conduct disorder, substance use disorders

3. Alcohol use disorder or a disruptive/impulse control disorder

Psychotic features definition

-Delusion or hallucinations are present at any time in the episode

Mood congruent definition

-During manic episodes the content of all delusion and hallucinations is consistent with typical mania themes or grandiosity, invulnerability.. ect but may also include themes of suspiciousness and paranoia

Mood incongruent definition

-Content of the delusions and hallucinations are inconsistent with the episode polarity themes

Depressive episode (sx of bipolar disorder) definition

SIGECAPS basically

-Episode of either depressed or sad mood

-Anhedonia

-Change in eating or sleeping patterns,

-Feelings of guilt and worthlessness

-Lack of concentration

-Suicidal ideation or behavior

Mixed episode (sx of bipolar disorder) definition

-Symptoms consistent with both mania and depression last at least 1 week

Hypomania (sx of bipolar disorder) definition

-Episodes of at least 4 days of elevated, expansive, or irritable mood accompanied by same symptoms of mania (DIGFAST)

Prevalence of bipolar disorder

- Equal prevalence in gender and races

- Influenced by genetic and familial factors

Age of onset of bipolar disorder

- Onset of bipolar disorder 18-20 years

- Onset of manic symptoms in mid to late life should prompt consideration of medical conditions or substance/withdrawal

Children and onset of bipolar disorder

-Children usually has a more severe, chronic, and refractory course of illness

How does bipolar disorder affect children (6)

1. Neurodevelopmental delays (language, social, motor)

2. Greater vulnerability to stress and disruptions

3. Higher degree of associated psychotic symptoms

4. Poor/ineffective response to lithium

5. Increased alcohol disorders

6. 90% of children with BP disorder have comorbid ADHD

Reasons why bipolar disorder is difficult to manage (4)

1. 10% suicide rate (15x greater than general population)

2. Often presents with other psychiatric co-morbidities

3. Personality traits: ↑extraversion, neuroticism, openness

4. No simple treatment algorithm

Bipolar 2 criteria (5)

A. 3 or more symptoms of mania DIG FAST (4 if mood is only irritable)

B. 4 or more consecutive days and present nearly most of the day every day, of DIGFAST sx

C. Not severe enough to cause marked impairment in social or occupational functioning or to necessitate hospitalization

D. No Psychotic features

E. Must include depressive episode(s)

Bipolar 2 Characteristics (6)

1. Increased self-esteem

2. Thoughts are more organized

3. Thinking is quick and creative

4. Speech is loud and fast

5. Psychosocial functioning is good

6. Risk taking is mild to moderate

Bipolar 2 prevalence (Gender, onset age)

-Age of onset: 20 years

- More common in women

*RFs: genetic, familial

Bipolar 2 comorbidities

- 60% have 3 or more comorbid mental disorders

- 40% have eating disorder

Consequences and prognosis of Bipolar 2 disorder

- Economic burden: 4x greater than Bipolar I

- Better prognosis: married, higher ed. Level, fewer years ill.

Comparison of bipolar 1 and 2

- Bipolar 1 --> Manic episode and depressive episode

last more than 7 days

severe impairment

possible hospitalization and psychosis

- Bipolarr 2 --> hypomanic episode and depressive episode

lasts more than 4 days

Minore to no impairment

no hospitalization or psychosis

Cyclothymic Disorder Criteria (4)

A. For at least 2 years (1 yr. for children and adolescents) there have been numerous periods with hypomanic symptoms that do not meet criteria for hypomanic episode and numerous periods with depressive symptoms that do not meet criteria for a major depressive episode.

B. During the above 2-year period, the hypomanic and depressive periods have been persistent for at least half the time and the individual has not been without symptoms for more than 2 months at a time

C. Criteria for major depressive, manic, or hypomanic episode have never been met

D.Symptoms cause marked impairment in social or occupational functioning

Prevalence of cyclothymic Disorder (gender and onset)

-Equal prevalence in gender

-Begins in adolescence or early adult life

*RF --> familial

Comorbidities of cyclothymic disorder (3)

1. Substance abuse disorder

2. Sleep disorders

3. Children w/ADHD

Cyclothymic disorder is at risk of Developing what?

- 15-50% risk of developing bipolar I or bipolar II

Character traits of cyclothymic disorder (5)

1. Extroverted

2. Creative

3. Sociable

4. At times cheerful exuberance turns into irritability and extreme sensitivity to rejection or loss

5. Often impulsive

Treatment goals of bipolar disorders (4)

1.Full symptomatic remission

2.Return of psychosocial functioning

3.Prevention of relapse

4.Rapidly control agitation, aggression and impulsivity

Things to look at in bipolar disorder tx (3)

1. Assess for presence of alcohol or substance abuse or other factors that may contribute to disease or complicate treatment

2. Evaluated safety: suicidal evaluation , consider hospitalization

3. Directly related to the phase of episode, phase of treatment

a) Pt hx

b) Team approach: meds, CBT, family issues, social/school functioning

First line tx for bipolar disorder

- Mood stabilizers +/- antipsychotic

-They decrease the severity of mood episode

Different mood stabilizer

1. Lithium (gold standard)

2. Lamotrigine

3. Valproic acid

4. carbamazepine

Lithium

- Indicated for tx acute mania

- Prevention of recurrent manic and depressive episodes

- May have specific anti-suicidal effect

Starting dose of lithium

300-600 mg

Maintenance dose of lithium

600-1800 (lower in elderly pt)

What to measure when prescribing lithium

- Serum level

-Measure serum level 5-7 days after initiation or dose increase

* Should be drawn 12 hours after last dose

Acute side effects of lithium (6)

1. Nausea

2. Fine tremor

3. Polyuria and polydipsia

4. Weight gain

5. Loose stools

6. Cognitive impairment

Potential for serious side effects of lithium (4)

1. Weight gain

2. Diabetes insipidus

3. Renal failure

4. Hypothyroidism

S/S of toxicity for lithium (8)

1. Nausea,

2. Profuse vomiting, diarrhea, dehydration

4. ECG changes

5. Ataxia

6. Confusion

7. Tremor

8. Seizures

At what serum level can toxicity occur with lithium

-Can occur >1.5mmol/L

- >2.5mmol/L = medical emergency

Contraindication of lithium

1. Significant renal or cardiac disease (sick sinus syndrome)

2. Sodium depletion/extreme dehydration

3. Concurrent diuretic use

*kidney metabolism AVOID if CrCl <30mL/min

Preworkup when prescribing lithium (8)

1. UA

2. CBC with diff

3. BUN and Creatinine

4. TSH

5. Calcium

6. UPT

7. EKG

8. Weight

T/F you should taper lithium for discontinuation

TRUE

What is Valproate used to treat

1. Acute mania

2. Maintenance of bipolar disorder

* monotherapy or adjunct

*helpful with aggression

ADRs of Valproate (9)

1. Vomitting and nausea

2. Alopecia

3. Liver toxicity

4. Pancreatitis, PCOS, Low platelets

5. Rash

6. Obesity

7. Hyper ammonemia

8. Teratogenicity, tremors, thrombocytopenia

9. Exhaustion, encephalopathy

Black box warning of valproate (4)

1. Pancreatitis

2. Liver toxicity

3. Teratogenicity

4. Mitochondrial disease

Contraindications of valproate (4)

1. Significant hepatic impairment

2. Mitochondrial disorders

3. Urea cycle disorders

4. Pregnancy

Toxicity dose and S/S of valproate (5)

- Toxicity > 125 mcg/mL

1. Neurological: Can range from mild sedation, partial consciousness to coma

2. Cardiovascular

3. Hypotension

4. Tachycardia Gastrointestinal

5. Nausea, vomiting, diarrhea

*In severe toxicity must remove drug by dialysis

Monitoring for valproate (5)

1. VPA levels

2. LFTs

3. CBC w/ differential

4. Ammonia

5. Amylase/lipase

* may also do skin checks, body weight and waist size monthly

Use of Carbamazepine (3)

1. Acute mania

2. Mixed episodes

3. Maintenance of bipolar disorder

Contraindications of carbamazepine (4)

1. Hypersensitivity to carbamazepine or TCA's

2. Bone marrow depression

3. With or within 14 days of MAO inhibitor use

4. Auto-induces its own metabolism for first 4-8 weeks between dose changes.

When to check serum levels on carbamazepine

- 4 days after initiation or dose change

*Draw levels 12 hours after last dose

Toxicity S/S of carbamazepine (3)

1. Neurological:

Nystagmus, blurred vision, dizziness, convulsions

2. Cardiovascular

Arrhythmia, Hypotension, Tachycardia

3. Gastrointestinal

Nausea/vomiting, diarrhea

* In severe toxicity, remove via gastric lavage

Significant ADRs of carbamazepine (6)

1. Agranulocytosis/aplastic anemia

2. N/VD

3. Hepatotoxicity

4. Hyponatremia

5. CNS effects: drowsiness, nystagmus, blurred vision, dizziness

*risk suicide

6. Rash

Black box warning of carbamazepine (4)

1. Steven Johnson Syndrome

2. Toxic epidermal necrolysis in ppl with HLA- B 1502 allele

3. Aplastic anemia

4. Agranulocytosis

Carbamazepine (CBZ) drug interactions (8)

1. Oral contraceptive metabolism significantly induced

2. Phenobarbital, primidone, phenytoin can all induce CBZ

3. CBZ induces lamotrigine by 2-fold

4. Valproate inhibits epoxide hydrolase and increases active CBZ metabolite levels

5. CYP inducer induces metabolism antibiotics

6. Carbapenem antibiotics can decrease VPA levels

7. Psychiatric drugs: Clozapine

8. Antivirals

Most important drug related effects of CBZ

-Agranulocytosis

CBZ lab monitoring (4)

1. CBZ Levels

2. LFTs (every 2 weeks for first 2 months, then every 3 months)

3. CBC w/ differential (every 2 weeks for first 2 months, then every 3 months)

4. Sodium (baseline then periodically)

Other ways to monitor CBZ (3)

1. Skin checks for rashes at visits

2. Ophthalmologic exams

3. Patient's stance on pregnancy (if applicable)

Oxacarbazepine

- Structural derivative of carbamazepine

- Not effective for bipolar depression

- Improved adverse effect profile compared to CBZ

Oxacarbazepine (what it interferes with and the drug adjustments)

-May interfere with contraceptives

-Drug adjustments:

○ Hepatic: Use with caution in impairment

○ Renal: Cr Cl<30 mL/min: initiate at 1⁄2 usual dose

What drugs are used to treat Bipolar Depression (6)

1. Seroquel

2. Olanzapine/fluoxetine

3. Latuda, Lithium

4. Lamotrigine

5. Lumateperone

6. Vraylar

Drug that are indicated for both bipolar mania and depression (2)

1. Cariprazine (Vraylar)

2. Quetiapine (Seroquel)

Treatment for acute bipolar depression

1. Consider lithium (if appropriate/no contraindications) if patient reports suicidality

2. Use atypical antipsychotics (AAP)

3. Psychotherapy

4. Avoid lamotrigine as initial therapy

What drug to avoid when treating bipolar Depression and why?

- Avoid antidepressants as first line tx

- Bc they can precipitate a switch to mania or hypomania and are not effective for bipolar depression as monotherapy

Lamotrigine indication

-Used for bipolar maintenance and bipolar depression

-Generally well tolerated and safe for pregnancy

Drug interactions of Lamotrigine (4)

1. VPA: inhibits glucuronidation metabolism of LTG

2. CBZ: induces metabolism of LTG

3. Estrogen- containing contraceptives: induce LTG metabolism by 2x

4. Atazanavir, lopinavir, ritonavir: Induce LTG metabolism

ADRs or Lamotrigine (6)

1. Nausea/vomiting

2. Headache/dizziness

3. Somnolence

4. Ataxia

5. Diplopia, blurred vision

6. Rashes

Monitoring for Lamotrigine (4)

1. LFTs

2. CBC w/ differential

3. Skin check: no way to differentiate benign rashes from serious ones. If rash develops patient should stop LTG immediately

4. Adherence: if patient misses 5 days of LTG must restart titration

Blackbox warning for Lamotrigine

1. Life-threatening serious rashes, including SJS and Toxic epidermal necrolysis (TEN)

- Risk increased in pediatric patients, coadministration with valproate, exceeding recommendations for LTG initial dose or recommended dose escalation

SGA side effects

1. Sedation

2. Weight gain

3. EPS (drug induced movement disorder)

What drugs to avoid in pregnancy while treating bipolar disorder

1. Avoid CBZ and VPA in pregnancy whenever possible (VPA has higher right of birth defect)

2. Avoid lithium use in the first trimester (can be used in 2nd and 3rd trimester)

T/F in pregnancy antipsychotics are preferred over mood stabilizers in acute mania

TRUE

T/F for the first 6 months of treatment pts are at high right for relapse

TRUE

First line Treatments for bipolar disorder

- Lithium and VPA

Maintenance goal for bipolar disorder (4)

1. To treat relapse and recurrence,

2. Decrease subthreshold symptoms

3. Decrease suicide symptoms

4. Decrease cycling

Purpose of psychological interventions (3)

1. Reduce distress

2. Improve patient functioning between episodes

3. Decrease likelihood and/or severity of future episodes