2019 New York State Office of Mental Health

19  Download (0)

Full text

(1)

Bipolar Disorder:

Treatment

Brett Nelson, MD

Medical Director, Project TEACH Region 2

(2)

Speaker:

Brett Nelson, MD

Medical Director, Child and Adolescent

Psychiatry Outpatient Clinic, Four Winds

Saratoga

Contact:

(3)

Neither I nor my spouse/partner has a relevant financial relationship

with a commercial interest to disclose

(4)

Bipolar Disorder Treatment Options

Multimodal treatment is essential

Medications have limitations & possible adverse effects

Psychoeducation for the patient & family

School Based interventions

Psychotherapies

• Cognitive behavioral therapy

• Interpersonal therapy

• Group therapy

• Bibliotherapy

(5)

Common Bipolar Medications

• Mood Stabilizers

• Lithium

Depakote (valproate)

Lamictal (lamtrigine)

Tegretol (carbamaezpine)

• Antipsychotics

• Typical Antipsychotics

Haldol, Thorazine, Trilafon

(6)

We Need More Studies!

Pediatric Bipolar Manic & Mixed States

• Asenapine, Abilify, Seroquel, Risperdal

• ages 10-17

• Lithium

• ages 12-17

• Zyprexa

• ages 13-17

(7)

2

nd

Generation Antipsychotics

Clinical Application

• Mania, Mixed Episodes

• Augmentation for depressive episodes

• Psychotic symptoms / agitation

Mechanism

• D2 receptor antagonism

• 5HT2a (serotonin) receptor antagonism

Labs

• CBC, CMP, FLP, A1C

• EKG

(8)

2

nd

Generation Antipsychotics

Side Effects:

Sedation

Metabolic Syndrome

• ↑ Weight

• ↑ blood pressure

• Elevated blood sugar

• Cholesterol/Triglycerides

Extra-pyramidal symptoms (EPS)

• Tremor, rigidity, dystonia, akathisia

• Treat with Cogentin 0.5-1 mg or Benadryl 25 mg - 50 mg; Propranolol 10 mg

Neuroleptic malignant syndrome

Blood dyscrasias (agranulocytosis)

(9)

2

nd

Generation Antipsychotics

Risperdal

• Dose- 0.5 – 1 mg PO QD or BID

• Available in M-tab form (melt tab) & tablet

• Mechanism: D2 receptor tightly bound

• Higher incidence of EPS

• Weight gain is prominent

• Prolactin levels, Gynecomastia

Zyprexa

• Dose: 2.5 – 5 mg QHS

• Very sedating

(10)

Risperidone in Bipolar Disorder:

Response Pre- & Post-Treatment

0

1

2

3

4

5

6

7

Mania

ADHD

Psychosis

Aggression

Pre-treatment

Post-treatment

Mean CGI Severity

(11)

2

nd

Generation Antipsychotics

Abilify

• Partial D2 receptor agonist

• Dose: 2 – 5 mg PO QHS

• Available as a “disc-melt” & liquid

Seroquel

• Very sedating at ↓ doses

• More anticholinergic, less EPS

• Dose: 25 – 50 mg start, ↑ as tolerated

Saphris

(12)

Lithium

Indications

• Grandfathered indication for use

• Acute Mania, Mixed Features,

Maintenance

Dose

• 150 mg – 300 mg PO BID

• Advance to about 900-1200 mg total

daily dose

Labs

• Baseline: CBC, Kidney Function Test,

TSH/FT4

• Lithium Level (12 hours after last dose)

0.6-1.2 mEq/L

(13)

Lithium

Mechanism

• Inhibits inositol monophosptase, protein

kinase C, ion transports

Pharmacokinetics

• 95% renal excretion

• use cautiously in renal impairment,

maintain hydration

Side Effects

• Sedation

• Weight Gain

• Thyroid dysfunction (goiter, elevated

TSH/FT4)

• Neurological (ataxia, dysarthria, delirium,

tremor, memory)

• Renal toxicity (polyuria, nephrogenic

diabetes insipidus)

(14)

Depakote (Valproic Acid)

Indications:

• OFF-LABEL for use in children & adolescence

• Acute Mania, Mixed Features, Maintenance

Dose:

• 1200 - 1500 mg / day goal dose (>10 years old)

• Start 250-500 mg (mild) or 500 mg PO BID (severe) mania

• VPA level 45-125 ug/mL (steady state)

• Check on 5

th

day after starting prior to AM dose for trough

level

Labs:

(15)

Depakote (Valproic Acid)

Mechanism

• Blocks voltage-sensitive sodium channels

• ↑ GABA

Pharmacokinetics

• Inhibitor of CYP450 2C9

Side Effects

• Sedation

• Weight Gain

• Hepatotoxicty/Pancreatitis

• Alopecia

• PCOS

(16)

Other

medications

Lamictal

• Anticonvulsant

• Not well supported in evidence for Bipolar Disorder in children

• ↓ r/o weight gain, somnolence, EPS

• r/o Stevens Johnson Rash (normal rash is common)

Tegretol / Trileptal

• Anticonvulsant

(17)

Treatment Options for Juvenile Bipolar & Related Disorders:

Double-Blind Control Trials

Authors

Treatment

Sample

Diagnosis

Results

MOOD STABILIZERS

Geller et al. (1998) Lithium N=25; 16.3 ± 1.2 y.o. (12-18); Outpatient

Bipolar I or II, substance dependency

Li > PC (measures of psychopathology & urine tests)

Kafantaris et al. (2001) Lithium (Discontinuation) N=40; 15.2 ± 1.7 y.o. (12-18); Inpatient

BD-I manic episode, responders to Li

Li = PC in preventing exacerbation (although trend in favor of Li 52.6% vs. 61.9%)

Findling et al. (2005) Lithium vs. Divalproex

(Maintenace; stable after Li/DVP combo)

N=60; 10.8 ± 3.5 y.o. (5-17); Outpatient

BD-I or II Li = DVP (time to relapse, time to discontinuation)

DelBello et al. (2006) Divalproex vs. Quetiapine N=50; 15 ± 1.5 y.o. (12-18); Inpatient

Bipolar-I, manic or mixed episode

Quet = DVP (diff in YMRS scores); Quet > DVP (time to improvement & response/remission)

Donovan et al. (2000) Divalproex (Crossover) N=20; 13.8 ± 2.4 y.o. (10-18); Outpatient

*CD or ODD with explosive temper & mood lability

Phase 1: DVP > PC Phase 2: DVP > PC

Dineen-Wagner et al., (2006)

Oxcarbazepine N=116; 7-18 y.o.; Outpatient Bipolar-I, manic or mixed episode

Oxcarbazepine = PC (change in YMRS)

DelBello et al. (2005) Topiramate N=56; 6-17 y.o.; Inpatient/outpatient

Bipolar-I, manic or mixed episode

Discontinued early when adult studies failed to show efficacy; trend toward improvement

ATYPICALS

DelBello et al. (2002) Quetiapine as adjunct to Divalproex

N=30; 12-18 y.o. Bipolar-I, manic or mixed episode

Significant ↓ in YMRS scores after 6 wks.

(18)

Common Pediatric Bipolar Medications

• Mood Stabilizers

• Lithium

Depakote (valproate)

Lamictal (lamtrigine)

Tegretol (carbamaezpine)

• Antipsychotics

• Typical Antipsychotics

Haldol, Thorazine, Trilafon

(19)

Figure

Updating...

References

Related subjects :