Bipolar Disorder & Mood Stabilizers

1. Bipolar Disorder & Mood Stabilizers BabatundeIdowuOgundipe M.D. M.P.H. Comprehensive Clinical Services P.C. December 16 2011

2. What is Bipolar Disorder • Manic-depressive disorder • Actually several conditions with overlapping symptomatology: • (1)Bipolar I • (2)Bipolar II • (3)Cyclothymic disorder • (4)Bipolar not otherwise specified (NOS)

3. What is Bipolar Disorder • Involves a manic episode characterized: • A. One week of an abnormally & persistently elevated (“euphoria”), expansive, or irritable mood (Any duration if hospitalization is necessary). • B. Three of the following symptoms must be present for one week (Four if the mood is irritable): • (1)Distractibility (i.e. attention too easily drawn to unimportant or irrelevant external stimuli). • (2)Insomnia (decreased need for sleep, i.e. feels rested after only 3 hours of sleep). • (3)Grandiosity or inflated self-esteem. • (4)Flight of ideas or subjective experience that thoughts are racing. • (5)Activity increased(increase in goal directed activity either socially, at work or school, or sexually) or psychomotor agitation.

4. What is Bipolar Disorder • (6)Speech pressured (more talkative than usual) • (7)Thoughtlessness = Excessive involvement in pleasurable activities that have a high potential for painful consequences (i.e. engagement in unrestrained buying sprees, sexual indiscretions, or foolish business investments). • Remember this with pneumonic: DIGFAST. • C. Symptoms do not meet criteria for a mixed episode (Mania & Depression for > 1 week. • D. Mood disturbance sufficiently severe to cause marked impairment in occupational functioning or in usual social activities or relationships with others, or to necessitate hospitalization to prevent harm to self or others, or there are psychotic features. • E. Symptoms not due to direct physiological effects of a substance (i.e. drug of abuse, a medication, or other treatment) or to a general medical condition (i.e.hyperthyroidism).

5. Bipolar Disorder Epidemiology • Family history Bipolar disorder increases risk having it. • Lifetime prevalence Bipolar I & II disorders general population 3.7%-3.9%. • Male:Female ratio is 1:1. • Symptoms usually begin late in adolescence. • ~10-15 % die by suicide. http://www.bipolar-health.com/

6. Bipolar Disorder Differential • Cyclothymic disorder: chronic cycles of mild depression & hypomania X > 2 years. • Substance induced mood disorder( i.e. manic symptoms due to amphetamines, PCP). Also medication induced mania from : antidepressants, amantadine, bromocriptine, corticosteroids, disulfiram, isoniazid, levodopa, procarbazine, levothyroxine, CNS stimulants. • Schizophrenia (in single clinical evaluation of a psychotic patient mania may be indistinguishable from schizophrenia; proper diagnosis needs basis on patient’s history). • Schizoaffective disorder. • Personality Disorders (i.e.Borderline personality disorder) • Medical disorders(i.e. temporal lobe epilepsy, hyperthyroidism, renal failure, vitamin B3 deficiency, carcinoid syndrome, Huntington’s disease, Wilson’s disease, CNS infection, neoplastic disease, cerebrovascular accidents, head trauma, multiple sclerosis, Pick’s disease) • ADHD. (highly comorbid, 30% ADHD with Bipolar disorder) • Major Depressive Disorder (MDD)/Postpartum Depression

7. Bipolar Disorder Evaluation • What is depression? • A.Five or more of following symptoms present during the same 2 week period & represent change from previous functioning; at least one of symptoms is either (1) depressed mood or (2)loss of interest or pleasure: • (1) Sleep disturbance. Insomnia or hypersomnia. • (2) Interest lost. Diminished interest or pleasure in all, almost all, activities most of the day, nearly everyday(subjective or account made by others). • (3)Guilt (innapropriate, & may be delusional), feelings of worthlessness nearly everyday. • (4)Energy loss or fatigue nearly everyday. • (5)Mood depressed most of day, nearly everyday. • (6)Concentration loss. Diminished ability to think or indecisiveness, nearly everyday.

8. Bipolar Disorder Evaluation • (7)Appetite change. Increase or decrease in appetite  increase (> 5 % body weight in a month) or decrease weight (when not dieting). • (8)Psychomotor agitation or retardation nearly everyday (observable by others, not merely subjective feelings of restlessness or being slowed down). • (9)Suicidal ideation + thoughts of death that are recurrent without a specific plan, or a suicide attempt or a specific plan for committing suicide. • Remember: SIGECAPS or SIGEMCAPS

9. Bipolar Disorder Evaluation • B.Symptoms do not meet criteria for a mixed episode. • C.Symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning. • D.Symptoms not due to direct physiological effects of a substance (i.e. drug of abuse, or medication) or a general medical condition (i.e.hypothyroidism). • E. Symptoms not better accounted for by bereavement, persisting for longer than 2 months or are characterized by marked functional impairment, morbid preoccupation with worthlessness, suicidal ideation, psychotic symptoms, or psychomotor retardation.

10. An Overview of Primary Care Assessment and Management of Bipolar Disorder Bipolar Disorder Evaluation • Diagnosis: • Bipolar I Disorder: > 1 mixed or manic episodes. Depressive episodes common but not required for diagnosis. • Bipolar II Disorder: Characterized by hypomania rather than mania. • Hypomania: > 4 < 7 days of manic symptoms : • (1) Do not cause marked functional impairment. • (2) Do not require hospitalization. • (3)Do not present with psychotic features

11. Bipolar Disorder Evaluation • Other diagnostic elements can assist in correct diagnosis: • Bipolar Disorder commonly runs in family • H/o poor response to antidepressant therapy. Treatment failure p/w agitation, restlessness, or insomnia. • High risk for postpartum depression. • Specific behaviors may raise suspicion Bipolar disorder.

12. Mood Stabilizers • Lithium: • Use: • Long-term maintenance or prophylaxis bipolar disorder. • First line bipolar depression • Effective vs mania + in augmenting antidepressants in depression & OCD. • Decreases suicidal behavior/risk Bipolar disorder. • Side effects: • Narrow therapeutic index. Requires monitoring serum levels. • Diabetes insipidus (thirst, polyuria). • Fine tremor, weight gain, diarrhea, nausea, acne. • Thyroid dysfunction (hypothyroidism, goiter). Check thyroid function before initiating therapy. sciencephoto.com

13. Mood Stabilizers • Also check renal function prior to initiation & monitor along with thyroid function while on drug. Lithium contraindicated in patients with renal insufficiency (Any factor  decreased renal excretion: renal insufficiency, effective volume depletion i.e. diuretics/CHF elevated serum lithium levels/toxicity. • Lithium toxicity: Can get with overdose lethargy, confusion, fasciculation's, seizures, vomiting, arrhythmias, tremors, ataxia. • In pregnant women  increases risk cardiac malformations (i.e. ebsteins anomaly) if fetus exposed in first trimester. If exposed in 2nd & 3rd trimester  fetal thyroid goiter.

14. Mood Stabilizers • Valproic Acid (Depakote): • Use: • First line for acute mania & Bipolar disorder. • Effective with rapid cyclers(> 4 episodes per year). • Antiepileptic. • Side Effects: • Sedation, somnolence, dizziness, weight gain, hair loss (alopecia), tremor, ataxia, GI distress (nausea, vomiting, diarrhea) • Less commonly: Pancreatitis, thrombocytopenia, & fatal hepatotoxicity (thus requires regular monitoring of liver function, platelets, & serum drug levels). • Longterm use: urinary frequency & incontinence. valparin.110mb.com

15. Mood Stabilizers • Carbamazepine (Tegretol): • Use: • Second-line acute mania & bipolar disorder. • Anti-epileptic. • Trigeminal neuralgia. • Side Effects: • Common: nausea, sedation, rash, & ataxia. • Rare: hepatic toxicity, hyponatremia (SIADH in elderly), Stevens-Johnson Syndrome, bone marrow suppression (patients should be made aware that early symptoms such as fever, mouth ulcers, easy bruising, or petechiae may be markers of development of neutropenia, aplastic anemia, or thrombocytopenia). • Monitor blood counts with CBC, transaminases, & electrolytes. • Mild anticholinergic effects: increased risk glaucoma, urinary retention, constipation. littlemountainhomeopathy.wordpress.com

16. Mood Stabilizers • Other anticonvulsants used as mood stabilizers: • Lamotrigine, Gabapentin, Topiramate. • Efficacy not well documented. • Do not require blood level monitoring & do not cause weight gain. • Lamotrigine( as with lithium) used as first line for bipolar depression. Lamotrigine associated with Stevens-Johnson Syndrome.

17. Management of Bipolar Disorder • Acute management: • Manic or Mixed Episodes: • Lithium: first line treatment manic episodes. • Other options are numerous & based on studies include: • (1)Monotherapy with atypical antipsychotic: • Olanzapinemonotherapy. Olanzapine also effective as adjunctive agent to traditional mood stabilizers (i.e. added to divalproex or lithium more efficacious than lithium or valproatemonotherapy). • Risperidonemonotherapy. Risperidone (as adjunctive) + traditional mood stabilizer (i.e. lithium or divalproex) more efficacious than mood stabilizer alone. However Risperidone Extrapyramidal symptoms. bipolarhappens.com

18. Management of Bipolar Disorder • Ziprasidonemonotherapy. • Aripiprazolemonotherapy. • Quetiapinemonotherapy. • Quetiapine + lithium or divalproex more efficacious than mood stabilizer alone. • (2)Carbamazepine extended release (anticonvulsant) monotherapy also efficacious (onset of action similar to antipsychotics) • (3)Divalproex (Depakote) also effective. • (4)Benzodiazepines. • Besides common side effects of most concern are metabolic effects associated with second generation antipsychotics: • (1) Weight gain. Especially with Olanzapine & Clozapine> other antipsychotics. • (2)Diabetes Mellitus & dyslipidemia. Especially of concern with Clozapine & olanzapine more than others. • Important to monitor weight, waist circumference, blood pressure, glucose, & lipids at baseline + at monthly intervals.

19. Management of Bipolar Disorder • Depressive Episodes: • Olanzapine + fluoxetine combination approved by FDA for acute treatment bipolar depression. No concerns for switch into mania or hypomania. • Quetiapinemonotherapy effective. • Lamotriginemonotherapy effective. • Some evidence that adjunctive use Pramipexole (dopamine agonist) with traditional mood stabilizers may be helpful. • Minimal evidence of efficacy antidepressant with adjunctive mood stabilizer. • Antidepressant without mood stabilizer not recommended for bipolar I patients.

20. Management of Bipolar Disorder • Maintenance Treatment: • Pharmacotherapy: • When patients recently depressed lamotrigine & lithium monotherapy effective in preventing any mood episode. • Lamotrigine (not lithium) effective in preventing depressive episode. • Lithium (not lamotrigine) effective in preventing manic, hypomanic, or mixed episode. • When patients recently manic or hypomanic both lamotrigine & lithium effective in delaying onset mood episode. • Lithium (not lamotrigine) effective in preventing a manic episode. • *Both lamotrigine & lithium effective in maintenance treatment patients with bipolar disorder. Utility lamotrigine > lithium for prevention depressive episodes than for manic episodes. Utility lithium > lamotrigine for prevention manic episodes than for depressive episodes.

21. Management of Bipolar Disorder • Psychosocial Interventions: • Family-focused therapy: manualized psychosocial program involving all family members in which weekly psychoeducation, communication enhancement training, & problem-solving skills training occur adjunctively with pharmacotherapy. • Family-focused therapy + pharmacotherapy combination efficacious in postepisode symptomatic adjustment & drug adherence. • Cognitive therapy + pharmacotherapy  fewer bipolar episodes; days in episode, & number of admissions. • Psychoeducation enhances lifestyle regularity & early syndrome detection. • Psychosocial intervention with focus on addressing interpersonal problems & regulating social rhythms during acute treatment bipolar I patients extended time to new episode & reduces likelihood of recurrence.

23. References • Pocket Handbook of Primary Care Psychiatry. Harold I kaplan, M.D. Benjamin J. Sadock, M.D. • Guideline Watch for the Practice Guideline for the Treatment of Patients With Bipolar Disorder. Robert M.A. Hirschfeld, M.D. • Wikipedia. • FIRST AID for the USMLE 3, Tao Le, VikasBhushan, Robert W. Grow, Veronique Tache. • Psychiatry History Taking. Third Edition. A Current Clinical Strategies medical book. Alex Kolevzon, Craig L.Katz. • Lewis, Frederick T. D.O., Kass, Ethan D.O. M.B.A., Klein, Robert M. D.O. An Overview of Primary Care Assessment and Management of Bipolar Disorder(2004). Journal of the American Osteopathic Association, 104, 2-8.