Bipolar Disorder 4/6/2014. Bipolar Disorder. Symptoms of Depression. Mania. Depression

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1 Bipolar Disorder J. H. Atkinson, M.D. Professor of Psychiatry HIV Neurobehavioral Research Programs University of California, San Diego KETHEA, Athens Slides courtesy of John Kelsoe, M.D. Bipolar Disorder Previously called manic-depressive illness Alternation between opposite states of mania and depression Highs and lows Less common than Major Depression More complex to manage Mania Depression Symptoms of Depression Symptoms of mood:» Low mood, sadness, or sometimes irritability» Loss of interest and pleasure» Hopelessness» Suicidality Cognitive symptoms:» Problems with memory & concentration (often most prominent symptom in older people)» Indecisiveness» Low self esteem, worthless, guilt Somatic symptoms:» Low energy» Insomnia, hypersomnia, early morning awakening» Loss of appetite, weight loss or increased appetite and wt. gain 1

2 Symptoms of Major Depression DSM4 Criteria» 5 of 9 criteria» Two week duration» Clinically significant distress or impairment Other Associated Symptoms» Decreased libido» Anxiety or panic attacks» Somatization» Psychosis Mood congruent» Pseudo-dementia» Alcohol and substance abuse Symptoms of Mania DSM4 Criteria» One week duration» Elevated or irritable mood» Inflated self esteem or grandiosity» Decreased need for sleep» Increased or pressured speech» Flight of ideas or racing thoughts» Distractibility» Increased goal directed activity» Risky pleasures» Functional impairment Symptoms of Mania Severity» Mania Bipolar I» Hypomania No functional impairment Bipolar II Other Associated Symptoms» Increased libido» Spending sprees» Psychosis» Antisocial behavior» Alcohol and substance abuse» Suicidality 2

3 Progression of mania Rapid Cycling Mania Sometimes Superior Functioning Depression Dysphoric mania Hypomania Mania Psychotic mania Mixed state Mixed States Co-occurrence of mania and depression» Ultra rapid cycling» Simultaneous DSM 4 both mania and depression criteria Milder mixed states very common» Mania with some depressive symptoms» Depression with some mania symptoms» Agitated depressions Rapid cycling Mixed state Suicidality 15% lifetime rate of suicide Risk factors» Older white men at higher risk» Social isolation» Substance abuse» Chronic medical problems» Chronic pain» Family history of suicide 3

4 Assessing Suicidality Spectrum» Passive ideas» Plan» Assembling the means» Intent» Immediacy Psychosis» Command hallucinations Risk factors Hopelessness Future orientation Past history of attempts Stigma Merely the ups and downs of daily life A character flaw, a moral weakness, laziness It is not generally responsive to the well meaning exhortation of friends and family to pull yourself up by your bootstraps Classification of Mood Disorders Unipolar single episode Unipolar Unipolar recurrent Dysthymia Bipolar I Bipolar Bipolar II Cyclothymia Unipolar- Hyperthymic 4

5 Clinical Features of Bipolar Disorder Age of onset early twenties 1-2% prevalence Unipolar depression is about 5 times more common Male and Female prevalence equal 60-80% of cases begin with mania 4-18% of those with depression later have mania Stable features» Seasonality (Seasonal Affective Disorder)» Psychosis» Rapid cycling Related syndromes and disorders» Mixed states» Schizoaffective disorder» Substance abuse and alcoholism Psychotic Spectrum? Bipolar Disorder Schizoaffective Disorder Schizophrenia Psychotic symptoms outside a mood episode Prominent mania or depression Bipolar Genes Common Genes Schizophrenia Genes Bipolar Disorder 3.4% of the US Population Screened Positive by MDQ Overall Prevalence Age Group Income * Weighted to match US census data. Hirschfeld et al. J Clin Psychiatry. 2003; 64:

6 Depression is the Dominant Symptom in Bipolar Disorder Data from a prospective natural history study of bipolar I patients show» Patients were symptomatic nearly half the time» Time spent depressed was approximately 3 times more than time spent manic» Time spent manic accounted for only 9.3% of the time 9.3% Manic 5.9% Cycling/Mixed 52.7% No Symptoms 31.9% Depressed Judd LL, et al. Arch HIV Gen NEUROBEHAVIORAL Psychiatry 2002;59: RESEARCH PROGRAMS UNIVERSITY OF CALIFORNIA, SAN DIEGO Bipolar Disorder A Diagnostic Challenge Total Base (n) 600 Misdiagnosis (%) 69% Years to accurate diagnosis 7 Times misdiagnosed 3.5 MDs consulted before Dx 4 Misdiagnosed as (%): Depression 60 Anxiety disorder 26 Schizophrenia 18 Borderline personality or antisocial personality disorder 17 Hirschfeld et al. J Clin Psychiatry. 2003;64: Etiology of Bipolar Disorder Genes» Explains 50-70% of etiology Environment» Stress may precipitate episodes» Early life stress increases vulnerability Substance abuse Neurotransmitters» Serotonin increased by AD meds» Norepinephrine increased by AD meds» Dopamine amphetamine mimics mania» Glutamate atypical antipsychotics» Intracellular signaling pathways Neuronal atrophy» Glucocorticoids cause neuron loss» Lithium and antidepressants induces Brain Derived Neuronal Growth Factor 6

7 Bipolar Disorder is Genetic Twin Studies of Affective Illness Study Monozygotic Dizygotic Concordance (%) Concordance (%) Luxenberger, / / Rosanoff et al., / / Slater, / / Kallman, / / Harvald and Hauge, / / Allen et al., / / Bertelsen, / / TOTAL 95/ / The Universe of Bipolar Genes Spectrum temperaments Gene B Bipolar 1 Gene A Gene D Bipolar 3 Unipolar Gene E Bipolar 2 Gene C Balanced Selection for Bipolar Disorder? Primary genetic transmission Population Frequency More fit Less fit More Bipolar Genes Hyperthymia Bipolar Disorder 7

8 Pathophysiological pathways Gene subset A Pathophysiology A Environment Gene subset B Pathophysiology B Gene subset C Pathophysiology C Final Common pathway Disease Susceptibility Genes Pathophysiological Changes Clinical evaluation of mood disorder Systematic review of symptoms over time Longitudinal diagnosis Lifechart Information from other informants State-dependent memory Mixed states Psychosis Medical history» Thyroid, steroids, etc. Substance abuse history Stressors Seasonality Death of parent Lifechart Meth Lithium Prozac Exogenous factors Medical» Thyroid disorders» Medications Steroids Beta blockers» CNS disease Stroke Neoplasm» Rare Pheochromocytoma Hypercortisolemia Paraneoplastic syndromes Substance abuse» Stimulants» Alcohol» Sedative/hypnotics Abuse or withdrawal Time course 8

9 Genes and Environment Childhood Life events Adult Life events Proximate Stressor Genetic predisposition Mood Episode Treatment of Acute Mania Mood stabilizers» Lithium First choice for euphoric mania» Valproic acid Better for dysphoric mania» Loading?» Other anticonvulsants second line Carbamazepine Lamotrigine Antipsychotics» Essential for psychotic mania» Dysphoric mania / Mixed states» Atypical olanzapine, clozapine, quetiapine, risperidone, ziprasidone, aripiprizole» Typical - chlorpromazine, haloperidol, etc., Benzodiazepines ECT Treatment of Bipolar Depression Mood stabilizers essential Antidepressants or not? Antidepressant induced mania» Rapid cyclers may be at higher risk» Assess severity of past mania» TCA s worst» Other antidepressants have equal risk» Long term treatment may increase frequency of cycling Antidepressant treatment» Recent large studies show no additional benefit over mood stabilizers alone» Brief 1-3 months if necessary» Maybe lower dose Mood stabilizers alone if possible Lamotrigine Atypical antipsychotics eg. Olanzapine, aripiprizole ECT 9

10 Maintenance Treatment of Bipolar Disorder Mood stabilizers» Lithium Best evidence for reduction of suicide!» Valproic acid» Carbamazepine» Lamotrigine» Gabapentin?» Topiramate? Antipsychotics» Atypical olanzapine, clozapine, risperidone, ziprasidone, quetiapine, aripiprizole» Typical - chlorpromazine, haloperidol, etc. Antidepressants Treatment of mixed states Antipsychotics» Especially atypicals Anticonvulsants» Valproic acid ECT DO NOT treat with an antidepressant Antidepressants make it worse Danger!!!!» Confusing a mixed state for a depression and treating it with an antidepressant Pt complaint may be depression Rapid cycling Mixed state Treatment Algorithms for Bipolar Disorder 10

11 Psychotherapies Education Supportive Cognitive Behavior Therapy Insight Oriented Therapy Group Therapy Social Rhythms Therapy QUESTIONS? Thank you 11

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