Bipolar Depression or Unipolar Depression?

Bipolar Depression or Unipolar Depression? Todd P. Hill, D.O. Diplomate American Academy of Psychiatry and Neurology Northland Psychiatric Associates, LLC Consultation-Liaison Psychiatrist North Kansas City Hospital Assistant Professor and Department Chairman of Psychiatry, Kansas City University of Medicine and Biosciences Kansas City, MO

DECLARATIONS Speakers Bureau (past and present): Cephalon Pharmaceuticals, Pfizer, GlaxoSmithKline, Forest Pharmaceuticals, Wyeth, Takeda Pharmaceuticals, Astra- Zeneca, Jazz Pharmaceuticals, Sepracor Pharmaceuticals, Lilly, Bristol-Myers Squibb

Presentation Overview Review the under recognition and misdiagnosis of bipolar disorder Discuss the differential diagnosis and valid screening tools for diagnosis of bipolar mood disorder Discuss the challenges for primary care in diagnosing bipolar depression vs. unipolar depression Review treatment options for Bipolar Mood Disorder Review challenges of treatment adherence and discuss steps towards a more productive patient dialogue

The Numbers Lifetime incidence of major depressive disorder is 20% in women and 12% in men. Prevalence of bipolar depression is as high as 10% in patients observed in a medical setting. Estimates indicate almost 2% of the population is affected by bipolar disorder and up to 6% by bipolar spectrum disorder. The World Health Organization identified bipolar disorder as the sixth leading cause of disabilityadjusted life years worldwide among people ages 15 to 44 years

Historically Bipolar disorder, or manic-depressive illness, has been recognized since at least the time of Hippocrates Described such patients as "amic" and "melancholic." In 1899, Emil Kraepelin defined manicdepressive illness and noted that persons with manic-depressive illness lacked deterioration and dementia, which he associated with schizophrenia.

Morbidity/Mortality Suicide ranks as a leading cause of death in the United States, with a yearly rate of approximately 200,000 attempts. The number of completed suicides for 2005 was 32,000. One suicide approximately every 16 minutes in United States. Suicide continues to rank as the second leading cause of death in adolescents and represents 10-30% of deaths in those aged 20-35 years.

Morbidity/Mortality Death rate from suicide among those with depression can exceed 15% 25-50% of individuals with bipolar disorder attempt suicide, and also up to 15% actually commit suicide higher proportion of attempts among patients with bipolar disorder than among those with other psychiatric diagnoses, including depression. Epidemiologic Catchment Area Database found the following lifetime rates of suicide attempts: bipolar disorder 29% unipolar depression 16% Death rates associated from mania more difficult to asses (i.e. accidents)

Review of Bipolar Bipolar disorder is an illness characterized by periods of extreme mood elevation and fluctuation Bipolar I disorder: episodes of sustained mania, and frequent depressive episodes Bipolar II disorder: have one or more major depressive episodes, with at least one hypomanic episode (Hypomania may be thought of as a less severe form of mania that does not include psychotic symptoms or lead to major impairment of social or occupational function) Rapid cycling: 4 or more episodes a year cycling between depression and mania accelerates with age

Mania Diagnosis Diagnostic criteria for mania from the American Psychiatric Association (DSM IV-TR) distinct period of abnormally and persistently elevated, expansive, or irritable mood, lasting at least one week (or any duration if hospitalization is necessary) During the period of mood disturbance, at least three or more of the following symptoms are present: - inflated self esteem or grandiosity - decreased need for sleep - more talkative than usual - racing thoughts or flight of ideas - distractibility - increase in goal-directed activity - excessive involvement in pleasurable activities that have a high potential for painful consequences, such as spending money or sexual indiscretion. The mood is not the result of substance abuse or a medical condition American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, DSM-IV- TR. Washington, DC: 2000.

Depression Diagnosis DSM-IV-TR diagnostic criteria for a major depressive episode are as follows: A. At least 5 of the following, during the same 2-week period, representing a change from previous functioning; must include either (a) or (b): (a) Depressed mood (b) Diminished interest or pleasure (c) Significant weight loss or gain (d) Insomnia or hypersomnia (e) Psychomotor agitation or retardation (f) Fatigue or loss of energy (g) Feelings of worthlessness (h) Diminished ability to think or concentrate; indecisiveness (i) Recurrent thoughts of death, suicidal ideation, suicide attempt, or specific plan for suicide B. Symptoms do not meet criteria for a mixed episode (ie, meets criteria for both manic and depressive episode). C. Symptoms cause clinically significant distress or impairment of functioning. D. Symptoms are not due to the direct physiologic effects of a substance or a general medical condition. E. Symptoms are not better accounted for by bereavement, ie, the symptoms persist for longer than 2 months or are characterized by marked functional impairment, morbid preoccupation with worthlessness, suicidal ideation, psychotic symptoms, or psychomotor retardation.

Common Behavioral Symptoms In pressured speech hyperverbal Mania physical hyperactivity and agitation, decreased need for sleep hypersexuality extravagance (ie, financial, social, and recreational)

Violence Less Common Behavioral Religiosity Symptoms In Mania Pronounced regression Catatonia Impaired insight is a frequent component of the manic state and may impair compliance with medications.

Mixed Episode irritability, racing or crowded thoughts, psychomotor agitation, or increased talkativeness concurrent with symptoms of depression may occur with bipolar I, bipolar II, or major depression more common with bipolar disorders frequency with these conditions is estimated between 20 and 70 percent

Cyclothymia Presence of numerous periods of hypomania and of depression, persisting for at least two years, that do not meet DSM criteria for a major depression It is considered to be one of the bipolar disorders treated with mood stabilizing medications

Differential Diagnosis Schizophrenia schizoaffective disorder posttraumatic stress disorder ADHD abuse of alcohol, cocaine, or amphetamines personality disorders such as narcissistic, borderline and histrionic personalities Oppositional defiant disorder (in children) Medical illnesses: thyrotoxicosis partial complex seizures systemic lupus erythematosus cerebrovascular accident human immunodeficiency virus tertiary syphilis steroid-induced mood symptoms

Laboratory Studies CBC count with differential Sedimentation rate Glucose-level fasting Electrolytes Serum calcium Serum proteins Thyroid studies Substance and alcohol screen VDRL test

Imaging Studies and Other Tests MRI: primarily if psychotic symptoms are present ECG: pretreatment ECG is important EEG: rule out a seizure disorder and brain tumor

Distinguishing Unipolar and Bipolar Depression Patients with bipolar disorder, particularly those with bipolar II disorder who do not exhibit overt symptoms of mania, are frequently misdiagnosed as having unipolar depression Establishing the diagnosis of bipolar disorder is essential Mood stabilizing medications are indicated for most patients with depression and bipolar disorder to prevent mood swings to manic or hypomanic states.

Distinguishing Unipolar and Bipolar Depression Family History Course of Illness: first onset of bipolar mood disorder occurs in the midteens to 20s until the 30s usually manifests as a major depressive episode or hypomania Treatment Response: suboptimal outcome with antidepressant therapy antidepressant-induced manic switch Mania Symptoms Associated Features: unevenness in intimate relationships, frequent career changes, and high prevalence of co-morbidities (e.g., substance use disorders).

Distinguishing Unipolar and Bipolar Depression Diagnosis is likely to be missed when patients are seen with depression and not specifically asked about symptoms suggesting prior episodes of mania or hypomania 2/3 of the episodes in a bipolar illness are spent in the depressive phase

Under Diagnosed A study of outpatients being treated for depression in a family medicine clinic, a screening questionnaire for bipolar disorder (the Mood Disorder Questionnaire or MDQ ) was positive in 21.3 percent; two thirds of those screening positive had never been diagnosed with bipolar disorder

Mood Disorder Questionnaire 1. Has there ever been a period of time when you were not your usual self and......you felt so good or so hyper that other people thought you were not your normal self or you were so hyper that you got into trouble?...you were so irritable that you shouted at people or started fights or arguments?...you felt much more self-confident than usual?...you got much less sleep than usual and found you didn't really miss it?...you were much more talkative or spoke much faster than usual?...thoughts raced through your head or you couldn't slow your mind down?

Mood Disorder Questionnaire...you were so easily distracted by things around you that you had trouble concentrating or staying on track?...you had much more energy than usual?...you were much more active or did many more things than usual?...you were much more social or outgoing than usual, for example, you telephoned friends in the middle of the night?...you were much more interested in sex than usual?...you did things that were unusual for you or that other people might have thought were excessive, foolish, or risky?...spending money got you or your family into trouble?

Mood Disorder Questionnaire 2. If you checked YES to more than one of the above, have several of these ever happened during the same period of time? 3. How much of a problem did any of these cause you like being unable to work; having family, money, or legal troubles; getting into arguments or fights? One response only: No Problem, Minor Problem, Moderate Problem, Serious Problem

Mood Disorder Questionnaire Answering Yes to 7 or more of the events in question #1 Answering Yes to question #2 Answering Moderate problem or Serious problem to question #3 is considered a positive screen for bipolar disorder. sensitivity and specificity of the MDQ in this population is usually around 0.6 and 0.9 respectively, when results of screening are compared to DSM-IV criteria

Importance of Proper Diagnosis Bipolar depression is a significant concern for both bipolar I and II patients, causing equal if not greater psychosocial disability in these patients Studies indicate more patients with bipolar depression report disruptions in work, school, social activities and family life compared to patients with MDD. Depression is the predominate symptomatic state in both bipolar I and II patients Diagnosis may be delayed up to 10 years

Importance of Proper Diagnosis Preventing Switch to Mania tricyclic antidepressants and venlafaxine most common effect might not be seen until 10 weeks of treatment

Treatment Options Medications indicated to treat Bipolar Mania: Lithium: commonly used for prophylaxis and treatment of manic episodes Acute manic episode: 600-2400 mg PO qd Maintenance, preventive use: 400-1200 mg PO qd some efficacy in bipolar depression and is also used to augment treatment resistant depression (may have a specific antisuicide effect) Side effects: tremors, thyroid and kidney problems Narrow therapeutic window Drug interactions: NSAIDS, diuretics

Treatment Options Medications indicated to treat Bipolar Mania: Valproic Acid (Depakote): can be used alone or in combination with lithium rapid-cycling bipolar disorders Start with 250 mg PO tid, initially in increments until a mania is improved; serum level should be in the range of 50-100 mcg/ml (Treat Patients not Labs!) Loading dose of 20 mg/kg/d PO in Mania can be given Monitor for hepatic toxicity (obtain liver function tests prior to initiating therapy and thereafter

Treatment Options Medications indicated to treat Bipolar Mania: Tegretol (Carbemazepine) often used in patients who have not responded to lithium therapy Initial: 200 mg PO qd in divided doses with increments of 100 mg 2 times/wk Dose range: 300-1600 mg PO qd Serum level range: 4-12 mcg/ml Category D in pregnancy may lower effectiveness of OCP hyponatremia

Treatment Options Other medication options to treat mania: ANTIPSYCHOTICS Aripiprazole Abilify Ziprasidone Geodon Risperidone Risperdal Asenapine Saphris Quetiapine Seroquel (XR) Chlorpromazine Thorazine Olanzapine Zyprexa

Treatment Options most FDA-approved therapies for bipolar disorder are not indicated for bipolar depression Lamotrigine: indicated for maintenance only in bipolar (robust response on depressive symptoms) Other Maintenance Medications: Atypical Antipsychotics Aripiprazole Olanzapine Quetiapine (as an adjunct to lithium or divalproex)

Treatment Options Medications indicated for Bipolar Depression: Olanzapine/fluoxetine: Symbyax Quetiapine/Quetiapine XR

Generic Name Trade Name Manic Mixed Maintenance Depression Valproate Depakote X Carbamazepine extended release Equetro X X Lamotrigine Lamictal X Lithium X X Aripiprazole Abilify X X X Ziprasidone Geodon X X Risperidone Risperdal X X Asenapine Saphris X X Quetiapine Seroquel (XR) Chlorpromazine Thorazine X X X X X Olanzapine Zyprexa X X X Olanzapine/fluoxetine Combination Symbyax X

Treatment Options Clinical reminders: Lamotrigine: Stevens-Johnsons Syndrome Atypical Antipsychotics: Metabolic syndrome/weight gain EPS Akathisia Tardive dykinesia

Treatment Options Do antidepressants help? NIMH Funded, Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) Trials After mood stabilizer doses were optimized, participants were then randomized to receive either one of the antidepressants paroxetine (Paxil) or bupropion (Wellbutrin) or a placebo using a mood stabilizing medication alone results in a similar outcome compared to using a mood stabilizer plus an antidepressant medication. Therefore, there is no additional benefit from adding the antidepressant medications used in this trial. I In addition, the results suggest that there is no increased risk of hypomanic or manic symptoms when paroxetine or bupropion is added to a mood stabilizer.

Treatment Options Psychosocial Therapy Used mainly for the depressive episodes Cognitive Therapy Interpersonal Therapy Insight-oriented Therapy Supportive Therapy

Treatment Options Inpatient hospital treatment Danger to self: A patient, when in a severe depressive episode, may present with a significant risk for suicide. Danger to others: Patients with bipolar disorder can often become a threat to others Total inability to function (although HMOs will fight you on this one) Totally out of control: severe manic behaviors putting one s safety or career at risk

Treatment Options Electroconvulsive therapy (ECT): highly effective in the treatment of acute mania Used when symptoms are severe Treatment resistant patients

Treatment Options Partial hospitalization or a daytreatment program May still have severe symptoms but not completely out of control and have a stable living environment Provides a great deal of interpersonal support Sees a psychiatrist daily for medication management Often provides a bridge to return to work

Prognosis Worse if: Poor job history Alcohol abuse Psychotic features Depressive features between periods of mania and depression Evidence of depression Male sex

Prognosis Better if: Manic phases (short in duration) Late age of onset Few thoughts of suicide Few psychotic symptoms Few medical problems

Treatment Adherence Outpatient treatment-patient EDUCATION!!!: set reasonable expectations for patient and family monitor efficacy side effects risks and benefits of treatment individualize treatment active patient participation

SUMMARY Screening for Bipolar disorder should always be part of the evaluation for patients meeting criteria major depressive disorder Increased suicide risk Use mood stabilizing medications as first line treatment Educate patients!!

References American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 4 th Edition, Text Revision; 2000. Washington D.C. Kaplan and Sadock's Synopsis of Psychiatry: Behavioral Sciences/Clinical Psychiatry. 9 th Edition. 2007 Sachs GS, Nierenberg AA, Calabrese JR, et al. Effectiveness of Adjunctive Antidepressant Treatment for Bipolar Depression. N Engl J Med. 2007;26;356:1711-1722. Miklowitz DJ, Otto MW, Frank E, et al. Psychosocial treatments for bipolar depression: a 1-year randomized trial from the systematic treatment enhancement program. Arch Gen Psychiatry. 2007;64:419-426. Medscape: August 17,2010 http://emedicine.medscape.com/article/286759-overview Medscape: Jan 11, 2011 http://emedicine.medscape.com/article/286342-overview