Bipolar-I Disorder

Single Manic Episode

1. Presence of only one Manic Episode and no past Major Depressive Episodes. Note: Recurrence is defined as either a change in polarity from depression or an interval of at least 2 months without manic symptoms.
2. The Manic Episode is not better accounted for by Schizoaffective Disorder and is not superimposed on Schizophrenia, Schizophreniform Disorder, Delusional Disorder, or Psychotic Disorder Not Otherwise Specified.

Most Recent Episode Hypomanic

1. Currently (or most recently) in a Hypomanic Episode
2. There has previously been at least one Manic Episode or Mixed Episode.
3. The mood symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.
4. The mood episodes in Criteria A and B are not better accounted for by Schizoaffective Disorder and is not superimposed on Schizophrenia, Schizophreniform Disorder, Delusional Disorder, or Psychotic Disorder Not Otherwise Specified.

Most Recent Episode Manic

1. Currently (or most recently) in a Manic Episode.
2. There has previously been at least one Major Depressive Episode, Manic Episode, or Mixed Episode.
3. The mood episodes in Criteria A and B are not better accounted for by Schizoaffective Disorder and is not superimposed on Schizophrenia, Schizophreniform Disorder, Delusional Disorder, or Psychotic Disorder Not Otherwise Specified.

Most Recent Episode Mixed

1. Currently (or most recently) in a Mixed Episode.
2. There has previously been at least one Major Depressive Episode, Manic Episode, or Mixed Episode.
3. The mood episodes in Criteria A and B are not better accounted for by Schizoaffective Disorder and is not superimposed on Schizophrenia, Schizophreniform Disorder, Delusional Disorder, or Psychotic Disorder Not Otherwise Specified.

Most Recent Episode Depressed

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1. Currently (or most recently) in a Major Depressive Episode.
2. There has previously been at least one Manic Episode or Mixed Episode.
3. The mood episodes in Criteria A and B are not better accounted for by Schizoaffective Disorder and is not superimposed on Schizophrenia, Schizophreniform Disorder, Delusional Disorder, or Psychotic Disorder Not Otherwise Specified.

Most Recent Episode Unspecified

1. Criteria, except for duration, are currently (or most recently) met for a Manic, a Hypomanic, a Mixed, or a Major Depressive Episode.
2. There has previously been at least one Manic Episode or Mixed Episode.
3. The mood symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.
4. The mood episodes in Criteria A and B are not better accounted for by Schizoaffective Disorder and is not superimposed on Schizophrenia, Schizophreniform Disorder, Delusional Disorder, or Psychotic Disorder Not Otherwise Specified.

see also ---> Bipolar II Disorder

Major Depressive Episode:

1. Five (or more) of the following symptoms have been present during the same 2-week period and represent a change from previous functioning; at least one of the symptoms is either (1) depressed mood or (2) loss of interest or pleasure.

   Note: Do not include symptoms that are clearly due to a general medical condition, or mood-incongruent delusions or hallucinations.

   1. depressed mood most of the day, nearly every day, as indicated by either subjective report (e.g., feels sad or empty) or observation made by others (e.g., appears tearful). Note: In children and adolescents, can be irritable mood.
   2. markedly diminished interest or pleasure in all, or almost all, activities most of the day, nearly every day (as indicated by either subjective account or observation made by others)
   3. significant weight loss when not dieting or weight gain (e.g., a change of more than 5% of body weight in a month), or decrease or increase in appetite nearly every day. Note: In children, consider failure to make expected weight gains.
   4. insomnia or hypersomnia nearly every day
   5. psychomotor agitation or retardation nearly every day (observable by others, not merely subjective feelings of restlessness or being slowed down)
   6. fatigue or loss of energy nearly every day
   7. feelings of worthlessness or excessive or inappropriate guilt (which may be delusional) nearly every day (not merely self-reproach or guilt about being sick)
   8. diminished ability to think or concentrate, or indecisiveness, nearly every day (either by subjective account or as observed by others)
   9. recurrent thoughts of death (not just fear of dying), recurrent suicidal ideation without a specific plan, or a suicide attempt or a specific plan for committing suicide
2. The symptoms do not meet criteria for a Mixed Episode
3. The symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.
4. The symptoms are not due to the direct physiological effects of a substance (e.g., a drug of abuse, a medication) or a general medical condition (e.g., hypothyroidism).
5. The symptoms are not better accounted for by Bereavement, i.e., after the loss of a loved one, 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.

Manic Episode:

1. A distinct period of abnormally and persistently elevated, expansive, or irritable mood, lasting at least 1 week (or any duration if hospitalization is necessary).
2. During the period of mood disturbance, three (or more) of the following symptoms have persisted (four if the mood is only irritable) and have been present to a significant degree:
   1. inflated self-esteem or grandiosity
   2. decreased need for sleep (e.g., feels rested after only 3 hours of sleep)
   3. more talkative than usual or pressure to keep talking
   4. insomnia or hypersomnia nearly every day
   5. psychomotor agitation or retardation nearly every day (observable by others, not merely subjective feelings of restlessness or being slowed down)
   6. flight of ideas or subjective experience that thoughts are racing
   7. distractibility (i.e., attention too easily drawn to unimportant or irrelevant external stimuli)
   8. increase in goal-directed activity (either socially, at work or school, or sexually) or psychomotor agitation
   9. excessive involvement in pleasurable activities that have a high potential for painful consequences (e.g., engaging in unrestrained buying sprees, sexual indiscretions, or foolish business investments)
3. The symptoms do not meet criteria for a Mixed Episode
4. The mood disturbance is 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.
5. The symptoms are not due to the direct physiological effects of a substance (e.g., a drug of abuse, a medication, or other treatment) or a general medical condition (e.g., hyperthyroidism).

Mixed Episode:

1. The criteria are met both for a Manic Episode and for a Major Depressive Episode (except for duration) nearly every day during at least a 1-week period.
2. The mood disturbance is 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.
3. The symptoms are not due to the direct physiological effects of a substance (e.g., a drug of abuse, a medication, or other treatment) or a general medical condition (e.g., hyperthyroidism).

Hypomanic Episode:

1. A distinct period of persistently elevated, expansive, or irritable mood, lasting throughout at least 4 days, that is clearly different from the usual nondepressed mood.
2. During the period of mood disturbance, three (or more) of the following symptoms have persisted (four if the mood is only irritable) and have been present to a significant degree:
   1. inflated self-esteem or grandiosity
   2. decreased need for sleep (e.g., feels rested after only 3 hours of sleep)
   3. more talkative than usual or pressure to keep talking
   4. flight of ideas or subjective experience that thoughts are racing
   5. distractibility (i.e., attention too easily drawn to unimportant or irrelevant external stimuli)
   6. increase in goal-directed activity (either socially, at work or school, or sexually) or psychomotor agitation
   7. excessive involvement in pleasurable activities that have a high potential for painful consequences (e.g., the person engages in unrestrained buying sprees, sexual indiscretions, or foolish business investments)
3. The episode is associated with an unequivocal change in functioning that is uncharacteristic of the person when not symptomatic.
4. The disturbance in mood and the change in functioning are observable by others.
5. The episode is not severe enough to cause marked impairment in social or occupational functioning, or to necessitate hospitalization, and there are no psychotic features.
6. The symptoms are not due to the direct physiological effects of a substance (e.g., a drug of abuse, a medication, or other treatment) or a general medical condition (e.g., hyperthyroidism).

   Note: Hypomanic-like episodes that are clearly caused by somatic antidepressant treatment (e.g., medication, electroconvulsive therapy, light therapy) should not count toward a diagnosis of Bipolar II Disorder.

1. History: Interviews with family or friends are essential. Often a family history of affective disorders and alcoholism is present in first-degree relatives. If patient is >40 years of age and has first manic episode, look for medical causes.
2. Examination: Evaluate for medical cause, such as drug abuse or intoxication.
3. Laboratory Tests: Tests are needed before starting lithium carbonate, carbamazepine, or valproate (see below under specific medications). They should also be performed to rule out certain causes of secondary mania, such as megaloblastic anemia, hyperglycemia and hypoglycemia, hyperthyroidism and hypothyroidism, systemic lupus erythematosus, syphilis, HIV, and liver disease induced by alcohol or other substances.

Treatment Options

• Expert Guidelines: Treatment of Bipolar Disorder (very extensive desription of treatment options for professionals)

Hospitalization is usually indicated for full manic syndromes, since the patient's well-being is at risk because of impaired judgment. This includes a risk of death from exhaustion. Consider ECT in medication nonresponders and pregnant women.

1. Antipsychotics (such as haloperidol). Often required initially for sedation, control of behavior, or psychotic symptoms. Benzodiazepines may be a useful adjunct for sedation.

   Antipsychotics: Doses and Side Effects for Chronic Use

   Antipsychotics (typical)	Dose mg/day	Anti- cholineric¹	EPS²	Sedation	Hypotension (orthostatic)
   Chlorpromazine (Thorazine)	100-2000	++++	++	+++++	+++++
   Thioridazine (Mellaril)	100-600	+++++	+	++++	+++++
   Trifluoperazine (Stelazine)	5-60	++	++++	+	++
   Thiothixene (Navane)	5-60	++	++++	++	++
   Fluphenazine (Prolixin)	5-30	++	+++++	++	++
   Haloperidol (Haldol)	2-200	+	+++++	++	+

   
   

   Antipsychotics (atypical)	Dose mg/day	Anti- cholineric¹	EPS²	Sedation	Hypotension (orthostatic)
   Risperidone (Risperdal)	1-6	+	+	+	++
   Olanzapine (Zyprexa)	5-20	+	+	++	+
   Clozapine³ (Clozaril)	5-60	+++++	+	+++++	+++++

   ¹Dry mouth, constipation, blurred vision, urinary retention.
   ²Extrapyramidal side effects (dystonia, parkinsonism, akathisia, tardive dyskinesia).

   ³Requires weekly White Blood Cell (WBC) count because of risk of agranulocytosis.
   Adapted from Bernstein JG: Handbook of drug therapy in psychiatry, ed 3, St. Louis, 1995, Mosby.

2. Antimanic drugs (mood stabilizers).
   1. Lithium Carbonate: Best studied and usually the drug of choice for mania with response rates of 80%. Up to 3 weeks generally needed at therapeutic blood levels before clinical effects noted. Also beneficial for prophylaxis of depressive episodes associated with bipolar illness.
      • Dose is 600 to 2400 mg/day. Give with food and initially in divided doses to minimize GI side effects. Then change to a single dose QHS (if less than or equal to 1800 mg/day) or BID (if less than or equal to 3000 mg/day) to minimize potential tremor and polyuria.
      • Monitor Serum trough levels (12 hours after last dose) at least twice weekly initially and then Q2-3 months for maintenance. In acute mania, 0.9 to 1.4 mEq/L levels needed. Maintenance levels range from 0.4 to 0.8 mEq/L (with elderly requiring the higher range).
      • Side effects. Polyuria and polydipsia, muscle weakness, tremor, GI upset or diarrhea, and hypothyroidism.
      • Toxicity may occur at serum levels just over the therapeutic range. Mild toxicity symptoms are exacerbations of side effects listed above. More severe toxicity includes primarily neurologic manifestations (lethargy, confusion, coma, seizures, ataxia, dysarthria, nystagmus) and nephropathy. Overdose not responsive to charcoal but may respond to polystyrene resins and dialysis.
      • Lab Monitoring Baseline tests before starting lithium include BUN and creatinine, pregnancy test, thyroid function tests (TFTs) (lithium may induce hypothyroidism), ECG for patient >40 years of age and consider a CBC. During the first 6 months of lithium treatment, monitor BUN and Cr every 2 to 3 months and TFTs 1 or 2 times. Subsequently check creatinine (Q6-12 months) and thyroid functions (every year) while patient is receiving maintenance lithium treatment.
      • Warnings Avoid use in pregnancy (especially first trimester) unless benefits outweigh risks. Dehydration and sodium-restricted diets may increase lithium levels and risk for toxicity.
      • Drug Interactions. Any medication that can decrease renal clearance (such as NSAIDs); sodium-depleting diuretics should be used with caution.
   2. Carbamazepine (Tegretol): Second-line treatment to lithium for treatment of mania. Dosage 600 to 2000 mg/day for acute mania. Onset of action 1 to 2 weeks; therapeutic trial 3 weeks. No established therapeutic blood levels for treatment of mania. Monitor for leukopenia and liver dysfunction. Avoid use in pregnancy unless benefits outweigh risks.
   3. Valproic Acid (Depakene, Depakote): Third-line treatment for mania behind lithium and carbamazepine. However, it is the preferred choice in rapid cycling and mixed mania. Usual starting dose is 15 mg/kg/day in 2 or more divided doses. Therapeutic blood level not established for mania. Increase dose until therapeutic response or adverse effects occur. Obtain baseline hematologic and hepatic tests. Instruct patients about potential symptoms of leukopenia and liver disease. Depakote may be less likely to produce GI side effects than Depakene. Avoid use in pregnancy unless benefits outweigh risks.
   4. Verapamil (Calan): Fourth-line treatment for mania until its efficacy compared to other treatments is determined. Antimanic dosages range from 160 to 480 mg/day.

Some disorders have similar symptoms. The clinician, therefore, in his diagnostic attempt has to differentiate against the following disorders which need to be ruled out to establish a precise diagnosis.

• Mood Disorder Due to a General Medical Condition;
• Substance-Induced Mood Disorder;
• Major Depressive Disorder;
• Dysthymic Disorder;
• Bipolar II Disorder;
• Cyclothymic Disorder;
• Psychotic Disorders (e.g., Schizoaffective Disorder, Schizophrenia, and Delusional Disorder).