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ErkkiIsometsä

Bipolar Disorder

Essentials

  • The most common problems related to the treatment of bipolar disorder are associated with recognition and diagnosis. Always assess whether a depressive patient has had earlier periods of mania or hypomania, i.e., if he/she has bipolar disorder.
  • The main aim of therapy is acute treatment and prevention of recurrences of manic and depressive episodes.
  • The diagnosis of bipolar disorder and the treatment of acute phases usually takes place in specialized psychiatric care; mania is usually treated in a hospital.

Epidemiology and main types of disease

  • The lifetime incidence of bipolar disorder is 1-2%.
  • The disorder is classified into two categories that are roughly equally common:
    • In type I disorder, there are manic, depressive and mixed episodes
    • In type II disorder, there are episodes of hypomania and depression.

Clinical picture and diagnosis

  • The patient usually has episodes of both major depression and mania or hypomania, very rarely only hypomanic/manic episodes. Uninterrupted disease episodes may consist of several different phases.
    • Usually the depressive episodes dominate the temporal course of the disease.
  • Mood Disorder Questionnaire (MDQ http://www.ncbi.nlm.nih.gov/pmc/articles/PMC314375/) is a useful tool for screening for bipolar disorder in all depressed patients. A positive result in the test warrants further diagnostic assessment.
    • Some patients deny their symptoms, and in these patients the screening result remains negative.
    • A positive screening result is not equal to a diagnosis (< 50% of those with a positive screening result have bipolar disorder).
  • The diagnosis of bipolar disorder is made by a psychiatrist.
  • Bipolar disorder is associated with high suicidal mortality A Patient at Risk of Suicide during depressive and mixed episodes. As many as half of the patients make at least one suicide attempt during their illness.
  • Comorbidity is common. Concomitant anxiety disorder Anxiety Disorder is common particularly during depressive episodes; substance use disorders Recognition of Alcohol and Drug Abuseare more commonly associated with (hypo)manic episodes.

Hypomania

  • Mild, but clearly perceivable rise in mood that differs clearly from the patient's normal psychological functioning.
    • Diagnosis requires a duration of at least 4 days; normally the duration is from days to weeks.
  • Concomitantly with hypomania, at least three of the following symptoms are present:
    • increase in activity and physical restlessness
    • increase in talkativeness
    • difficulties in concentrating and distractibility
    • reduced need for sleep
    • increased sexual interest and drive
    • mild money spending sprees or other irresponsible behaviour
    • increase in sociability or over-familiarity.

Mania

  • The symptoms are much the same as in hypomania but stronger and thus result in a clear decline of functional ability. Due to lack of judgement and to overactivity, manic patients usually cause serious harm to their family relations and working career, and frequently expose themselves and outsiders to dangerous situations.
  • Mania is often preceded by a milder presymptomatic phase; the patient feels increasingly energetic, need for sleep diminishes, and excitement starts to rise.
  • Patients may pull themselves together during the consultation and behave normally for a moment giving good explanations for their behaviour. The history should be taken from other people in addition to the patient.
  • For diagnosis, three (four if there is irritated mood) of the following symptoms must have been present for at least one week:
    • increase in activity and physical restlessness
    • increase in talkativeness or pressure of speech
    • racing thoughts or feeling of accelerated thinking
    • lack of social inhibitions
    • reduced need for sleep (the patient typically sleeps no more than a few hours a night)
    • heightened self-esteem or delusions of grandiosity
    • distractibility or constant changes to actions or plans
    • reckless of irresponsible behaviour with risks that the patient does not recognize
    • increased sexual drive and promiscuity.
  • In psychotic mania the patient has either delusions or hallucinations.
  • Sometimes the condition can develop into a delirium-type state of confusion that necessitates immediate treatment Delirium in the Elderly.

Episodes of depression

Mixed episodes

  • The symptoms of manic and depressive episodes are present at the same time or alternate rapidly (rapid cycling)
  • The mood can be depressed but activity may be accelerated.
  • Typically, the patient´s condition varies and both extreme moods and periods of concurrent symptoms occur.
  • There is a high risk of suicide during a mixed episode.

Maintenance phase

  • Between disease episodes, the patient may be either completely healthy or suffer from milder residual symptoms. These are most often symptoms of depression but sometimes milder but recurring mood swings from depressed to hypomanic.
  • Disease episodes are usually preceded by a prodromal stage that is important to recognize to be able to start treatment early enough to prevent the development of an actual disease phase.

Differential diagnosis

  • Certain drugs of abuse and medications (amphetamines derivatives, glucocorticoids, levodopa) and certain brain disorders may cause secondary mania. These should be assessed especially if the patient develops the first manic episode at the age of more than 50 years.
  • For alcohol or substance abuse, see A Patient with Legal Drug Addiction in Primary Care.
  • Hypomania or mania provoked by the initiation of an antidepressant drug should only lead to bipolar disorder diagnosis only if it is recurrent. A specialist physician will assess the situation based on the overall picture.
  • Emotionally unstable (borderline) personality disorder Enterovirus Infections is associated with changes of mood, but not hypomanic or manic mood elevation.
  • The most common reason for a misdiagnosis is that the earlier phases of elevated mood are not registered, and the patient in the depressive phase is believed to have ordinary depression.

Treatment

  • As a rule, the acute phases of a bipolar disorder are treated by psychiatrists.
  • The profile of pharmacotherapy varies in the different phases of the disease.
  • The treatment protocol in type II disorder is principally similar to type I. There are differences in the use of antidepressive medications (fewer risks in type II) and the suitability of lamotrigine in maintenance treatment (not for monotherapy in type I).
  • After the acute phase preventing new episodes and functional impairment is essential. Monitor the patient's psychiatric status, educate the patient and his or her family or close friends about bipolar disorder to enable them to identify new episodes as early as possible and to avoid provoking risk factors, such as stress and lack of sleep.
  • Treatment options in the different phases of the disorder are listed in table T1.

Summary or treatment options in type I bipolar disorder in the various phases of the disorder

Valproic acid is highly teratogenic. It should not be prescribed for women if there is a possibility of becoming pregnant.
PhaseTreatment
Acute maniaAntipsychotics: aripiprazole (15-30 mg/day) Aripiprazole Alone or in Combination for Acute Mania, asenapine (10-20 mg/day), haloperidol (2-15 mg/day), cariprazine (1.5-6 mg/day), quetiapine (300-800 mg/day), olanzapine (5-20 mg/day), risperidone (1-6 mg/day) or ziprasidone (80-120 mg/day)
Lithium (target concentration 0.80-1.20 mmol/l)
Valproic acid* (target concentration 450-900 μmol/l) Valproate in the Treatment of Mania
Carbamazepine (400-1 600 mg/day)
Mood stabilizers and antipsychotics in combination
Electroconvulsive therapy (in selected therapy-resistant or psychotic cases)
Depression episodeLamotrigine (50-200 mg/day)
Lithium (target concentration 0.80-1.20 mmol/l)
Valproic acid* (target concentration 450-600 µmol/l)
Olanzapine + fluoxetine 5 + 20 - 10 + 40 mg/day
Lurasidone (20-120 mg/day)
Cariprazine (1.5 mg/day)
Quetiapine (300-600 mg/day)
Antidepressants (only in combination with mood stabilizers; discontinued gradually when remission is achieved)
Electroconvulsive therapy (ECT)
Mixed episodeTreatment as in mania (but specific evidence of efficacy for mixed episodes is absent for haloperidol, quetiapine and lithium)
Maintenance treatmentLithium (target concentration 0.60-0.80 mmol/l)
Carbamazepine (400-1 600 mg/day)
Valproic acid* (target concentration 450-900 μmol/l)
Lamotrigine (50-400 mg/day; not as monotherapy in type I)
Aripiprazole (15-30 mg/day), quetiapine (300-600 mg/day) or olanzapine (5-20 mg/day); depot risperidone (25-50 mg/2 weeks)
The above drugs in combination

Treatment of mania and hypomania Topiramate for Acute Affective Episodes in Bipolar Disorder in Adults, Lithium for Acute Mania

  • Manic patients usually need hospitalization; compulsory treatment may be required. Mania itself makes compulsory treatment possible, if other legal prerequisites are fulfilled. The existence of delusions or hallucinations is not decisive.
  • Mild manic episodes in cooperative patients can be treated by intensive psychiatric outpatient care within specialized care.
  • In the pharmacological treatment of mania, usually at least two drugs have to be combined, e.g. by giving lithium or valproate concomitantly with a second generation antipsychotic.
  • Hypomania is usually a mild condition of short duration; it can be treated in outpatient care by increasing the dose of the stabilizing maintenance drug and/or with second generation atipsychotics (olanzapine, aripiprazole).

Treatment of bipolar depression

Treatment of mixed episodes

  • Usually the same medicines are used as in the treatment of mania.
  • Antidepressant use during mixed episodes may worsen the symptoms by provoking manic symptoms and changes in mood, and therefore they must not be used.

Maintenance therapy

  • In maintenance phase, continuous pharmacotherapy is used to prevent episodes of disease.
  • Drugs that can provoke mania or hypomania (antidepressants) or depression (traditional neuroleptics) should be avoided.
  • If there have been recurrent episodes of illness, the need for maintenance treatment is usually lifelong. Even after a very long (> 10 years) symptomless phase with maintenance therapy, episodes of illness usually restart if maintenance therapy is ceased.
  • A general practitioner may also take responsibility for the maintenance therapy when the patient's condition has been stabilized and compliance with treatment is good.
  • Valproate (valproic acid) is highly teratogenic, and should not be used in the treatment of women, if there is a possibility of the patient becoming pregnant.
  • The optimum concentration range of lithium in maintenance treatment is usually 0.60-0.80 mmol/l, and lower in the elderly. Lithium has a narrow therapeutic range; concentrations > 1.50 mmol/l may already be toxic. Lithium clearance is reduced by dehydration, hyponatraemia, use of NSAIDs and renal insufficiency.
    • If overdosing is suspected, the serum lithium concentration should quickly be measured and the dose lowered or the medication paused for a while, as necessary; in case of intoxication, immediate referral to a hospital is necessary.
  • The lithium concentration should be monitored every 3 months during the first 6 months and thereafter once every 6 months.
    • TSH, plasma creatinine (eGFR), urine osmolality, plasma sodium, potassium, albumin-corrected calcium, basic blood count with platelet count, weight and BMI should also be monitored at least once a year.
  • Lithium medication is usually tapered down gradually over 1-6 months; abrupt cessation may provoke mania or depression.

Psychosocial treatment in specialized care

  • Psychosocial interventions in the maintenance phase are very useful in adaptation to the disease and in prevention of new episodes. Cognitive psychotherapy may also help to treat symptoms of depression.
  • Specific forms of psychosocial individual, group or family therapy to be combined with pharmacotherapy are:
    • psychoeducational group therapy
    • cognitive psychotherapy
    • cognitive treatment of sleeplessness
    • Family Focused Therapy (FFT)
    • Interpersonal and Social Rhythm Therapy (IPSRT)
  • Patient education in groups is recommended for all patients during the maintenance phase, after establishing the diagnosis.

Cyclothymia

  • Cyclothymia (F34.0) is a milder mental disorder in which hypomanic and mild depressive episodes alternate. Actual depressive or manic episodes do not occur.
  • The estimated life-time prevalence is 0.4-1%.
  • Up to half of the patients later develop bipolar disorder.
  • There is no established mode of treatment. At the physician's discretion, the same drugs that are used for bipolar disorder are options for pharmacotherapy; however, most patients do not seek treatment because of the mildness of the symptoms.
  • The patients should be informed of the risk of bipolar disorder, particularly if the family history suggests a high risk.

Evidence Summaries ⬆