Bipolar affective disorder is a mental illness characterized by periods of mania and depression.

Bipolar disorder is a chronic condition of unclear origin. It is primarily marked by episodic shifts in mood and activity levels, though motivation, cognition, and motor functions are also affected. These affective episodes vary in duration, with patients often experiencing symptom-free periods in between.

The affective episodes can be classified as depression, mania, or a mix of symptoms from both.

• Depression is characterized by persistent sadness, loss of pleasure (anhedonia), and lack of interest (apathy). A depressive episode meeting DSM-5 criteria is referred to as major depression, and in ICD-11 as a depressive episode.
• Mania typically involves sustained increases in activity and energy with an abnormally elevated, expansive, or irritable mood. Between episodes, the individual may experience a state of normal mood and functioning, called euthymia.
• Mixed states may involve overactivity, irritability, and racing thoughts combined with hopelessness, sadness, reduced sleep, and suicidal thoughts.

Treatment under involuntary psychiatric commitment may be necessary, particularly during manic episodes or when there is an acute risk of suicide.

Types of bipolar disorder

Bipolar disorder is classified into two main types:

1. Bipolar Disorder Type I:
   • Diagnosis requires at least one manic episode.
   • 80–90% of those with a manic episode have a history of depression.
2. Bipolar Disorder Type II:
   • Diagnosis requires at least one hypomanic episode and one depressive episode.
   • Hypomania shares features with mania but does not significantly impair functioning, lacks psychotic symptoms, and typically does not require hospitalization.
   • 5–15% of those with hypomania may later develop mania.

Additional classifications, such as cyclothymia, refer to low-grade bipolar conditions involving recurrent episodes of hypomanic symptoms and depressive states that do not meet criteria for major depression or hypomania. About 15–50% of patients with cyclothymia eventually develop bipolar disorder.

Around 5–15% of bipolar patients experience rapid cycling disorder, defined as four or more affective episodes per year.

Prevalence

• Lifetime prevalence of Bipolar I: 0.4–1.6%.
• Lifetime prevalence of Bipolar II: ~1%.
• Most cases emerge between ages 13–30, with wide variation.
• Initial episodes are more likely to be depressive than manic.

It often takes years before treatment is initiated, and even longer before a patient is hospitalized. Suicidal tendencies are frequently present before diagnosis. On average, bipolar disorder is diagnosed around ten years after the first affective episode.

Without mood-stabilizing treatment, individuals typically experience four affective episodes over ten years. Episodes tend to become more frequent and severe with age, a phenomenon known as the kindling effect.

Etiology

The exact cause of bipolar disorder remains unknown, though genetics play a significant role, accounting for an estimated 56–62% of the risk.

• First-degree relatives of bipolar individuals have a tenfold higher risk of developing the disorder.
• Possible mechanisms include increased cortisol release, alterations in glutamate and monoamine neurotransmission, changes in glial cells, increased calcium signaling, and disruptions in intracellular second messenger systems.

Brain imaging studies have shown changes in white matter, morphology, and functioning in the frontal lobe, paralimbic, and limbic structures. Factors like sleep deprivation, travel across time zones, pregnancy, and menopause may increase the risk of affective episodes.

This summary is based on diagnostic criteria from the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) and the ICD-10, which align closely with a few minor differences.

Mania and hypomania

Mania and hypomania typically have no clear triggering cause, often develop gradually over a few days, and last for weeks to months if untreated. Episodes of mania or hypomania are often closely associated with depression. Mania can present in various clinical forms, sometimes described as euphoric mania, irritable mania, or confusional (delirious) mania, also known as Bell’s mania. Individuals may also exhibit mood-congruent psychotic symptoms such as delusions and hallucinations. For a diagnosis of mania, symptoms must persist for at least 7 days or shorter if hospitalization is required.

Hypomania shares the same symptoms as mania but is less intense and causes less impairment in daily functioning. The duration of a hypomanic episode is more variable than that of a manic episode. According to DSM-5, symptoms of hypomania must last for at least 4 days.

To diagnose either mania or hypomania, DSM-5 criteria require a change in mood and at least three additional symptoms (four if the mood is primarily irritable).

Mania and hypomania in bipolar affective disorder are characterized by a distinct and sustained period of elevated, irritable, or expansive mood and increased goal-directed activity or energy. Additionally, the episode must include at least three of the following symptoms:

• Grandiosity and inflated self-esteem
• Decreased need for sleep
• Pressured speech
• Distractibility
• Increased goal-directed activity
• Psychomotor agitation
• Engagement in pleasurable activities with potential negative consequences

Bipolar depression

Depression typically has no clear triggering cause, develops gradually over days to weeks, and, if untreated, often lasts for 4 months or more. For a diagnosis of major depression, either a depressed mood or apathy/anhedonia is required, along with four additional symptoms. Symptoms must persist for at least 2 weeks.

A depressive episode is characterized by:

• Persistent and pervasive low mood
• Apathy and anhedonia (loss of interest or pleasure)
• Weight and appetite changes
• Psychomotor disturbances
• Sleep disturbances
• Feelings of guilt and worthlessness
• Impaired thinking and concentration
• Suicidal ideation or thoughts of death

Bipolar depression sometimes differs slightly from unipolar depression. Features such as hypersomnia, psychomotor slowing, and psychotic symptoms are more common in bipolar depression. Symptoms suggesting bipolar depression include:

• Hypersomnia
• Heaviness in the arms and legs
• Psychomotor retardation
• Psychotic symptoms or pathological guilt
• Manic features, mood lability
• Early onset (< 25 years)
• Multiple episodes (> 5)
• Family history of bipolar disorder

Mixed states

Symptoms of both mania and depression can coexist during certain periods, known as a mixed affective state. According to DSM-5, a mixed state is diagnosed when a person meets criteria for a manic, hypomanic, or depressive episode while also exhibiting at least three symptoms from the opposite pole.

Subsyndromal mixed states can still cause significant functional impairment.

Research shows that two-thirds of individuals with bipolar depression display at least some manic symptoms.

Euthymia and residual symptoms

Most individuals with bipolar disorder experience clear periods of normal mood (euthymia). However, 20-30% have lingering affective symptoms (residual symptoms) that do not meet criteria for a full affective episode. Affective episodes may also leave cognitive impairments in areas such as attention, verbal learning, memory, and executive function.

These impairments are often moderate and not always clinically obvious but can pose significant challenges during rehabilitation.

Being diagnosed with bipolar

There is no established diagnostic biomarker for bipolar disorder. The diagnosis is clinical, based on a thorough history supported by clinical rating scales. A comprehensive history should include:

• The long-term episodic course of the condition with symptom-free intervals
• Timing and circumstances of onset
• Family history of psychiatric illness and suicide
• Response to previous treatments
• Presence of substance abuse
• Non-psychiatric illnesses and their treatments
• Social situation

This diagnostic approach ensures a holistic understanding of the individual’s condition.

Suicide risk assessment

A suicide risk assessment in patients with bipolar disorder should always be conducted, with attention to changes relative to the person’s normal state. Assessment scales can support the clinical interview but should not replace it and should only be used under the correct indications. Examples include:

• MDQ: Screening for bipolarity.
• YMRS: Assessing the severity of mania.
• MADRS: Assessing the severity of depression.
• AUDIT: Screening for alcohol misuse.
• DUDIT: Screening for drug misuse.
• Bipolar Index: Evaluating symptoms indicative of bipolar disorder.

Semi-structured diagnostic interview tools like SCID or MINI can aid diagnosis. For adolescents, the K-SADS-PL interview scale is useful.

Interpreting assessment tools

Careful judgment is necessary when interpreting results, as both false positives and false negatives can occur. For example:

• A positive MDQ result may reflect mood dysregulation from conditions like ADHD, impulse control disorders, anxiety disorders, or personality disorders, not just bipolar disorder.
• Screening for substance misuse using AUDIT or DUDIT might yield incomplete results and is best supplemented with blood and urine tests or detailed history-taking methods like the Timeline Followback approach.

Radiological examinations

These are used to exclude neurological conditions. Currently, no radiological markers have adequate sensitivity or specificity for diagnosing or ruling out bipolar disorder.

Physiological Testing

Such tests are relevant for neurological and neuro-geriatric conditions and for monitoring cardiac health (e.g., QT interval and heart rhythm). Certain psychotropic drugs are cardiotoxic and may cause rhythm disturbances or prolonged QT intervals.

Other testing and examinations

• Glucose, Lipid Profile
• Sodium (Na), Potassium (K), Creatinine, Albumin
• Calcium (Ca), Thyroid-Stimulating Hormone (TSH), Prolactin
• Complete Blood Count (CBC), C-Reactive Protein (CRP), Erythrocyte Sedimentation Rate (ESR)
• Liver Function Tests (including Gamma-Glutamyl Transferase [GGT])
• Vitamin B12, Folate
• If Wilson’s disease is suspected, order serum copper (S-Cu) tests.
• If rheumatic disease or syphilis is suspected, conduct specific tests.
• Drug Screening: Especially for stimulants, THC, and benzodiazepines.
• Height and Weight
• Pulse and Blood Pressure
• Neurological Examination
• CT Brain or MRI Brain: For suspected neurological conditions.
• EEG: For suspected epilepsy or degenerative brain diseases.
• ECG: For suspected heart disease or in older patients.

Other conditions mimicking bipolar disorder

Mood shifts can occur in other conditions, which must be ruled out:

• Schizophrenia
• ADHD with affective dysregulation
• Anxiety disorders (e.g., generalized anxiety disorder, GAD)
• Intellectual disability
• Personality disorders marked by negative affectivity and impulsivity
• Hypersexual disorder
• Impulse control disorders
• Thyroid dysfunctions (e.g., hypothyroidism, hyperthyroidism)
• Systemic Lupus Erythematosus (SLE)
• Head trauma
• Epilepsy, particularly temporal lobe epilepsy
• Encephalitis
• Frontal lobe dysfunction (due to dementia or acquired brain injury)
• Multiple Sclerosis
• Huntington’s disease
• Parkinson’s disease
• Basal ganglia calcifications (Fahr’s disease)
• Brain tumors
• Cushing’s syndrome
• Neurosyphilis
• Medications (e.g., pro-dopaminergic drugs, corticosteroids)
• Substance abuse (e.g., stimulants, hallucinogens, opiates)

Management

Bipolar disorder should be managed in consultation with a psychiatry specialist. Suicide risk assessments are essential. Laboratory tests and other investigations are necessary to:

1. Rule out secondary mood disorders.
2. Monitor physiological parameters during medication initiation.
3. Evaluate long-term treatment effects.

Suicide risk

Between 8–20% of individuals with bipolar disorder die by suicide, making the risk 10–20 times higher than the general population. Suicide risk assessments should be performed regularly, considering external risk factors, clinical status, and current suicidal intent. Studies suggest that lithium has a suicide-preventive effect.

Social and occupational challenges

Interpersonal and occupational difficulties affect 60% of euthymic (symptom-free) patients. Bipolar disorder can have profound social consequences, impacting personal finances, family life, and work. Social recovery often requires extended time due to persistent affective residual symptoms and cognitive impairments, which hinder rehabilitation. Social workers and occupational therapists may need to be involved.

Pharmacological treatment goals

The primary objectives of pharmacological treatment for bipolar disorder are:

1. Managing acute affective episodes.
2. Preventing relapse (secondary prevention).

There is no cure for bipolar disorder. Treatment strategies are based on evidence, clinical expertise, and tolerability. Formal guidelines from medical organizations and regulatory agencies should also guide care.

 

Condition	Treatment	Details
Acute Mania	Lithium	Example: Lithionit
	Valproic Acid	Examples: Ergenyl, Absenor, Orifil
	Atypical Antipsychotics	Examples: Quetiapine (Seroquel), Olanzapine (Zyprexa), Ziprasidone (Zeldox), Aripiprazole (Abilify)
	Combination Therapy	Lithium or valproic acid with atypical antipsychotics like quetiapine, ziprasidone, aripiprazole, or olanzapine
	Benzodiazepines	For behavioral disturbances as needed
	ECT (Electroconvulsive Therapy)	Indicated for severe or treatment-resistant mania, particularly with confusion/delirium. Lorazepam injection may be used if catatonia is present.
Acute Bipolar Depression	Sertraline	May be considered instead of fluoxetine due to its shorter half-life.
	Lamotrigine	– May be considered as monotherapy, primarily to prevent relapse. – Evidence for treating a depressive episode is conflicting. – Addition to lithium can be effective.
	Combination Therapy	Antidepressants like fluoxetine must be combined with prophylactic treatments against mania, such as lithium, valproic acid, or atypical antipsychotics.
	ECT (Electroconvulsive Therapy)	Recommended for severe depression, particularly with psychotic features or psychomotor retardation.
	Seroquel	– Day 1: 100 mg (0+0+1) – Day 2: 200 mg (0+0+2) – Day 3: 300 mg (0+0+3) – Avoid in elderly or physically ill patients.
	Latuda	37.5-75 mg/day
	Zyprexa	10-20 mg/day. Avoid in elderly or physically ill patients.
	Abilify	10-15 mg/day
	Fluoxetine	20-60 mg/day
Ergenyl Retard	600-1000 mg/day
Lithionit	42-168 mg/day (see lithium information below)
Lamotrigine	50-400 mg/day (see lamotrigine information below)

The same treatment as for acute mania applies, but lithium is considered less effective than in pure mania.

Prophylaxis

When selecting prophylaxis, it is essential to consider which mood state has predominated during the affective episodes.

• Lithium
  (Lithionit, lithium sulfate) is a first-line option for prophylaxis in bipolar disorder type I. Other forms, such as lithium carbonate or lithium citrate, may be considered if tolerability is reduced. However, these are not approved medications in Sweden and can only be prescribed on a special license.
• If lithium is unsuitable, olanzapine (Zyprexa) or valproate (Ergenyl Retard) may be considered as alternatives.
  • The use of olanzapine is limited due to its metabolic side effects.
  • Valproate should ideally be avoided for women of childbearing age because of the risk of fetal harm and hormonal effects.
• For bipolar disorder type II with predominantly depressive episodes:
  • Lithium or lamotrigine monotherapy can be considered.
  • If quetiapine was effective during the acute phase, it may also be considered for prophylaxis.
• If monotherapy is ineffective, combination therapy should be considered:
  • Lithium or valproate can be combined with atypical antipsychotics.
  • Lithium combined with lamotrigine is another option.
  • If valproate is combined with lamotrigine, their interaction must be accounted for (lamotrigine dosage should be halved).

Suggested medication choices and dosages

Medication	Dosage	Notes
Seroquel	– Day 1: 100 mg (0+0+1) – Day 2: 200 mg (0+0+2) – Day 3: 300 mg (0+0+3)	Should be avoided in elderly and physically ill patients.
Zyprexa	10-20 mg/day	Olanzapine should be avoided in elderly and physically ill patients.
Abilify	10-15 mg/day	–
Fluoxetine	20-60 mg/day	–
Ergenyl Retard	600-1000 mg/day	–
Lithionit	42-168 mg/day	See detailed lithium information below.
Lamotrigine	50-400 mg/day	See detailed lamotrigine information below.

Other measures

• Psychoeducational Groups
  Including family members in psychoeducational groups, in addition to medication, can reduce the risk of recurrence of new affective episodes.
• Cognitive Behavioral Therapy (CBT)
  For bipolar disorder, CBT can facilitate a return to euthymia, delay recurrence of affective episodes, and improve overall functionality when combined with pharmacological therapy

Addressing comorbidities

In addition to treating bipolar disorder, it is important to address comorbidities and other problems, which often require treatment, such as:

• ADHD (only after stable treatment of bipolar disorder)
• Anxiety disorders
• Obsessive-compulsive disorder
• Personality disorders
• Substance use disorders
• Social problems