Bipolar disorder is a disease that is characterized by periods of depression and mania/hypomania. It is a rare disease affecting approximately 1% of the general population. The disease results from genetic mutations in multiple loci and environmental influence in these patients who are genetically predisposed. The presentation takes various forms, ranging from maniac signs and symptoms of hyperactivity and irritability, to depression episodes with reduced activity, lethargy and loss of interest, and a mixed picture of maniac and depressive episode features. Treatment of bipolar disease involves pharmacotherapy with mood stabilizers, behavioral therapy, and electroconvulsive therapy. Mortality and morbidity are mainly due to the associated suicidal tendencies alongside adverse effects associated with the drugs.
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Bipolar disorder is a severe mental illness that is characterized by periods of low mood (depression) and periods of elevated mood (mania/hypomania). Thus, it is also known as manic-depressive illness (MDI) or bipolar affective disorder. The episodes are either:

  • Depression episode where the patient has low mood and feels lethargic.
  • Maniac episode where the patient is very active, has abnormal energy and an elevated mood.
  • Hypomanic episodes are like maniac episodes but they are usually less severe and rarely affecting the social functioning of the patient.

The occurrence of the episodes may take the form of several episodes a year or rarely one episode or none in a year. They may also vary in the presence/absence of emotional episodes in between the maniac and depressive episodes.

Epidemiology of Bipolar Disorder

The internationally bipolar affective disorder affects 0.3 – 1.5% of the world’s population with an average prevalence of 1% in the population. The diseases of the bipolar spectrum of diseases account for 2.4% of the population. However, recent studies point towards an increase in the prevalence of the disease with the prevalence being documented at 5 – 7%.  The disease begins manifesting clinically in early adulthood from 25 years. The mean age of the occurrence of the disease is 21 years and it is rare beyond 40 years of age.

Bipolar disorder has no racial or sexual predisposing, although there seems to be a female preponderance for bipolar II or hypomania.

Classification of Bipolar Disorder

The bipolar affective disorder can be classified into:

  1. Bipolar I disorder: mainly characterized by the presence of one maniac episode with or without a depressive episode involvement. The episodes may tip over to frank psychosis.
  2. Bipolar II disorder: that is characterized by 1 hypomanic episode, no manic episodes, and one major depressive disorder.
  3. Cyclothymic disorder: which is a rare entity that is characterized by childhood or adolescent episodes of hypomania and depression for 1 or 2 years.

It should be noted that bipolar II disorder is not a less severe form of bipolar I disorder, rather; the diseases are different entities. Nevertheless, patients with bipolar I disorder have severe and dangerous episodes that are likely to cause a change in behavior and onset of psychosis, while patients with bipolar II disorder remain depressed for longer posting a challenge in recovery.

Etiology and Pathophysiology of Bipolar Disorder

The disease is thought to arise from environmental influence in individuals who are genetically predisposed to developing the disease due to mutations in their genes. These people who have an increased risk of developing the disease have structural and biochemical abnormalities that are easily tipped over into bipolar disorder by an array of environmental triggers; therefore, the influencing factors can be grouped into:

Genetic predisposition

People with a positive family history of a first-degree relative with bipolar disorder have a seven-fold increase in developing the disease. This history also increases the chance of developing any other mood disorder more so depressive disorders. The genetic component is thought to be linked to the presence of multiple small alleles. These loci are known as major affective disorder (MAFD) loci which are numbered according to their location in various chromosomes as MAFD-1/2/5/8.

Biochemical and biological influence

Patients with a genetic risk have structural abnormalities, such as a decrease in the amount and availability of neurotransmitters leading to the development of the disorder. They may also possess some anatomical defects in the central nervous system neuronal structure.

Environmental influence

The influence of external factors in the environment exacerbates the genetic and biological defects in these patients, leading to the development of the bipolar disease. These environmental triggers include childhood abuse, exposure to long-term stress and pregnancy that could predispose to the development of postpartum psychosis.

Pharmacological factors

Antidepressant use is considered an additional risk factor for bipolar and mania development.

Clinical Features of Bipolar Disorder

Bipolar disorder presents with features that characterize the manic episode, hypomanic episode, depressive episode, or a mixed picture. The disease may also present with other additional features such as:

  • Anxiety
  • Psychosis
  • Prior psychiatric treatment and use of antipsychotic medications
  • Comorbid medical conditions

Maniac episode features

The patient has at least three features of disturbed mood with elation, irritability, and expansiveness for at least one week.

  1. Having a feeling of self-importance
  2. Reduce the need for sleep
  3. Reduced the need for food
  4. Grandiosity
  5. Excessive talking or quick talking
  6. Easily distracted
  7. Racing thoughts
  8. Excessive pleasurable activities with painful consequences
  9. Spending large sums of money on things you cannot afford
  10. Lack of substance abuse or general medical condition to explain the patient’s state

Hypomanic episode features

They are like features of a manic episode but do not cause any noticeable symptoms at social places such as work and school.

The episode is referred as hypomanic if the symptoms are seen for at least 4 days, but not long and severe enough to be labeled maniac type.

Depressive episode features

This episode is indicated by the presence of 5 or more symptoms for 2 weeks which include:

  1. Depressed mood
  2. Weight loss
  3. Psychomotor retardation and agitation
  4. Feeling of despair, worthlessness, and guilt
  5. Preoccupation with death and suicidal ideation
  6. Lack of appetite
  7. Loss of interest in activities
  8. Hypersomnia/insomnia
  9. Loss of energy/fatigue
  10. Reduced concentration
  11. Pessimistic tendencies

Investigations of Bipolar Disorder

The work up to achieve the diagnosis of bipolar disorder requires supportive investigations that rule out other diagnosis and help in tracing baseline values for future comparison is situations of derangement. They include:

  • Full hemogram with ESR: some drugs may cause bone marrow suppression
  • Renal function tests
  • Liver function tests

Other laboratory workups may be done to rule out a medical condition that may be causing the disease. They include:

  • Thyroid function tests
  • Cerebrospinal fluid analysis
  • Venereal disease research laboratory tests (VDRL)
  • Human immunodeficiency virus testing
  • Drug screen to rule out alcohol and substance abuse as a cause of the depression
  • Enzyme assays, such as dexamethasone suppression tests and ACTH stress test

Neuroimaging methods to identify any organic disease and study neuroanatomy for possible etiologies of bipolar disorder. These are:

  • Computed Tomography (CT) scan of the brain
  • Magnetic Resonance and Imaging (MRI) scans

Differential Diagnosis of Bipolar Disorder

Dysthymic disorder A unipolar mood disorder with a similar history of longstanding low mood but does not meet the criteria for bipolar disorder.
Schizophrenia Psychotic diseases that have negative symptoms that may mimic depression.
Bereavement Patients will have a similar presentation of mood alteration.
Bereavement lacks functional impairment and rarely lasts beyond 2 months.
Mood disorders secondary to substance Change of mood may occur in the presence of an identifiable trigger such as abuse of alcohol.
Hyperthyroidism and thyrotoxicosis Mania and low mood that has an identified general medical condition of the thyroid gland.

Treatment of Bipolar Disorder

Treatment of bipolar disorder should begin with identification and management of behavior that would harm other patients. It is further based on severity and presenting symptoms and severity of the episode. The modalities of treatment include the following:


It is indicated for moderate to severe disease that requires hospital admission in the acute phase of treatment. Several classes of drugs exist and selection is based on:

  • Identification of response to a drug during treatment of a close relative may render a certain drug suitable.
  • Clinical judgment of the anticipated response based on symptomatology and experience of the clinician.
  • Tolerance in patients with comorbidities such as cardiac diseases or renal disease.

The drugs are mainly administered for mood stabilization and control of psychotic episodes. The groups of drugs to select from include:

  1. Tricyclic antidepressants (TCAs) such as Amitriptyline and Clomipramine: They are effective in the management of the depressive episode of the disorder. They have a good response rate but are associated with dangerous adverse effects such as sedation and anticholinergic effect.
  2. Selective serotonin reuptake inhibitors (SSRIs) such as sertraline (Zoloft) and Citalopram (Celexa): They are administered in a once a day dosing and have a safer side effect profile thus are a desirable group of drugs. Common side effects include gastrointestinal upset, sexual dysfunction, and insomnia.
  3. Mood stabilizers and antipsychotics: Drugs such as Lithium are used in combination with antidepressants in patients who present with anxiety. They are also important in the reduction of recurrence rates.
  4. Antianxiety medications: Benzodiazepines, such as Lorazepam or Clonazepam, have also been used in the treatment of anxiety seen in these patients.

Psychotherapy of Bipolar Disorder

It is the treatment of choice for mild disease and mainly undertaken in the outpatient setting. The forms of psychotherapy include:

  1. Psychological counseling/psychoeducation where the patient is educated about his/her condition and learns how to take care of oneself.
  2. Cognitive-behavioral therapy (CBT) is a type of therapy where the bad behavior that triggers the development of maniac or depressive episodes is discouraged, while the good behaviors are reinforced.
  3. Interpersonal and social rhythm therapy (IPSRT) is a form of therapy where one develops a mood management plan that contains activities which help in controlling mood. This plan is inclusive of activities, such as exercises, that decrease the occurrence of episodes.
  4. Family-focused therapy allows for the education of family members and close friends around you that participate in your care. This allows them to offer good care that works to reduce the occurrence of stress.

Combination therapy

A combination of psychotherapy and pharmacotherapy is considered in the management of bipolar disorder, especially in patients with refractory disease.

Electroconvulsive therapy (ECT)

It is a safe and effective method of treatment. The treatment is considered in a situation where there is severe refractory disease and on patient’s self-demands.

The treatment begins with a clinical assessment and laboratory investigations such as CT scans, electrocardiograms, complete blood count and renal function tests.

Informed consent is obtained from the patient and the patient is instructed to remain nil per mouth at least for 8 hours prior to the procedure.

Cardiac monitoring is initiated, airway secured, and the following drugs are administered:

  • A short-acting anesthetic agent
  • A short-acting muscle relaxant
  • Atropine

A rubber mouth block is placed and electrical stimulus introduced in the temporal and occipital aspect of the head.

The desired dosage is seizure activity lasting 25 seconds – 2 minutes at a rate of 2 – 3 schedules per week to a total of 6 treatments. If the seizure activity is too little, restart again and, if it’s too much, administer intravenous diazepam.

Transcranial magnetic stimulation (TMS)

It is a new form of therapy that is at clinical trials stages.

Complications of Bipolar Disorder

  1. Suicidal attempts and acts are also seen with untreated disease and they are the most common causes of death in depression.
  2. The patients may also be violent and express homicidal tendencies to their colleagues.
  3. Pharmacotherapy may lead to undesired effects of sedation, sexual dysfunction, vomiting, insomnia, and hypertension.
  4. The impulse delivered to the brain during electroconvulsive therapy may cause headaches, anterograde and retrograde amnesia.
  5. Social isolation and dysfunction are seen with damaged relationships and poor performance at school and work.

Course and Prognosis of Bipolar Disorder

Morbidity and mortality are mainly associated with suicidal and homicidal tendencies. 25 – 50% of the patient’s attempt, and 11% are successful. The patients also exhibit higher mortality rates compared to the general population.

For a patient with Bipolar II disorder who is on lithium, 40 – 50% will have another attack, while only 50 – 60% have total control of their symptoms.

The disease can be prevented/controlled by early initiation of medication, early psychological counseling to avoid stresses in early life and lifestyle changes such as dietary modification and increase in exercise activity to reduce the impact of stress.

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