2.1.2 Bipolar Disorder

Bipolar Disorder

Prevalence and incidence:

The lifetime prevalence of bipolar disorder ranges from 0.3% to 1.5%, with 0.8% being bipolar I and 0.5% being bipolar II. The disorder affects males and females equally, but bipolar II and rapid cycling are more prevalent in females. The first episodes tend to be manic in males and depressive in females. There are no significant racial differences in prevalence. The disorder typically affects individuals between the ages of 15 and 50 years old, with peaks occurring at 15-19 years and 20-24 years and a mean age of onset of 21 years.

Aetiology:

The exact aetiology of bipolar disorder is unknown, but genetic, environmental, and neurobiological factors are believed to contribute to its development. Genetic studies have identified several genes that are associated with an increased risk of bipolar disorder. One to note is CACNA1C, located on chromosome 12-p-13, and ANK3 which have been implicated by genome-wide significant single nucleotide polymorphisms associations in several studies of bipolar disorder. Environmental factors such as stressful life events, substance abuse, and sleep disturbances can also trigger bipolar episodes.

Factor:	Description
Genetic	Bipolar disorder has a significant genetic contribution with an overall heritability of about 70%. First-degree relatives are seven times more likely to develop the condition than the general population, and there is shared genetic susceptibility to schizophrenia.
Candidate genes	ANK3 and CACNA1C have strong support from genome-wide association studies, and there are other candidates associated with biochemical pathways that lithium regulates, neuronal migration, circadian periodicity, and more.
Neuroimaging	Structural and functional brain imaging studies have shown graphic activation and reduced grey matter in areas associated with emotional regulation, and graphic activation in ventral limbic brain regions that mediate and generate emotional responses.
Biochemical factors	Glutamate, adrenaline, noradrenaline, DA, 5-HT, and Ca2+ regulation are all implicated in bipolar disorder.
Environmental factors	Stressful life events may precipitate episodes, particularly in vulnerable individuals. Pregnancy carries a high risk of mixed affective presentation or puerperal psychosis.
Pharmacological risk factors	Antidepressant treatment may precipitate mania, and prior antidepressant treatment increases the likelihood of conversion to bipolar disorder.

Presentation:

Bipolar disorder is characterized by episodes of mania or hypomania and depression. During manic or hypomanic episodes, individuals may experience elevated or irritable mood, grandiosity, decreased need for sleep, increased energy, and impulsive behaviour. During depressive episodes, individuals may experience symptoms similar to those of unipolar depression.

Differential diagnosis:

• Agitated depression
• OCD/other anxiety disorders
• Circadian rhythm sleep-wake disorders
• Substance misuse/physical illness/medication-related
• ADHD
• Borderline personality disorder

Treatment:

The treatment of bipolar disorder involves a combination of medication and psychotherapy. Mood stabilizers such as lithium and antipsychotic medication are commonly used to manage manic and hypomanic episodes. Antidepressant medication may be used during depressive episodes, but caution must be exercised to avoid triggering manic episodes. Psychotherapy, particularly CBT and family-focused therapy, can also be helpful in managing the symptoms of bipolar disorder.

The NICE guidelines for bipolar disorder recommend medication as a key component of treatment. The specific medications prescribed will depend on the type and severity of the individual’s symptoms. Some general medication recommendations include:

1. For acute mania:
   • A mood stabilizer such as lithium, semisodium valproate, or carbamazepine
   • An antipsychotic such as olanzapine, risperidone, or quetiapine
2. For acute depression:
   • A mood stabilizer such as lithium or lamotrigine
   • Similar treatment rationale as in unipolar depression, commence SSRIs first line. If no response to SSRI then consider alternative antidepressants such as fluoxetine, venlafaxine, mirtazapine, or augmentation strategies.
   • Psychological interventions such as CBT or interpersonal therapy may also be considered
3. For long-term management and prevention of relapse:
   • A mood stabilizer such as lithium, valproate, or lamotrigine
   • Antipsychotics may also be used in combination with mood stabilizers
   • Psychological interventions such as CBT, family therapy, and psychoeducation

It is important to note that medication should always be prescribed and monitored by a qualified healthcare professional. The NICE guidelines stress the importance of regular medication reviews and monitoring for adverse effects.

Outcome:

With proper treatment, many individuals with bipolar disorder can achieve symptom remission and maintain stability. However, bipolar disorder is a chronic condition, and long-term medication management is typically required.

Around 40-50% of patients experience another manic episode within the first two years after their initial episode. Among patients treated with lithium, about 50-60% gain symptom control, with 7% reporting no recurrence, 45% experiencing future episodes, and 40% experiencing persistent recurrence. The cycling between mania and depression tends to accelerate with age. Several factors may indicate a poor prognosis, including a history of poor employment, alcohol abuse, presence of psychotic or depressive features during periods of mania or depression, evidence of depression, male sex, and treatment non-compliance. Conversely, good prognostic factors include short manic episodes, later age of onset, few thoughts of suicide, few psychotic symptoms, few comorbid physical problems, and good response and compliance with treatment.

	Bipolar Disorder
Prevalence	1-2% global population
Onset	Late adolescence or early adulthood
Gender	Equal prevalence between men and women
Aetiology	Genetic, environmental, and neurobiological factors
Presentation	Episodes of mania or hypomania and depression, with symptoms of elevated or irritable mood, grandiosity, decreased need for sleep, increased energy, and impulsive behaviour during manic episodes
Treatment	Medication (mood stabilizers and antipsychotics) and psychotherapy (CBT and family-focused therapy)
Outcome	Symptom remission and stability are achievable with proper treatment, but long-term medication management is typically required

Important Studies

BALANCE:

The BALANCE trial, also known as Lithium plus valproate combination therapy versus monotherapy for relapse prevention in bipolar I disorder, is an important clinical trial that investigated the effectiveness of combination therapy versus monotherapy for preventing relapse in individuals with bipolar I disorder. The study found that the combination of lithium and valproate was more effective than either medication alone in preventing relapse, making it a promising treatment option for individuals with bipolar I disorder. The findings of the BALANCE trial have important implications for improving treatment options and outcomes for individuals with bipolar I disorder, a condition that can have a significant impact on quality of life and daily functioning. Overall, the BALANCE trial is a valuable contribution to the field of mental health research and highlights the importance of continued research and development of effective treatment options for individuals with bipolar I disorder.

References:

1. American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.). https://doi.org/10.1176/appi.books.9780890425596
2. Kessler, R. C., Berglund, P., Demler, O., Jin, R., Merikangas, K. R., & Walters, E. E. (2005). Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Archives of General Psychiatry, 62(6), 593–602. https://doi.org/10.1001/archpsyc.62.6.593
3. Semple, D., Smyth, R., & Burns, J. (Eds.). (2013). Oxford handbook of psychiatry (3rd ed.). Oxford University Press.