28th January 2024

Bipolar Affective Disorder (BPD)

A long-term mental disorder featuring 2 or more episodes of significantly disturbed mood and activity levels. On some occasions, their mood is elevated, and in some, it is depressed.

Incidence and impact

Patients will experience periods of relapse and remission, especially in the presence of poor treatment adherence. Recovery may not be complete between episodes, and episodes may become more frequent over time.

Around 2% of the UK population screen positive for BPD, rates are similar between males and females. It is more common between the ages of 16 and 24.

BPD has the highest risk for suicide attempts and completion of all psychiatric conditions. Up to 56% of patients will make at least 1 suicide attempt in their lifetime, and up to 59% have suicidal ideation.

Other consequences of BPD include those resulting from impaired disinhibition and functioning, for example, damage to reputation, occupation and relationships, financial difficulties due to overspending, injuries, accidents, unplanned pregnancy, self-neglect, substance misuse and exploitation by others.

BPD is often comorbid with anxiety disorders, substance misuse disorders, ADHD, and personality disorders. Additionally, mortality from cardiovascular disease is twice that of the general population.

Definitions

The Diagnostic and Statistical Manual of Mental Disorders (DSM-5) subtypes BPD into Bipolar I disorder and Bipolar II disorder:

• Manic episode: a period of at least 1 week of an abnormally and persistently elevated or irritable mood, plus at least 3 additional symptoms which are severe enough to cause significant impairment in social or occupational functioning, or which requires hospitalisation, or which includes psychotic features.
• Hypomanic episode: a period of at least 4 days of a mildly elevated or irritable mood, which is not severe enough to cause a significant impairment in social or occupational functioning or necessitate hospitalisation without psychotic features.
• Depressive episode: a period of at least 2 weeks of depressed mood or anhedonia, with additional symptoms.
• Mixed episode: A period of rapid alteration between manic and depressive symptoms OR a period of at least 1 week in which symptoms meet the criteria for a manic/hypomanic episode, and at least 3 symptoms of depression are present on most days OR a period of at least 1 week in which symptoms meet the criteria for a depressive episode, and at least 3 symptoms of mania/hypomania are present on most days.
• Rapid-cycling bipolar disorder: when at least 4 mood (depressive, manic, hypomanic, or mixed) episodes are experienced within a 12-month period.

Pathophysiology

BPD is considered one of the most heritable psychiatric disorders, with 1st degree relatives having a 5x increased risk compared to the general population. A number of risk alleles have been identified by genomic studies as having a small effect.

Environmental factors such as early life stress, maternal death before age 5, childhood trauma or abuse, emotional neglect, cannabis use, cocaine exposure and Toxoplasma Gonddi exposure have all been associated with onset or relapse of BPD.

Symptoms and diagnosis

A diagnosis of BPD can be suspected in primary care, but a specialist psychiatric assessment must be carried out in order to confirm diagnosis.

Use clinical judgement to determine the urgency of referral or admission.

Symptoms of mania may include:

• Increased energy and activity
• Marked feelings of wellbeing
• Feelings of physical and mental efficiency
• Increased sociability, talkativeness, over-familiarity
• Increased sexual energy
• Decreased need for sleep
• Irritability
• Conceit
• Impolite behaviour and loss of social inhibitions
• Inattention and distractibility
• Elation
• Pressured speech
• Inflated self-esteem and grandiose ideas
• Overconfidence

In episodes of mania with psychotic features, the following may be seen:

• Delusions
• Hallucinations
• Flight of ideas
• Manic stupor

Symptoms may be mood-congruent or mood-incongruent

Management

BPD is best managed through a combination of treatment modalities, the choice of which should consider suicide risk, disease polarity, treatment adherence and pharmacokinetics.

Mania

The treatment aims for a manic patient are to reduce the core symptoms, reduce psychotic symptoms, minimise abnormal behaviour, and minimise the side effects of treatment.

Dopamine antagonists are the first line choice, typically one of Haloperidol, Olanzapine, Quetiapine, or Risperidone.

• If this is not effective or tolerated, an alternative from the above may be tried
• Following this, Lithium or Sodium valproate may be added

If the patient is already on an antidepressant medication, this should be tapered and discontinued.

Mixed episodes

Usually treated in the same way as manic episodes.

Depression

One of the difficulties in pharmacological management of bipolar depression is the risk of (hypo-)manic or mixed switch resulting from antidepressant treatment. For this reason, antidepressants may be judiciously used as long as antidepressant monotherapy is avoided and they are co-prescribed with an anti-manic agent.

Options are:

• Quetiapine alone
• Fluoxetine + olanzapine
• Olanzapine alone
• Lamotrigine alone

Maintenance

Maintenance therapy aims to prevent new (hypo)manic, mixed, and depressive episodes, as well as to improve residual symptoms.

Long-term management is typically commenced 4 weeks after the acute episode has resolved. The options for maintenance include:

• Continuing current anti-manic agent
• Starting long-term therapy with Lithium (or, failing this valproate* or olanzapine alone or in combination with lithium)

Lithium

Lithium is highly effective in reducing relapse risk and is the only drug to meet the stringent criteria of being a true mood stabiliser. It works in acute mania, depression and as a maintenance therapy.

It can be combined with other drugs, commonly anticonvulsants and dopamine antagonists. Most patients will respond to one of these drugs.

The exact pharmacological mechanism by which lithium benefits mood disorders is unknown.

Monitoring

All patients on lithium therapy must be routinely monitored via blood tests.

• Lithium levels are measured 12 hours post-dose
• The first level should be taken 1 week after initiation
• Subsequent measurements should occur 1 week after every dose change and weekly until levels stabilise
• After levels have stabilised, they can be measured every 3 months

Individual serum lithium targets will be prescribed. Typically 0.6-0.8 mmol/L is suitable for those prescribed lithium for the first time, with higher levels suggested for those who have relapsed on lithium treatment previously.

Adverse effects

• Nausea, diarrhoea
• Muscle weakness
• Fine tremors
• Polyuria, polydipsia, diabetes insipidus
• Hypo- or hyperthyroidism
• Hyperparathyroidism
• Nephrotoxicity
• Rhabdomyolysis

Toxicity

Toxicity occurs at concentrations greater than 1.5 mmol/L.

Severe toxicity occurs when levels exceed 2 mmol/L.

Signs of toxicity include:

• Diarrhoea
• Vomiting
• Anorexia
• Muscle weakness
• Lethargy
• Ataxia
• Tinnitus
• Blurred vision
• Coarse tremor
• Choreoathetoid movements
• Dysarthria
• Drowsiness
• Hyperreflexia
• Psychosis
• Seizures
• Coma
• Renal failure

Note: there is a list of conditions in which lithium is contraindicated, including patients who refuse regular blood tests.

Women of childbearing potential should be advised to use reliable contraception.

* Note on Sodium valproate:

• There is significant risk of fetal malformations and adverse neurodevelopmental outcomes due to Valproate exposure during pregnancy. It is not recommended for women of childbearing potential unless all other alternatives are inappropriate, ineffective, or not tolerated.
• If prescribed to females of childbearing potential, they should be placed on a pregnancy prevention plan.

Electroconvulsive Therapy

As in unipolar major depression, ECT can be used in cases of bipolar major depression, as well as mixed episodes and occasionally mania. The indications for its use include failure to respond to multiple medication trials, acute life-threatening illness (such as suicidality or severe neglect), severe psychosis and catatonia.

There is a risk of precipitating hypo-/mania with the use of ECT, but is lower than that posed by antidepressant medications.

• In patients who develop mania during their ECT treatment course, ECT is often continued alongside an antipsychotic as ECT is effective for mania.

It is used in mania less commonly than in depression, as manic patients often respond to pharmacological therapy.

Psychotherapy

It is recommended that targeted psychotherapy is provided alongside pharmacotherapy.

Psychoeducational approaches are considered best as these allow patients to develop skills to recognise and manage their moods, stressors and maximise their quality of life. These approaches may include:

• Structured group psychoeducation
• Family interventions
• Cognitive behavioural therapy
• Interpersonal therapy

Other advice for preventing relapse should be given to patients, for example:

• Encouraging treatment compliance
• Maintaining good sleep hygiene and adequate sleep duration
• Avoiding shift work, night flying and routinely working excessive hours
• Structuring their day with activities and social contact
• Self-monitoring symptoms, triggers, and early warning signs
• Coping strategies
• Reduction or cessation of smoking (nicotine is a stimulant)
• Avoiding misuse of alcohol and drugs
• Avoiding excessive caffeine

References

• Churchill, G. C., Nisha, S., & Berridge, M. J. (2020). Bipolar Disorder. In J. R. Geddes, N. C. Andreasen, & G. M. Goodwin (Eds.), New Oxford Textbook of Psychiatry (2nd ed.). https://doi.org/10.1093/med/9780198713005.001.0001
• Solomon, D. (2014). Bipolar disorder in adults: Indications for and efficacy of electroconvulsive therapy (ECT). Retrieved July 18, 2022, from https://www-uptodate-com.ezproxy.is.ed.ac.uk/contents/bipolar-disorder-in-adults-indications-for-and-efficacy-of-electroconvulsive-therapy-ect?search=Bipolar disorder in adults: Indications for and efficacy of electroconvulsive therapy (ECT)&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1#H518772946
• NICE. (2021). Bipolar disorder. Retrieved July 6, 2022, from https://cks.nice.org.uk/topics/bipolar-disorder
• NICE. (n.d.). Lithium carbonate. Retrieved July 4, 2022, from https://bnf.nice.org.uk/drugs/lithium-carbonate/#monitoring-requirements
• NICE. (2021). Valproate | Prescribing information | Bipolar disorder | CKS | NICE. Retrieved July 6, 2022, from https://cks.nice.org.uk/topics/bipolar-disorder/prescribing-information/valproate/#monitoring
• Vieta, E., Pacchiarotti, I., & Miklowitz, D. J. (2020). Management and treatment of bipolar disorder. In J. R. Geddes, N. C. Andreasen, & G. M. Goodwin (Eds.), New Oxford Textbook of Psychiatry (2nd ed.).
• WHO. (2019). ICD-10 Version: 2019. In ICD-10 Version: 2019. Retrieved from https://icd.who.int/browse10/2019/en#/V
• Key points on Lithium therapy (NICE, n.d.-b; Vieta, Pacchiarotti, & Miklowitz, 2020) NICE. (n.d.). Lithium carbonate. Retrieved July 4, 2022, from https://bnf.nice.org.uk/drugs/lithium-carbonate/#monitoring-requirements Vieta, E., Pacchiarotti, I., & Miklowitz, D. J. (2020). Management and treatment of bipolar disorder. In J. R. Geddes, N. C. Andreasen, & G. M. Goodwin (Eds.), New Oxford Textbook of Psychiatry (2nd ed.).