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Continuing education - Brain disease - Bipolar affective disorder with focus on mania

Dalia Albahari and Siobhan Rooney provide an overview of the symptoms, management and treatment of bipolar affective disorder

The International Statistical Classification of Diseases and Related Health Problems tenth revision (ICD-10) defines the disorder as repeated episodes in which the patient’s mood and activity levels are significantly disturbed, this disturbance consists on some occasions of an elevation of mood and increased energy and activity (mania or hypomania), and on other occasions of a lowering of mood and decreased energy and activity (depression). The onset of bipolar symptoms typically occurs early in life, between the mid-teenage years and early 20s.1 The true prevalence of bipolar disorder is difficult to estimate as often illness can be misdiagnosed due to presenting depressive symptoms. The literature suggests prevalence between 1-1.5%.2,3 The World Health Organization identified bipolar disorder as the sixth leading cause of disability-adjusted life years worldwide among people aged 15 to 44 years,4 and between 25 and 50% of people with this diagnosis attempt suicide, and 15% die by suicide.5 Early diagnosis and treatment has a great impact on the outcome of the disorder.

ICD10 classifies the disorder into: hypomanic episode; manic episode, with or without psychotic symptoms; depressive episode, with or without psychotic symptoms; and mixed episode. The disorder can be divided into three subtypes:

  • Bipolar affective disorder type I: A history of at least one episode of mania, a history of depression is not required
  • Bipolar affective disorder type II: A history of at least one hypomanic episode plus at least one episode of depression
  • Bipolar affective disorder not otherwise specified (NOS).

Signs and symptoms
Manic patients typically present with elevated mood varying from carefree joviality to almost uncontrollable excitement, irritability can dominate mood too. Patients may experience high levels of energy with over activity and a decreased need for sleep. Increased sense of well-being and grandiosity are also common. Sexual desire is also increased.

Patients have excessive speech at a rapid rate (pressure of speech) that may involve unrelated topics (ie. flight of ideas). Attention and concentration is impaired and impaired judgment is common. Patients can become socially disinhibited. Considerable disruption to social functioning occurs. Patients may become occupied by and get involved in extravagant schemes and pleasurable activity and may behave recklessly which imposes risk to their social life, finances physical and mental health.

Persecutory and grandiose delusions are the commonest types of delusions in manic episode with psychotic symptom; other psychotic symptoms may include other types of delusions, perceptual disorder and formal thought disorder. Psychotic symptoms do not occur in hypomanic episode.

Patients with acute episodes of mania are subjected to many risks which include: risk of deterioration of mental illness and suicide; risk of self-neglect; risk of dehydration and malnourishment; risk of sexual and financial exploitation; risk to children; risk of accidents; risk of driving; risk of alcohol and substance misuse; risk of aggression; and disruption to work and relationships.


Management of manic episodes should start with a comprehensive assessment of symptoms. A psychiatric history should focus on presenting complaints, whether there is past history of either mania, depression or other mental health illness, and any previous or current contact with psychiatric services. It is important to assess whether the patient was compliant with previous treatment, and what treatment was offered.

It is important to ascertain whether there were previous admissions and whether the Mental Health Act was applied or not. Insight assessment is important as it may influences adherence to treatment in the future.

A history of alcohol and drug use should be explored and urine screen and blood toxicology are useful. Any family history of mental health illness should be documented. The taking of a medical history alongside a physical examination with appropriate laboratory tests are important to exclude any organic causes for such presentations. This is especially true in older patients. A collateral history from primary healthcare professionals, family members, mental health services etc. should be sought.

Risk management
Health professionals assessing a patient should explore all static and dynamic risk factors involved and the multidisciplinary team should design a comprehensive risk management plan. Safety of patients and others is a priority in the management, and admission to an inpatient unit possibly under the Mental Health Act, may prove necessary.

Patients should be nursed in a quiet environment and over stimulation should be avoided.

Antidepressant medications should be stopped as they contribute to a switch in polarity and can precipitate rapid cycling affective disorder. The pharmacological treatment recommended by Maudsley prescribing guidelines is a trial of a second generation antipsychotic medication if symptoms are severe and behaviour is disturbed. Mood stabilisers are another option of treatment.

If symptoms are severe and poor response is observed to treatment with a single agent, combination of an antipsychotic and a mood stabiliser medication is recommended. A short-term benzodiazepine prescription can be used in the acute phase of management. If the patient is already receiving pharmacological treatment, compliance and dose should be checked, and if the patient is prescribed lithium or sodium valproate, plasma levels should be obtained.

In women of child-bearing age, history of menstrual period and a pregnancy test are important as lithium, valproate and carbamazepine can cause congenital anomalies, thus their use is not advised during pregnancy. Education about contraception during treatment with these medications is crucial.

Olanzapine, risperidone, quetiapine and aripiprazole have been most robustly evaluated. Clozapine seems to be effective in refractory bipolar conditions.6, 7, 8, 9

NICE recommends that a mood-stabiliser should be prescribed as prophylaxis after a single manic episode that was associated with significant risk and adverse consequences, or in the case of bipolar I illness, after two or more acute episodes or in the case of bipolar II illness, if there is significant functional impairment, frequent episodes or significant risk of suicide. Evidence supports the efficacy of some second-generation antipsychotics particularly olanzapine, quetiapine and aripiprazole for prophylaxis.

Pharmacological treatment of bipolar affective disorder should be part of a comprehensive bio-psycho-social management plan that includes a multidisciplinary team with a focus on rehabilitation and recovery.

Side effects
Metabolic problems such as weight gain, glucose intolerance, diabetes mellitus, and hyperlipidaemia are most likely to occur with use of clozapine and olanzapine, followed by quetiapine and risperidone. Thus, patients should be regularly monitored for weight, waist circumference, blood pressure, and serum glucose and lipids.

Hyperglycaemia, impaired glucose tolerance and diabetic ketoacidosis seem to occur even in the absence of obesity and a family history of diabetes. All patients should have oral glucose tolerance tests (OGTT) performed as this is the most sensitive method of detection of glucose impaired tolerance. Fasting plasma glucose tests are less sensitive but recommended in conjunction with glycosylated haemoglobin (HbA 1C).

Frequency of monitoring should then be determined by physical factors, such as weight gain, and known risk factors, such as family history of diabetes, lipid abnormalities. According to the Maudsley prescribing guidelines, the absolute minimum frequency for testing for diabetes in all patients is yearly.

Second-generation antipsychotics have a profound effect on triglycerides. And raised triglycerides are in general, associated with obesity and diabetes. All patients treated with second-generation antipsychotics should have their lipids measured at baseline, and those prescribed clozapine, olanzapine, quetiapine should ideally have their serum lipids measured every three months for the first year of treatment and annually afterwards.

Some antipsychotics block cardiac potassium channels and are linked to prolongation of the cardiac QT interval, a risk factor for the ventricular arrhythmia Torsade de Pointes, which can be fatal. ECG monitoring is essential for all patients prescribed antipsychotics. An estimate of QTc interval should be made on admission to in-patient units and on discharge, and yearly thereafter (NICE guidelines).

The majority of side-effects associated with antipsychotic treatment are dose-related. These include extra pyramidal symptoms, sedation, postural hypotension, anticholinergic effects, sexual dysfunction and weight gain. Clozapine can cause fatal agranulocytosis.

Most lithium’s side-effects are dose (plasma level) related. These include mild gastrointestinal upset, fine tremor, hypothyroidism, congenital anomalies in unborn babies, polyuria and polydipsia and diabetes insipidus. Psoriasis and acne can also be aggravated by lithium.

Lithium toxicity occur at levels >1.5 mmol/L and usually consist of gastrointestinal effects (anorexia, nausea and diarrhoea) and central nervous system effects – muscle weakness, drowsiness, ataxia, course tremor and muscle twitching – which can be fatal in severe cases. Information about toxicity should be repeated at appropriate intervals to make sure that it is clearly understood.

Sodium valproate can cause gastric irritation, hair loss, congenital anomalies in unborn babies, weight gain, thrombocytopenia, leucopenia, red cell hypoplasia and pancreatitis.

Dalia Albahari is a psychiatric registrar and Siobhan Rooney is a consultant psychiatrist in addictions, both at the National Drug Treatment Centre in Dublin


  1. Goodwin, A, 2007. ECNP consensus meeting Bipolar depression. NICE
  2. Bebbington P, 1995. The epidemiology of Bipolar Affective Disorder. Social Psychiatry and Psychiatric Epidemiology.
  3. Merikangas KR, AHAJ, 2007. Life time and 12 month prevalence of bipolar spectrum disorder in the National Comorbidity Survey replication. Arch Gen Psychiatry, 64(543).
  4. Woods SW, 2000. The economic burden of bipolar disease. J Clin Psychiatry, 13(38)
  5. Jamison KR, 2006. Suicide and bipolar disorder. J Clin Psychiatry , 9(47)
  6. Chang JS, 2006. The effects of long term clozapine add on therapy on the rehospitalization rate and the mood polarity patterns in bipolar disorders.. J Clin Psychiatry, Issue 67, pp. 461-7.
  7. Calabrese JR, 1996. Clozapine for treatment-refractory mania. Am J Psychiatry, Issue 153, pp. 759-64
  8. Green, 2000. Clozapine in the treatment of refractory psychotic mania. Am J Psychiatry, Issue 157, pp. 982-6
  9. Kimmel SE, 1994. Clozapine in the treatment -refractory mood disorders. J Clin Psychiatry, Issue 55 suppl B, pp. 91-3
Continuing education - Brain disease - Bipolar affective disorder with focus on mania


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