Approach

Bipolar disorder is marked by occurrence of mania, or episodes of hypomania and depression.[1] Hypomania and mania are defined as elevated, expansive, or irritable mood states associated with functional impairment; a longer duration and a higher level of dysfunction differentiate mania from hypomania.[1] According to DSM-5-TR a diagnosis of a mania episode requires the presence of significantly elevated or irritable mood, lasting for one week or longer, and associated with at least 3 of the following symptoms (4 if the mood is irritable): decreased sleep, increased energy, increased goal directed activity or psychomotor agitation, pressured speech, flight of ideas, distractibility, impulsivity, and grandiosity. The mood changes are at a level of severity that leads to significant functional impairment or results in psychiatric hospitalisation.[1] Although episodes of hypomania are milder than mania and do not typically warrant hospitalisation, they may still nonetheless be associated with substantial negative impacts on interpersonal, occupational, and financial function. Bipolar I disorder is characterised by the occurrence of 1 or more manic episodes, and bipolar II disorder is characterised by the occurrence of 1 or more hypomanic episodes and at least one depressive episode.[1] Both individuals with bipolar I disorder and those with bipolar II disorder commonly experience major depressive episodes.

Making a diagnosis of bipolar disorder can be difficult, and delayed diagnosis is common, with the average duration between the onset of symptoms characteristic of bipolar disorder, and the beginning of treatment, being around 6 years.[28]​ Although bipolar disorder is characterised by manic and hypomanic episodes, patients are more likely to seek treatment during a depressive episode, and depression is usually the initial presentation.[83] People may initially present with symptoms diagnostic of major depressive disorder, and only later develop mania or hypomania; although figures in the published literature vary, rates of diagnostic conversion from depression to bipolar disorder may be as high as 30% within 3 years.[17][18]

In addition to the common presentations, in classic manic, hypomanic, or depressed phases of the illness, individuals may also present with other variants or complex comorbidities that make diagnosis challenging. Mixed features are characterised by the co-existence of simultaneous depression and mania symptoms, and represent a more difficult-to-treat state.[1] Mixed symptoms may be continuously present or manifest sporadically.[5]​ Rapid-cycling bipolar disorder is defined by 4 or more mood episodes in a 12-month period, is more resistant to pharmacological treatment, and may be worsened by traditional antidepressants.[1] In some people with bipolar disorder, severe psychotic symptoms and thought disorder may mimic schizophrenia.

Most people with bipolar disorder suffer with at least one comorbid condition complicating diagnosis and treatment. The most common comorbidities include substance use disorders, anxiety disorders, panic disorders, attention-deficit hyperactivity disorder (ADHD) or subthreshold attentional symptoms, and common medical conditions such as obesity, diabetes, hypertension, migraine, and irritable bowel syndrome.[7][8][9][10][11][12][16]​​​ Comorbid personality disorders, particularly borderline and narcissistic, are identifiable in about 20% to 50% of people with bipolar disorder.[13][14][15]​​​ Given the high prevalence of comorbid psychiatric and substance use disorders in people with bipolar disorder, many experts advocate for routine screening for concurrent mental health conditions and substance use problems in this patient group.[84]

In women who have recently given birth (typically 3-10 days after birth, but it may also occur beyond 4 weeks postnatal), the first presentation of bipolar disorder may be with postnatal psychosis.[1][6]​​​ This psychiatric emergency presents as a severe episode of mania, depression, or a mixed episode accompanied by psychotic symptoms or psychosis that occurs without a mood episode.[85]

While bipolar disorders have been linked to creativity, as well as with career, educational and other achievements, most people living with bipolar disorder encounter substantial illness-related impairment and diminished psychosocial functioning.[86][87]​​ Early recognition and treatment are important, and a growing body of evidence suggests that early intervention is associated with improved outcomes.[88][89]​​​

History

Take a comprehensive current and past history and corroborate information with medical records and family interviews.[90] Collateral history is important because hypomanic and manic symptoms may be more apparent to those who are familiar with the person’s usual behaviour and levels of psychosocial functioning. Ask about current and past symptoms of mania/hypomania in line with Diagnostic and Statistical Manual of Mental Disorders (DSM-5-TR) criteria and consider the impact of symptoms on a patient's life and the pattern of mood episodes over the lifetime course to reduce the risk of missing the diagnosis.[91]

Depressive symptoms are the most common initial symptom complex reported by most patients. Differentiating bipolar from major depressive disorder may be a challenge. When evaluating a patient with a major depressive episode, for example, in primary care, establish whether a prior or current history of mania, hypomania or psychosis exist, or if there is a family history of mania or psychosis. Other clues that the diagnosis may be bipolar rather than major depressive disorder include an early age at onset (e.g., less than 20 years), high frequency of mood episodes (e.g., 3 or more previous episodes), and presence of comorbidities (e.g., substance use disorders, anxiety disorders, attention deficit hyperactivity symptoms). A lack of response to antidepressants, or worsening of anxiety and/or mood instability following antidepressant treatment, may also suggest an underlying bipolar disorder.[84]​ Given that people with bipolar disorder may present initially with depressive symptoms, clinicians should remain alert for the later development of manic or hypomanic symptoms, which would require a change of the diagnosis to bipolar disorder.[17][18]

Assess the DSM-5-TR criteria for bipolar disorder in all patients with a diagnosis of depression, a family history of bipolar disorder, or a history indicative of past episodes of increased energy and decreased sleep. Enquire about a history of elevated, expansive, or irritable mood; increased energy; decreased need for sleep; increased levels of activity; impulsivity; increased self-esteem or grandiosity; pressured speech; and increased psychomotor agitation.[1] These symptoms may have been noted by the patient themselves, or by other people who may have noted a change in the patient’s usual state of mind or behaviour. Of note, often people experiencing a manic episode do not perceive that they are ill or in need of treatment.[1]

Depression questionnaires

Options include the Primary Care Evaluation of Mental Disorders (PRIME-MD) and Patient Health Questionnaire (PHQ-9) for adults.[92][93] Screen all patients with depression for bipolar disorder prior to prescribing antidepressant therapy.

  • PRIME-MD

    • A useful tool for identifying mental disorders in primary care practice and research.

  • PHQ-9

    • A self-administered 9-item questionnaire that reflects the DSM-IV-TR criteria.

    • This questionnaire is still being used in clinical practice, despite the release of DSM-5-TR.

    • It classifies current symptoms based on duration on a scale of 0 (no symptoms) to 4 (daily symptoms).

  • PHQ-2

    • A briefer, validated version of PHQ-9, with only 2 screening questions:[94]

      • 'Over the past 2 weeks have you felt down, depressed, hopeless?'

      • 'Over the past 2 weeks have you felt little interest or pleasure in doing things?'

    • A positive response to either question warrants a thorough review of the DSM criteria, or the use of an equivalent diagnostic tool.

Mania/hypomania questionnaires

Rapid Mood Screener (RMS)

  • The RMS is a rapid (6-question) tool developed to screen for manic symptoms/bipolar I disorder features in patients presenting with a depressive episode, for example, in primary care.[95]

  • If patient answers ‘yes’ to at least 4 questions this is viewed as a positive screening result, and further assessment to determine a potential diagnosis of bipolar disorder is required.

  • A positive screening result is associated with a sensitivity of 88%, and a specificity of 80%.[95]

Mood Disorder Questionnaire (MDQ) Mood Disorder Questionnaire (MDQ) Opens in new window

  • The MDQ is a screening instrument for bipolar disorder that has been validated in a variety of populations. This self-assessment instrument includes 13 questions that ask about symptoms of mania/hypomania based on DSM-IV-TR criteria. A score of at least 7 positive responses to the 13 questions, as well as endorsing the clustering of the symptoms into an episode that caused at least moderate distress or negative consequences, is a positive MDQ screen and has been correlated with a diagnosis of bipolar disorder.[96]

  • This questionnaire is still being used in clinical practice, despite the release of DSM-5.

Bipolarity Index Bipolarity Index Opens in new window

  • This recently described system of evaluating bipolar disorder risk considers 5 dimensions of bipolarity: episode characteristics (mania or hypomania); age at onset; illness course; response to medications; family history. Each dimension is scored up to a maximum of 20 points for a maximum total score of 100. A cut-off score of ≥50 on the Bipolarity Index corresponds to a sensitivity of 0.91 and specificity of 0.90 for distinguishing bipolar from non-bipolar disorders.[97]

Young Mania Rating Scale (YMRS) Young Mania Rating Scale Opens in new window

  • A validated symptom severity scale with point-score ranges generally associated with degrees of severity. Contains 11 items scored on the basis of subjective reporting of symptoms in the previous 48 hours and clinical observations during the course of an interview.

  • Commonly used to measure changes in manic symptoms in response to treatment.[98]

Examination

Mental state examination may reveal the following symptoms, which can be present to a significant degree during a manic or hypomanic episode in bipolar disorder:[1]

  • Inflated self-esteem or grandiosity

  • Decreased need for sleep

  • More talkative than usual, or feeling pressure to keep talking

  • Flight of ideas, or subjective experience that thoughts are racing

  • Distractibility

  • Increase in goal-directed activity or psychomotor agitation (purposeless, non-goal-directed activity)

  • Excessive involvement in pleasurable activities that have a high potential for adverse consequences (e.g., engaging in unrestrained buying sprees, sexual indiscretions, or unwise business investments).

Also according to DSM-5-TR, the mood symptoms should result in functional impairment in, for example, social or occupational functions. A key distinction is made between manic and hypomanic episodes:[1]

  • With manic episodes, marked impairment or hospitalisation results

  • With hypomanic episodes, DSM criteria do not require marked impairment to occur but do require that the disturbance in mood and the change in functioning are observable by others.

Mood symptoms should not be due to substance misuse or a general medical condition (e.g., hyperthyroidism).[1] Patients with manic-like or hypomanic-like episodes clearly caused by antidepressant treatment (e.g., medication, electroconvulsive therapy, light therapy) or other prescribed medication causing secondary mania (e.g., levodopa, corticosteroid, prescribed stimulant), or non-prescribed or illicit drug use (e.g., stimulants, cocaine) should be monitored closely. If symptoms persist beyond the physiological period of effect of a substance, a diagnosis of bipolar disorder can be made.

While there are no definitive physical findings associated with bipolar disorder, a physical examination is recommended to rule out conditions that can cause or aggravate mood disorders (e.g., hypothyroidism or hyperthyroidism, central nervous system pathology such as multiple sclerosis) and to assess for common comorbid illnesses (e.g., obesity, metabolic syndrome).[99]​ Given the increased cardiovascular burden in people with bipolar disorder, with associated reduction in life expectancy of approximately 10-20 years, early integration between mental and physical health services is likely to be of benefit.[84]

Investigations

Perform simple laboratory tests to exclude other causes of mood symptoms. Initial tests include thyroid function tests, full blood count, vitamin D, and possibly a toxicology screen to assess for evidence of substances of misuse, as guided by the individual clinical picture. Order a serum glucose and lipid profile, particularly given the common co-occurrence of metabolic dysfunction in people with bipolar disorder and complications from mood-stabilising medications.[99]

For new-onset mania or atypical presentations, brain magnetic resonance imaging is recommended when there is a clinical suspicion for central nervous system pathology, such as brain tumour or multiple sclerosis; although some evidence points to non-specific whole brain and regional brain volume changes in patients with bipolar disorder, such findings are not diagnostic and should therefore not alter clinical management.[53]

Sleep disruptions are a common feature of bipolar disorders. If there is a suspicion of obstructive sleep apnoea, which is frequently comorbid with obesity, a sleep study might be recommended. A systematic review and meta-analysis of 13 studies using actigraphy to detect changes in activity and sleep patterns in people with bipolar disorder versus healthy controls showed a decrease in activity mean and an altered pattern of sleep in the bipolar patient group. Further analyses suggested that these results might mean that a bipolar condition that underlies manic, depressed episodes and euthymic phases can be identified.[100]

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