Recognizing and Treating Prodrome in Bipolar Disorder

Recognizing and Treating Prodrome in Bipolar Disorder
Recognizing and Treating Prodrome in Bipolar Disorder

Bipolar disorder is a chronic, episodic, progressive illness.1 Each episode substantially increases the risk that another will occur and will be less responsive to treatment than previous episodes, leading to a progressive degeneration in functionality, neurocognition, and quality of life, [McIntyre, 2011] and to an increased risk of suicide.2 Intervening prior to an episode (either the first episode, or an episodic relapse) can therefore mitigate disease progression.

One of the most significant impediments to first-episode prevention is the underdiagnosis of bipolar disorder.3  Since most patients initially present during a depressive episode, the disorder is frequently misdiagnosed as unipolar depression,4 resulting in a missed opportunity for appropriate intervention.

A second frequently missed "window" of early intervention involves relapse prevention. Bipolar disorder was once thought to consist of discrete episodes of mania or depression, with intervening periods of euthymia. But it is now understood that even during inter-episode periods, subsyndromal symptoms (e.g., emotional dysregulation, sleep and circadian rhythm disturbances, cognitive impairment, and increased risk for psychiatric and medical comorbidity) continue to exist,5  progressing to prodrome and increased relapse risk.

In their article "Is There a Clinical Prodrome of Bipolar Disorder: A Review of the Evidence,"6 Martin and Smith analyze the characteristics of bipolar prodrome, focusing on interventions at critical junctures so the prodrome does not develop into an acute episode.

Differentiating Between Unipolar and Bipolar Depression

Historically, unipolar and bipolar depression were regarded as identical. However, they may actually represent two distinct clinical entities.6 Unipolar depression tends to present with symptoms of excessive self-reproach, anergia, decreased libido, initial insomnia, weight loss, normal or low activity levels, somatic complaints, tendency to blame others, and anxiety. Bipolar depression, on the other hand, can present with psychotic features, diurnal mood variations, and hypersomnia. Additionally, individuals with BD may experience increased number and shorter duration of depressive episodes, abrupt onset and discontinuation, leaden paralysis, psychomotor retardation, lability of mood, and pathological guilt.6 There are also differences in memory and executive function: unipolar depression is characterized by impaired attention, mental processing speed, and mental flexibility, while bipolar disorder is characterized by deficits in sustained attention, verbal recall, memory, verbal fluency, and emotion-dependent cognitive processing. 6

Commonly Reported Prodromal Symptoms of BD

Patients with bipolar disorder commonly experience subthreshold symptoms, which increase during a prodrome and are also associated with significant functional decline.7 They are summarized in Table 1.

Table 1: Commonly Reported Prodromal Symptoms of Bipolar Disorder

Subthreshold Manic Symptoms

Subthreshold Depressive Symptoms

Other Prodromal Symptoms

· Elevated/irritable mood (>6 hours/day)

· Racing thoughts

· Rapid speech

· Increased energy

· Reckless/dangerous behavior

· Depressed mood (>6 hours/day)

· Anhedonia

· Self-harm

· Suicidal thoughts

· Mood swings

· Sleep disturbances

· Anxiety

· Functional decline

· Decreased concentration

· Social isolation

· Appetite changes

· Hearing voices

Recognizing an Incipient Prodrome

It is important to be alert to signs of incipient prodrome both before a formal diagnosis of bipolar disorder and when there is an already established diagnosis. Early personality or temperamental traits (e.g., childhood irritability or dyscontrol) may be predictors of later development of bipolar disorder,6 gradually increasing in number, frequency, and severity before the first manic episode. These should be monitored closely. Beyond the classic hypomanic symptoms described above, each individual may have his or her own unique set of idiosyncratic warning signs.8  It can be helpful for patients to create a "relapse profile" consisting of potential triggers, early warning signs, and prevention strategies.9

Staging and Screening Instruments

Although clinical screening tools have been designed to screen for full disorder, they may be potentially useful as an adjunct to clinical assessment in early-stage bipolar disorder.6 Tools include the Hypomania Checklist-32, which helps discriminate between bipolar disorder and major depressive disorder (MDD),10 the Mood Disorder Questionnaire (MDQ),11 and the Bipolar Spectrum Diagnostic Scale (BSDS).12

Treatment of Prodromal Bipolar Disorder

Long-term pharmacotherapy should be initiated after a single manic episode, together with psychosocial support.6 Lithium monotherapy is a first-line treatment, effective against both manic and depressive relapse. Combination treatment is recommended when monotherapy fails or subsyndromal symptoms are ongoing. Adjunctive antimanic agents (e.g., valproate and/or antipsychotics] for manic symptoms, and lamotrigine or quetiapine for predominantly depressive symptoms should be utilized.6 Antidepressant monotherapy is not recommended, due to increased risk of manic switch. Helpful nonpharmacologic interventions include cognitive behavioral therapy (CBT) and psychoeducation.6

The authors conclude, "a substantial and growing body of evidence exists that bipolar disorder . . . has a number of early clinical, biological, and neuropsychological features, which may represent a prodromal state and predict onset of the disorder." They note that early diagnosis and treatment of BD may introduce "stigmatization and unnecessary side effects from the use of potentially harmful psychotropic medication." However, "the benefits of robust early identification and intervention services are likely to outweigh these possible disadvantages."


1.    McIntyre RS. Long-term treatment of bipolar disorder in adults. J Clin Psychiatry. 2011;72(2):e06.

2.    Howes OD, Falkenberg I. Early detection and intervention in bipolar affective disorder: targeting the development of the disorder. Curr. Psychiatry Rep. 2011;13(6), 493–499.

3.    Smith DJ, Ghaemi N. Is underdiagnosis the main pitfall when diagnosing bipolar disorder?BMJ. 2010;340:c854.

4.    Angst J, Azorin J-M, Bowden CL, et al. Prevalence and Characteristics of Undiagnosed Bipolar Disorders in Patients With a Major Depressive Episode. Arch Gen Psychiatry. 2011;68(8):791-799.

5.    Leboyer M, Kupfer DJ. Bipolar disorder: new perspectives in health care and prevention. J Clin Psychiatry. 2010;71(12):1689-1695

6.    Martin DJ, Smith DJ. Is there a clinical prodrome of bipolar disorder? A review of the evidence. Expert Rev Neurother. 2013;13(1):81-98.

7.    Skjelstad DV, Malt UF, Holte A. Symptoms and signs of the initial prodrome of bipolar disorder: a systematic review. J. Affect. Disord. 126(1–2), 1–13 (2010).

8.    Morriss R. The early warning symptom intervention for patients with bipolar affective disorder. Adv Psychiatr Treat. 2004;10:18-26.

9.     Perugi G, Fornaro M, Marennani I, et al. Discriminative hypomania checklist-32 factors in unipolar and bipolar major depressive patients. Psychopathology. 2012;45(6):390-398.

10. Mitchell PB, Ball JR, Best JA, et al. The management of bipolar disorder in general practice. Med J Aust. 2006;184(11):566-570.

11. Hirschfeld RMA. et, al. Development and validation of a screening instrument for bipolar spectrum disorder: The Mood Disorder Questionnaire. Am J Psychiatr. 2000, 157:1873-1875.

12. Ghaemi NS, Miller CJ, Berry DA. Sensitivity and specificity of a new bipolar spectrum diagnostic scale. J Affect Disord. 2005 Feb;84(2-3):273-297.

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