Tips and pearls

A majority of bipolar patients spend much more time depressed than manic

The depressive component of bipolar disorder is often the most disabling cumulatively over time

Therefore, reasonable yet aggressive treatment of depressed phase symptomatology is warranted

Bipolar I treatment guidelines often suggest

• – Always use a mood stabilizer or approved atypical antipsychotic

• – If bipolar depression occurs, use an approved bipolar depression-specific treatment

  • These often act as an antidepressant but with the least risk of manic escalation

  • Examples include olanzapine–fluoxetine combination (Symbyax), quetiapine (Seroquel), quetiapine-XR (Seroquel-XR), lurasidone (Latuda)

  • These often carry significant side effects such as metabolic and movement disorders

  • The atypical antipsychotics appear to be more antidepressant-like at lower doses and more antimanic- or antipsychotic-like at middle to higher doses

    • This likely occurs due to the fact that D2 receptor affinity is lower compared to the serotonin receptor affinities of the atypical antipsychotics

• – Unipolar antidepressants may be used in the presence of an adequately dosed mood stabilizing agent

  • Must be dosed slowly and emergence of mania closely monitored

Conservatively, these guidelines should likely be utilized when treating bipolar II patients as well

Some bipolar II patients will escalate to bipolar I disorder, and therefore, following good mood stabilization guidelines may help to lower this risk of disease progression

Two-minute tutorial

What is the bipolar spectrum?

Based on Akiskal and Pinto’s work,¹ clinicians might encounter patients meeting formal DSM-5 diagnostic criteria noted as bipolar I or II or unspecified

• – Otherwise, the following expanded system of bipolar spectrum symptom presentations might afford better classification and communication while treating these patients

• – Ultimately, it must be assumed that if a patient enters in the weaker, less severe end of the spectrum, they could escalate toward the more severe end without treatment or with the administration of noncompliant or reckless prescribing practices

• – Therefore, despite the classification system used, the primary goal should be mood stabilization

First, some unipolar patients may have soft symptoms suggestive of future bipolarity where they report

• – Their mood often changes, happiness to sadness, with and without social reasons or stressors

• – They have frequent ups and downs in mood, with and without apparent cause

• – They often feel guilty without a good reason

• – Their feelings are rather easily hurt

• – They often feel as though their future looks dark

• – Ideas run through their minds so that they cannot sleep

• – They often find it difficult to go to sleep because of thinking about what happened during the day

• – They often feel disgruntled

  • In retrospect, the patient in this case experienced many of these during his pre-bipolaring or prodromal phase

Second, a more formal operationalizing of the bipolar spectrum of disorders may be, theoretically, as follows

• – Bipolar I: full mania with full MDEs (like the DSM-5 disorder)

• – Bipolar I and ½: depression with protracted hypomania (similar to the DSM-5’s cyclothymic disorder but with associated full MDEs instead of minor depressive episodes

• – Bipolar II: depression with hypomania (like the DSM-5 disorder)

• – Bipolar II and ½: cyclothymic depressions (similar to the DSM-5 cyclothymic disorder)

• – Bipolar III: antidepressant-induced mania (similar to this case initially where short and less severe manias were precipitated by SSRI use)

  • In the DSM-5, an antidepressant-induced (hypo)mania is no longer considered a drug-induced side effect but is, in fact, counted toward a bona fide bipolar I or II disorder

• – Bipolar III and ½: bipolarity masked – and unmasked – by stimulant abuse (self-explanatory)

• – Bipolar IV: hyperthymic depression (patients with persistent depressive disorder [dysthymia] but underlying traits of a hyperthymic temperament)

  • This latter temperament suggests that certain personality traits may lend to the development of bipolarity or be prodromal

  • Hyperthymic temperament or personality traits might include

    • Increased energy and productivity

    • Short sleep patterns

    • Vivid, active, extroverted behavior

    • Self-assured/self-confidence

    • Strong willed

    • Extremely conversational

    • Tendency to repeat oneself

    • Risk taking/sensation seeking

    • Breaking social norms of others

    • Strong libido

    • Attention loving

    • Low threshold for boredom

    • Generous and spendthrift

    • Emotion sensing

    • Cheerful and jovial

    • Unusual warmth

    • Expansiveness

    • Robust tirelessness

    • Irrepressible, infectious quality in interpersonal interactions

Of note is the new DSM-5 mixed features specifier. If during the course of Bipolar 1 or 2 (hypo)mania, the patient experiences three or more depressive disorder symptoms, they are said to meet this specifier. In theory, this could occur in any of the bipolar spectrum areas noted above

Posttest self-assessment question and answer

If a manic spell is instigated by initiation of an antidepressant, which of the following is likely to happen?

A. The induced mania will be more severe

B. The induced mania will last longer

C. The induced mania will be less severe and shorter in duration

D. None of the above

Answer: C

Available data is minimal but suggests that antidepressant-induced mania is often less severe and of a shorter duration, assuming the offending antidepressant is stopped.

References

1.Akiskal HS, Pinto O.The evolving bipolar spectrum: prototypes I, II, III, and IV. Psychiatr Clin North Am 1999; 22:517–34.

2.Doran CM. The Hypomania Handbook: The Challenge of Elevated Mood. Philadelphia, PA: Lippincott Williams & Wilkins, 2007.

3.Stoll AL, Mayer PV, Kolbrener M, et al. Antidepressant-associated mania: a controlled comparison with spontaneous mania. Am J Psychiatry 1994; 151:1642–5.

4.Parker G, Parker K. Which antidepressants flick the switch? Aust NZ J Psychiatry 2003; 37:464–8.

5.Wehr TA, Goodwin FK. Can antidepressants cause mania and worsen the course of affective illness? Am J Psychiatry 1987; 144:1403–11.

6.Leverich GS, Altshuler LL, Frye MA, et al. Risk of switch in mood polarity to hypomania or mania in patients with bipolar depression during acute and continuation trials of venlafaxine, sertraline, and bupropion as adjuncts to mood stabilizers. Am J Psychiatry 2006; 163:232–9.

7.Amsterdam JD, Shults J. Efficacy and safety of long-term fluoxetine versus lithium monotherapy of bipolar II disorder: a randomized, double-blind, placebo-substitution study. Am J Psychiatry 2010; 167:792–800.

8.Frye MA, Helleman G, McElroy SL, et al. Correlates of treatment-emergent mania associated with antidepressant treatment in bipolar depression. Am J Psychiatry 2009; 166:164–72.

9.Suppes T. Is there a role for antidepressants in the treatment of bipolar II depression? Am J Psychiatry 2010; 167:738–40.

10.Akiskal HS, Hantouche EG, Allilaire JF, et al. Validating antidepressant-associated hypomania (bipolar III): a systematic comparison with spontaneous hypomania (bipolar II). J Affect Disord 2003; 73:65–74.

11.Depue RA, Slater JF, Wolfstetter-Kausch H, et al. A behavioral paradigm for identifying persons at risk for bipolar depressive disorder: a conceptual framework and five validation studies. J Abnorm Psychol 1981; 90:381–437.

12.Taylor L, Faraone SV, Tsuang MT. Family, twin, and adoption studies of bipolar disease. Curr Psychiatry Rep 2002; 4:130–3.

13.Craddock N, Jones I. Genetics of bipolar disorder. J Med Genet 1999; 36:585–94.

14.Mortensen PB, Pedersen CB, Melbye M, Mors O, Ewald H. Individual and familial risk factors for bipolar affective disorders in Denmark. Arch Gen Psychiatry 2003; 60:1209–15.

15.Twiss J, Jones S, Anderson I. Validation of the mood disorder questionnaire for screening for bipolar disorder in a UK sample. J Affect Disord 2008; 110:180–4.

16.Rice JP, McDonald-Scott P, Endicott J, et al. The stability of diagnosis with an application to bipolar II disorder. Psychiatry Res 1986; 19:285–96.

17.Schwartz TL, Stahl SM. Treatment strategies for dosing the second generation antipsychotics. CNS Neurosci Ther 2011; 17:110–17.

18.Hantouche EG, Angst J, Akiskal HS. Factor structure of hypomania: interrelationships with cyclothymia and the soft bipolar spectrum. J Affect Disord 2003; 73:39–47.

¹ See References.

Patient file

The Case:

The patient who was not lyming

The Question:

Can Lyme disease cause depression?

The Dilemma:

Managing depression and possible neuropsychiatric illness

Pretest self-assessment question (answer at the end of the case)

Regarding Lyme disease as a neuropsychiatric illness, which is most accurate?

A. Almost all patients bitten by infected Lyme disease-carrying ticks will develop an easily diagnosable rash

B. Once bitten, most patients will develop clinical Lyme disease

C. Depression as a result of Lyme disease infection is a common clinical presentation

D. Blood antibody testing is often a definitive diagnosis and should be followed by antibiotic treatment