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S. Khan and J. Hassan
frequently underdiagnosed presenting symptom of multiple myeloma. A thorough
history, including the family history of the presence of multiple myeloma in families and the typical and nontypical symptoms in families, is important. Also, early
urine electrophoresis and plasma electrophoresis can prevent misdiagnosis.
References
1. Till JE, Mcculloch EA.A direct measurement of the radiation sensitivity of normal mouse
bone marrow cells. Radiat Res. 1961;14:213–22. https://doi.org/10.2307/3570892.
2. Rajkumar SV, Kumar S. Multiple myeloma: diagnosis and treatment. Mayo Clin Proc.
2016;91:101–19. https://doi.org/10.1016/j.mayocp.2015.11.007.
3. Key statistics for multiple myeloma. American cancer society [Internet] 2018. http://www.
cancer.org/cancer/multiplemyeloma/detailedguide/multiple- myeloma- key- statistics
4. Brenner H, Gondos A, Pulte D. Recent major improvement in long-term survival of
younger patients with multiple myeloma. Blood. 2008;111:2521–6. https://doi.org/10.1182/
blood- 2007- 08- 104984.
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types- of- multiple- myeloma
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Healthcare. 2013;22:64–9. https://doi.org/10.1177/201010581302200110.
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Part XII
Psychiatry
Chapter 60
Bipolar Disorder Misdiagnosed asMajor
Depressive Disorder
AemilPalm andCarlaRodriguez
Learning Objectives
By the end of this presentation, the clinician will be able to:
1. Analyze ways in which bipolar disorder can be more accurately diagnosed and
prevent misdiagnosis.
2. Discuss why bipolar disorder is often misdiagnosed or goes undiagnosed.
3. Enumerate the consequences of misdiagnosing bipolar disorder.
4. Analyze the similarities and differences between bipolar disorder and major
depressive disorder.
5. Critique the current diagnostic criteria of bipolar disorder.
Introduction
Bipolar disorder (BD) is a psychiatric affective illness characterized by moderate to
severe mood swings that mainly present themselves in denable episodes. Although
both depressive and manic episodes are possible, according to DSM V criteria, only
once a patient has presented with a manic or a hypomanic episode may they be
diagnosed with BP.A manic episode is an elevated mood state lasting for 1week
and must include at least three of the following symptoms:
A. Palm (*) · C. Rodriguez
St. Martinus University Faculty of Medicine, Willemstad, Curacao
e-mail: aemil.palm@martinus.edu; carla.rodriguez@martinus.edu
© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023
H. Tohid et al. (eds.), The Misdiagnosis Casebook in Clinical Medicine,
https://doi.org/10.1007/978-3-031-28296-6_60
443
444
A. Palm and C. Rodriguez
1. Inated self-esteem or grandiosity
2. Decreased need for sleep (e.g., feels rested after only 3h of sleep)
3. Increased talkativeness
4. Racing thoughts
5. Distractibility
6. Increase in goal-directed activity or psychomotor agitation
7. Engaging in activities that hold the potential for painful consequences, e.g.,
unrestrained buying sprees
Note that there is a subclassication in the diagnosis of bipolar disorder: bipolar
disorder II, in which hypomania is present as opposed to mania. Criteria for this
diagnosis are met when there is evidence of a milder manic episode that typically
has a shorter duration (4days or less) [1].
Approximately 2.8% of US adults have bipolar disorder, with a lifetime prevalence of 2.9% [2]. The lifetime prevalence of unipolar depression is 3.5 times greater
than bipolar depression, making it by far the more common disorder [3, 4]. The
etiology of BD is an area that requires more study. Investigation of serotonin transport genes has yielded promising results of association with BD, but more research
is required [5].
Clinical Case Presentation
A 25-year-old female presents to an outpatient department with psychiatric symptoms that have been refractory to treatment for the last 5 years. She reports difculty
expressing herself during interpersonal interactions and weeps during the
consultation.
This patient has undergone a diverse course of pharmacological treatments for
the last 3 years. These consisted of lamotrigine 100 mg/day and moclobemide
600mg/day for the last 1.5years. Despite these treatments, the patient reported no
improvement in her symptoms, including melancholy, apathy, and food aversion. In
contrast, she also felt exasperation, restlessness, and an overwhelming urge to wander outside her household, especially at night. She reported greater self-assuredness,
greater sociability, aggression, and inappropriate laughter during these periods.
The patient recalled that her symptoms arose during a sixth-grade class at school
when she had started to wear spectacles. She felt embarrassed, anhedonic, and apathetic even on joyous occasions; her appetite and sleep schedule, however, were
normal. Her symptoms worsened when she went to a university, where she reported
less free time and less social interaction fulllment. She recalled experiencing being
uncomfortable in crowded places such as lecture halls, libraries, and cafeterias.
Similar to her younger years, she felt apathy and also lethargy. In addition, she also
started to overeat, stayed in bed all day, and experienced periods of agitation. It was
at this time that a psychiatrist diagnosed her with depression and prescribed her
60 Bipolar Disorder Misdiagnosed asMajor Depressive Disorder
445
uoxetine 20 mg/day and triuoperazine 1 mg/day. She admits that she did not
consistently adhere to her medication regimen. After 1year of symptoms resistant
to medication, she sought treatment at a university’s psychiatric day outpatient
clinic, where she was given a diagnosis of bipolar disorder type II and a new regimen consisting of valproic acid 1000mg/d and sertraline 50mg/day. She adhered to
this regimen for 1 year but reported feeling too mellow and elected to stop her regimen, feeling that she no longer needed it.
Additionally, another psychiatrist claimed that she did not have bipolar disorder
(BD); they reasoned that BD is difcult to diagnose and that her previous treatment
regimen should not be changed; these conicting narratives confused the patient,
and this confusion also inuenced her decision to stop taking the drugs. After a
short time, the patient started to experience uncontrollable bouts of crying and
sought consultation with another psychiatrist who, upon hearing that she had been
previously diagnosed with BD, prescribed her lithium. Due to nausea caused by the
lithium, she also elected to stop taking lithium. Fivemonths after this, she sought
the help of yet another psychiatrist with complaints of uncontrollable crying and
general feelings of apathy. The patient was given lamotrigine and moclobemide but
failed to adhere to the treatment regimen properly; subsequently, her symptoms did
not improve.
The ndings from the psychiatric evaluation of the patient were as follows: Her
physical appearance corresponded to her biological age. She was dressed casually
with disheveled hair, she was bashful and apprehensive, and she had difculty
expressing herself. Her mental status examination revealed that she was alert and
oriented, with no apparent issues relating to attention, memory, or perception. She
had a at affect and expressed a lack of self-esteem. No psychosis or suicidal ideation was detected, and her symptoms seemed to be at least partially egodystonic. A
thorough laboratory analysis, which included thyroid tests, yielded normal results.
A brain CT yielded no abnormal ndings. The patient underwent psychometric
evaluations and received the following results: Young Mania Rating Scale, 2/60;
Hamilton Depression Rating Scale, 23/51; Avoidance Rating, 62/96; and Liebowitz
Social Phobia-Anxiety Rating, 76/96. The MMPI results described her as being
withdrawn socially with a low activity level, shy, and not being able to interact
with others.
During the evaluation, the patient expressed herself using an analogy; there were
times when she laughed for no reason, which she understood as not being very
healthy. She continued that her laughter felt like “cream on spinach” where the
cream (laughter) was “ne, but it felt very awkward because it was on spinach.”
The patient was ultimately diagnosed with “bipolar mood disorder, unspecied
type” in accordance with the DSM V criteria due to several factors: (1) onset of
symptoms during adolescence, (2) atypical depressive episodes and chronicity, (3)
psychomotor agitation, and symptoms very similar to (but not completely meeting
the criteria for) (4) hypomania. Additionally, the patient was diagnosed with a social
anxiety disorder because of her avoidant nature, anxiety symptoms in social situations (especially around strangers), and general aversion to social situations.
446
Because of other signs such as mood swings, low self-esteem, lack of meaningful
relationships, frequent change of psychiatrist, and low adherence to treatment, the
patient was evaluated for personality disorders but did not satisfy the diagnostic
criteria for any specic personality disorder. Dysthymia was also considered as a
diagnosis, but seeing as how her social phobias and antidepressant-induced hypomania could not be ruled out, it was decided that the diagnosis of bipolar was clinically satisfactory.
The diagnosis was discussed in detail with the patient, and she was advised to
take lamotrigine and moclobemide regularly. Subsequent to follow-ups, her valproic acid dosage was increased up to 1000mg/day, and her lamotrigine dosage was
halved. The patient also attended regular individual psychotherapy sessions, which
aided in the partial remission of her depressive symptoms. The patient subsequently
began to work as a private tutor for high school students, which indicates a considerable improvement in her social functioning. The patient herself stated that she
believes her issues with interpersonal communication have diminished greatly [6].
A. Palm and C. Rodriguez
Differential Diagnosis
1. Major depressive disorder—The patient presented with classic symptoms of uni-
polar depression and was even diagnosed with it initially. However, the patient
also presented with classic symptoms of (hypo)mania (psychomotor agitation,
uncontrolled laughter, grandiosity, aggressiveness), making BD the stronger
diagnosis.
2. Unspecied personality disorder—Due to low self-esteem, frequent changes of
their psychiatrist, and low medication adherence, the patient was evaluated for
personality disorders but did not meet DSM criteria for any of these.
3. Dysthymia—Although dysthymia is a good differential diagnosis, BD is a better
tting diagnosis in this case, especially because the patient’s hypomanic episodes could not be ruled out.
What WasMisdiagnosed inThis Case, andWhy?
Initially, the patient was diagnosed with depression. The depression proved to be
treatment-resistant, and the patient was diagnosed with bipolar disorder type II. Due
to conicting narratives from her psychiatrists, one of them stating that she did not
have BD and should not take medication, the patient felt confused and decided to
quit her medication regimen, at which point her symptoms worsened. Ultimately,
the patient was diagnosed with bipolar disorder: unspecied type, as well as social
anxiety disorder. The diagnosis was thoroughly discussed with the patient so as to
avoid another instance of confusion, and the patient also attended psychotherapy
sessions and followed up regularly, both of which improved her prognosis.
60 Bipolar Disorder Misdiagnosed asMajor Depressive Disorder
447
Discussion
Patients with bipolar disorder spend half of their lives symptomatic, and the majority of symptoms are depressive symptoms [7]. Bipolar disorder initially presents
with a depressive episode in up to 78.7% of cases that were initially misdiagnosed
[7, 8]. In one study (Fig. 1) with 177 patients diagnosed with BD, 136 (76.8%)
reported a previous misdiagnosis. Of the 136 misdiagnoses, the most common misdiagnosis was depression at 96 (70.6%). That means that 54.2% of bipolar patients
are likely to have been initially misdiagnosed with unipolar depression [7].
The aforementioned statistics speak to a larger issue than clinical error. In the
event that a patient who in actuality has BD presents with no detectable mania but a
depressive episode, their symptom prole would be nearly identical to a patient suffering from unipolar depression. Because of the aforementioned DSM diagnostic
criterion, which states that a manic episode must have occurred in order for a patient
to be diagnosed with BD, patients who may have BD but have not yet had a manic
episode (e.g., the aforementioned 78.7% of initially misdiagnosed patients) will not
receive the proper diagnosis. Oftentimes for these patients, the period between initial treatment and correct diagnosis can last more than 10years [9, 10].
40 patients
(22.6%)-
Misdisgnosed
with other
psychiatric
disorders
41 patients (23.2%)Correctly diagnosed
with bipolar disorder
Fig. 60.1 Distribution of bipolar patients who were misdiagnosed and correctly diagnosed [7]
96 patients
(54.2%)-
Misdiagnosed
with deprerssion
448
A. Palm and C. Rodriguez
Plan ofAction, Points theClinician Should Consider, Pitfalls
toAvoid, andPearls ofKnowledge toConsider
1. The clinician should be alert to any symptoms the patient describes that point
toward mania. Even if the patient is presenting in a depressive state, the clinician
should inquire if the patient has had any episodes of markedly elevated mood,
decreased need for sleep, hypersexuality, or impulsivity [1].
2. Patients with bipolar disorder tend to have a family history of psychiatric disor-
ders. The clinician should inquire about psychiatric illness in the patient’s family. Additionally, the clinician should also inquire about the patient’s interpersonal
relationships and social network [8, 11, 12].
3. Bipolar patients tend to have more incidents of psychiatric hospitalizations than
unipolar depression patients. The clinician should inquire about any previous
psychiatric hospitalizations [8, 10–12].
4. The mean age of onset in bipolar disorder is younger (22years) than in unipolar
depression (26years) [4, 8, 11, 12].
5. Bipolar patients tend to have a history of treatment-resistant depression [8, 12].
Conclusion
Bipolar disorder is often initially misdiagnosed as major depressive disorder (unipolar depression), leading to unrealistic expectations regarding prognosis and incorrect pharmacotherapy. Current diagnostic criteria are not sophisticated or nuanced
enough to differentiate major depressive disorder from a suspected case of bipolar
disorder without previous manic episodes. Therefore, careful history-taking combined with psychometric analysis and consistent patient follow-ups are vital in
detecting potentially misdiagnosed cases.
References
1. Diagnostic and statistical manual of mental disorders (5th ed.). American Psychiatric
Association; 2013.
2. Bipolar disorder. National Institute of Mental Health. 2009. https://www.nimh.nih.gov/health/
topics/bipolar- disorder
3. Sidor MM, MacQueen GM.Antidepressants for the acute treatment of bipolar depression: a
systematic review and meta-analysis. J Clin Psychiatry. 2011;72(2):156–67.
4. Zisook S, Lesser I, Stewart JW, Wisniewski SR, Balasubramani GK, Fava M, Gilmer WS,
Dresselhaus TR, Thase ME, Nierenberg AA, Trivedi MH, Rush AJ.Effect of age at onset on
the course of major depressive disorder. Am J Psychiatry. 2007;164(10):1539–46.
5. D; SADADR. HTR2A gene variants and psychiatric disorders: a review of current literature and selection of snps for future studies. Curr Med Chem. https://pubmed.ncbi.nlm.nih.
gov/17691947/
6. Kocbiyik, S., Batmaz, S. and Turhan, L.A case in the bipolar spectrum. Ncbi; 2022.
60 Bipolar Disorder Misdiagnosed asMajor Depressive Disorder
7. Shen H, Zhang L, Xu C, Zhu J, Chen M, Fang Y.Analysis of misdiagnosis of bipolar disorder in an outpatient setting. Shanghai archives of psychiatry. https://pubmed.ncbi.nlm.nih.
gov/29736129/. Published April 25, 2018.
8. Hirschfeld RM. Differential diagnosis of bipolar disorder and major depressive disorder. J
Affect Disord. https://www.sciencedirect.com/science/article/pii/S0165032714700047?via%3
Dihub. Published December 19, 2014.
9. Zimmerman M, Morgan TA. The relationship between borderline personality disorder and
bipolar disorder. Dialogues Clin Neurosci. 2013;15(2):155–69.
10. Hirscheld RM, Lewis L, Vornik LA.Perceptions and impact of bipolar disorder: how far have
we really come? Results of the national depressive and manic-depressive association 2000
survey of individuals with bipolar disorder. J Clin Psychiatry. 2003;64(2):161–74.
11. Fiedorowicz JG, Black DW.Borderline, bipolar or both? Frame your diagnosis on patient history. Curr Psychiat. 2010;9(1).
12. Goodwin FK, Jamison KR.Manic-depressive illness: bipolar disorders and recurrent depression. 2nd ed. NewYork, NY: Oxford University Press; 2007.
449
Chapter 61
Schizoaffective Disorder Bipolar Type
Misdiagnosed asBipolar IwithPsychotic
Features
JonathanSeok
Learning Objectives
By the end of this presentation, the clinician will be able to:
1. Create an appropriate differential diagnosis in patients presenting with schizoaffective disorder (SZA) by considering all relevant details of the medical history
together with proper SZA screening and diagnostic tools.
2. Enumerate the new parameters of the DSM-5in order to discuss both the changes
made and how it assists providers in making the correct diagnosis of SZA.
3. Evaluate the different components of the medical history and physical examination which indicate the most appropriate screening and diagnostic tools so the
most correct course of further diagnostic procedures needed to reach a denitive
diagnosis can be reached.
4. Appreciate the consequences of a misdiagnosis or delay in reaching a correct
diagnosis for the individual patient prognosis.
5. Discuss the relationship between bipolar type 1 disorder with psychotic features
and SZA to correctly diagnose SZA between the two.
6. Apply the knowledge gained from the case in a clinical setting where appropriate.
J. Seok (*)
St. Martinus University Faculty of Medicine, Willemstad, Curacao
e-mail: jonathan.seok@martinus.edu
The Author(s), under exclusive license to Springer Nature Switzerland AG 2023
©
H. Tohid et al. (eds.), The Misdiagnosis Casebook in Clinical Medicine,
https://doi.org/10.1007/978-3-031-28296-6_61
451