Bipolar and Related Disorders, Unspecified
(formerly Bipolar Disorder NOS)

Bipolar and Related Disorders, Unspecified is a diagnostic category defined in the DSM-5 that encompasses all mood manifestations with bipolar features that do not fully meet the criteria for any specific bipolar disorder.
This category replaces the former Bipolar Disorder Not Otherwise Specified (NOS) from the DSM-IV-TR, a term still frequently used in current clinical practice.

It includes patients with mixed, hypomanic, or atypical depressive episodes, or with rapid and irregular mood fluctuations that do not fulfill the duration, number, or intensity criteria required for a diagnosis of Bipolar I Disorder, Bipolar II Disorder, or Cyclothymic Disorder.

Etiology and Risk Factors

The causes of unspecified bipolar disorder are similar to those of major bipolar disorders and include genetic, neurobiological, and environmental factors. However, the incomplete or atypical nature of the symptomatology prevents classification into standard forms.

At the neurobiological level, dysfunction of the serotonergic, dopaminergic, and noradrenergic systems is hypothesized, with alterations in the prefrontal cortex, limbic system, and basal ganglia circuits. In some cases, undiagnosed underlying organic factors may be involved.

Main risk factors include:

• Family history of bipolar or other mood disorders
• Early onset of atypical affective symptoms
• Childhood trauma or acute psychosocial stress
• Use of psychoactive substances or chronic alcohol abuse
• Presence of unstable personality traits (e.g., borderline, histrionic)

Clinical Manifestations and Diagnosis

The clinical picture is heterogeneous and often elusive. Possible presentations include:

• Rapid or ultra-rapid mood shifts not classifiable as defined episodes
• Isolated hypomanic phases not followed by depression
• Persistent affective instability with alternating expansiveness and melancholy
• Chronic depressive symptoms with atypical features (e.g., hypersomnia, hyperphagia, marked irritability)

Symptoms do not suffice for diagnosing a major depressive, manic, or hypomanic episode, or the episode duration is too brief. Nevertheless, subjective distress and functional impairment may be considerable.

Bipolar and Related Disorders, Unspecified (DSM-5) is a residual category used when mood alteration symptoms are clearly bipolar in nature but do not fully meet criteria for any of the specific disorders (Bipolar I, II, or Cyclothymia).

This is a diagnosis of exclusion and may be applied in the following situations:

• Presence of manic, hypomanic, or depressive symptoms causing significant distress or functional impairment, but not fully meeting criteria for a specific bipolar disorder.
• Presence of rapid or ultra-rapid mood shifts over a short time span, without meeting duration criteria.
• Presence of recurrent hypomanic episodes without documented major depressive episodes (thus not qualifying for Bipolar II).
• Presence of subthreshold bipolar symptoms (e.g., hypomanic or atypical depressive symptoms) in individuals with a family history or personal history of mood disorders, but no defined episode.
• Presence of bipolar-like symptoms attributable to unclear clinical contexts or situations with insufficient information (e.g., emergencies, initial clinical observation, communication difficulties).

This diagnosis can also be used when the clinician suspects a bipolar syndrome, but the symptoms are atypical, incomplete, or not yet evolved into a clearly defined picture.

According to the DSM-IV-TR, this condition was labeled Bipolar Disorder Not Otherwise Specified (NOS), a designation still commonly used in clinical practice, particularly in health information systems and documentation in Italy.

• Duration or quantitative criteria for mood episodes are not fully met
• The presentation is strongly suggestive of bipolar disorder but atypical, inconsistent, or incomplete
• No other diagnosis is more appropriate (e.g., cyclothymia, major depressive disorder, borderline personality disorder)

Helpful tools may include the Hypomania Checklist (HCL-32), MOODS-SR, or the Questionnaire for Bipolar Spectrum Disorders to detect latent cyclic patterns.

Treatment, Prognosis, and Complications

Treatment must be individualized. Mood stabilizers commonly used include:

• Lithium
• Anticonvulsants (e.g., valproate, lamotrigine)
• Atypical antipsychotics (e.g., quetiapine, aripiprazole) in markedly unstable forms

Antidepressants should be used cautiously and only in combination with a mood stabilizer to prevent switching to mania or mood instability.

Cognitive-behavioral therapy and psychoeducation are often supportive, especially in cases with poor illness awareness.

Prognosis is variable and depends on the nature of the symptoms, early diagnosis, and response to treatment. In most cases, unspecified bipolar disorder represents an initial or atypical form that may evolve over time into a more defined condition (Bipolar I, II, or Cyclothymia).

Suicide risk may be present and should not be underestimated. Treatment adherence is often hindered by the unstable nature of the disorder and low insight.

Common complications include:

• Progression to major bipolar disorders (I or II)
• Substance abuse as a form of self-medication
• Relational and occupational difficulties due to affective instability
• Comorbidity with personality disorders (especially borderline)

Early diagnosis and integrated management are essential to minimize clinical impact and prevent worsening of the disorder.

References
1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). American Psychiatric Publishing. 2013.
2. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR). American Psychiatric Publishing. 2000.
3. Vieta E, et al. Bipolar disorders. Nature Reviews Disease Primers. 2018;4:18008.
4. Grande I, et al. Bipolar disorder. The Lancet. 2016;387(10027):1561-1572.
5. McIntyre RS, et al. Measurement-based care in bipolar disorder: A systematic review. Canadian Journal of Psychiatry. 2017;62(8):556–565.
6. Kessing LV, et al. The bipolar spectrum: a clinical reality or a disordered construct? Current Psychiatry Reports. 2015;17(3):33.
7. Carvalho AF, et al. The bipolar spectrum: critical appraisal of a still-dormant concept. Current Psychiatry Reports. 2014;16(11):519.
8. Phillips ML, et al. Neuroimaging in bipolar disorder: a critical review. Current Psychiatry Reports. 2015;17(11):77.
9. Goodwin FK, Jamison KR. Manic-Depressive Illness: Bipolar Disorders and Recurrent Depression. Oxford University Press. 2007.
10. Baldessarini RJ, et al. Illness risk following initial hypomanic episodes: prospective follow-up of 40 first-episode patients. Journal of Affective Disorders. 2014;158:410–415.