Secondary mood syndrome

ICD-10F06.3	Organic mood [affective] disorders
DSM-5-TRF06.3x	Depressive Disorder Due to Another Medical Condition

1. Definition and nosology

Secondary mood syndrome (ICD-11: 6E62; DSM-5-TR: F06.3x Mood Disorder Due to Another Medical Condition) — depressive, manic, or mixed mood episodes as a direct physiological consequence of another medical condition.

2. History

The term “Organic Affective Disorder” belongs to the 20th century; current clinical practice has moved toward the biopsychosocial model.

3. Epidemiology

• Depressive symptoms are prevalent in chronic medical conditions; some meet criteria for clinical depressive episode.
• Steroid-induced mood disorders — high-dose prednisone 5–18% mania/hypomania, depression.
• Interferon-induced depression — 20–40% in HCV treatment.
• Post-stroke depression — 30%.

4. Etiology and pathogenesis

• Endocrine — hypothyroid (depression), hyperthyroid (mania-like), Cushing, Addison.
• Neurological — stroke (left frontal — depression, right — mania), Parkinson’s, MS, brain tumor, dementia, TBI.
• Substance/medication — steroids, interferon, dopamine agonists, isotretinoin, β-blocker, anticonvulsant.
• Metabolic — uremia, B12, folate.
• Infectious — HIV, syphilis, COVID.
• Autoimmune — lupus, Hashimoto.
• Oncology — pancreatic cancer (classic depressive presentation), paraneoplastic.

5. Clinical features

• Symptoms of depressive, manic, mixed, and hypomanic episodes.
• Medical condition or substance-related temporal association.
• Features not characteristic of classic affective disorder (late onset, atypical presentation).

6. Diagnosis

6.1 Unified diagnostic criteria

A. Persistent mood disturbance (depressive, manic, or mixed).

B. Evidence of a medical condition (non-psychiatric).

C. Not better explained by a primary affective disorder.

D. Does not occur in the context of delirium

6.2 Differences between sources

• ICD-11 — a substance-induced mood disorder does NOT belong here: it lives in the substance chapter. 6E62 covers only health conditions outside the mental-disorders chapter and is assigned alongside the diagnosis of the underlying disease.
• Consultation-liaison protocols.

6.3 Diagnostic algorithm

1. Clinical interview + medical history.
2. Medical and laboratory assessment (TSH, B12, cortisol, renal, hepatic).
3. Medication list review.
4. Brain imaging (stroke, MS, tumor).
5. Toxicology.
6. Comorbid disorders.

6.4 Differential diagnosis

7. Examination and assessment

• PHQ-9, MADRS, YMRS.
• Laboratory: TSH, B12, cortisol, ANA, kidney, liver.
• MRI in atypical cases.
• C-SSRS.

8. Treatment

1. Etiological treatment — correction of medical condition or medication.
2. Symptomatic psychiatric treatment:
   • Depressive — SSRIs (disease-specific selection; cardiac — sertraline, escitalopram; oncology — mirtazapine);
   • Manic — antipsychotic (quetiapine, olanzapine); in steroid-induced mania, taper steroids or use antipsychotic;
   • Mixed or refractory — ECT. Multidisciplinary approach — psychiatrist, the specialist treating the underlying illness, and social support.

8.1 Treatment methods

1. SSRI Illness-Specific — Choice appropriate to cardiac, oncological, neurological context.
2. ECT — In refractory and severe cases.

9. Prognosis

Most remissions with etiological intervention.

10. Myths and misconceptions

Myth 1: “Depression is ‘normal’ for a patient with a medical illness”

Evidence: Clinical depression worsens the course of the medical condition; requires active intervention.

Myth 2: “Steroid-induced mania resolves on its own”

Evidence: dose reduction or antipsychotic addition required.

Myth 3: “Antidepressant is first-line in hypothyroidism”

Evidence: thyroid correction first; antidepressants for residual symptoms.

Myth 4: “Interferon depression is rare”

Evidence: HCV interferon therapy 20–40% — active monitoring required.

11. Sources

1. WHO. ICD-11. 6E62 Secondary mood syndrome. 2024.
2. APA. DSM-5-TR. 2022.
3. Levenson J.L. (ed.). APA Publishing Textbook of Psychosomatic Medicine and Consultation-Liaison Psychiatry. 3rd ed. 2018.
4. Robinson R.G., Jorge R.E. Post-stroke depression: a review. Am J Psychiatry 2016;173(3):221–231.