ICD-116A71	RECURRENT DEPRESSIVE DISORDER Recurrent depressive disorder
ICD-10F33	Recurrent depressive disorder
DSM-5-TRF33.x	Major Depressive Disorder, Recurrent Episode

1. Definition and nosology

Recurrent depressive disorder (ICD-11: 6A71 Recurrent Depressive Disorder; DSM-5-TR: Major Depressive Disorder, Recurrent — F33.x) — presence of at least two major depressive episodes, with partial or full remission lasting at least 2 months between episodes. No history of manic or hypomanic episodes (if present, diagnosis is bipolar disorder).

Differs from single episode depressive disorder (6A70) only by number of episodes; clinical manifestations, diagnostic criteria, and treatment principles are identical, but long-term maintenance pharmacotherapy plays a more important role here.

2. History

• Kraepelin (1899) — Within the framework of manic-depressive disorder, recurrent depressive episodes.
• Leonhard K. (1957) — concept of unipolar depression.
• DSM-III (1980), DSM-5 (2013) — Major Depressive Disorder, Recurrent official designation.
• ICD-11 (2019) — Single episode (6A70) and Recurrent (6A71) are coded separately.

3. Epidemiology

• Major depressive disorder lifetime prevalence 15–20%; of which ~50–80% have a recurrent course.
• The risk of a subsequent episode increases after each episode (Solomon D.A. et al. Am J Psychiatry 2000) — ~50% after the 1st episode, ~70% after the 2nd, ~90% after the 3rd.
• Suicide risk higher than in single episodes, particularly in untreated episodes.

4. Aetiology and pathogenesis

• Same as single episode (6A70) — heritability ~35–40% (Sullivan 2000); GWAS loci.
• Relapse predisposition — predominantly cognitive predisposition, neurobiological “kindling” (Post R.M.) concept — threshold decreases for the next episode after each one.
• Risk factors — childhood trauma, family history, chronic stress, comorbid anxiety, somatic illness.

5. Clinical features

Same as a single episode (see 6A70 §5). In recurrent patients, additional features:

• Episode presentation may change from previous episodes (atypical features, seasonal pattern).
• Recurrent episodes typically begin more rapidly than previous ones (kindling concept — Post R.M. Am J Psychiatry 1992).
• Comorbid anxiety disorders with increased frequency.
• Chronic cognitive deficits may be observed (especially after multiple episodes).

6. Diagnosis

6.1 Unified diagnostic criteria (DSM-5-TR · ICD-11)

A. At least 2 major depressive episodes (according to 6A70 §6.1 criteria).

B. ≥ 2 months partial or full remission between episodes.

C. Never had a manic or hypomanic episode.

D. Not better explained by schizoaffective, schizophrenia or other psychotic disorder.

6.2 Source-specific clarifications

• ICD-11: current episode severity (mild, moderate, severe) and psychotic feature qualifiers; remission status (partial, full).
• DSM-5-TR: qualifiers are the same as 6A70.
• NICE NG222: ≥3 episodes — MBCT (Mindfulness-Based Cognitive Therapy) is specifically recommended for relapse prevention in patients.

6.3 Diagnostic algorithm

1. History — number of previous episodes, duration, triggers, quality of remission.
2. Bipolar screening (MDQ, HCL-32) — to rule out hypomanic episodes.
3. PHQ-9 / HAM-D / MADRS — severity of current episode.
4. C-SSRS — suicide risk (high in recurrent patients).
5. Laboratory (thyroid, B12, folate, ferritin); somatic comorbidity assessment.

6.4 Differential diagnosis

Same as 6A70 (see single episode). Special attention — exclude bipolar episodes.

7. Examination and assessment

Same as 6A70. Special attention — assessment of cognitive deficits (after multiple episodes).

8. Treatment

8.1 General Principles (NICE NG222 · APA 2010 · CANMAT 2016)

1. Acute episode treatment — Same as 6A70 (SSRI, CBT, combination).
2. Maintenance pharmacotherapy — long-term.
   • After 2 episodes — continue for 1–2 years after remission.
   • ≥3 episodes — long-term (years) or lifelong maintenance.
   • Effective antidepressant is maintained at the same dose after remission (dose reduction increases relapse risk).
3. MBCT (Mindfulness-Based Cognitive Therapy) — comparable effect to antidepressant continuation for relapse prophylaxis in patients with ≥3 episode history (Kuyken W. et al. Lancet 2015).
4. Lithium adjunct — in refractory or high relapse risk patients; suicide reduction effect (Cipriani BMJ 2013).
5. Recognition of relapse markers — psychoeducation for patient and family (sleep disturbance, irritability, social withdrawal, anhedonia).
6. Comorbidity treatment — anxiety disorders, substance use, cardiovascular — parallel.
7. Suicide risk monitoring — high, particularly at onset of new episode.

8.2 Source-specific clarifications

• NICE NG222 (2022): ≥3 episode history — MBCT or antidepressant maintenance; both are comparably effective.
• APA 2010: maintenance pharmacotherapy after ≥ 2 episodes; long-term after ≥ 3 episodes.
• Geddes J.R. et al. Lancet 2003 meta-analysis: Antidepressant continuation significantly superior to placebo in relapse reduction (NNT 5).

Treatment methods

1. Mindfulness-Based Cognitive Therapy (MBCT) — 8-week group program; 2.5-hour sessions + home practice. Effective in relapse prevention for patients with history of ≥3 episodes. RCT: Kuyken W. et al. Lancet 2015. mbct.com.
2. Antidepressant Maintenance Therapy — Long-term use with the same drug and dose; at least 2 years (≥ 3 episodes); gradual discontinuation (4–8 weeks).
3. CBT and IPT maintenance formats — Monthly or every 2 weeks per session; relapse prevention.
4. Lithium adjunct — In refractory unipolar depression with high suicide risk; Cipriani BMJ 2013.

9. Prognosis

• Relapse risk increases after each episode (Solomon 2000).
• Relapse risk significantly reduced with adequate maintenance treatment (NNT 5).
• Comorbid anxiety, somatic illnesses, compliance disturbance — poor prognosis.
• Monitoring — PHQ-9 monitoring; relapse markers; antidepressant levels and side effects; suicide risk.

10. Myths and misconceptions

Myth 1: “Antidepressants cannot be used lifelong, they cause ‘addiction’”

Evidence: SSRI/SNRI do not cause dependency; lifelong maintenance is recommended for patients with ≥3 episode history (NICE NG222, APA 2010). Reducing the maintenance dose increases the risk of relapse.

Myth 2: “Antidepressants should be stopped immediately after remission”

Evidence: After remission continue at least 6–12 months (single episode) or years (recurrent); early discontinuation significantly increases relapse risk (Geddes Lancet 2003).

Myth 3: “Medication should be changed with every episode”

Evidence: The medication effective in the previous episode should be reused in the next episode (patient-specific efficacy).

Myth 4: “Recurrent depressive disorder is a ‘personality weakness’, treatment should not be long”

Evidence: Neurobiological ‘kindling’ concept — each episode increases risk of new episode; long-term treatment ‘protects’ the brain.

Myth 5: “Only MBCT is sufficient for relapse prevention; pharmacotherapy is unnecessary”

Evidence: Kuyken Lancet 2015 — MBCT vs. maintenance antidepressant comparative; but individual choice — based on patient values, accessibility, prior treatment response.

11. Sources

1. WHO. ICD-11. 6A71 Recurrent depressive disorder. 2024.
2. APA. DSM-5-TR. 2022.
3. NICE NG222. 2022.
4. APA. Practice Guideline for MDD. 3rd ed. 2010.
5. Kennedy S.H. et al. CANMAT 2016. Can J Psychiatry 2016;61(9):540–560.
6. Solomon D.A. et al. Multiple recurrences of major depressive disorder. Am J Psychiatry 2000;157(2):229–233.
7. Post R.M. Transduction of psychosocial stress into the neurobiology of recurrent affective disorder. Am J Psychiatry 1992;149(8):999–1010.
8. Geddes J.R. et al. Relapse prevention with antidepressant drug treatment in depressive disorders: a systematic review. Lancet 2003;361(9358):653–661.
9. Kuyken W. et al. Lancet 2015;386(9988):63–73.
10. Cipriani A. et al. BMJ 2013;346:f3646.