Psych · General adult psychiatry — bipolar and related disorders
Mixed features and rapid cycling
Also known as Mixed episode · Mixed features specifier · Dysphoric mania · Mixed depression · Rapid cycling bipolar · Ultra-rapid cycling · Ultradian cycling
Exam-exhaustive fellowship reference on DSM-5-TR mixed features specifier versus historical mixed episode, ICD-11 framing, rapid cycling (≥4 episodes in 12 months), suicide risk in mixed states, antidepressant monotherapy prohibition, lithium/valproate/SGA algorithms, thyroid and substance drivers, STEP-BD and olanzapine mixed-features evidence, and RANZCP/NICE/CANMAT/BAP deltas. FRANZCP-primary, globally tagged.
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Red flags
- Depression plus energy, agitation, or decreased sleep need — treat as high suicide-risk mixed features phenotype, not ordinary unipolar depression
- Antidepressant monotherapy in bipolar I or highly suspected bipolar spectrum — switch and cycle-acceleration risk
- Four or more full mood episodes in 12 months — diagnose rapid cycling and hunt for antidepressants, thyroid dysfunction, substances, and sleep chaos
- Valproate in people who can become pregnant without a documented pregnancy-prevention programme — major teratogen hierarchy
- Lithium toxicity: coarse tremor, ataxia, confusion, vomiting — stop lithium, check level and renal function urgently
- First mixed or manic presentation after mid-life, fever, fluctuating attention, or focal neurology — intensify organic work-up
Meet the patient
It is 2am on the ward. A 29-year-old woman is pacing the corridor in tears. She has slept three hours a night for a week and does not feel tired. She has bought two sofas online since midnight. She tells you, between sobs and at speed, that she is worthless and that she wants to be dead by the weekend.[2][3]
The nurse's note says "agitated depression, for review." The registrar's plan says "increase the venlafaxine."[3][8]
Both are wrong, and one of them is dangerous. This is depression plus energy — the phenotype that kills — and the whole topic is about recognising it before you prescribe into it.[3][8][14]
References20ShowHide
- [1]Tohen M, McIntyre RS, Kanba S, et al. Efficacy of olanzapine in the treatment of bipolar mania with mixed features defined by DSM-5 J Affect Disord, 2014.PMID 25046739
- [2]McIntyre RS, Tohen M, Berk M, et al. DSM-5 mixed specifier for manic episodes: evaluating the effect of depressive features on severity and treatment outcome J Affect Disord, 2013.PMID 23712026
- [3]Goldberg JF, Perlis RH, Bowden CL, et al. Manic symptoms during depressive episodes in 1,380 patients with bipolar disorder: findings from the STEP-BD Am J Psychiatry, 2009.PMID 19122008
- [4]Kupka RW, Luckenbaugh DA, Post RM, et al. Comparison of rapid-cycling and non-rapid-cycling bipolar disorder based on prospective mood ratings in 539 outpatients Am J Psychiatry, 2005.PMID 15994709
- [5]Wehr TA, Sack DA, Rosenthal NE, et al. Rapid cycling affective disorder: contributing factors and treatment responses in 51 patients Am J Psychiatry, 1988.PMID 3341463
- [6]Carvalho AF, Dimellis D, Gonda X, et al. Rapid cycling in bipolar disorder: a systematic review J Clin Psychiatry, 2014.PMID 25004199
- [7]Roosen L, Sienaert P Evidence-based treatment strategies for rapid cycling bipolar disorder, a systematic review J Affect Disord, 2022.PMID 35545157
- [8]Sachs GS, Nierenberg AA, Calabrese JR, et al. Effectiveness of adjunctive antidepressant treatment for bipolar depression N Engl J Med, 2007.PMID 17392295
- [9]Perlis RH, Ostacher MJ, Goldberg JF, et al. Transition to mania during treatment of bipolar depression Neuropsychopharmacology, 2010.PMID 20827274
- [10]Geddes JR, Goodwin GM, Rendell J, et al. Lithium plus valproate combination therapy versus monotherapy for relapse prevention in bipolar I disorder (BALANCE): a randomised open-label trial Lancet, 2010.PMID 20092882
- [11]Cipriani A, Barbui C, Salanti G, et al. Comparative efficacy and acceptability of antimanic drugs in acute mania: a multiple-treatments meta-analysis Lancet, 2011.PMID 21851976
- [12]Cipriani A, Hawton K, Stockton S, et al. Lithium in the prevention of suicide in mood disorders: updated systematic review and meta-analysis BMJ, 2013.PMID 23814104
- [13]Yatham LN, Kennedy SH, Parikh SV, et al. Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) 2018 guidelines for the management of patients with bipolar disorder Bipolar Disord, 2018.PMID 29536616
- [14]Malhi GS, Bell E, Bassett D, et al. The 2020 Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for mood disorders Aust N Z J Psychiatry, 2021.PMID 33353391
- [15]Goodwin GM, Haddad PM, Ferrier IN, et al. Evidence-based guidelines for treating bipolar disorder: Revised third edition recommendations from the British Association for Psychopharmacology J Psychopharmacol, 2016.PMID 26979387
- [16]Bowden CL, Brugger AM, Swann AC, et al. Efficacy of divalproex vs lithium and placebo in the treatment of mania. The Depakote Mania Study Group JAMA, 1994.PMID 8120960
- [17]Tohen M, Vieta E, Calabrese J, et al. Efficacy of olanzapine and olanzapine-fluoxetine combination in the treatment of bipolar I depression Arch Gen Psychiatry, 2003.PMID 14609883
- [18]McKnight RF, Adida M, Budge K, et al. Lithium toxicity profile: a systematic review and meta-analysis Lancet, 2012.PMID 22265699
- [19]Grande I, Berk M, Birmaher B, et al. Bipolar disorder Lancet, 2016.PMID 26388529
- [20]Mackin P, Young AH Rapid cycling bipolar disorder: historical overview and focus on emerging treatments Bipolar Disord, 2004.PMID 15541068