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Satellite symposium z 12th Latest Advances in Symposium

Characteristics and duration of : implications for continuation treatment

12TH LATEST ADVANCES IN PSYCHIATRY SYMPOSIUM In the continuation phase of treatment for acute mania, knowledge of the PSYCHIATRY IN THE 21st CENTURY: FROM MOLECULE TO

Wednesday 13th March 2013 Royal College of , Regent’s Park, natural duration of an untreated episode and the recognition of mixed states are key issues. Steve Titmarsh reports on Professor Allan Young’s lecture on this important topic given at a satellite symposium organised by Lundbeck at

A collaboration between Progress and the Special Interest Group of the Royal College of the 12th Latest Advances in Psychiatry meeting in London in March.

rofessor Allan Young from the Table 1). Its core symptom is an recognition of this phenomenon, PCentre for at abnormally and persistently ele- in DSM-5, there is a proposal to Imperial College, London dis- vated, expansive or irritable allow for the modification of cussed the issue of continuation , lasting at least one week, or episode characterisation through following an acute episode any duration if hospitalisation is the introduction of a specifier of mania. Guidelines recommend needed. DSM-IV requires that at describing the presence of symp- that continuation treatment least three other symptoms are toms of the opposite pole. should last for 6-12 months after present to a significant degree and symptom remission; much longer that they persist. These include: Duration of mania than might be thought.1 increased -esteem or grandios- The onset and duration of a manic Episodes of mania are often ity; a decreased need for ; episode is influenced by many fac- managed by several treating teams being more talkative than usual or tors, especially medication. The at different phases of the illness. A feeling pressure to keep talking; background risk of a switch to clear overview of the individual’s flight of ideas or the subjective post- mania is 10-20 per pattern of illness and continuity of experience of ; dis- cent. A manic switch may occur in care in the transition periods tractibility; increased goal-directed some cases through the use of between phases is increasingly activity; and excessive involvement .5 Mania may be important. Goodwin and Jamison2 in pleasurable activities with high precipitated by stopping defined the treatment phases of potential for painful results.3 abruptly:6 this may also be true of mania: , a milder form of other medications. Misuse of sub- • Acute treatment: until clinical mania, lasts at least four days in stances such as cannabis is associ- response, ideally symptomatic the DSM-IV definition. ated with an increased duration of remission Mixed mania is very strin- mania.7 • Continuation phase: ongoing treat- gently defined by DSM-IV: the cri- The Royal College of ment ‘from the point of clinical teria for both major depressive Psychiatry’s website states that response to the point at which and manic episodes must be met. untreated, a manic episode gen- spontaneous recovery might be Many affective episodes include erally last three to six months.8 expected in untreated ’ subsyndromal symptoms from the However, there may be substan- • Maintenance treatment: ‘to prevent opposite pole. When manic or tial inter-individual variation. or attenuate future mood hypomanic episodes occur with Angst and Sellaro reviewed well- episodes’. subsyndromal depressive symp- conducted studies on bipolar dis- However, there may be some toms, the term ‘dysphoric mania’ order, published before the era of doubt about the natural duration is often used. The incidence of effective treatment.9 One of the of mania among practitioners fol- subsyndromal mania in bipolar largest of these was by Wertham, lowing the development of effective depression was illustrated in the published in 1929, which involved treatments over the past 60 years. Systematic Treatment Enhance - 2000 patients with mania. This The characteristics of mania ment Program for Bipolar study found that the median are defined in the Diagnostic and Disorder (STEP-BD) study where duration of untreated mania was Statistical Manual of Mental it was found in more than half (54 four to six months, but interquar- Disorders, 4th edition (DSM-IV; see per cent) of the 1380 subjects.4 In tile values ranged between two to

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12th Latest Advances in Psychiatry Symposium z Satellite symposium

four (Q1) and eight to ten • A distinct period of abnormally and persistently elevated, expansive or 10 months (Q3). irritable mood, lasting at least one week (or any duration if hospitalisation So what might have been is needed thought of as episode recurrence • Three or more of the following symptoms are present to a significant just a few weeks after an initial degree and persist: episode has been treated is likely - Increased self-esteem or to be a of the initial - Decreased need for sleep episode. It is probably not a true - More talkative than usual or pressure to keep talking recurrence at all, rather a break- - Flight of ideas or subjective experience that thoughts are racing through of the initial episode. - Distractibility - Increased goal-directed activity or Therefore recurrence should - Excessive involvement in pleasurable activities with a high potential for only be thought of as occurring painful consequences after the period of spontaneous natural recovery – which could Table 1. DSM-IV symptoms in a manic episode3 even be a year or more after the initial episode, Professor Young continuation and maintenance 2009;166:173-81. explained. treatment is supported by trials of 5. Salvadore G, Quiroz JA, Machado-Vieira R, et al. The neurobiology of the switch process 13,14 up to around 52 weeks. In con- in : a review. J Clin Psychiatry Implications for continuation trast, a continuation trial of 2010;71:1488-501. treatment lasted only nine 6. Mander AJ, Loudon JB. The rapid recurrence 15 of mania following abrupt discontinuation of Understanding the natural weeks. lithium. Lancet 1988;2(8601):15-7. course of mania has significant Professor Young concluded by 7. Strakowski SM, DelBello MP, Fleck DE, et al. implications for continuation emphasising that the continua- The impact of substance on the course of bipolar disorder. Biol Psychiatry 2000; treatment. Following an acute tion phase of treatment covers a 48:477-85. manic episode, the duration of period of ongoing vulnerability to 8. www.rcpsych.ac.uk/expertadvice/problems/ the hypothetical ‘untreated’ relapse following acute mania, bipolardisorder /bipolardisorder.aspx (accessed 3 April 2013). episode represents a period of commensurate with the estimated 9. Angst J, Sellaro R. Historical perspectives ongoing vulnerability to episode duration of an untreated manic and natural history of bipolar disorder. Biol relapse, hence the recommenda- episode. In mixed states, this Psychiatry 2000;48:445-57. 10. Wertham FI. A group of benign chronic tion that continuation treatment phase of vulnerability may be psychoses: prolonged manic excitements with should be for 6-12 months after even more prolonged. Current a statistical study of age, duration and fre- remission.1 guidelines recommend that con- quency in 2000 manic attacks. Am J Psychiatry 1929;86:17-78. Data on the natural duration of tinuation treatment should last 11. Keller MB, Lavori PW, Coryell W, et al. mixed episodes are rare. However, for 6-12 months after symptom Differential outcome of pure manic, in treating mixed mania, it is remission. mixed/cycling and pure depressive episodes in patients with bipolar illness. JAMA 1986;225 important to consider that 3138-42. episodes of mixed or rapid cycling References 12. Angst J, Preisig M. Course of a clinical may well have a longer duration 1. Grunze H, Vieta E, Goodwin GM, et al. The cohort of unipolar, bipolar and schizoaffective 11,12 World Federation of Societies of Biological patients. Results of a prospective study from than pure mania and a med- Psychiatry (WFSBP) guidelines for the 1959 to 1985. Schweiz Arch Neurol Psychiatr ication that is effective in pure biological treatment of bipolar disorders: 1995;146:5-16. mania may not be the treatment update 2009 on the treatment of acute 13. McIntyre RS, Cohen M, Zhao J, et al. mania. World J Biol Psychiatry 2009;10: of choice for a mixed episode. For for long-term treatment of 85-116. bipolar disorder: a double-blind 40-week instance, most efficacy data on the 2. Goodwin FK, Jamison KR. Manic-Depressive extension study. J Disord 2010;126: treatment of mixed mania comes Illness: Bipolar Disorder and Recurrent 358-65. from the post hoc analysis of ran- Depression. 2nd edition. New York: Oxford 14. Quiroz JA, Yatham LN, Palumbo JM, et al. University Press, 2007. Part V: Treatment. long-acting injectable domised controlled trials. These Chapter 17: Fundamentals of treatment. monotherapy in the maintenance treatment data suggest that lithium may not ‘Stages of treatment’, pp702-3. of . Biol Psychiatry 2010; be so efficacious in mixed states as 3. American Psychiatric Association. Diagnostic 68:156-62. and Statistical Manual of Mental Disorders, 15. Smulevich AB, Khanna S, Eerdekens M, et , risperidone or olanzap- 4th edition (DSM-IV). Washington DC: al. Acute and continuation risperidone ine.1 However, these data are not American Psychiatric Association, 1994. monotherapy in bipolar mania: a 3-week conclusive. 4. Goldberg JF, Perlis RH, Bowden CL, et al. placebo-controlled trial followed by a 9-week Manic symptoms during depressive episodes double-blind trial of risperidone and haloperi- Professor Young added that the in 1,380 patients with bipolar disorder: find- dol. Eur Neuropsychopharmacol 2005;15: use of newer anti-manic agents in ings from the STEP-BD. Am J Psychiatry 75-84.

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