there is clear evidence of a previous good response to ECT; evidence for resistance or into lerance to pharmacotherapy; the patient is able to provide informed consent; evidence that the patient \200\231s cognitive function and physical condition do not preclude the ongoing administration of ECT; 07_Semple_Chap07.indd 292 12/10/2012 6:36:15 PM ECT 5: FURTHER NOTES ON TREATMENT 293 the patient \200\231s attitude, circumstances, and level of social support are conducive to ensuring treatment compliance and safety after treatment. There is no speci \201 c or universally supported treatment schedule for C-ECT; however, a fter completing a course of conventional bi-weekly ECT, a common strategy is: weekly for 1m th; fortnightly for 1mth; monthly for up to 6mths after remission. Only in exceptional circ umstances should M-ECT (i.e. > 6mths after remission) be considered as a treatment option, in close consultation with the patient, and a formal review by another consultant, preferab ly with speci \201 c ECT experience. Usually patients are aware of how effective ECT has b een for them and a collaborative approach can be established (balancing frequency of ECT ag ainst return of symptoms and side-effects, esp. memory problems). Outpatient ECT ECT is given to outpatients in exceptional circumstances only: \200 \200 \200 \200 Mild to moderate illness as de \201 ned by a psychiatrist (e.g. CGI 2 \200\2234). Availabi lity of 24hr supervision to ensure safety and observation. The patient should not have acti ve thoughts of suicide. Regular (weekly) assessment by the consultant (or deputy). ECT in pregnancy \200 \200 ECT may be the preferred treatment choice due to its rapid action. ECT in the second or thi rd trimesters may present more technical dif \201 culties for the anesthetist as the risk of aspiration of stomach contents increases. The patient \200\231s obstetrician and the ane sthetist should be involved before a decision is taken to proceed to treatment. Preparation for ECT should be as per routine with the addition of any instructions from the anesthetis t, for example the administration of antacids on the morning of treatment. Any concerns sho uld be reported urgently to the obstetrician. ECT in children and adolescents An exceptionally rare circumstance \200\224hence, special p rovisions apply: \200 The Royal College of Psychiatrists recommends that for those under 16yrs two further opinio ns are sought in addition to the treating consultant: one from a child and adolescent psych iatrist, and one from another psychiatrist from a different clinical unit. Adolescents aged 16 \200\22318 are able to consent and refuse treatment in the same way as an adult, but pa rental approval is advised. In Scotland those under 16 can consent if they understand the p rocess but again parental approval is advised. For compulsory treatment it should be noted that the provisions of legislation governing ECT have no lower age limit. 1 Trevino BA, McClintock SM, and Husain MM (2010) A review of Continuation Eloctroconvulsiv e Therapy: application, safety, and ef \201 cacy. Journal of ECT 26: 186 \200\22395. 07_Semple_Chap07.indd 293 12/10/2012 6:36:15 PM CHAPTER 7 Depressive illness 294 ECT 6: side-effects and other speci \201 c problems Side-effects \200 Early: retrograde amnesia \200\224usually resolves completely (64%), headache (48% \200\224 if recurrent, use simple analgesia), temporary confusion (10 \200\22327%, nausea/vomiting ( 9%), clumsiness (5%), muscular aches. Late: Mortality: no greater than for general anesthes ia in minor surgery (2:100 000) \200\224usually due to cardiac complications in patients wi th known cardiac disease (hence need for close monitoring). some loss of short-term memory see ECT and memory loss. \200 loss of long-term memory (rare \200\224see ECT and memory loss). Speci \201 c problems \200 Persistent ineffective seizures: threshold, consider use of IV caffeine or theophylline. Pr olonged seizures repeated every 30s until seizure stops (alternative \200\224midazolam). Lo wer energy dosing for next treatment. Post-seizure confusion: ensure safety of patient, if necessary consider sedation (e.g. diazemuls/ midazolam). If a recurrent problem, use a low dose of a BDZ prophylactically during recovery, immediately after ECT. check use of drugs that may raise seizure (i.e. over 150 \200\223180s): administer IV diazemuls (5mg) reassurance, nurse in a calm environment, ECT and memory loss \200 Research has focused on retrograde amnesia because of (highly publicized) claims that ECT c auses more enduring de \201 cits in past memories (esp. autobiographical) than new memorie s. These studies show that the period closest to receiving ECT is least well remembered and can be permanently lost. Recent systematic reviews of the evidence for loss of past memori es highlight the dif \201 culties in interpreting the literature, e.g. unknown sensitivity of autobiographical memory measures, need for premorbid measures of cognitive status. Neve rtheless, they \201 nd: \200 \200 Speci \201 c recommendations to minimize memory lo ss include: use of right UECT; brief pulse rather than sine wave ECT; dose titration; limit ed number and frequency of ECT sessions. 1 autobiographical memory loss does occur; it is related to how ECT is administered. Does ECT damage the brain? \200 Psychiatrists \200\224such as Peter Breggin, author of and \200\230Brain-Disabling Treatme nts in Psychiatry \200\231 (2007) \200\224have been very vocal opponents of ECT, believing of \201 cial reports have deliberately ignored evidence of negative effects. Even proponen ts of ECT in early writings suggested they believed that a degree of cerebral damage (akin to a concussion) was necessary for ECT to work \200\224the rejected brain injury theory. \200\230Toxic Psychiatry \200\231 (1993) 07_Semple_Chap07.indd 294 12/10/2012 6:36:16 PM ECT 6: SIDE-EFFECTS AND OTHER SPECIFIC PROBLEMS 295 Strong evidence against ECT causing damage comes from a primate study comparing ECT, MCT, o r anesthesia alone which reports no histological lesions after 6wks of daily treatment.2 Th ere are few post-mortem reports, but one study found no histopathological evidence of brain injury in the brain of a 92-year-old lady with major depression who had received 91 sessio ns of ECT during the last 22yrs of her life.3 Most mental health associations and colleges including the APA and RCPsych have concluded there is no evidence that ECT causes structura l brain damage (see Box 7.9). Box 7.9 Structural brain damage from ECT \200\230Prospective CT and MRI studies show no evidence of ECT-induced structural changes. Some early human autopsy case reports from the unmodi \201 ed ECT era reported cerebrovas cular lesions that were due to agonal changes or undiagnosed disease. In animal ECS studies that used a stimulus intensity and frequency comparable to human ECT, no neuronal loss was seen when appropriate control animals, blind ratings, and perfusion \201 xation techniqu es were employed. Controlled studies using quantitative cell counts have failed to show neu ronal loss even after prolonged courses of ECS. Several well-controlled studies have demons trated that neuronal loss occurs only after 1.5 to 2 hours of continuous seizure activity i n primates, and adequate muscle paralysis and oxygenation further delay these changes. Thes e conditions are not approached during ECT. \200\231 Devanand DP, Dwork AJ, Hutchinson ER, et al. (1994) Does ECT alter brain structure? Am J Ps ychiat 151: 957 \200\22370. \200\230It is more dangerous to drive to the hospital than to have the treatment. The unfa ir stigma against ECT is denying a remarkably effective medical treatment to patients who n eed it. \200\231 Charles Kellner, Professor of Psychiatry, Mount Sinai Hospital, New York City quoted in USA Today (Dec. 6, 1995) whilst editor of Convulsive Therapy (now Journal of ECT). 1 Fraser LM, O \200\231Carroll RE, Ebmeier KP (2008) The effect of electroconvulsive therap y on autobio- graphical memory: a systematic review. J ECT 24: 10 \200\22317. 2 Dwork AJ, A rango V, Underwood M, et al. (2004) Absence of histological lesions in primate models of EC T and magnetic seizure therapy. Am J Psychiat 161: 576 \200\2238. 3 Scalia J, Lisanby SH, D work AJ, et al. (2007) Neuropathological examination after 91 ECT treat- ments in a 92-year -old woman with late-onset depression. J ECT 23: 96 \200\2238. 07_Semple_Chap07.indd 295 12/10/2012 6:36:16 PM CHAPTER 7 Depressive illness 296 Neurosurgery for mental disorder (NMD) Despite the controversial nature of irreversible neu rosurgery for mental disorders, it is surprising that patients \200\224rather than psychiat rists \200\224often raise the issue, particularly when they retain insight into the chronic , intractable nature of their illness. Neurosurgery is only performed in exceptional cases (see Box 7.10) when all other treatments have failed, and its use is governed by speci \201 c mental health legislation. It is still pos- sible, however, to encounter patients wh o have had surgical procedures performed in the past, and this may complicate the diagnosis of current problems (e.g. depression, OCD, dementia, esp. frontal lobe symptoms) when ther e is demonstrable damage to key brain structures on CT/MRI. Current criteria for NMD1 \200 \200 \200 Severe mood disorders, OCD, severe anxiety disorders. The patient must want the operation. All other reasonable treatments have repeatedly failed (i.e. pharmacological, ECT, psycholo gical). The patient remains ill, but has capacity to provide informed consent. Current surgical techniques These employ stereotactic methods, using pre-operative MRI to e stab- lish target coordinates and a \201 xed stereotactic frame (or new \200\230frameles s \200\231 stereotactic instruments utilizing infrared positioning). Lesioning may be effec ted by implantation of yttrium rods or radio-frequency lesioning. Lesions are localized to the orbito-frontal and anterior cingulate loop (the \200\230limbic \200\231 loop), which i s strongly implicated in the regulation of emotion and mood,2 e.g.: \200 \200 \200 Stereotactic subcaudate tractotomy (SST). Anterior cingulotomy (ACING). Stereotactic limbic leucotomy (SLL) (combining subcaudate tractotomy and anterior cingulotomy). Anterior capsu lotomy (ACAPS). Adverse effects Older techniques were associated with severe amotivational syndromes (up to 24%), marked personality change (up to 60%), and epilepsy (up to 15%). Stereotactic techni ques report minimal post-operative problems with confusion (3 \200\22310%), incontinence (1 \200\2239%), apathy, weight gain, and sei- zures (dependent on the type of surgery). More signi \201 cant personality change and impaired social or cognitive functioning are infreq uent and there is more likely to be improvement. Outcome Given the treatment-resistant nature of the patients receiving surgery, reports of good outcome are surprisingly high (e.g. depression: 34 \200\22368%; OCD: 27 \200\22367%), although results should be cautiously interpreted in view of the obvious lack of any contro l data. ACAPS and SLL appear better for OCD, and ACING and SST for severe mood disorder. 07_Semple_Chap07.indd 296 12/10/2012 6:36:16 PM NEUROSURGERY FOR MENTAL DISORDER 297 Box 7.10 Psychosurgery \200\224an historical perspective In 1935, Egas Moniz and Almeida Lima carried out the \201 rst \200\230prefrontal leucoto my \200\231 (based on the work of Fulton and Jacobsen in bilateral abla- tion of prefrontal cortices in chimpanzees, 1934). At the time this was viewed with great enthusiasm (culmina ting in Moniz being awarded a Nobel Prize for his work in 1949) and other practitioners ada pted the early procedures, with Freeman and Watts introducing the standard \200\230prefron tal leucotomy \200\231 (the notorious lobotomy) in 1936, publishing a standard textbook Psy chosurgery in 1942, and Freeman pioneering \200\230trans- orbital leucotomy \200\231 in 19 46. The impact of surgical treatment at a time when there were few other physical treatments sh ould not be underestimated, and around 12 000 procedures were performed between 1936 and 19 61 in the UK alone (over 40 000 in the US). Techniques were re \201 ned (e.g. open cingulo t- omy, bimedial leucotomy, orbital undercut) from earlier blind, freehand procedures. Howe ver, the advent of effective psychopharmacological treatments and changes in the social cli mate led to a marked decline in practice from the 1960s onwards. Nowadays, the term \200\230psychosurgery \200\231 has been abandoned, and replaced with th e more accurate \200\230neurosurgery for mental disorder \200\231. Modern techniques could not be further removed from older procedures and uti- lize neuroimaging and neurosurgical techniques to lesion clearly de \201 ned neuroanatomical targets (see b p. 296). Between 1 984 and 1994 there were a total of only 20 operations per year performed in the UK,1 and si nce then the number has diminished further. Available data for England and Wales report 5 p rocedures in 2005 \200\2237 and 2 procedures in 2007 \200\2239.2 In Scotland the Dundee Adv anced Intervention Service reported only 5 procedures for 2010/11.3 1 CRAG Working Group (1996) Neurosurgery for mental disorder. Scotland: HMSO (J2318 7/96). 2 The Mental Health Act Commission (2009) Thirteenth Biennial Report (2007 \200\2232009). M http:// www.cqc.org.uk/sites/default/ \201 les/media/documents/mhac_biennial_report_0709_ \201 nal.pdf 3 M http://www.advancedinterventions.org.uk/pdf/Reports/AIS_Annual_Report_20 11.pdf 1 For current criteria in UK see Dundee Advanced Intervention Service website: M http://www . advancedinterventions.org.uk/referrals_criteria_NMD.htm 2 Alexander GE, Crutcher MD, DeLo ng MR (1990) Basal ganglia-thalamocortical circuits: parallel substrates for motor, oculomo tor, \200\230prefrontal \200\231 and \200\230limbic \200\231 functions. Progr Brain Res 8 5: 119 \200\22346. 07_Semple_Chap07.indd 297 12/10/2012 6:36:16 PM CHAPTER 7 Depressive illness 298 Other physical treatments Light therapy (phototherapy) First introduced for the treatment o f SAD (a proposed new syndrome at the time) by Rosenthal,1 on the basis that bright light t herapy might ameliorate symptoms of winter depression, due to effects on circadian and seas onal rhythms mediated by melatonin. Recent research has sug- gested that the effects of pho totherapy may be independent of melatonin and produce a \200\230phase advance \200\231 in circadian rhythms (hence, treatment may be best given \201 rst thing in the morning). It is usually administered by use of a light box (alternatives include light visors) producing 2500 \200\223 10 000 lux. Treatment duration is for 2hrs (with 2500 lux) or 30min (with 10 000 lux) a day, with a course lasting 1 \200\2233wks (treatment response is usually notice able within 5 days). If no response within 3wks, discontinue. When effective, continue unti l time of natural remission to prevent relapse. Dawn-stimulating alarm clocks that graduall y illuminate the bedroom over 2hrs to around 250 lux at the point of waking may also be eff ective. Adverse effects Particularly with 10 000 lux: headache, visual problems \200\224 e.g. eye s train, blurred vision \200\224usually settle; if persistent, reduce dura- tion or intensity of exposure; increased irritability; rarely: manic episodes, increased thoughts of suicide (possibly due to alerting effect and increased energy). Indications SAD (see b p. 263), ci rcadian rhythm disorders (see b p. 436), possibly other depressive disorders and dysthymia. Contraindications Agitation, insomnia, history of hypomania/mania. Repetitive transcranial magnetic stimulation (rTMS) Currently being researched. However, th e difference in stimulation parameters used across reported studies makes comparisons dif \201 cult. The rationale for treatment is either to increase activity in the left dorso- la teral prefrontal cortex (using high-frequency stimulation, e.g. 20Hz) or to reduce activity in the right dorsolateral prefrontal cortex (using low- frequency stimulation, e.g. 1Hz). Initial results in treatment-resistant depression ought to be viewed with caution (see Coch rane review2), although this mode of therapy presents an attractive alternative to ECT, wit hout the accompanying risks and adverse effects. NICE recommenda- tions suggest rTMS ought to be used only in research.3 Adverse effects Minimal, but patients often report headache or facial dis- comfort; rarely seizure induction. Indications Experimental treatment for treatment-resistant depression; possible use in trea tment of treatment-resistant auditory hallucinations; negative symptoms of schizophrenia; O CD; panic disorder. Contraindications History of stroke, brain tumor, or epilepsy. Magneto-convulsive therapy (MCT) Another experimental treatment that utilizes the potential problem of sei- zure induction by rTMS. A varying magnetic \201 eld is used to induce se izures 07_Semple_Chap07.indd 298 12/10/2012 6:36:16 PM OTHER PHYSICAL TREATMENTS 299 in a more controlled way than is possible with ECT. The potential advan- tages include targ eting of brain structures essential for treatment response, and reduction in side-effects ( particularly memory impairment).4 Vagus nerve stimulation (VNS) Vagus stimulation by implanted pacemaker ( \201 rst used as a treatment for epilepsy) has been tested as a treatment of depression since 1998. Stimulat ion is of the left cervical vagus nerve using bipolar electrodes, attached below the cardia c branch (usually 0.5ms pulse-width, at 20 \200\22330Hz, with 30s stimulation periods alter nating with 5min breaks). Response rates of 31 \200\22340% (short-term)5 and 27 \200\22358% (long-term) have been quoted for treatment-resistant depressive disorder, but the quality of this evi- dence is low and further research is required. NICE recommends special arrange ments.6 Adverse effects May include voice alteration (e.g. hoarseness), pain, coughing, and dysphag ia. Deep brain stimulation (DBS) Best regarded as an experimental treatment for OCD and depress ion. Has been used in the treatment of neurological disorders including: Parkinson \200\231 s disease, tremor, dystonia, refractory pain syndromes, and epi- lepsy. Involves implantati on of bilateral electrodes under stereotactic guid- ance and MRI con \201 rmation. Targets for DBS in OCD include the anterior limb of the internal capsule (like ACAPS NMD) and for depression the subgenual cingulate gyrus (like ACING NMD). Initial reports of long-term out comes are promising.7 Adverse effects Reported problems include throbbing/buzzing sensations, nausea, jaw tinglin g, and unexpected battery failure resulting in rebound depression with marked suicidal idea tion. 1 Rosenthal NE, Sack DA, Gillin JC, et al. (1984) Seasonal affective disorder. A descriptio n of the syndrome and preliminary \201 ndings with light therapy. Arch Gen Psychiat 41: 7 2 \200\22380. 2 Rodriguez-Martin JL, Barbanoj JM, Schlaepfer T, et al. (2002) Transcranial magnetic stimulation for treating depression. Cochrane Database System Rev 2: CD00393. 3 NI CE (2007) Transcranial magnetic stimulation for depression. Interventional procedure guidan ce IPG242. M http://www.nice.org.uk/nicemedia/live/11327/38391/38391.pdf 4 Lisanby SH, Schl aepfer TE, Fisch HU, et al. (2001) Magnetic seizure therapy of major depression. Arch Gen P sychiat 58: 303 \200\2235. 5 George MS, Sackeim HA, Rush AJ, et al. (2000) Vagus nerve stim ulation: a new tool for brain research and therapy. Biol Psychiat 47: 287 \200\22395. 6 NIC E (2009) Vagal nerve stimulation for treatment-resistant depression. Interventional procedu re guidance IPG330. M http://www.nice.org.uk/nicemedia/live/12149/46667/46667.pdf 7 Kennedy SH, Giacobbe P, Rizvi SJ, et al. (2011) Deep brain stimulation for treatment-resistant dep ression: follow-up after 3 to 6 years. Am J Psychiat 168: 502 \200\22310. 07_Semple_Chap07.indd 299 12/10/2012 6:36:16 PM This page intentionally left blank 301 Chapter 8 Bipolar illness Introduction 302 Historical perspective 304 Mania/manic episode 306 Hypomania/hypomanic epi sode 310 Bipolar spectrum disorder 312 Bipolar (affective) disorder 1: classi \201 cation 314 Bipolar (affective) disorder 2: clinical notes 316 Bipolar (affective) disorder 3: etio logy 320 Bipolar (affective) disorder 4: management principles 322 Other issues affecting m anagement decisions 324 Treatment of acute manic episodes 326 Treatment of depressive episo des 328 Prophylaxis 330 Psychotherapeutic interventions 332 Cyclothymia 334 Lithium 336 Lit hium: adverse effects 338 Valproate/valproic acid 342 Carbamazepine 346 Lamotrigine 348 08_Semple_Chap08.indd 301 12/7/2012 6:52:36 PM CHAPTER 8 Bipolar illness 302 Introduction Bipolar affective disorder (commonly known as manic depression) is one of the most common, severe, and persistent psychiatric illnesses. In the public mind it is associa ted with notions of \200\230creative madness \200\231, and indeed it has affected many cre ative people \200\224both past and present (see Box 8.1). Appealing as such notions are, mo st people who battle with the effects of the disorder would rather live a normal life, free from the unpredictability of mood swings, which most of us take for granted. Chameleon-like in its presentation, the symptoms may vary from one patient to the next, and from one episode to the next within the same patient. The variety of presentations make th is one of the most dif \201 cult conditions to diagnose. More than other psychiatric disor ders, the clinician needs to pay attention to the life history of the patient, and to third -party information from family and friends. Classically, periods of prolonged and profound depression alternate with periods of excessi vely elevated and/or irritable mood, known as mania. The symptoms of mania characteristical ly include a decreased need for sleep, pressured speech, increased libido, reckless behavio r without regard for consequences, and grandiosity (see b p. 306). In severe cases, there m ay be severe thought disturbances and even psychotic symptoms. Between these highs and lows , patients usually experience periods of full remission. This classic presentation appears, however, to be one pole of a spec- trum of mood disorder s (see b p. 312). A milder form of mania (hypo- mania), associated with episodes of depress ion, may also occur (see b p. 310). There is also a subclinical presentation \200\224cyclot hymia \200\224in which an individual may experience oscillating high and low moods, without ever having a signi \201 cant manic or depressive episode (see b p. 334). Equally, it may be dif \201 cult to distinguish a manic episode with psychotic symp- toms from schizoaffe ctive disorder (see b p. 218) on the basis of a single episode. Full assessment should consider: the number of previous episodes (which may have been subcl inical); the average length of previous episodes; the average time between episodes; the le vel of psychosocial functioning between episodes; previous responses to treatment (especial ly treatment of early depressive episodes); family history of psychiatric problems; and cur rent (and past) use of alcohol and drugs. Although at the present time there is no cure for bipolar disorder, for most cases effectiv e treatment is possible and can substantially decrease the associated morbidity and mortali ty (the suicide rate is high). Some patients do develop severe or chronic impairments and m ay need speci \201 c rehabilitative services. In general, however, the speci \201 c aims of treatment are to decrease the frequency, severity, and psychosocial consequences of epis odes, and to improve psychosocial functioning between episodes. 08_Semple_Chap08.indd 302 12/7/2012 6:52:36 PM INTRODUCTION 303 Box 8.1 Famous people and bipolar disorder Famous people who have publicly stated they have bipolar disorder Buzz Aldrin, astronaut Ti m Burton, artist, movie director Francis Ford Coppola, director Patricia Cornwell, writer R ay Davies, musician Robert Downey Jr, actor Carrie Fisher, writer, actor Larry Flynt, magaz ine publisher Connie Francis, actor, musician Stephen Fry, actor, author, comedian Stuart G oddard (Adam Ant), musician Linda Hamilton, actor Kay Red \201 eld Jamison, psychologist, writer Ilie Nastase, athlete (tennis), politician Axl Rose, musician Ben Stiller, actor, co median Gordon Sumner (Sting), musician, composer Jean-Claude Van Damme, athlete (martial ar ts), actor Tom Waits, musician, composer Brian Wilson, musician, composer, arranger Famous people (deceased) who had a con \201 rmed diagnosis of bipolar disorder Louis Althu sser, 1918 \200\2231990, philosopher, writer Clifford Beers, 1876 \200\2231943, humanitaria n Neal Cassady, 1926 \200\2231968, writer Graham Greene, 1904 \200\2231991, writer Frances Lear, 1923 \200\2231996, writer, editor, women \200\231s rights activist Vivien Leigh, 1913 \200\2231967, actor Robert Lowell, 1917 \200\2231977, poet Burgess Meredith, 1908 \200\223 1997, actor, director Spike Milligan, 1919 \200\2232002, comic actor, writer Theodore Roeth ke, 1908 \200\2231963, writer Don Simpson, 1944 \200\2231996, movie producer David Strickla nd, 1970 \200\2231999, actor Joseph Vasquez, 1963 \200\2231996, writer, movie director Mary Jane Ward, 1905 \200\2231981, writer Virginia Woolf, 1882 \200\2231941, writer Other famous people thought to have had bipolar disorder William Blake, Napoleon Bonaparte, Agatha Christie, Winston Churchill, TS Eliot, F. Scott Fitzgerald, Cary Grant, Victor Hugo , Samuel Johnson, Robert E. Lee, Abraham Lincoln, Marilyn Monroe, Mozart, Isaac Newton, Pla to (according to Aristotle), Edgar Allan Poe, St Francis, St John, St Theresa, Rod Steiger, Robert Louis Stevenson, Lord Tennyson, Mark Twain, Van Gogh, Walt Whitman, Tennessee Willi ams. 08_Semple_Chap08.indd 303 12/7/2012 6:52:36 PM CHAPTER 8 Bipolar illness 304 Historical perspective Bipolar affective disorder has been known since ancient times. Hippo crates described patients as \200\230amic \200\231 and \200\230melancholic \200\231, and clear connections between melancholia and mania date back to the descriptions of the two sy ndromes by Aretaius of Cappadocia (c.150 BC) and Paul of Aegina (625 \200\223 690). Thinkin g at that time re \202 ected \200\230humoral \200\231 theories, with melancholia believed to be caused by excess of \200\230black bile \200\231 and mania by excess of \200\230yel low bile \200\231. Despite the view of some clinicians in the eighteenth century that mel- ancholia and mania were interconnected (e.g. Robert James, 1705 \200\2231776), it was the middle of the ninete enth century before this was more widely accepted. In 1854 Jules Baillarger (1809 \200\2231 890) published a paper in the Bulletin of the Imperial Academy of Medicine describing la fo lie double forme, closely followed 2 wks later by a paper in the same journal by Jean-Pi erre Falret (1794 \200\2231870), who claimed that he had been teaching students at the Salp tri re about la folie circulaire for 10 years. Although the two men were to continue arg uing about who originated the idea, they at least agreed that the illness was characterized by alternating periods of melancholia and mania, often separated by periods of normal mood . In 1899, Emil Kraepelin comprehensively described \200\230manic-depressive insan- ity \200\231 in the 6th edition of his textbook Psychiatrie: Ein Lehrbuch f r Studirende und \204rzte. In the 5th edition he had already divided severe mental illnesses into those with a deteriorating course (i.e. schizophrenia and related psy- choses) and those with a perio dic course (i.e. the mood disorders). It was his view that the mood disorders \200\230repr esented manifestations of a single morbid process \200\231. At the turn of the twentieth century, hopes were high that understand- ing of the pathophys iology of mental illness might be within reach. In 1906, the German microbiologist August W assermann discovered a method of detecting syphilitic infection in the CNS, and in the same year an effective treatment was developed by Paul Ehrlich using arsenic compounds. Syphili s was, at that time, one of the most common causes of severe (often mania-like) psychiatric symptoms \200\224general paralysis of the insane. Reliably diagnosing and treating such a condition was a huge step forward. In cases of manic-depressive illness, however, neuropath ologists failed to \201 nd any structural brain abnormalities. Although some still mainta ined it was a physical illness, caused by disruptions in biological functioning, the pervas ive new psychodynamic theories regarded functional illnesses (i.e. schizophrenia and manic- depressive illness) as illnesses of the mind, not the brain. The idea that they could be un derstood and treated only if the traumatic childhood events, repressed sexual feelings, or interpersonal con \202 icts were uncovered, in \202 uenced psychiatric thinking for over half a century. It was not until speci \201 c drug treatments for these functional illnesses were found th at psychiatry came full circle again, and new life was breathed into the old search for bio logical mechanisms. In 1949 John Cade published a report on the use of lithium salts in man ic patients, but it took nearly three decades, and the work of many psychiatrists, includin g Morgens Schou in Denmark and Ronald Fieve in the US, before lithium would 08_Semple_Chap08.indd 304 12/7/2012 6:52:36 PM HISTORICAL PERSPECTIVE 305 become the mainstay of treatment for manic-depressive illness. Equally signi \201 cant was the observation by Ronald Kuhn that when patients with \200\230manic- depressive psychosi s \200\231 were treated with imipramine they could switch from depression to mania. That th is did not occur in all patients with depression suggested that there was a different biolo gical mechanism underlying depressive illness compared to manic-depressive illness. With di fferent pharmacological agents treating different psychiatric disorders, the stage was set for classifying psychiatric disorders in line with their presumed differing aetiologies. Th e quest had begun to understand the biological mechanisms and, in doing so, to develop bett er treatments. 08_Semple_Chap08.indd 305 12/7/2012 6:52:36 PM CHAPTER 8 Bipolar illness 306 Mania/manic episode Essence A distinct period of abnormally and persistently elevated, expansive, or irritable mood, with 3 or more characteristic symptoms of mania (see Box 8.2. Both DSM-IV and ICD-10 specify the episode should last at least 1 wk, or less if admission to hospital is necessar y. By de \201 nition, the disturbance is suf \201 ciently severe to impair occupational a nd social func- tioning. Psychotic features may be present. Clinical features \200 \200 Elevated mood (usually out of keeping with circumstances). Increased energy, which may mani fest as: \200 \200 \200 \200 Increased self-esteem, evident as: \200 \200 \200 \200 \200 Reduced attention/increased distractibility. Tendency to engage in behavior that could have serious consequences: \200 preoccupation with extravagant, impracticable schemes; \200 spending recklessly; inappropriate sexual encounters. \200 Other behavio ral manifestations: \200 \200 \200 \200 Marked disruption of work, usual social act ivities, and family life. over-activity; pressured speech ( \200\230 \202 ight of ideas \200\231); racing thoughts; reduced need for sleep. over-optimistic ideation; grandiosity; reduced social inhibitions; over-familiarity (which may be overly amorous); facetiousness. \200 excitement; irritability; aggressiveness; suspiciousness. Psychotic symptoms In its more severe form, mania may be associated with psychotic symp- to ms (usually mood-congruent, but may also be incongruent): \200 Grandiose ideas may be delusional, related to identity or role (with special powers or reli gious content). Suspiciousness may develop into well-formed persecutory delusions. Pressure d speech may become so great that clear associations are lost and speech becomes incomprehe nsible. Irritability and aggression may lead to violent behavior. Preoccupation with though ts and schemes may lead to self-neglect, to the point of not eating or drinking, and poor l iving conditions. Catatonic behavior \200\224also termed manic stupor. Total loss of insigh t. \200 \200 \200 08_Semple_Chap08.indd 306 12/7/2012 6:52:36 PM MANIA/MANIC EPISODE 307 Differential diagnosis \200 Schizophrenia, schizoaffective disorder, delusional disorder, other psychotic disorders. An xiety disorders/PTSD. Circadian rhythm disorders (see ADHD/conduct disorder. Alcohol or dru g misuse (e.g. stimulants, hallucinogens, opiates). Physical illness (e.g. hyper/hypothyroi dism, Cushing \200\231s syndrome, SLE, MS, head injury, brain tumor, epilepsy, HIV and othe r encephalopathies, neurosyphilis, Fahr \200\231s disease). Other antidepressant treatment or drug-related causes (Box 8.2). \200 \200 \200 \200 b p. 436). Management \200 \200 \200 b p. 316). Exclusion of other causes and appropriate investigations ( Address any speci \201 c psycho social stressors. For speci \201 c management, see b p. 326. 08_Semple_Chap08.indd 307 12/7/2012 6:52:36 PM CHAPTER 8 Bipolar illness 308 Box 8.2 Medications that may induce symptoms of hypomania/mania \200 Antidepressants antidepressants (or withdrawal, see b p. 964), less so with SSRIs and bupro pion (also seen with ECT and light therapy). Other psychotropic medication: \200 : drug-induced mania described with most benzodiazepines (b p. 929); antipsychotics lithium anticonvulsants gabapentin; psychostimul ants methylphenidate; \200 \200\224disul \201 ram. other Anti-Parkinsonian medication: procyclidine. Cardiovascular drugs: hydralazine, methyldopa withdrawal, procainamide, propr anolol (and withdrawal), reserpine. Respiratory drugs: pseudoephedrine. Anti-infection: dap sone, isoniazid, zidovudine. Analgesics: pentazocine, tramadol. cimetidine, metoclopramide, ranitidine. GI drugs: Steroids: ACTH, beclometasone, corticosteroids, cortisone, dexametha sone, DHEA, hydrocortisone, prednisolone, testosterone. Other: \200\224may be confused with \200\230paradoxical \200\231 reactions \200 \200 \200\224olanzapine, risperidone; \200\224toxicity, and when combined with TCAs; (rare) \200\224carbamazepine (and withdrawal), valproate, \200\224fen \202 uramine, amfetamine, dexamfetamine, amantadine, bromocriptine, levodopa, captopril, clonidine, digoxin, diltiazem, aminophylline, ephedrine, salbutamol, terfenadine, anti-TB medication, chloroquine, clarithromycin, buprenorphine, codeine, indometacin, nefopam (IM), \200 baclofen (and withdrawal), cyclizine, ciclosporin, interferon. 08_Semple_Chap08.indd 308 12/7/2012 6:52:36 PM This page intentionally left blank CHAPTER 8 Bipolar illness 310 Hypomania/hypomanic episode Essence Three or more characteristic symptoms (see Clinical features) lasting at least 4 da ys (DSM-IV), and are clearly different from \200\230normal \200\231 mood (third-party corr oboration). By de \201 nition, not severe enough to interfere with social or occupational functioning, require admission to hospital, or include psychotic features. Clinical features Hypomania shares symptoms with mania, but these are evident to a lesser d egree and do not signi \201 cantly disrupt work or lead to social rejection: \200 \200 \200 \200 \200 \200 \200 \200 \200 \200 Mildly elevated, expansive, or irritable mood. Increased energy and activity. Marked feelin gs of well-being, physical, and mental ef \201 ciency. Increased self-esteem. Sociability. Talkativeness. Over-familiarity. Increased sex drive. Reduced need for sleep. Dif \201 cu lty in focusing on one task alone (tasks often started, but not \201 nished). Differential diagnosis \200 Agitated depression. \200 OCD/other anxiety disorders. \200 Circadian rhythm disorders (see \200 Substance misuse/physical illness/medication-r elated (see Box 8.2). b p. 436). b p. 308, Management \200 Exclusion of other possible causes with appropriate investigations (see b p. 316). Address any speci \201 c psychosocial stressors. If sleep disturbance is a problem, consider use o f an hypnotic. If episode is prolonged, discuss medication possibilities (see and the possi bility of prophylaxis (b p. 330). \200 \200 b p. 326) 08_Semple_Chap08.indd 310 12/7/2012 6:52:37 PM This page intentionally left blank CHAPTER 8 Bipolar illness 312 Bipolar spectrum disorder One view of the affective disorders is that they consist of a con tinuum (see Box 8.3) with bipolar spectrum sitting uneasily between cyclothymia and bipolar II. Whether or not such \200\230subsyndromal \200\231 disorders are of clinical rel- evan ce remains controversial and there are other unexpected diagnostic concerns (see b p. 318). Proposed clinical features Bipolar spectrum disorder is characterized by:1 \200 \200 At least one major depressive episode. No spontaneous hypomanic or manic episodes. The history will include some of the following: \200 \200 \200 \200 \200 \200 \200 \200 \200 \200 \200 A family history of bipolar disorder in a \201 rst-degree relative. Antidepressant-induce d mania or hypomania. Hyperthymic personality Recurrent major depressive episodes (>3). Bri ef major depressive episodes (on average, <3mths). Atypical depressive symptoms (DSM-IV cri teria). Psychotic major depressive episodes. Early age of onset of major depressive episode (<age 25). Post-partum depression. Antidepressant \200\230wear-off \200\231 (acute but no t prophylactic response). Lack of response to up to 3 antidepressant treatment trials. 2 (at baseline, non-depressed state). Management Patients with features of bipolar spectrum disorder may represent a sub- set of patients who do not respond well to antidepressants (often pre- cipitating a switch to a hy pomanic or manic episode) and for whom an anticonvulsant may be the drug of choice (e.g. va lproate, see b p. 342). Box 8.3 The \200\230affective continuum \200\231 Dysthymia Unipolar depression Atypical depression Psychotic depression Recurrent depression Cyclothymia Bipolar spectrum disorder Bipolar II Bipolar I } Unipolar spectrum disorder 1 Ghaemi SN, Ko JY, Goodwin FK (2002) \200\230Cade \200\231s disease \200\231 and beyond: misdiagnosis, antidepressant use, and a proposed de \201 nition for bipolar spectrum disor der. Can J Psychiat 47: 125 \200\22334. 2 Characterized by cheerful, optimistic personality style, tendency to become easily irritated, extroverted and sociable, and requiring little sleep (less than 6hrs/night) \200\224a lifelong disposition, unlike short-lived hypomania. Neither in ICD-10 nor DSM-IV, but signi \201 cant overlap with narcis- sistic or antisoci al personality. 08_Semple_Chap08.indd 312 12/7/2012 6:52:37 PM This page intentionally left blank CHAPTER 8 Bipolar illness 314 Bipolar (affective) disorder 1: classi \201 cation Diagnostic classi \201 cation (see Box 8.4 and Table 8.1)