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Bipolar disorder is a common, chronicand highly morbid mental illness char-

acterised by manic and depressiveepisodes that often run a relapsing andremitting course (see Table 1).1 The keyfeature differentiating bipolar disorderfrom recurrent depressive disorder is alifetime presence of mania, hypomania ormixed affective episodes.

The Diagnostic and Statistical

Manual of Mental Disorders 4th Edition(DSM-IV) distinguishes between bipolar Idisorder, where mania occurs, and bipo-lar II disorder, where hypomania occursusually alongside one or more episodesof major depression.2

Epidemiology and diagnosticchallengesBipolar disorder type I affects around 1per cent of the population and type II dis-order affects a further 2–3 per cent.3 Thedisorder is a significant cause of disabilityand suffering.4,5 A recent internationalstudy reported that the median age atonset is 24 years for men and 27 yearsfor women with a range of 10 to 42years,6 although most individuals withbipolar disorder report problems withmood and anxiety symptoms in adoles-cence and early adulthood. Bipolar I and II and bipolar spectrumdisorders can pose significant diagnosticchallenges. Many bipolar I and II patientswill experience a delay of several yearsbetween the onset of significant manicsymptoms and receiving the correct diag-nosis.7 Misdiagnosis as unipolar depres-sion, personality disorder, a primary drugor alcohol problem or even schizophreniais a common problem that has beenlinked to poorer long-term outcomes.7

Despite significant interindividualvariation, most patients with bipolar dis-order suffer a predominance of depres-sive symptoms during their lifetime.8

There are a variety of barriers to theaccurate and timely diagnosis of bipolardisorder. Perhaps most commonly encoun-tered is the difficulty in differentiating bipo-lar from unipolar depression. Although notpathognomonic, there are a number of fea-tures thought to be associated withdepressive episodes within bipolar disor-der. Such features include atypical depres-sive features such as hypersomnia,hyperphagia, leaden paralysis, psychomo-tor retardation, psychotic features, patho-logical guilt and lability of mood.9 Theimportance of early identification of bipo-lar depression as a discrete clinical entityis highlighted by work suggesting that upto 90 per cent of initial presentations ofeventual bipolar patients are depressive.10

Bipolar disorder – diagnosis and current treatment optionsDaniel Martin BMSc, MRCPsych and Daniel Smith MD, FRCPsych

Bipolar disorder is a complex condition characterised byboth manic and depressive episodes. Here the authors dis-cuss the challenges faced in both diagnosis and treatment.

KEY POINTS

nmisdiagnosis as unipolar depression, personality disorder, a primary drug or alcoholproblem or even schizophrenia is a common problem

n it is important that GPs develop awareness and competencies in the assessment,diagnosis and treatment of bipolar disorder

n few primary-care clinicians make use of available screening instruments for hypo-mania – the BSDS may be particularly useful for identifying hypomania

n cardinal symptoms of mania include elevated mood, flight of ideas, pressure ofspeech, increased energy levels, reduced need for sleep and increased activity levels

n antidepressants may be of limited therapeutic benefit in the treatment of bipolardepression and may cause destabilisation of mood in some patients

n treatment with lamotrigine or quetiapine is recommended by the BAP

nmost patients with mania will require short-term pharmacological treatment in anappropriate clinical setting

n valproate or an atypical antipsychotic has a rapid antimanic effect and can bestarted in severely unwell manic patients not already on treatment

n long-term treatment of bipolar disorder should be started after a single severemanic episode – lithium monotherapy should be considered as an initial treatment

n long-term combination treatment is recommended when monotherapy fails orsubthreshold affective symptoms are ongoing

Although the majority of psychiatriccare for patients suffering with bipolardisorder is delivered by local communitymental health teams, the level of theseservices varies across the UK. It istherefore important that GPs developawareness and competencies in theassessment, diagnosis and treatmentof bipolar disorder. Screening instruments for the detec-tion of depression in primary care suchas the Patient Health Questionnaire(PHQ), the Hospital Anxiety andDepression Scale (HADS) and the BeckDepression Inventory (BDI) are routinelyused but very few primary-care cliniciansmake use of available screening instru-ments for hypomania. Relevant screening tools for hypoma-nia include as the Mood DisorderQuestionnaire (MDQ), the BipolarSpectrum Diagnostic Scale (BSDS), andthe Hypomania Checklist (HCL-32). All ofthese instruments are relatively briefand have been validated for use in arange of clinical settings. The BSDS maybe particularly useful for identifyinghypomania in primary-care patients withdepression.7

CausesThere is a significant association betweenthe risk of development of bipolar disor-der and a family history of affective dis-order, in particular bipolar affectivedisorder. Although the majority of patientswith bipolar disorder have no family his-tory of the condition, genetic risk haslong been identified as an important fac-tor in identifying at-risk individuals. A2009 population-based study foundthere to be a relative risk of 6.4 for chil-dren of bipolar patients and 7.9 for sib-lings of bipolar patients. The totalheritability for the disorder was calcu-lated as 59 per cent.11

Many candidate gene associationstudies have been carried out but resultshave generally been inconsistent. Thereis currently no consensus on robust can-didate genes for bipolar disorder. It islikely that many genes, each of smalleffect, will be implicated. Environmental risk factors are alsoimportant aetiologically. A 2003 system-

atic review found that noncaucasian ethnicity, pregnancy and obstetric com-plications, lower premorbid IQ, poor pre-morbid adjustment, early parental loss,seizure disorder and childbirth are allassociated with the development of bipo-lar disorder.12

Signs and symptoms Manic episodes may be preceded by aprodrome, which can last from a few daysto a few months, of mild and often tran-sitory and indistinct manic symptoms. Attimes, however, no prodromal warningsigns occur and the episode can startabruptly. The cardinal symptoms of maniainclude elevated mood (this can includeirritability or euphoria), flight of ideas, pres-sure of speech, increased energy levels,reduced need for sleep and increasedactivity levels. These symptoms can beexaggerated and accompanied by delu-sions (often mood congruent) in moresevere manic episodes. Psychotic symp-toms in mania are often florid and bizarreand most episodes of mania last from several weeks to around three months induration.13

Depressive episodes in bipolar dis-order may have a relatively abrupt onsetand include several atypical features.Sufferers of bipolar depression displayhigher rates of psychotic symptoms com-pared with their unipolar depressedcounterparts. Furthermore they reportincreased rates of irritability, discon-tented mood and profound anergia.3 Ifuntreated, episodes of bipolar depres-sion can persist for many months.

Management of bipolar disorderOne of the most important practicalissues in the management of diagnosedor suspected bipolar disorder is the useof antidepressants. Recent evidence suggests that anti-depressants may be of limited therapeu-tic benefit in the treatment of bipolardepression and may for a proportion ofpatients be unhelpful by causing desta-bilisation of mood (particularly with tri-cyclic antidepressants and venlafaxine13),more frequent mood episodes, treatmentresistance and possibly also (especially

in young bipolar patients) an increase insuicidal behaviour.7

It may be prudent to avoid antidepres-sant monotherapy in patients with bipolardepression who have previously foundantidepressants unhelpful – either due tolack of efficacy or adverse effects.Treatment with lamotrigine or quetiapineis recommended by the British Associationfor Psycho pharma cology (BAP).

Acute mania or mixed affective stateMost patients with mania will requireshort-term pharmacological treatment inan appropriate clinical setting. No psy-chotherapy currently provides an alterna-tive strategy for management. A lessnoisy and stimulating environment withhigher nursing staff-patient ratios mayreduce behavioural disturbance in somepatients with mania.14

Valproate or an atypical antipsychotichas a rapid antimanic effect and can bestarted in severely unwell manic patientsnot already on treatment for bipolar dis-order. Asenapine (Sycrest) is also used inthe acute treatment of manic or mixedepisodes of bipolar I disorder. Recent evi-dence indicates that this agent is well tolerated and may also be suitable forlonger-term maintenance therapy of bipo-lar I disorder.15

For less unwell manic patientslithium or carbamazepine may also beconsidered as a short-term treatment.Short-term adjunctive sedative treat-ment with a benzodiazepine such as

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Table 1. Definition of bipolar I and bipolar IIdisorder according to the American Psychi-atric Association (1994)

Bipolar I disorder Characterised by at least one manicepisode or mixed affective episode(clear manic and depressive featurespresent in the same episode). There isalmost always a history of depressiveepisodes, although these are not nec-essary for establishing a diagnosis.

Bipolar II disorder Characterised by one or more majordepressive episodes, together with atleast one hypomanic episode in theclinical course.

diazepam or clonazepam can also behelpful. Antidepressant therapy shouldbe tapered and discontinued. Treatment,where possible, should be guided bypatient preference.14

Bipolar depressionQuetiapine should be considered wherean early response to treatment isdesired for patients who suffer an acuteepisode of bipolar depression and whoare not already on long-term treatmentfor bipolar disorder. Lamotrigine with anappropriate dose titration should also beconsidered. These medications shouldbe considered closely when there is evi-dence that previous antidepressanttreatment has caused a change in moodpolarity.14

Antidepressant treatment (typicallyan SSRI) with an antimanic agent (eglithium, valproate or an antipsychotic)may be considered for depressedpatients with no prior history of mania.Antidepressant monotherapy is not rec-ommended in patients who have previ-ously been manic due to an increasedrisk of switch into mania. Although notabsolutely contraindicated, antidepres-sants should be used with caution inpatients with a history of hypomania andusually alongside mood stabiliser cover. Tricyclic antidepressants and otherdual reuptake inhibitor agents such asvenlafaxine – and possibly duloxetine(Cymbalta) – carry a greater risk of precip-itating a switch into mania than otherantidepressants and are not recom-

mended except for patients who fail torespond to an initial treatment. Slow, tapered antidepressant discon-tinuation (preferably within three monthsof resolution of a depressive episode7)can be considered following appropriateresponse to treatment.14

Antipsychotic medication should beconsidered in the presence of psychoticsymptoms,14 and electroconvulsive ther-apy should be considered for patientswith high suicidal risk, psychosis, severedepression during pregnancy or life-threatening features of depression. Whendepressive symptoms are less severe,lithium or possibly valproate may be con-sidered (although valproate should notgenerally be prescribed for women ofchild-bearing potential due to risks of ter-atogenicity).14

Interpersonal therapy, cognitivebehaviour therapy or family-focused ther-apy (FFT) are also useful as there is evi-dence that these therapies can shortenan episode of bipolar depression.14

Relapse prevention Long-term treatment of bipolar disordershould be started after a single severemanic episode; although there is no con-trolled evidence, early recognition andtreatment of bipolar disorder may lead toa more benign illness course. Long-termpharmacological treatment should bealongside appropriate psychological andsocial support.14

Lithium monotherapy should be con-sidered as an initial treatment as it isprobably effective against both manicand depressive relapse, although it ismore effective in preventing mania.14 Dueto possible toxicity serum lithium concen-tration monitoring is required. Patientsoften carry a lithium alert card due to thispossibility (see Figure 1). If lithium is inef-fective or poorly tolerated there are anumber of alternatives recommended bythe BAP (see Table 2). If lithium or one of the medicationslisted in Table 2 is effective in achievingremission from a depressive or manicepisode it should be considered for long-term relapse prevention.14

Long-term combination treatment isrecommended when monotherapy fails orsubthreshold affective symptoms are ongo-

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Table 2. Alternatives to lithium for relapse prevention in bipolar disorder14

• aripiprazole prevents manic relapse • carbamazepine is less effective than lithium but may sometimes be employed asmonotherapy if lithium is ineffective and especially in patients who do not showthe classical pattern of episodic euphoric mania; pharmacokinetic interactionsare a particular problem for carbamazepine and caution is advised

• oxcarbazepine may be considered by extrapolation because of its lower potentialfor such interactions

• lamotrigine prevents depressive more than manic relapse • olanzapine prevents manic more than depressive relapse • quetiapine prevents both manic and depressive relapse • valproate probably prevents both manic and depressive relapse

Figure 1. Patients receiving lithium therapy often carry an alert card due to possible toxicity

ing.14When a patient experiences predom-inantly manic relapses it may be logical tocombine predominantly antimanic agents(eg lithium, valproate or an antipsychotic).When a patient experiences predominantlydepressive symptoms, lamotrigine or que-tiapine may be more appropriate. Long-term antidepressant treatment should beused with caution where indicated.14

Psychoeducation for bipolar disorder Despite significant benefits of medicationin bipolar disorder, poor insight and med-ication adherence can lead to reducedlong-term outcomes for bipolar disorder.16

There is evidence that psychoeduca-tional interventions are effective in bipolardisorder with particular benefits in relapserates17 and medication adherence.18

Availability of psychoeducational interven-tions for bipolar disorder is increasing withparticular emphasis on online psycho -educational packages (www.bep-c.org).19

ConclusionBipolar disorder is a complex disorder ofmood and behaviour that requires a

multi modal treatment and diagnosticapproach. Particular attention should begiven to the early features of the condi-tion, heterogeneity of presentations,relapse prevention and evolving thera-pies for the condition.

References1. World Health Organisation. ICD-10 classifi-cations of mental and behavioural disorder:clinical descriptions and diagnostic guidelines.1992.2. Taylor M, et al. Rev Bras Psiquiatr 2011;33Suppl 2:s197–212.3. Goodwin FK, et al. Manic-depressive illness:bipolar disorders and recurrent depression.2nd edition. New York: Oxford University Press,2007.4. Elanjithara T, et al. APT 2011;17:283–91.5. Homish GG, et al. Journal of AffectiveDisorders 2013;144:129–33. 6. Wingo AP, et al. Bipolar Disorders 2009;11:113–25.7. Smith DJ, et al. Br J Gen Pract 2010;60(574):322–4. 8. Judd LL, et al. Arch Gen Psychiatry 2002;59(6):530–7.9. Mitchell PB, et al. Bipolar Disord 2008:10:144–152.10. Duffy A, et al. British Journal of Psychiatry

2009;195:457–8. 11. Howes OD, et al. Psychol Med 2010:1–11. 12. Tsuchiya KJ, et al. Bipolar Disord2003:5:231–42.13. Altshuler LL, et al. Am J Psychiatry 2005;152:1130–8.14. Goodwin G, et al. Journal of Psycho -pharmacology 2009;23(4):346–88.15. McIntyre RS, et al. J Affect Disord 2010;126(3):358.16. Colom F, et al. European Psychiatry 2005;20:359–64.17. Colom F, et al. Archives of GeneralPsychiatry 2003;60:402–7.18. Colom F, et al. Bipolar Disorders 2005;7(s5):32–6.19. Smith DJ, et al. Bipolar Disorders 2005;13:571–7.

Declaration of interestsNone to declare.

Dr Martin is clinical research fellow andDr Smith is reader in mental health atthe Institute of Health and Wellbeing,University of Glasgow, and theDepartment of Mental Health andWellbeing, Gartnavel Royal Hospital,Glasgow

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