Mahmood A, Ebmeier KP. Optimising the management of bipolar disorder. Practitioner 2015; 259 (1782):11-15

Optimising the management of bipolar disorder

21 May 2015


Ms Abda Mahmood MSc, Research Assistant

Professor Klaus P. Ebmeier MD. Professor of Old Age Psychiatry

Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, UK


The prevalence of bipolar disorder in primary care patients is estimated to be between 0.5 and 4.3%, with 9.3% having bipolar spectrum illness.1 As many as 38% of patients are treated exclusively in primary care.2

The GP’s role is therefore vital in improving and maintaining patients’ quality of life.3 In particular, accurate and timely recognition and assessment of often lifelong and disabling symptoms is essential for long-term engagement in treatment and support at primary care level. This can reduce the use of inpatient services and prevent long-term loss of function.4

This article updates our previous review,5 in light of the most recent NICE clinical guidance, published in 2014, which reflects advances in the treatment approaches for patients with bipolar disorder.6


Any history of depression increases the risk of bipolar disorder. A diagnosis of bipolar disorder would have implications for any planned antidepressant treatment. NICE recommends that when adults present in primary care with depression, they should be asked about previous periods of overactivity or disinhibited behaviour.6 If this behaviour has lasted for four or more days, referral for a specialist mental health assessment should be considered.

The Diagnostic and Statistical Manual of Mental Disorders (DSM 5) defines bipolar disorder using the criteria listed in table 1.7 If a manic episode has been present during the history, the diagnosis is bipolar I disorder, while a hypomanic episode is indicative of bipolar II disorder. Cyclothymia refers to a chronic (two years and longer) mood disturbance with depression and hypomanic symptoms that does not meet criteria for a full episode. Although depressive episodes are not necessary for a diagnosis of bipolar disorder, they are common and dominate the lifetime pattern of the condition: 50% of the time is spent in a euthymic (well) state, 38% in a depressed and 12% in a manic state.8

If there have only been depressive symptoms, it is not possible to exclude bipolar disorder. Whether depressed patients will develop bipolar disorder is not clear until the first (hypo-) manic symptoms actually occur (in around 10% of depressed patients), typically by their thirties.8

Over three years, one in 25 people with major depression will develop bipolar disorder.9 Comorbid social anxiety disorder, generalised anxiety disorder, childhood abuse and problems with the patient’s social support group within the past year may predict this transition.9

A family history of bipolar disorder also provides an index of suspicion, with diagnostic concordance highest in identical twins (40-70%) and first-degree relatives (a 5 to 10 times greater risk than in the general population).10

Psychosocial influences, including childhood maltreatment, may predispose an individual to develop bipolar disorder in adult life, while social class, social support, and self-esteem may modify the course of episodes.6


NICE6 recommends that patients should undergo a risk assessment at the time of diagnosis, whenever there is a significant change in personal circumstances or mental state, and at the time of discharge or leave of absence from inpatient care. This implies that the GP has an ongoing therapeutic relationship with the patient and carer to support care plans and recovery goals, follow-up on crisis plans developed in secondary care, facilitate the transition between secondary and primary care, and review treatment regularly.

NICE advises that questionnaires are not useful to identify bipolar disorder in adults, young people and children in primary care.6 Clinical assessment should include dependency or abuse of drugs and alcohol. The possible benefits and risks of psychological and pharmacological interventions should be discussed with the patient, especially during remission of symptoms, as patients may be more susceptible to information, but also less motivated to continue treatment.

If bipolar disorder is diagnosed in secondary care, the secondary care team should liaise with primary care to generate a care plan developed in collaboration with the patient, and monitor mood and activity levels.

Care that is integrated and contiguous between primary and secondary agencies favours the overall success of management.

If patients do not have the capacity to make decisions, healthcare professionals should follow the code of practice that accompanies the Mental Capacity Act and the supplementary code of practice on deprivation of liberty safeguards, unless the respective Mental Health Act needs to be invoked.

Confirming diagnosis

A diagnosis of bipolar disorder is supported by diagnostic criteria and usually confirmed by a psychiatrist. The individual should be monitored appropriately following diagnosis, especially after the first episode, when diagnostic uncertainty is common. Individuals may present a significant period after the condition first arises, which may make the diagnosis difficult, as insight into previous episodes may be poor.

Further complications arise from inconsistencies between diagnostic criteria. The two classification systems (DSM 57 and ICD-1011) are not identical, with differences in the number of required episodes and distinction between bipolar I and II disorders.

NICE recommends that for children or young people, diagnosis of bipolar disorder should be made only after a period of intensive, longitudinal monitoring by a healthcare professional or multidisciplinary team trained and experienced in the assessment, diagnosis and management of bipolar disorder for that age group, and in collaboration with parents or carers.6 Mania and euphoria must be present for a diagnosis of bipolar disorder; irritability should be taken into account but is not a core diagnostic criterion.

Children or young people with depression and a family history of bipolar disorder should be followed up, but a diagnosis cannot be made on family history alone.

The updated guidance includes specific recommendations for diagnosis in these age groups, as the presentation of symptoms can be complicated by other conditions, such as ADHD.6


If the GP suspects mania or severe depression, or if patients are a danger to themselves or others an urgent referral should be made for a specialist mental health assessment. If bipolar disorder is managed solely in primary care, patients should be re-referred to secondary care under any of the circumstances listed in table 2.


Pharmacological treatment

Although the evidence base is rapidly expanding, the pharmacological treatment of bipolar disorder continues largely to consist of a two-drug combination approach, which includes lithium as a mood stabiliser, and acutely anti-manic and antidepressant drugs of several different drug classes. As acute antimanic treatments, olanzapine, risperidone and haloperidol are recommended.12

The evidence base for the use of antidepressants has almost doubled since the 2006 NICE guideline was published.

Recent specific recommendations suggest combining fluoxetine with olanzapine to protect against both poles of the illness.6 Quetiapine too has empirical support as an antidepressant treatment in bipolar disorder13-15 and more recently as a maintenance treatment on a par with lithium.16

With its recent official FDA approval in the USA, the use of lurasidone as an effective and tolerable antidepressant in bipolar disorder is also gaining ground.17-19

Although its acute anti-manic efficacy remains less impressive, lithium continues to have the best evidence base for the long-term management and relapse prevention of bipolar disorder, reducing the risk of suicide by more than 50%.20 NICE recommends  other drugs, such as olanzapine, quetiapine and valproate as second-line prophylactics, if there is little or no response to lithium.6 However, there is limited evidence for the efficacy of valproate in the long-term management of bipolar disorder,21 but lamotrigine has been shown to reduce the risk of relapse by 36% over 18 months.22

Valproate should not be started in primary care to treat bipolar disorder, nor should lithium for people who have not taken lithium previously, except under shared-care arrangements.5 Furthermore, women of childbearing potential should not be prescribed valproate, but if no alternative can be identified, adequate contraception should be used, and teratogenic and other risks of taking valproate explained.6


Non-pharmacological therapy

NICE emphasises the importance of non-pharmacological therapy, including structured psychological interventions, such as cognitive behaviour, interpersonal, psycho-education, or behavioural couple therapy, which could be used independently to develop coping strategies and crisis plans in milder bipolar disorder. Interventions should be limited to those with published evidence-based manuals describing in detail how they should be delivered.

Psychological treatments are preferred in children and young people, because of the potential of drug treatments to impact on growth and development. If the response to a psychological therapy is poor after 4-6 weeks, alternative individual or family psychological interventions should be considered.

If the young person’s condition is moderate to severe, combining psychological and pharmacological interventions should be considered.

If drug treatment is necessary, the same drugs used to treat adult bipolar disorder are used for children and young people, but modified with reference to the BNF for Children, and with the addition of aripiprazole for moderate to severe mania, based on a positive technology appraisal by NICE.23 Antipsychotics should not be prescribed for longer than 12 weeks without review.6

Patients with bipolar I and bipolar II disorder should be offered the same treatment interventions in the first instance, as should those with rapid cycling bipolar disorder, as there is no strong evidence to suggest that the latter should be treated differently.6 Supportive and empathetic relationships should be maintained to encourage full adherence to treatment regimens.



The quality and outcomes framework (QOF) mental health indicators state that practices should produce a register of patients with bipolar disorder and review their physical health annually,

see table 3, p13.

The contract further suggests that the patient’s care plan should include current health status, social situation, social support, co-ordination arrangements with secondary care, details of early warning signs, and the patient’s preferred course of action in the event of a clinical relapse.

This is in accordance with the NICE recommendation that registers should be developed and used to monitor the physical and mental health of people with bipolar disorder in primary care.6

Physical health should be monitored whenever responsibility is transferred from secondary to primary care, and then at least annually, see table 4, above. Shared care protocols should be developed between primary and secondary care physicians to clarify arrangements and responsibilities for physical health monitoring.

Checks should focus on cardiovascular disease, diabetes, obesity and respiratory disease given the heightened risk for these illnesses in bipolar disorder. The identification of any of these should lead to further assessment, treatment and management. Those with bipolar disorder and diabetes or cardiovascular disease should be offered treatment in primary care in line with the relevant guidance on diabetes and lipid modification.

Several medications used to treat bipolar disorder can result in weight increase. If a patient gains weight during treatment, the GP should provide dietary advice, recommend regular aerobic exercise, consider referral to a dietician or to mental health services for a weight management programme.


Although bipolar disorder has been described as the heartland of psychiatry,24 with the introduction of New Ways of Working psychiatrists have relinquished the medical outpatient model of practice, and the GP plays an increasingly central role in monitoring and maintaining the long-term mental stability and general health of patients with bipolar disorder.25

Given that clinical guidance applies to the average patient (possibly selected for evidence generating studies from a less severe, healthier and more

co-operative sub-sample), adhering to guidelines uncritically may not be beneficial.26 Guidelines are continually adjusted and will change as more is understood about the aetiology of the bipolar spectrum, the efficacy of specific and combination treatments, and the complicated presentation of symptoms, when other physical and mental conditions are present.

The implementation of guidelines is further complicated by significant social, financial, personality and other risks. Crises may arise from suicide attempts, exploitation and self-neglect, engagement problems through lack of insight and other unique individual circumstances. The pooling and

co-ordination of the resources of primary and secondary care as well as other community resources are essential to maintain support for patients with bipolar disorder.


1 Cerimele JM, Chwastiak LA, Dodson S, Katon WJ. The prevalence of bipolar disorder in general primary care samples: a systematic review. Gen Hosp Psychiatry 2014;36(1):19-25

2 Reilly S, Planner C, Hann M et al. The role of primary care in service provision for people with severe mental illness in the United Kingdom. PLoS One 2012;7(5):e36468

3 Connolly KR, Thase ME. The clinical management of bipolar disorder: a review of evidence-based guidelines. Prim Care Companion CNS Disord 2011;13(4)

4 de Girolamo G, Dagani J, Purcell R et al. Age of onset of mental disorders and use of mental health services: needs, opportunities and obstacles. Epidemiol Psychiatr Sci 2012;21(1):47-57

5 Ebmeier KP. Managing bipolar disorder in primary care. Practitioner 2010;254(1729):19-22

6 National Institute for Health and Care Excellence. CG185. Bipolar disorder: the assessment and management of bipolar disorders in adults, children and young people in primary and secondary care. NICE. London. 2014

7 American Psychiatric Association (APA). Diagnostic and Statistical Manual of Mental Disorders, 5th edition. American Psychiatric Publishing. Washington DC, USA. 2013

8 Goodwin GM, Anderson I, Arango C et al. ECNP consensus meeting. Bipolar depression. Nice, March 2007. Eur Neuropsychopharmacol 2008;18(7):535-49

9 Gilman SE, Dupuy JM, Perlis RH. Risks for the transition from major depressive disorder to bipolar disorder in the National Epidemiologic Survey on Alcohol and Related Conditions. J Clin Psychiatry 2012;73(6):829-36

10 Craddock N, Jones I. Molecular genetics of bipolar disorder. Br J Psychiatry Suppl 2001;41:s128-33

11 World Health Organization. ICD-10 Classifications of Mental and Behavioural Disorder: Clinical Descriptions and Diagnostic Guidelines. WHO. Geneva. 1992

12 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;378(9799):1306-15

13 Vieta E, Parramon G, Padrell E et al. Quetiapine in the treatment of rapid cycling bipolar disorder. Bipolar Disord 2002;4(5):335-40

14 Suppes T, McElroy SL, Keck PE et al. Use of quetiapine in bipolar disorder: a case series with prospective evaluation. Int Clin Psychopharmacol 2004;19(3):173-4

15 Calabrese JR, Keck PE Jr, Macfadden W et al. A randomized, double-blind, placebo-controlled trial of quetiapine in the treatment of bipolar I or II depression. Am J Psychiatry 2005;162(7):1351-60

16 Weisler RH, Nolen WA, Neijber A et al. Trial 144 Study I. Continuation of quetiapine versus switching to placebo or lithium for maintenance treatment of bipolar I disorder (Trial 144: a randomized controlled study). J Clin Psychiatry 2011;72(11):1452-64

17 Sanford M, Dhillon S. Lurasidone: A Review of Its Use in Adult Patients with Bipolar I Depression. CNS Drugs 2015;29(3):253-63

18 Ketter TA, Miller S, Dell'Osso B et al. Balancing benefits and harms of treatments for acute bipolar depression. J Affect Disord 2014;169 Suppl 1:S24-33

19 Fountoulakis KN, Gazouli M, Kelsoe J, Akiskal H. The pharmacodynamic properties of lurasidone and their role in its antidepressant efficacy in bipolar disorder. Eur Neuropsychopharmacol 2015;25(3):335-42

20 Cipriani A, Pretty H, Hawton K, Geddes JR. Lithium in the prevention of suicidal behavior and all-cause mortality in patients with mood disorders: A systematic review of randomized trials. Am J Psychiatry 2005;162(10):1805-19

21 Cipriani A, Reid K, Young AH et al. Valproic acid, valproate and divalproex in the maintenance treatment of bipolar disorder. Cochrane Database Syst Rev 2013;10:CD003196

22 Goodwin GM, Bowden CL, Calabrese JR et al. A pooled analysis of 2 placebo-controlled 18-month trials of lamotrigine and lithium maintenance in bipolar I disorder. J Clin Psychiatry 2004;65(3):432-41

23 National Institute for Health and Care Excellence. TA292. Aripiprazole for treating moderate to severe manic episodes in adolescents with bipolar I disorder. NICE. London. 2013

24 Goodwin GM, Geddes JR. What is the heartland of psychiatry? Br J Psychiatry 2007;191:189-91

25 Department of Health. Mental health: New ways of working for everyone - Developing and sustaining a capable and flexible workforce. HMSO. London. 2007 

26 Goodwin GM for Consensus Group of the British Association for Psychopharmacology. Evidence-based guidelines for treating bipolar disorder: recommendations from the British Association for Psychopharmacology. J Psychopharmacol 2003;17(2):149-73



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