This article has been updated
1. Don’t medicalise normal moods and personality traits, but don’t miss bipolar, either.
GPs will see many patients with self-limiting low mood, stress and irritability, fewer with depression and many fewer still with bipolar disorder. But bipolar has a high suicide rate (up to 15% make an attempt1) and causes significant cognitive, functional and economical impairment. And physical comorbidity is common, with cardiovascular disease being the main cause of premature death.2 Importantly, correct diagnosis and management can improve prognosis and quality of life.
Yet bipolar can be difficult to diagnose,3 may be ‘missed’ for many years, and prescribing antidepressants to someone with unrecognised bipolar can be dangerous (see below). And although bipolar medications are lifesaving for some, they may cause serious side-effects.
But do not formally diagnose bipolar disorder in primary care. This is difficult medicine, so NICE recommends referring suspected cases for a specialist opinion, and it may take some time for a definitive diagnosis. The risks of both ‘underdiagnosis’ and ‘overdiagnosis’ should be appreciated – (including ‘labelling,’ driving and insurance implications, and medication risk/benefits). Refer patients with mania (see below), psychosis or severe depression, and consider referring patients with recurrent depression/anxiety/irritability – especially if there is no response to two or more antidepressants – substance misuse or borderline personality disorder.4 Prior to referral, watchful waiting is often helpful to see if time heals and to review mood diaries, mood questionnaires, family history and response to non-drug approaches. Consider a second opinion if your patient is not improving and the diagnosis is uncertain.
2. There are several types of bipolar (see figure 1, 2 – available to download on the left – and box below)
The presence of mania or hypomania – characterised by abnormally and persistently increased activity or energy – is essential for diagnosis. The ‘bipolar spectrum’ includes varying severity:
- Bipolar I – mania (more than one week) with or without depression, previously called ‘manic depression’.
- Bipolar II – hypomania (more than four days) and depression.
There may also be milder forms of ‘subthreshold’ bipolar, and there is ongoing debate and research about this. In all subtypes, so-called ‘mixed symptoms’ (simultaneous depression and mania/hypomania – ’agitated depression’) are frequent and increase the risk of suicide.5 Bipolar ‘episodes’ (mania, hypomania, depression or ‘mixed’) usually recur – these cycles may be years apart or within the same day, so accurate diagnosis and long-term planning are crucial.
WHO, ICD-10 Version: 2010
Note: ICD-11 update in progress. DSM-V criteria (2013) are similar, and now include abnormally and persistently increased activity or energy as a core criteria, for both mania and hypomania
F30.1 Mania without Psychosis
A Mood predominantly elevated, expansive or irritable & definitely abnormal for the individual. The Mood change must be prominent and sustained for at least a week (unless it is severe enough to require hospital admission).
B >3 of following (4 if merely irritable) leading to severe interference with functioning.
- Increased activity or restlessness
- Increased talkativeness (’pressure of speech’)
- Flight of ideas or racing thoughts
- Loss of inhibitions – inappropriate behaviour
- Decreased need for sleep
- Inflated self-esteem or grandiosity
- Distractibility or constant changes in activity or plans
- Foolhardy or reckless behaviour whose risks the subject does not recognize e.g. spending sprees, foolish enterprises, reckless driving;
- Marked sexual energy or sexual indiscretions.
C. The absence of hallucinations or delusions, although perceptual disorders may occur (e.g. subjective hyperacusis, appreciation of colours as specially vivid, etc.).
D. Most commonly used exclusion criteria: the episode is not attributable to psychoactive substance use (F1) or any organic mental disorder.
See ICD-10 for other relevant bipolar diagnostic criteria
3. Bipolar I is usually straightforward to diagnose – mania is dramatic, but severe depression (for example, in a teenager or young adult) may be the first sign
Bipolar I affects approximately 1% of individuals – 16 patients in an average GP list size of 1600. The criteria for mania are clear (see figures 1 and 2, and ICD-10), but bipolar depression is more common and far more likely to be seen by GPs.6 Sometimes, mania is incorrectly called ‘hypomania’, but it’s important to be clear because it makes a difference to the diagnosis, treatment and prognosis.7 Euphoria, loss of insight or psychosis mean that manic patients may not feel unwell and may not ask for help, so a third party may contact you instead. The prodrome of mania (increased activity, anxiety, insomnia and irritability) can be subtle unless you already know the patient and recognise that something has changed.
4. Bipolar II is serious but difficult to diagnose.
Consider the diagnosis in people with recurrent anxiety depression or irritability if they have unusually variable mood, energy and activity levels. Bipolar II was first formally described in 1976 – recurrent severe depression and hypomania, with a high suicide rate,8 and may affect 1-2% of people. Bipolar II is not ’bipolar lite’, but it must be diagnosed accurately. Fatigue, cognitive slowing, functional impairment and suicide rates are higher and treatment often more difficult than Bipolar I. Consider the diagnosis in people with recurrent anxiety depression or irritability if they have unusually variable mood, energy and activity levels, or a poor response to antidepressants. Refer to psychiatry if you suspect this.
5. Ask about a history of overactivity or irritability (possible mania or hypomania) in people with recurrent depression.
Think ‘is this, or was that, mania or hypomania’? Mood questionnaires, such as MDQ9 and HCL32,10 while not diagnostic, can help identify previous mania/hypomania, but NICE recommends that they are not sensitive enough to be used for diagnosis in primary care. Additional clues that your ‘depressed’, ‘anxious’ or ‘irritable’ patient may actually have bipolar include:11
- A family history of bipolar or psychosis
- Borderline personality disorder (may be misdiagnosed).
- ‘Atypical’ depression:
- Sleeping or eating more
- Psychomotor retardation
- Marked fatigue with ‘lead-like’ slowness and heaviness
- Marked guilt
- Lack of response to two or more antidepressants
6. Non-pharmacological interventions are important
Psychoeducation programmes, such as Beating Bipolar, help understanding, reduce recurrence and may allow for reduced medication.12 Key points include awareness of mood triggers, body clock rhythms (regular daily schedules) and sleep.
Mania is characterised by a reduced need for sleep, while sleep deprivation can also trigger mania. So a nap during the day, with or without judicious short-term benzodiazepines, can reduce hypomanic symptoms and may prevent an episode escalating.
Reducing fatigue and hypersomnia in bipolar depression is difficult. Light therapy may help, as can ‘activating’ medications such as lamotrigine and modafinil, but these may cause a ‘switch’ to mania and must be used with caution.
Good nutrition is important, ideally based around the ‘Mediterranean’ diet, which may also help reduce comorbid physical health problems (obesity, type 2 diabetes, cardiovascular disease). Ensure a regular intake of fish and tree nuts (inositol may reduce anxiety), and avoid alcohol, excess sugar and possibly gluten (both depressive in some).13-15 Many ask about supplements – evidence is limited and treatment effects are small, but omega-3 fish oil may reduce depression/anxiety, as may inositol, N-acetyl-cysteine and multivitamins.16-19
7. Be cautious with antidepressants and steroids
In general, antidepressants don’t work well in people with bipolar, so think about a diagnosis of bipolar if response is poor. Antidepressants:
- Can trigger hypomania/mania.
- May cause rapid cycling.
- May increase the risk of suicide.20,21
So don’t prescribe antidepressants in bipolar unless discussed with psychiatry, and even then, usually with a mood stabiliser.
Systemic steroids (for example, for acute asthma) can cause mood instability, even in those without bipolar. If steroids are essential in someone with bipolar, discuss with psychiatry and consider increased or additional mood stabiliser.
8. Where medication is needed, do not initiate lithium, antipsychotics or anticonvulsant medications in primary care – discuss with psychiatry first
The pharmacological treatments of bipolar I and II are often different and specialist advice is essential, especially as side effects can be serious. In contrast to unipolar depression, bipolar medications and dose may need to vary and it can take months or years to get the right balance.
Patients with less severe illness and good insight may only need prn medication, for example, judicious benzodiazepines or antipsychotics for brief periods of irritability and insomnia. But others may need a combination of mood stabilisers, including lithium, antipsychotics, anticonvulsants and, occasionally, cautious short-term antidepressants.
9. Lithium remains the gold standard in many situations.22
Lithium is neuroprotective and reduces suicide risk by 80%, probably by reducing relapse and impulsivity.23 Efficacy is best in ‘classical’ euphoric mania, but less in mixed states or bipolar depression.24 Therapeutic serum levels take four to 14 days and optimal effect may take several months, so antipsychotics or valproate, which work faster, are often combined with lithium. It should be noted that even when patients have been well for years, stopping lithium can be dangerous because there is a high risk of relapse – discuss with psychiatry first.25
10. GPs play a key role in management – continuity, longer consultations and good communication between the GP and secondary care are crucial.
The GPs’ overall perspective is invaluable. This includes physical health monitoring and, in conjunction with psychiatry, consideration if any medications can be safely stopped or if an increased dose would be beneficial. Advance planning to prevent relapse is also important, for example for university exams, seasonal changes, jet lag and pregnancy. These issues could be included in care plans.
Dr Daniel Dietch is a GP partner in north west London with a special interest in mental health, including nutritional aspects
Professor Allan H Young is a professor in mood disorders at the Institute of Psychiatry and King’s College London
Dr Dietch and Professor Young have donated their fees for this article to Bipolar UK and the International Society for Affective Disorders (ISAD)
Competing interests – Professor Young has the following competing interests:
- Paid lectures and advisory boards for all major pharmaceutical companies with drugs used in affective and related disorders
- Lead investigator for Embolden study (AZ), BCI neuroplasticity study and Aripiprazole mania study
- Investigator initiated studies from AZ, Eli Lilly, Lundbeck and Wyeth
- Grant funding (past and present): NIMH (USA); CIHR (Canada); NARSAD (USA); Stanley Medical Research Institute (USA); MRC (UK); Wellcome Trust (UK); RCP(Ed) (UK); BMA (UK); UBC-VGH Foundation (Canada); WEDC (Canada); CCS Depression Research Fund (Canada); MSFHR (Canada).
1. Rihmer Z, Kiss K. Bipolar disorders and suicidal behaviour. Bipolar Disord. 2002;4 Suppl 1(SUPPL. 1):21–25.
2. Westman, J., Hällgren, J., Wahlbeck, K., Erlinge, D., Alfredsson, L., & Osby, U. Cardiovascular mortality in bipolar disorder: a population-based cohort study in Sweden. BMJ Open, (2013), 3(4), e002373-.
3. Dietch D, Martin D, Smith DJ, Chew-Graham C. Bipolar Disorder – guidance on recognition in Primary Care. Cut Edge Psychiatry Pract. 2013:361–376.
4. Angst J, Azorin JM, Bowden CL et al. Prevalence and characteristics of undiagnosed bipolar disorders in patients with a major depressive episode: the BRIDGE study. Arch Gen Psychiatry, 2011;68(8):791–8
5. Benazzi F. Bipolar disorder–focus on bipolar II disorder and mixed depression. Lancet, 2007;369(9565):935–45
6. Judd LL. The long-term natural history of the weekly symptomatic status of bipolar I disorder. Arch Gen Psychiatry, 2002;59(6):530–537
7. Goodwin G. Hypomania: what’s in a name? Br J Psychiatry, 2002;181(2):94–95
8. Dunner DL, Gershon ES, Goodwin FK. Heritable factors in the severity of affective illness. Biol Psychiatry. 1976;11(1):31–42.
9. Hirschfeld RM, Williams JB, Spitzer RL, et al. Development and validation of a screening instrument for bipolar spectrum disorder: the Mood Disorder Questionnaire. Am J Psychiatry. 2000;157(11):1873–5.
10. Angst J, Adolfsson R, Benazzi F, et al. The HCL-32: towards a self-assessment tool for hypomanic symptoms in outpatients. J Affect Disord. 2005;88(2):217–33.
11. Mitchell PB, Goodwin GM, Johnson GF, Hirschfeld RMA. Diagnostic guidelines for bipolar depression: a probabilistic approach. Bipolar Disord. 2008;10(1 Pt 2):144–52.
12. Vieta E. The package of care for patients with bipolar depression. J Clin Psychiatry. 2005;66 Suppl 5(suppl 5):34–39.
13. Opie, R. S., O’Neil, A., Itsiopoulos, C., & Jacka, F. N. (2014). The impact of whole-of-diet interventions on depression and anxiety: a systematic review of randomised controlled trials. Public Health Nutrition, 18(11), 1–20.
14. Dickerson F, Stallings C, Origoni A, Vaughan C, Khushalani S, Yolken R. Markers of gluten sensitivity in acute mania: a longitudinal study. Psychiatry Res.2012;196(1):68–71.
15. Carr AC. Depressed mood associated with gluten sensitivity–resolution of symptoms with a gluten-free diet. N Z Med J. 2012;125(1366):81–2.
16. Frangou S, Lewis M, McCrone P. Efficacy of ethyl-eicosapentaenoic acid in bipolar depression: randomised double-blind placebo-controlled study. Br J Psychiatry. 2006;188(1):46–50.
17. Mukai T, Kishi T, Matsuda Y, Iwata N. A meta-analysis of inositol for depression and anxiety disorders.Hum Psychopharmacol. 2014;29(1):55–63.
18. Berk M, Copolov DL, Dean O, et al. N-acetyl cysteine for depressive symptoms in bipolar disorder–a double-blind randomized placebo-controlled trial.Biol Psychiatry. 2008;64(6):468–75.
19. Sarris J, Mischoulon D, Schweitzer I. Adjunctive nutraceuticals with standard pharmacotherapies in bipolar disorder: a systematic review of clinical trials.Bipolar Disord. 13(5-6):454–65.
20. Ghaemi SN, Ko JY, Goodwin FK. “Cade’s disease” and beyond: misdiagnosis, antidepressant use, and a proposed definition for bipolar spectrum disorder.Can J Psychiatry. 2002;47(2):125–34
21. Berk M, Dodd S. Are treatment emergent suicidality and decreased response to antidepressants in younger patients due to bipolar disorder being misdiagnosed as unipolar depression? Med Hypotheses. 2005;65(1):39.
22. Young AH, Hammond JM. Lithium in mood disorders: increasing evidence base, declining use?Br J Psychiatry. 2007;191(6):474–6.
23. Cipriani A, Hawton K, Stockton S, Geddes JR. Lithium in the prevention of suicide in mood disorders: updated systematic review and meta-analysis.BMJ. 2013;346(jun27_4):f3646.
24. Srivastava S, Ketter TA. Clinical relevance of treatments for acute bipolar disorder: balancing therapeutic and adverse effects.Clin Ther. 2011;33(12):B40–8.
25. Goodwin GM. Recurrence of mania after lithium withdrawal. Implications for the use of lithium in the treatment of bipolar affective disorder.Br J Psychiatry. 1994;164(2):149–52.
- Bipolar UK www.bipolaruk.org.uk
- NPSA Safer Lithium therapy www.nrls.npsa.nhs.uk/alerts/
- NICE Bipolar Guidelines CG185
- Practical management of Bipolar Disorder AH Young, IN Ferrier and E Michalak (Cambridge University Press, 2010)
- Bipolar Disorder, Your Questions Answered. N Hunt (Churchill Livingstone, 2005)
- Bipolar Disorder L Yatham G Malhi (Oxford University Press, 2011)
- Dietch, D. (2015). Recognising Bipolar Disorders in Primary Care Psychiatria Danubina, 27, S188–S194. See suggested flowchart for GPs there
- Goodwin G, Haddad P, Ferrier I et al. Evidence-based guidelines for treating bipolar disorder: Revised third edition recommendations from the British Association for Psychopharmacology. J Psychopharm 2016;30:495-553