Related guidance:

Bipolar disorder information leaflet (Royal College of Psychiatrists)

Aripiprazole for treating moderate to severe manic episodes in adolescents with bipolar I disorder Technology appraisal guidance (TA292 July 2013)

Bipolar disorder: assessment and management Clinical guideline (CG185 September 2014, updated December 2023)

  • When adults present in primary care with depression, ask about previous periods of overactivity or disinhibited behaviour. If the overactivity or disinhibited behaviour lasted for 4 days or more, consider referral for a specialist mental health assessment.
  • Refer people urgently for a specialist mental health assessment if mania or severe depression is suspected or they are a danger to themselves or others.
  • Do not use questionnaires in primary care to identify bipolar disorder in adults.
  • When working with people with bipolar disorder in primary care:
    • engage with and develop an ongoing relationship with them and their carers
    • support them to carry out care plans developed in secondary care and achieve their recovery goals
    • follow crisis plans developed in secondary care and liaise with secondary care specialists if necessary
    • review their treatment and care, including medication, at least annually and more often if the person, carer or healthcare professional has any concerns.
  • Offer people with bipolar depression:
    • a psychological intervention that has been developed specifically for bipolar disorder and has a published evidence-based manual describing how it should be delivered or
    • a choice of psychological intervention (cognitive behavioural therapy, interpersonal therapy or behavioural couples therapy) in line with the advice on treatment options for more severe depression in the NICE guideline on depression.
    Discuss with the person the possible benefits and risks of psychological interventions and their preference. Monitor mood and if there are signs of hypomania or deterioration of the depressive symptoms, liaise with or refer the person to secondary care. If the person develops mania or severe depression, refer them urgently to secondary care.
  • Psychological therapists working with people with bipolar depression in primary care should have training in and experience of working with people with bipolar disorder.
  • Do not start lithium to treat bipolar disorder in primary care for people who have not taken lithium before, except under shared-care arrangements.
  • Do not start valproate in primary care to treat bipolar disorder.
  • If bipolar disorder is managed solely in primary care, re-refer to secondary care if any one of the following applies:
    • there is a poor or partial response to treatment
    • the person’s functioning declines significantly
    • treatment adherence is poor
    • the person develops intolerable or medically important side effects from medication
    • comorbid alcohol or drug misuse is suspected
    • the person is considering stopping any medication after a period of relatively stable mood
    • a woman with bipolar disorder is pregnant or planning a pregnancy.

Managing mania or hypomania in adults in secondary care

  • Ensure that people with mania or hypomania have access to calming environments and reduced stimulation. Advise them not to make important decisions until they have recovered from mania or hypomania and encourage them to maintain their relationships with their carers if possible.
  • If a person develops mania or hypomania and is taking an antidepressant as monotherapy:
    • consider stopping the antidepressant and
    • offer an antipsychotic, regardless of whether the antidepressant is stopped.
  • If a person develops mania or hypomania and is not taking an antipsychotic or mood stabiliser, offer haloperidol, olanzapine, quetiapine or risperidone, taking into account any advance statements, the person’s preference and clinical context (including physical comorbidity, previous response to treatment and side effects).
  • If the first antipsychotic is poorly tolerated at any dose (including rapid weight gain) or ineffective at the maximum licensed dose, offer an alternative antipsychotic taking into account any advance statements, the person’s preference and clinical context (including physical comorbidity, previous response to treatment and side effects).
  • If an alternative antipsychotic is not sufficiently effective at the maximum licensed dose, consider adding lithium. If adding lithium is ineffective, or if lithium is not suitable (for example, because the person does not agree
    to routine blood monitoring), consider adding valproate instead. Do not start valproate for the first time in people (male or female) younger than 55 years, unless 2 specialists independently agree and document that there is no other effective and tolerated treatment, or there are compelling reasons that the reproductive risks do not apply. Ensure the pregnancy prevention programme is in place if valproate is used in women and girls of childbearing potential (as per MHRA alerts).

For MHRA alerts see NHS Somerset Formulary Epilepsy and other seizure disorders

  • If a person develops mania or hypomania and is taking an antidepressant in combination with a mood stabiliser, consider stopping the antidepressant.
  • If the person is already taking lithium, check plasma lithium levels to optimise treatment (see NPSA alert below). Consider adding haloperidol, olanzapine, quetiapine or risperidone, depending on the person’s preference and previous response to treatment.
  • If the person is already taking valproate or another mood stabiliser as prophylactic treatment, consider increasing the dose, up to the maximum level in the BNF if necessary, depending on clinical response. If there is
    no improvement, consider adding haloperidol, olanzapine, quetiapine or risperidone, depending on the person’s preference and previous response to treatment.
  • If a woman or girl of childbearing potential is already taking valproate, advise her to gradually stop the drug because of the risk of fetal malformations and adverse neurodevelopmental outcomes after any exposure in pregnancy.
  • If the clinical presentation is of a mixed affective state, characterised by both manic and depressive symptoms, follow recommendations for the treatment of mania, and monitor closely for the emergence of depression.
  • Do not offer lamotrigine to treat mania.
  • Within 4 weeks of resolution of symptoms, discuss with the person, and their carers if appropriate, whether to continue treatment for mania or start long-term treatment. Explain the potential benefits of long-term treatment and the risks, including side effects of medication used for long-term treatment.
  • If the person decides to continue treatment for mania, offer it for a further 3 to 6 months, and then review.

Managing bipolar depression in adults in secondary care

  • Offer adults with bipolar depression:
    • a psychological intervention that has been developed specifically for bipolar disorder and has a published evidence-based manual describing how it should be delivered or
    • a choice of psychological intervention (cognitive behavioural therapy, interpersonal therapy or behavioural couples therapy) in line with the advice on treatment options for more severe depression in the NICE guideline on depression.
    Discuss with the person the possible benefits and risks of psychological interventions and their preference. Monitor mood for signs of mania or hypomania or deterioration of the depressive symptoms.
  • Psychological therapists working with people with bipolar depression should have training in, and experience of, working with people with bipolar disorder.
  • If a person develops moderate or severe bipolar depression and is not taking a drug to treat their bipolar disorder, offer fluoxetine combined with olanzapine, or quetiapine on its own, depending on the person’s preference and previous response to treatment.
    • If the person prefers, consider either olanzapine (without fluoxetine) or lamotrigine on its own.
    • If there is no response to fluoxetine combined with olanzapine, or quetiapine, consider lamotrigine on its own (off-label use of fluoxetine).
  • If a person develops moderate or severe bipolar depression and is already taking lithium, check their plasma lithium level. If it is inadequate, increase the dose of lithium; if it is at maximum level, add either fluoxetine combined with olanzapine or add quetiapine, depending on the person’s preference and previous response to treatment.
  • If the person prefers, consider adding olanzapine (without fluoxetine) or lamotrigine to lithium.
  • If there is no response to adding fluoxetine combined with olanzapine, or adding quetiapine, stop the additional treatment and consider adding lamotrigine to lithium.
  • If a person develops moderate or severe bipolar depression and is already taking valproate, consider increasing the dose within the therapeutic range. If the maximum tolerated dose, or the top of the therapeutic range, has been reached and there is a limited response to valproate, add fluoxetine combined with olanzapine or add quetiapine, depending on the person’s preference and previous response to treatment.
    • If the person prefers, consider adding olanzapine (without fluoxetine) or lamotrigine to valproate.
    • If there is no response to adding fluoxetine combined with olanzapine, or adding quetiapine, stop the additional treatment and consider adding lamotrigine to valproate. If a woman or girl of childbearing potential is already taking valproate, advise her to gradually stop the drug because of the risk of fetal malformations and adverse neurodevelopmental outcomes after any exposure in pregnancy as per MHRA alerts.

For MHRA alerts see NHS Somerset Formulary Epilepsy and other seizure disorders

  • Take into account toxicity in overdose when prescribing psychotropic medication during periods of high suicide risk. Assess the need to limit the quantity of medication supplied to reduce the risk to life if the person overdoses.

Reviewing treatment for bipolar depression

  • Within 4 weeks of resolution of symptoms, discuss with the person, and their carers if appropriate, whether to continue psychological or pharmacological treatment for bipolar depression or start long-term treatment. Explain the potential benefits of long-term treatment and the risks, including side effects of medication used for long-term treatment.
  • If the person decides to continue psychological or pharmacological treatment for bipolar depression, offer it for a further 3 to 6 months, and then review.
  • When planning long-term pharmacological treatment to prevent relapse, take into account drugs that have been effective during episodes of mania or bipolar depression. Discuss with the person whether they prefer to continue this treatment or switch to lithium, and explain that lithium is the most effective long-term treatment for bipolar disorder.
  • Offer lithium as a first-line, long-term pharmacological treatment for bipolar disorder and:
    • if lithium is ineffective, consider adding valproate
    • if lithium is poorly tolerated, or is not suitable (for example, because the person does not agree to routine blood monitoring), consider valproate or olanzapine instead or, if it has been effective during an episode of mania or bipolar depression, quetiapine.
    Discuss with the person the possible benefits and risks of each drug for them.
  • If stopping long-term pharmacological treatment:
    • discuss with the person how to recognise early signs of relapse and what to do if symptoms recur
    • stop treatment gradually and monitor the person for signs of relapse.
  • Continue monitoring symptoms, mood and mental state for 2 years after medication has stopped entirely. This may be undertaken in primary care.

Physical health

  • Develop and use practice case registers to monitor the physical and mental health of people with bipolar disorder in primary care.
  • Monitor the physical health of people with bipolar disorder when responsibility for monitoring is transferred from secondary care, and then at least annually. The health check should be comprehensive and focusing on
    physical health problems such as cardiovascular disease, diabetes, obesity and respiratory disease. A copy of the results should be sent to the care coordinator and psychiatrist, and put in the secondary care records.
  • Ensure that the physical health check for people with bipolar disorder, performed at least annually, includes:
    • weight or BMI, diet, nutritional status and level of physical activity
    • cardiovascular status, including pulse and blood pressure
    • metabolic status, including fasting blood glucose or glycosylated haemoglobin (HbA1c), and blood lipid profile
    • liver function
    • renal and thyroid function, and calcium levels, for people taking long-term lithium.
  • Identify people with bipolar disorder who have hypertension, have abnormal lipid levels, are obese or at risk of obesity, have diabetes or are at risk of diabetes (as indicated by abnormal blood glucose levels), or are
    physically inactive, at the earliest opportunity. Follow NICE’s guidelines on hypertension, lipid modification, prevention of cardiovascular disease, obesity, physical activity and preventing type 2 diabetes.
  • Offer treatment to people with bipolar disorder who have diabetes and/or cardiovascular disease in primary care in line with NICE’s guidelines on type 1 diabetes in adults: diagnosis and management, type 2 diabetes in adults: management and lipid modification.

Safer lithium therapy (NPSA 2009)

  • Patients prescribed lithium are monitored in accordance with NICE guidance.
  • There are reliable systems to ensure blood test results are communicated between laboratories and prescribers.
  • At the start of lithium therapy and throughout their treatment patients receive appropriate ongoing verbal and written information and a record book to track lithium blood levels and relevant clinical tests.
  • Prescribers and pharmacists check that blood tests are monitored regularly and that it is safe to issue a repeat prescription and/or dispense the prescribed lithium.
  • Systems are in place to identify and deal with medicines that might adversely interact with lithium therapy.
  • The NPSA has developed a patient information booklet, lithium alert card and record book for tracking blood tests.

Accessing resources for patients on high risk medicines (SPS)

Lithium monitoring (SPS)

NHS Somerset Lithium Shared Care Protocol 

For interactions, see NHS Somerset Formulary Appendix 1

For lamotrigine see NHS Somerset Formulary Epilepsy and other seizure disorders

For antidepressants see NHS Somerset Formulary Depression

For antipsychotics see NHS Somerset Formulary Psychoses and schizophrenia

Therapeutic AreaFormulary ChoicesCost for 28
(unless otherwise stated)		Rationale for decision / comments
Antipsychotics, Lithium saltsPreparations vary widely in bioavailability and therefore should be prescribed by brand. Switching from one brand or preparation to another preparation requires the same precautions as initiation of treatment.NHS Somerset classify as an Amber drug for the treatment and prophylaxis of mania, bipolar disorder and recurrent depression as per traffic light guidance.

Tablets can be broken in half, swallow whole - do not crush or chew.

Dose adjusted according to serum-lithium concentration, doses are initially divided throughout the day, but once daily administration is preferred when serum-lithium concentration stabilised.
Lithium carbonate

as Liskonum®		450mg modified-release tablet: £11.84 (60)Adult: Initially 450-675mg twice daily.

Elderly: Initially 225mg twice daily.
as Priadel®200mg modified-release tablet: £12.46 (100)Adult: (body-weight up to 50kg) Initially 200-400mg daily, (body-weight 50kg and above) Initially 0.4-1.2g once daily, alternatively 0.4-1.2g daily in divided doses.

Elderly: Initially 200-400mg daily.
400mg modified-release tablet: £14.12 (100)
as Camcolit 400®400mg modified-release tablet: £48.18 (100)Adult: Initially 1-1.5g daily.

Elderly: Reduce initial dose.
Lithium citrate

as Priadel®		520mg/5ml oral solution sugar free: £11.18 (150ml)Adult: (body-weight up to 50kg) Initially 520mg twice daily. (body-weight 50kg and above) Initially 1.04-3.12g daily in 2 divided doses.

Elderly: Initially 520mg twice daily.

For Priadel ® liquid: lithium citrate 520mg is equivalent to lithium carbonate 204mg.
as Li-Liquid®509mg/5ml oral: £5.79 (150ml)Adult: (body-weight up to 50kg) Initially 509mg daily in 2 divided doses. (body-weight 50kg and above) Initially 1.018-3.054g daily in 2 divided doses.

Elderly: Initially 509mg daily in 2 divided doses.

For Li-liquid®: lithium citrate 509mg is equivalent to lithium carbonate 200mg.
as Li-Liquid®1.018g/5ml oral solution: £17.49 (150ml)
AntiepilepticsValproic acid250mg gastro-resistant tablet: £5.69 (30)NHS Somerset classify as an Amber drug for the treatment of manic episodes associated with bipolar disorder as per traffic light guidance.

Adult: Initially 750mg daily in 2-3 divided doses, then increased to 1-2g daily, adjusted according to response, doses greater than 45mg/kg daily require careful monitoring.

Semisodium valproate comprises equimolar amounts of sodium valproate and valproic acid.


Do not start valproate for the first time in people (male or female) younger than 55 years, unless 2 specialists independently agree and document that there is no other effective and tolerated treatment, or there are compelling reasons that the reproductive risks do not apply. Ensure the pregnancy prevention programme is in place if valproate is used in women and girls of childbearing potential.
500mg gastro-resistant tablet: £11.37 (30)