Bipolar Affective Disorder

NHSL Medicines Guidance
NHS Lanarkshire

General Notes

Bipolar Affective Disorder (BPAD) is a chronic, recurrent cyclical mood disorder associated with high levels of suffering, occupational dysfunction, impaired social life and relationships, as well as increased morbidity and mortality. BPAD is often co-morbid with a range of other mental disorders (for example, psychosis, substance misuse, anxiety disorders, personality disorders and ADHD) and this has significant implications for both the course of the disorder and its treatment.

The treatment of BPAD is based primarily on psychotropic medication to reduce the severity of symptoms, stabilise mood and prevent relapse. The treatments are determined by the phase of illness and subtype of disorder. Individual variation in response to medication will often determine the choice of drug, as will age, side effects, interactions and associated cautions, child-bearing potential, previous history, medical co-morbidities and individual preferences. Clear, written information about BPAD, treatment options, benefits and side effects should be discussed and provided to service users and carers. Psychological interventions developed specifically for bipolar disorder or high-intensity psychological interventions should also be offered, particularly to prevent relapse and manage recurrent depressive episodes.

Treatment will always be initiated in secondary care.  Initial management of acute behavioural disturbance would follow BNF guidance and include combined use of an antipsychotic and benzodiazepine if required.

Treatment of rapid cycling subtypes of BPAD should follow preferred formulary options.

The Choice and Medication website offers patient information about mental health conditions and the treatments available to help make informed decisions about choosing the right medicine: www.choiceandmedication.org/nhs24/

MONITORING
BPAD is associated with poor physical health and drug treatments can add to this. NICE recommends a physical health check for people with bipolar disorder, performed at least annually, to include weight or BMI; diet, nutritional status and level of physical activity; cardiovascular status, including pulse and blood pressure; metabolic status, including fasting blood glucose, glycosylated haemoglobin (HbA1c), prolactin, blood lipid profile and liver function. Renal/thyroid function and calcium levels are necessary, for people taking long-term lithium. People identified as having rapid or excessive weight gain, hypertension, diabetes, abnormal lipid levels, obesity (or risk factors) or are physically inactive should be managed in line with the relevant NICE guidance. The impact of alcohol, tobacco and illicit drugs on physical and mental health and potential drug interactions with medication should be discussed.

MHRA VALPROATE AND DEVELOPMENTAL DISORDERS ALERT

IMPORTANT NEW RESTRICTIONS: MHRA DRUG SAFETY UPDATES JANUARY 2024 AND SEPTEMBER 2024: Additional safety measures include changes to initiation of Valproate and ongoing prescription review for MALES and FEMALES.

Valproate must not be prescribed to women/girls of childbearing potential unless enrolled in pregnancy prevention programme (PPP).

Inform male patients (of any age) who may father children of the possible increased risk of neurodevelopmental disorders in children conceived around the time of valproate use and the recommendation to use effective contraception (condoms, plus contraception used by the female sexual partner) during valproate treatment and for at least 3 months after stopping valproate.

Source: MHRA Drug Safety Update Jan 2024: New safety and educational materials to support regulatory measures in men and women under 55 years of age, and Sep 2024: Valproate use in men: as a precaution, men and their partners should use effective contraception.

MHRA Resources: MHRA information page, Patient Guide, Patient card, Patient Information Leaflet, Healthcare Professional Guide, Annual Risk Acknowledgement Form for female patients, Risk Acknowledgement Form for male patients starting valproate, Advice for male patients on valproate to use contraception and Visual risk communication diagram to be used by a healthcare professional when counselling on the risks.

USEFUL LINKS

Bipolar disorder: assessment and management (NICE guidelines [CG185] Published date: September 2014; last updated February 2020)

Evidence-based guidelines for treating bipolar disorder: revised third edition – G. M Goodwin, Consensus Group of the British Association for Psychopharmacology. Journal of Psychopharmacology (2016) 1-59. 

NHS Lanarkshire Information for patients: Lithium in hot weather (NHSL staff access only).

Acute Treatment of Mania / Hypomania

Specialist initiation (S1)

RISPERIDONE tablets

  • Licensed for 18 yrs and over.

QUETIAPINE immediate release tablets

  • Restriction: the modified release formulation should be reserved for patients intolerant of the immediate release formulation.
  • Licensed for 18 yrs and over.

OLANZAPINE tablets

  • Where dispersible tablets are required prescribe as orodispersible tablets.
  • Licensed for 18 yrs and over.

ARIPIPRAZOLE tablets

  • An option for treatment and recurrence prevention of mania in adults over 18 yrs and the treatment of mania (under expert supervision) in young people over 13 yrs.

HALOPERIDOL tablets

  • Always consider risk of movement disorders (EPSEs) and tolerability with haloperidol.
  • Licensed for 18 yrs and over.
  • Haloperidol should not be initiated without an up to date ECG being available.

LITHIUM CARBONATE tablets

SODIUM VALPROATE tablets

Prescribing Notes:

  • If episode is severe or life-threatening – consider electroconvulsive therapy (ECT) early.
  • Review and consider stopping antidepressant if it appears this could have contributed to manic / hypomanic episode.
  • If already on lithium or valproate ensure dosing is optimal.
  • Observe BNF guidance for initiating & monitoring antipsychotics, lithium and sodium valproate.
  • Other anticonvulsants (e.g. gabapentin, lamotrigine, pregabalin and topiramate) are not recommended as at this time, there is inadequate supporting evidence of their clinical effectiveness in acute mania / hypomania.

Treatment of Depressive Episode

Specialist initiation (S1)

  • Antidepressant medication should only be prescribed in bipolar depression as an adjunct to mood stabilisers, due to risk of switching and cycle acceleration. Such risks may be less with SSRIs/SNRIs. Avoid tricyclics or MAOIs. Check side effects and interactions. Review patient and consider stopping the antidepressant if in remission from depressive symptoms.
  • Treatment of depressive episodes should be in line with current formulary recommendations
  • Augmentation with a mood stabiliser should be considered if not already prescribed.

FLUOXETINE capsules (in combination with OLANZAPINE tablets)

  • Off-label but recommended by NICE in combination with olanzapine due to strong evidence base.

QUETIAPINE immediate release tablets

  • Licensed as monotherapy or in combination with another mood stabiliser.
  • Restriction: the modified release formulation should be reserved for patients intolerant of the immediate release formulation.
  • Licensed for 18 yrs and over.

OLANZAPINE tablets

  • No specific license but a NICE recommended alternative.
  • Where dispersible tablets are required prescribe as orodispersible tablets.

ARIPIPRAZOLE tablets

  • off-label, use of aripiprazole in bipolar depression is mainly extrapolated from its use in unipolar depression data.

LAMOTRIGINE tablets

  • NICE recommended. May be useful if marked mood instability is also present.
  • Licensed for prevention of depressive episodes in over 18 yrs.

LITHIUM CARBONATE tablets

SODIUM VALPROATE tablets

Prescribing Notes:

  • If episode is severe or life-threatening – consider electroconvulsive therapy (ECT) early.
  • If already on lithium or valproate ensure dosing is optimal.
  • Observe local and national guidance for initiating & monitoring antipsychotics, lithium and sodium valproate.

Long Term Maintenance Treatment

Specialist initiation (S1)

LITHIUM CARBONATE tablets

  • Lithium should be offered as a first-line, long-term pharmacological treatment. It reduces the risk of relapse, suicidal behaviour, self-harm and mortality.
  • Lithium should be prescribed by brand name. Current preferred formulary brand is Priadel®.
  • Licensed for 12 yrs and over.
  • National Guidance for Monitoring Lithium (SGHD/CMO(2019)4)

SODIUM VALPROATE tablets

OLANZAPINE tablets

  • Where dispersible tablets are required prescribe as orodispersible tablets.
  • Licensed as monotherapy or in combination with lithium or valproate. May be useful if lithium or valproate are contraindicated or not tolerated.
  • Licensed for 18 yrs and over.

QUETIAPINE immediate release tablets

  • Consider if lithium is poorly tolerated or is not suitable and quetiapine was effective during an acute episode of mania or bipolar depression.
  • Restriction: the modified release formulation should be reserved for patients intolerant of the immediate release formulation.
  • Licensed for 18 yrs and over.

ARIPIPRAZOLE tablets

  • Consider if lithium is poorly tolerated or is not suitable and aripiprazole was effective during an acute episode of mania.
  • Licensed for 18 yrs and over.

LAMOTRIGINE tablets

  • Licensed as monotherapy or adjunctive therapy of bipolar disorder – with possible superior efficacy for those who experience predominantly depressive episodes.
  • Licensed for 18 yrs and over.

Prescribing Notes:

  • NICE recommends that long-term treatment should be discussed with the service user/carer, within 4 weeks of resolution of each episode of mania or bipolar depression. Long-term pharmacological treatment to prevent relapse should take into account medicines that have been effective during acute episodes of mania or bipolar depression.
  • Long term treatment with lithium, anticonvulsants, and antipsychotics need careful monitoring. Observe local or national guidance.
  • Review and consider stopping the antidepressant if there is clear remission of depressive symptoms and the illness is not characterized by significant recurrent severe depressive episodes.
  • For patients who have experienced chronic recurrent depressive episodes consider long-term treatment with mood stabiliser combined with an antidepressant.
  • Carbamazepine is licensed for prophylaxis of bipolar affective disorder when lithium is not tolerated or ineffective but is not recommended due to difficulties in its use - slow dose initiation; numerous side effects and interactions involving enzyme induction; teratogenic – avoid in girls or women of child-bearing potential.
  • Other anticonvulsants (e.g. gabapentin, pregabalin and topiramate) are not recommended as at this time, there is inadequate supporting evidence of their clinical effectiveness.

NHSL Joint Adult Formulary Key

To indicate the category of a formulary medicine, updated sections adopt the following key:

Preferred list (P): First-line formulary choices.

Total list (T): Alternative choices when preferred list options not effective/not tolerated, or not indicated.

Specialist initiation (S1): Specialist initiation, or on the advice of a Consultant or Specialist Practitioner in this therapeutic area. Continuation in primary care is acceptable.

Specialist use only (S2): Supply via hospital, Homecare Service or a hospital based prescription (HBP) for dispensing by community pharmacy. Not prescribed in primary care setting.

Editorial Information

Last reviewed: 29/11/2023

Author(s): NHSL.

Version: Please refer to the introduction section for an explanation of the review dates above.

Approved By: ADTC

Reviewer name(s): ADTC.