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Evidence-based guidelines for treating bipolar disorder

Diagnosis

  • Make accurate diagnoses of hypomania, mania and depression:
    • consider identifying core symptoms using:
      • a check list as in DSM-5
      • a patient-completed screening instrument
    • use term 'hypomania' as defined in DSM-5
    • do not dismiss or minimise mood elevation when the cause of disturbed behaviour:
      • personality problems or situational disturbance should be invoked only if mania (or hypomania) is absent
    • in all patients with depression, ask about distinct periods of elated, excited or irritable mood of any duration and a family history of mania
    • diagnosis is only reliable after a clear-cut episode of (hypo)mania
  • Possible co-morbidities:
    • assess, monitor and treat:
      • alcohol and/or substance use disorder
      • anxiety disorders
      • borderline personality disorder
  • Possible differential diagnoses
    • stimulant drugs (e.g. levodopa and corticosteroids)
    • borderline personality disorder
    • organic conditions, e.g. thyroid disease, multiple sclerosis, or any lesion(s) involving right-sided sub-cortical or cortical areas
  • Borderline personality disorder:
    • should not be confused with episodes of mania or depression
    • may be co-morbid with an episodic mood disorder

Pre-pubertal children

  • Defining characteristics: unequivocal euphoria and an episodic course:
    • do not make the diagnosis in children or young people unless there has been a period of prospective longitudinal monitoring by appropriately experienced clinicians taking into account the child or young person’s educational and social functioning
  • Possible differential diagnosis:
    • disruptive mood dysregulation disorder (DMDD)

Management

  • When mania is diagnosed:
    • always consider admission to hospital or intensive community management
    • offer assessment by a trained psychiatrist
  • Risks to the patient and others are from poor judgement and associated actions
    • always try to obtain third party information if in doubt when making a risk assessment
  • If in a mixed state or depressed ask about suicidal ideation and plans/means/preparation for suicide
  • Assess risk of exploitation, violence and offending
  • Carefully document decisions in formulating a care plan
  • Establish and maintain a therapeutic alliance:
    • take responsibility for diagnosis, physical examination, investigations and explanation of management plan
    • communicate clearly and honestly
    • listen to what is bothering the patient
    • very disorganised psychotic patients will require assertive management of social needs
  • Educate the patient and their family about:
    • the disorder
    • the potential benefits and risks of medication and need to continue it long term
  • Enhance treatment adherence:
    • use known tolerability and safety to guide prescribing
    • inform patients about possible side-effects and monitor for emergence
    • prioritise reducing adverse reactions: use different scheduling, alternative formulations or lower doses
  • Promote awareness of stressors, sleep disturbance, early signs of relapse, and regular patterns of activity:
    • promote regular patterns of daily activities
      • identify and modify habitual, very irregular patterns
      • consider using diaries or apps to self-monitor mood or activities
    • assess and treat alcohol/drug use and offer advice
    • help the patient and significant others recognise emerging symptoms of manic or depressive episodes
  • Evaluate and manage functional impairments:
    • full functional recovery usually takes ≥12 weeks
      • advise patient about withdrawal from work or other responsibilities when necessary
      • discourage major life decisions while in a depressive or manic state
    • manage patient expectations of capacity to work
    • consider needs of patients’ carers and children: provide information about local or national support groups
  • Consider physical health in clinical assessment and treatment planning:
    • monitor weight and other relevant risk factors at least annually and offer treatment
    • consult BAP guidelines on management of weight gain and metabolic disturbances associated with psychosis and antipsychotic drug treatment
  • Consider the use of alcohol and drugs (including caffeine, tobacco):
    • assess and treat established addictive problems
  • Consider risks for adverse outcomes including self-harm, suicide, victimisation, violence and criminality:
    • modifiable risk factors include co-morbid drug and alcohol use disorders and illness severity
  • Increase the focus of care planning in women of childbearing potential:
    • address contraception and pregnancy prospectively
    • valproate and carbamazepine are teratogenic
    • risk/benefit of other medicines in pregnancy and breast feeding must reflect risks of relapse as well as their adverse effects
    • very high risk for relapse of bipolar disorder postpartum:
      • consider effective prophylactic treatment

Acute manic episodes

  • Patients not already taking long-term treatment:
    • severe manic episodes: oral dopamine antagonist (haloperidol, olanzapine, risperidone or quetiapine). Other options:
      • valproate (not for women of childbearing potential)
      • aripiprazole
      • other dopamine antagonists and partial agonists
      • carbamazepine
      • lithium
    • where parenteral treatment required without full patient consent:
      • dopamine antagonists/partial agonists and GABA modulators (benzodiazepines): follow established protocols and use lowest doses necessary
    • less ill, non-psychotic manic patients/hypomania:
      • extrapolate treatment from practice in mania
    • patient preference should guide treatment selection where possible
    • taper and discontinue antidepressants (drugs approved for the treatment of unipolar depression)
    • if initial treatment is successful, consider long-term treatment
  • Patients who suffer a manic episode while taking long-term treatment:
    • inadequate symptom control: ensure that highest well-tolerated dose is offered
    • lithium: check serum levels; consider establishing a higher level within the therapeutic range; consider adding dopamine antagonist or partial agonist, or valproate
    • in general, follow the same principles as for a first episode or episode occurring off long-term treatment
    • poor adherence: if associated with adverse reaction, consider dose reduction or more tolerable alternative regimen
    • lithium: may not be indicated long-term if adherence poor
  • If symptoms are inadequately controlled with optimised doses of the first-line medicine and/or mania is very severe, add another medicine:
    • lithium or valoproate with a dopamine antagonist/partial agonist
    • clozapine in more refractory illness
    • electroconvulsive therapy (ECT) if mania particularly severe/treatment resistant, patient's preference or severe mania during pregnancy
  • Mixed features in a manic or hypomanic episode:
    • identify as mixed features rather than a 'mixed episode' (DSM-5)
    • treat as for mania
  • Assess contribution of substance use and consider if medically assisted withdrawal is required
  • Discontinuation of short-term treatments:
    • plan drug discontinuation in relation to the need for long-term maintenance treatment
    • medicines used only for acute treatment of mania: after full remission of symptoms (≥8 weeks of euthymia), taper dose of over >4 weeks
    • adjunctive medication for symptomatic effect to promote sleep or sedation: discontinue gradually as soon as symptoms improve

Acute depressive episode

  • Patients not already taking long-term treatment:
    • consider quetiapine, lurasidone, or olanzapine
    • consider initial treatment with lamotrigine in combination with agents preventing recurrence of mania
    • if considering antidepressants (i.e. drugs for major depressive episode in unipolar illness), co-prescribe with a drug for mania (e.g. dopamine antagonists, lithium, valproate) in patients with a history of mania (e.g. fluoxetine with olanzapine)
    • consider ECT if high suicidal risk, treatment resistance, psychosis, severe depression during pregnancy or life-threatening inanition
    • where depressive symptoms less severe: lithium
    • additionally: family-focused, cognitive behaviour therapy or interpersonal rhythm therapy
  • Patients who suffer a depressive episode while taking long-term treatment:
    • ensure current choice of long-term treatments is likely to protect from manic relapse (e.g. lithium, valproate, dopamine receptor antagonist/partial agonist drugs)
    • ensure adequate doses of medicines, serum lithium levels within therapeutic range
    • address current stressors
    • if patient fails to respond to optimisation of long-term treatment, initiate treatment as above (or as for treatment-resistant depression, below)
  • Choice of drug for a depressive episode:
    • monotherapy with antidepressants may increase risk of switch to mania or mood instability during treatment
    • dual-action monoamine re-uptake inhibitors (venlafaxine, duloxetine, amitriptyline and imipramine) carry a greater risk of precipitating a switch to mania than single action drugs (especially selective serotonin re-uptake inhibitors)
    • antidepressant drugs appear unlikely to induce mania when used in combination with a drug for mania
    • antidepressant as monotherapy in bipolar II disorder: any increase in dose should be gradual; be vigilant for early management of any adverse reactions (e.g. hypomania, mixed states or agitation)
    • lamotrigine: effective in bipolar I and suitable for bipolar II disorder
    • if any treatment successful for depressive episode, consider long-term treatment
  • Consider tapered discontinuation of antidepressant drugs after as little as 12 weeks' full remission of symptoms:
    • longer treatment justified if patients relapse on withdrawal
  • Treatment of resistant depression:
    • consider ECT
    • manage augmentation strategies as in unipolar patients; ensure adequate anti-manic cover with lithium, valproate, or a dopamine antagonist/partial agonist

Long-term treatment

  • Prevention of new episodes:
    • consider long-term treatment following a single severe manic episode
    • consider a wider package of treatment with enhanced psychoeducation, motivational, and family support, especially in early stages of illness
    • patient has accepted treatment for several years and remains very well: advise continuing indefinitely, as high risk of relapse
  • Options for long-term treatment:
    • continuous rather than intermittent treatment with oral medicines preferred
    • optimum long-term treatment strategy is not established
    • acute stressor imminent or present, early symptoms of relapse, or anxiety prominent: short-term add-ons (e.g. GABA modulators or dopamine antagonists/partial agonists):
      • consider supplying prospectively to patients
    • higher doses of long-term treatments may be effective instead of add-ons
  • Choice of long-term medicines:
    • consider lithium as initial monotherapy
    • if lithium ineffective, poorly tolerated or poor adherence: valproate, dopamine antagonists/partial agonists
    • if a medicine led to prompt remission from the most recent depressive or manic episode, consider its long-term use:
      • consider lithium as a better alternative to dopamine agonists
    • alternative against manic relapse: carbamazepine (or oxcarbazepine)
    • if prophylaxis against recurrence of mania is required and adherence to oral medication is erratic or injection preferred:
      • consider long-acting (‘depot’) formulations
    • consider lamotrigine and quetiapine as monotherapy in bipolar II disorder:
      • in bipolar I disorder, lamotrigine usually requires combination with an anti-manic long-term
  • Failure to respond to monotherapy, continuing sub-threshold depressive symptoms/relapses:
    • consider long-term combination treatment:
      • predominantly manic: combine predominantly anti-manic agents (e.g. lithium, valproate, dopamine antagonist or dopamine partial agonist)
      • predominantly depressive: combine lithium, lamotrigine, quetiapine, lurasidone, or olanzapine
      • refractory mania: consider continuation of clozapine if effective
      • responsive to ECT during an acute episode, but poor on oral agents: consider maintenance ECT
      • consider adjunctive psychotherapy
  • Rapid cycling:
    • identify and treat contributing conditions (e.g. hypothyroidism or alcohol/drug use)
    • taper and discontinue antidepressants
    • combinations of medicines may be required
      • discontinue treatments ineffective after evaluation ≥6 months
  • Discontinuation of long-term treatment:
    • risk of relapse remains, even after years of sustained remission
    • make an informed assessment of the potential dangers
    • taper over ≥4 weeks
    • discontinuation of medicines does not imply withdrawal of services to patients
  • Specific psychosocial interventions:
    • may enhance care and reduce risk of relapse
    • structured psychoeducation appears to be key ingredient
    • more successful with patients early in illness course
    • user groups can provide useful support and information

Treatment of alcohol use disorder

  • Offer naltrexone or nalmefene as part of a behavioural programme
  • Offer acamprosate if naltrexone has not been effective to help patients remain abstinent

Treatment in special situations

  • Children and young people:
    • for mania:
      • consider aripiprazole or refer to adult recommendations
      • other options: olanzapine, quetiapine and risperidone
    • for moderate to severe bipolar depression:
      • consider medicines and psychological treatments as recommended for adults
    • refer to BNF for Children to modify doses and be aware of increased potential for adverse reactions and effects
  • Elderly
    • consider lower treatment doses and titrate carefully
  • Women and pregnancy
    • see management section

full guideline available from...The British Association for Psychopharmacology,
36 Cambridge Place, Hills Road, Cambridge, CB2 1N0S Tel – 01223 358395
www.bap.org.uk

GM Goodwin, PM Haddad, IN Ferrier, et al. Evidence-based guidelines for treating bipolar disorder: Revised third edition recommendations from the British Association for Psychopharmacology. Journal of Psychopharmacology 2016; (epub ahead of print).
First included: October 04. Updated February 2010, May 2016.