Evidence-based guidelines for treating bipolar disorder continued

Acute manic or mixed episode

• Patients not already on long-term treatment:
  • severe manic or mixed episodes: oral antipsychotic or valproate
  • parenteral treatment required: antipsychotics, benzodiazepines
  • less ill manic patients: lithium, carbamazepine
  • to promote sleep if agitated and overactive (short-term): benzodiazepine
  • consider atypical antipsychotics
  • patient preference should guide treatment selection where possible
  • taper and discontinue antidepressants

• Patients already on long-term treatment:
  • inadequate symptom control: ensure that the highest well-tolerated dose is offered
  • lithium: check serum levels; consider establishing a higher level within the therapeutic range
  • initiate antipsychotic or valproate
  • consider established patient preferences
  • in general, follow the same principles as for a first episode or an episode occurring off long-term treatment
  • poor adherence: if associated with actual or perceived side-effects, consider a more tolerable alternative regimen
    • lithium: may not be indicated long-term if adherence poor

• Second-line: consider adding:
  • lithium or valproate with an antipsychotic
  • clozapine in more refractory illness
  • electroconvulsive therapy (ECT) if severely ill/treatment resistant, patient’s preference or severe mania during pregnancy

• Psychosis during a manic or mixed episode that is not congruent with severe affective symptoms: treat with antipsychotic

• Discontinuation of short-term treatments:
  • after full remission of symptoms, taper dose over >2 weeks and discontinue
  • discontinue medication used for symptomatic effect as soon as symptoms improve
  • medicines effective in relapse prevention (e.g. lithium, valproate) may be continued long-term

Acute depressive episode

• Patients not already on long-term treatment:
  • consider quetiapine
  • consider lamotrigine with the necessary dose titration
  • consider antidepressant (e.g. selective serotonin reuptake inhibitor (SSRI)) + anti-manic agent (e.g. lithium, valproate, antipsychotic)
    • antidepressant monotherapy is not recommended for patients with a history of mania
  • consider ECT if high suicidal risk, psychosis, severe depression during pregnancy or life-threatening inanition
  • where depressive symptoms less severe: lithium or possibly valproate
  • be aware and inform patient of risk of mania, hypomania or rapid cycling in patients treated with antidepressants alone
  • consider interpersonal therapy, cognitive behaviour therapy, or family-focused therapy

• Patients already on long-term treatment:
  • ensure adequate doses of medicines, serum lithium levels within therapeutic range
  • address current stressors
  • ensure current long-term treatment is likely to protect the patient from manic relapse (e.g. lithium, valproate, antipsychotic)
  • if the patient fails to respond to optimisation of long-term treatment, initiate treatment as above (or consider augmenting/changing current treatment)

• Choice of antidepressant:
  • there remain doubts about the relative efficacy of antidepressants in bipolar disorder
  • less risk of inducing mania when added to lithium, valproate or an antipsychotic
  • tricyclic antidepressants and dual action agents (venlafaxine, duloxetine) are probably more likely to induce manic switch

• Consider tapered discontinuation of antidepressants after full symptom remission

• Treatment-resistant depression:
  • manage next step treatment as in unipolar patients

Evidence-based guidelines for treating bipolar disorder continued

Long-term treatment

• Prevention of new episodes:
  • consider long-term treatment following a single severe manic episode
  • consider enhanced psychological/social support
  • if a patient has accepted treatment for several years and remains very well, advise continuing indefinitely, as risk of relapse remains high

• Long-term treatment options (‘mood stabilisers’):
  • most medicines are more effective against one pole than the other
  • continuous rather than intermittent treatment with oral medicines is preferred
  • short-term add-ons (e.g. benzodiazepines, antipsychotics) are necessary when acute stressor imminent or present, early symptoms of relapse, or anxiety prominent
    • consider supplying these prospectively to patients to use at their discretion
  • higher doses of the long-term treatments may also be effective, instead of add-ons
  • participation in clinical trials is encouraged

• Choice of long-term medicines:
  • consider lithium as initial monotherapy
  • if lithium is ineffective or poorly tolerated: aripiprazole, carbamazepine (or oxcarbazepine), lamotrigine, olanzapine, quetiapine or valproate
  • lamotrigine or quetiapine may be effective in bipolar II disorder
  • if one of these led to prompt remission from the most recent depressive or manic episode, this favours its long-term use

• Failure to respond to monotherapy and continuing sub-threshold symptoms/relapses:
  • consider long-term combination treatment:
    • predominantly manic: combine predominantly anti-manic agents (e.g. lithium, valproate, antipsychotic)
    • predominantly depressive: quetiapine or lamotrigine (for bipolar I disorder in combination with an anti-manic long-term agent)
    • antidepressants in combination with an anti-manic long-term agent in a minority of patients
    • treatment resistant with psychosis: consider clozapine
    • responsive to ECT during an acute episode, but poor on oral agents: consider ECT

• Rapid cycling:
  • identify and treat contributing conditions such as hypothyroidism or substance misuse
  • taper and discontinue antidepressants
  • combinations of medicines may be required
    • discontinue treatments ineffective after >6 months’ evaluation

• Discontinuation of long-term treatment:
  • the risk of relapse remains, even after years of sustained remission
  • make an informed assessment of the potential costs and dangers
  • taper over >2 weeks
  • discontinuation of medicines does not imply withdrawal of services to patients

• Specific psychosocial interventions:
  • these enhance care, can increase adherence and reduce the risk of relapse
  • psychoeducation, a didactic approach to develop knowledge and disease self-management appears to be key ingredient
  • consider family therapy for patients from families with high expressed emotion
  • user groups can provide useful support and information

Treatment in special situations

• Elderly: consider substantially lower doses of psychotropic medicines

• Pregnancy and early motherhood
  • see management section

Physical health

• Bipolar patients are at increased risk for poor health (especially vascular disease and diabetes)
  • long-term medicines may add to the risk
  • enhance active screening and treatment of risk factors or declared disease

full guidelines available from…
BAP Office, 36 Cambridge Place, Hills Road, Cambridge CB2 1NS (Tel – 01223 358395)
http://www.bap.org.uk/

GM Goodwin, for the Consensus Group of the British Association for Psychopharmacology. Evidence-based guidelines for treating bipolar disorder: revised second edition—recommendations from the British Association for Psychopharmacology. Journal of Psychopharmacology 23 (4) (2009) 346–388