title: Evidence-based options for treatment-resistant adult bipolar disorder patients.
abstract: OBJECTIVE
  Many patients diagnosed with bipolar disorder (BD) respond incompletely or unsatisfactorily to available treatments. Given the potentially devastating nature of this prevalent disorder, there is a pressing need to improve clinical care of such patients.
  
  
  METHODS
  We performed a literature review of the research findings related to treatment-resistant BD reported through February 2012.
  
  
  RESULTS
  Therapeutic trials for treatment-resistant bipolar mania are uncommon, and provide few promising leads other than the use of clozapine. Far more pressing challenges are the depressive-dysthymic-dysphoric-mixed phases of BD and long-term prophylaxis. Therapeutic trials for treatment-resistant bipolar depression have assessed anticonvulsants, modern antipsychotics, glutamate [N-methyl-D-aspartate (NMDA)] antagonists, dopamine agonists, calcium-channel blockers, and thyroid hormones, as well as behavioral therapy, sleep deprivation, light therapy, electroconvulsive therapy (ECT), transcranial magnetic stimulation, and deep brain stimulation-all of which are promising but limited in effectiveness. Several innovative pharmacological treatments (an anticholinesterase, a glutamine antagonist, a calcium-channel blocker, triiodothyronine, olanzapine and topiramate), ECT, and cognitive-behavior therapy have some support for long-term treatment of resistant BD patients, but most of trials of these treatments have been methodologically limited.
  
  
  CONCLUSIONS
  Most studies identified were small, involved supplementation of typically complex ongoing treatments, varied in controls, randomization, and blinding, usually involved brief follow-up, and lacked replication. Clearer criteria for defining and predicting treatment resistance in BD are needed, as well as improved trial design with better controls, assessment of specific clinical subgroups, and longer follow-up.
authors.affiliation: Department of General Psychiatry, Institute of Mental Health, 10 Buangkok ViewSingapore 539747.
authors.forename: Shi Hui
authors.initials: SH
authors.lastname: Poon
authors.forename: Kang
authors.initials: K
authors.lastname: Sim
authors.forename: Min Yi
authors.initials: MY
authors.lastname: Sum
authors.forename: Carissa Nadia
authors.initials: CN
authors.lastname: Kuswanto
authors.forename: Ross J
authors.initials: RJ
authors.lastname: Baldessarini
mesh_terms: D000328:Adult; D000927:Anticonvulsants / Q000627:therapeutic use; D014150:Antipsychotic Agents / Q000627:therapeutic use; D001521:Behavior Therapy; D001714:Bipolar Disorder / Q000150:complications / Q000628:therapy*; D002121:Calcium Channel Blockers / Q000627:therapeutic use; D003131:Combined Modality Therapy; D046690:Deep Brain Stimulation; D061218:Depressive Disorder, Treatment-Resistant / Q000209:etiology / Q000628:therapy*; D018491:Dopamine Agonists / Q000627:therapeutic use; D004565:Electroconvulsive Therapy; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use; D006801:Humans; D010789:Phototherapy; D013963:Thyroid Hormones / Q000627:therapeutic use; D050781:Transcranial Magnetic Stimulation
chemical_list: D000927:Anticonvulsants; D014150:Antipsychotic Agents; D002121:Calcium Channel Blockers; D018491:Dopamine Agonists; D018691:Excitatory Amino Acid Antagonists; D013963:Thyroid Hormones