New Options in Bipolar Disorders

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BIPOLAR DISORDER FROM CLINICAL PRACTICE TO
GUIDELINES OR FROM GUIDELINES TO CLINICAL
PRACTICE?
Andrea Fagiolini, M.D. Medical Director Bipolar
Disorder Center and Depression Treatment and
Prevention Program Course Director
Psychopharmacology PG-Y 1 University of
Pittsburgh Medical Center
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Bipolar Disorders
GUIDELINES

• Are Subjects in Pharmacological Treatment Trials
  Representative of Patients in Routine Clinical
  Practice?
• Do the rigorous inclusion/exclusion criteria used
  to select subjects for participation in efficacy
  studies potentially limit the generalizability of
  these trials' results?

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Zimmerman

• 803 individuals, aged 16-65 years, who were seen
  at intake at an outpatient practice underwent a
  thorough diagnostic evaluation, including the
  administration of semistructured diagnostic
  interviews

• 346 patients had current major depression.
• Common inclusion/exclusion criteria used in
  efficacy studies of antidepressants were applied
  to the depressed patients to determine how many
  would have qualified for an efficacy trial.

American Journal of Psychiatry, 2002.
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Results

• 1/6 of the 346 depressed patients would have been
  excluded from an efficacy trial because they had
  a bipolar or psychotic subtype of depression.
• The presence of a comorbid anxiety or substance
  use disorder, insufficient severity of depressive
  symptoms, or current suicidal ideation would have
  excluded 86.0 (N252) of the remaining 293
  outpatients with nonpsychotic unipolar major
  depressive disorder from an antidepressant
  efficacy trial.

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Conclusions

• Subjects treated in antidepressant trials
  represent a minority of patients treated for
  major depression in routine clinical practice.
• These results show that antidepressant efficacy
  trials tend to evaluate a subset of depressed
  individuals with a specific clinical profile.

American Journal of Psychiatry, 2002.
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Bipolar Disorders
GUIDELINES

• Review of Literature
• Randomized Controlled Trials
• Consensus Surveys

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Bipolar Disorders
GUIDELINES

• Practice Guideline for the Treatment of Patients
  With Bipolar Disorder
• Expert Consensus Guideline Series
• Clinical Practice Guidelines for Bipolar Disorder
  From the Department of Veterans Affairs
• Texas Medication Algorithm Project
• Canadian Network for Mood and Anxiety Treatments

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Bipolar Disorders
Practice Guideline for the Treatment of Patients
With Bipolar Disorder

• Developed by psychiatrists in active clinical
  practice and by contributors primarily involved
  in research or other academic endeavors.
• Not intended to be construed or to serve as a
  standard of medical care.
• Standards of medical care are determined on the
  basis of all clinical data available for an
  individual case and are subject to change as
  scientific knowledge and technology advance and
  practice patterns evolve.

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Bipolar Disorders
Practice Guideline for the Treatment of Patients
With Bipolar Disorder

• Adherence to them will not ensure a successful
  outcome in every case, nor should they be
  construed as including all proper methods of care
  or excluding other acceptable methods of care
  aimed at the same results.
• The ultimate judgment regarding a particular
  clinical procedure or treatment plan must be made
  by the psychiatrist in light of the clinical data
  presented by the patient and the diagnostic and
  treatment options available.

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Bipolar Disorders
Practice Guideline for the Treatment of Patients
With Bipolar Disorder

• First-line Lithium plus an antipsychotic
• Valproate plus an antipsychotic
• For less ill patients, monotherapy with lithium,
  valproate, or an antipsychotic such as olanzapine
  may be sufficient
• Short-term adjunctive treatment with a
  benzodiazepine may also be helpful

Acute Treatment. Manic or mixed episodes
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Bipolar Disorders
Practice Guideline for the Treatment of Patients
With Bipolar Disorder

• For mixed episodes, valproate may be preferred
  over lithium
• Atypical antipsychotics are preferred over
  typical antipsychotics because of their more
  benign side effect profile, with most of the
  evidence supporting the use of olanzapine or
  risperidone.
• Alternatives include carbamazepine or
  oxcarbazepine in lieu of lithium or valproate .

• Acute Treatment. Manic or mixed episodes

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Bipolar Disorders
Practice Guideline for the Treatment of Patients
With Bipolar Disorder
Acute Treatment. Manic or mixed episodes

• Antidepressants should be tapered and
  discontinued if possible.
• If psychosocial therapy approaches are used, they
  should be combined with pharmacotherapy .

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Bipolar Disorders
Practice Guideline for the Treatment of Patients
With Bipolar Disorder

• Manic or mixed episodes with psychotic features
  usually require treatment with an antipsychotic
  medication.
• ECT may also be considered for patients with
  severe or treatment-resistant mania or if
  preferred by the patient. In addition, ECT is a
  potential treatment for patients experiencing
  mixed episodes or for patients experiencing
  severe mania during pregnancy.
• Clozapine may be particularly effective in the
  treatment of refractory illness.

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Bipolar Disorders
Practice Guideline for the Treatment of Patients
With Bipolar Disorder
Acute Treatment. Depressive episodes

• First-line initiation of either lithium or
  lamotrigine.
• Antidepressant monotherapy is not recommended
• As an alternative, especially for more severely
  ill patients, some clinicians will initiate
  simultaneous treatment with lithium and an
  antidepressant.

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Bipolar Disorders
Practice Guideline for the Treatment of Patients
With Bipolar Disorder
Acute Treatment. Depressive episodes

• In patients with life-threatening inanition,
  suicidality, or psychosis, ECT also represents a
  reasonable alternative.
• ECT is also a potential treatment for severe
  depression during pregnancy.

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Bipolar Disorders
Practice Guideline for the Treatment of Patients
With Bipolar Disorder

• A large body of evidence supports the efficacy of
  psychotherapy in the treatment of unipolar
  depression.
• In bipolar depression, interpersonal therapy and
  cognitive behavior therapy may be useful when
  added to pharmacotherapy.
• While psychodynamic psychotherapy has not been
  empirically studied in patients with bipolar
  depression, it is widely used in addition to
  medication.

Acute Treatment. Depressive episodes
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Bipolar Disorders
Practice Guideline for the Treatment of Patients
With Bipolar Disorder
Maintenance

• Maintenance regimens of medication are
  recommended following a manic episode
• Although few studies involving patients with
  bipolar II disorder have been conducted,
  consideration of maintenance treatment for this
  form of the illness is also strongly warranted
• The medications with the best empirical evidence
  to support their use in maintenance treatment
  include lithium and valproate

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Bipolar Disorders
Practice Guideline for the Treatment of Patients
With Bipolar Disorder
Maintenance

• Possible alternatives include lamotrigine or
  carbamazepine or oxcarbazepine
• For patients treated with an antipsychotic
  medication during the preceding acute episode,
  the need for ongoing antipsychotic treatment
  should be reassessed upon entering maintenance
  treatment

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Bipolar Disorders
Practice Guideline for the Treatment of Patients
With Bipolar Disorder
Maintenance

• Patients who continue to experience subthreshold
  symptoms or breakthrough mood episodes may
  require the addition of another maintenance
  medication, an atypical antipsychotic, or an
  antidepressant.
• Maintenance sessions of ECT may also be
  considered for patients whose acute episode
  responded to ECT.

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Bipolar Disorders
Practice Guideline for the Treatment of Patients
With Bipolar Disorder

• During maintenance treatment, patients with
  bipolar disorder are likely to benefit from a
  concomitant psychosocial intervention -including
  psychotherapy- that addresses illness management
  (i.e., adherence, lifestyle changes, and early
  detection of prodromal symptoms) and
  interpersonal difficulties.
• Group psychotherapy may also help patients
  address such issues as adherence to a treatment
  plan, adaptation to a chronic illness, regulation
  of self-esteem, and management of marital and
  other psychosocial issues . Support groups
  provide useful information about bipolar disorder
  and its treatment .