PART A:
Treatment Recommendations for Patients With Bipolar Disorder

I. EXECUTIVE SUMMARY OF RECOMMENDATIONS

Each recommendation is identified as falling into one of three categories of endorsement, indicated by a bracketed Roman numeral following the statement. The three categories represent varying levels of clinical confidence regarding the recommendation:

1. Recommended with substantial clinical confidence.
2. Recommended with moderate clinical confidence.
3. May be recommended on the basis of individual circumstances.

A. Psychiatric Management

At this time, there is no cure for bipolar disorder; however, treatment can decrease the associated morbidity and mortality [I]. Initially, the psychiatrist should perform a diagnostic evaluation and assess the patient's safety and level of functioning to arrive at a decision about the optimum treatment setting [I]. Subsequently, specific goals of psychiatric management include establishing and maintaining a therapeutic alliance, monitoring the patient's psychiatric status, providing education regarding bipolar disorder, enhancing treatment compliance, promoting regular patterns of activity and of sleep, anticipating stressors, identifying new episodes early, and minimizing functional impairments [I].

B. Acute Treatment

1. Manic or mixed episodes
The first-line pharmacological treatment for more severe manic or mixed episodes is the initiation of either lithium plus an antipsychotic or valproate (Valproic Acid) plus an antipsychotic [I]. For less ill patients, monotherapy with lithium, valproate, or an antipsychotic such as olanzapine (Zyprexa) may be sufficient [I]. Short-term adjunctive treatment with a benzodiazepine may also be helpful [II]. For mixed episodes, valproate may be preferred over lithium [II]. Atypical antipsychotics are preferred over typical antipsychotics because of their more benign side effect profile [I], with most of the evidence supporting the use of olanzapine or risperidone [II]. Alternatives include carbamazepine or oxcarbazepine in lieu of lithium or valproate [II]. Antidepressants should be tapered and discontinued if possible [I]. If psychosocial therapy approaches are used, they should be combined with pharmacotherapy [I].

For patients who, despite receiving maintenance medication treatment, experience a manic or mixed episode (i.e., a "breakthrough" episode), the first-line intervention should be to optimize the medication dose [I]. Introduction or resumption of an antipsychotic is sometimes necessary [II]. Severely ill or agitated patients may also require short-term adjunctive treatment with a benzodiazepine [I].

When first-line medication treatment at optimal doses fails to control symptoms, recommended treatment options include addition of another first-line medication [I]. Alternative treatment options include adding carbamazepine or oxcarbazepine in lieu of an additional first-line medication [II], adding an antipsychotic if not already prescribed [I], or changing from one antipsychotic to another [III]. Clozapine may be particularly effective in the treatment of refractory illness [II]. ECT may also be considered for patients with severe or treatment-resistant mania or if preferred by the patient in consultation with the psychiatrist [I]. In addition, ECT is a potential treatment for patients experiencing mixed episodes or for patients experiencing severe mania during pregnancy [II].

Manic or mixed episodes with psychotic features usually require treatment with an antipsychotic medication [II].

2. Depressive episodes
The first-line pharmacological treatment for bipolar depression is the initiation of either lithium [I] or lamotrigine (Lamictal) [II]. Antidepressant monotherapy is not recommended [I]. As an alternative, especially for more severely ill patients, some clinicians will initiate simultaneous treatment with lithium and an antidepressant [III]. In patients with life-threatening inanition, suicidality, or psychosis, ECT also represents a reasonable alternative [I]. ECT is also a potential treatment for severe depression during pregnancy [II].

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

For patients who, despite receiving maintenance medication treatment, suffer a breakthrough depressive episode, the first-line intervention should be to optimize the dose of maintenance medication [II].

When an acute depressive episode of bipolar disorder does not respond to first-line medication treatment at optimal doses, next steps include adding lamotrigine [I], bupropion [II], or paroxetine [II]. Alternative next steps include adding other newer antidepressants (e.g., a selective serotonin reuptake inhibitor [SSRI] or venlafaxine) [II] or a monoamine oxidase inhibitor (MAOI) [II]. For patients with severe or treatment-resistant depression or depression with psychotic or catatonic features, ECT should be considered [I].

The likelihood of antidepressant treatment precipitating a switch into a hypomanic episode is probably lower in patients with bipolar II depression than in patients with bipolar I depression. Therefore, clinicians may elect to recommend antidepressant treatment earlier in patients with bipolar II disorder [II].

Depressive episodes with psychotic features usually require adjunctive treatment with an antipsychotic medication [I]. ECT represents a reasonable alternative [I].