A Review of Current Bipolar Disorder Treatment Guidelines

Alan Podawiltz, DO, MS, FAPA

Department of Psychiatry, University of North Texas Health Science Center, Fort Worth

To provide guidance to primary care physicians, evidence-based strategies from the Texas Implementation of Medication Algorithms (TIMA)1,2 and the APA Practice Guidelines for the Treatment of Patients With Bipolar Disorder3,4 are described here. Newer guidelines have been published outside the United States, but these are the most recent American guidelines.5

Physicians should keep in mind that the goals2 of bipolar disorder treatment are:

  • symptomatic remission
  • full return of psychosocial functioning
  • prevention of relapses and recurrences

AV 1. When to Refer a Patient With Bipolar Disorder to a Psychiatrist or Hospital (00:20)

At the outset, physicians should discuss the diagnosis and the treatment options with the patient, and then engage the patient and significant others in the treatment plan. Clinicians should also encourage patients to keep a daily mood log and to take part in psychoeducation or cognitive therapy.2 Follow-up visits should generally take place after the first and third week of treatment, then monthly for at least 3 months, and then every 2 or 3 months; timelines can vary depending on medications used. In some cases, patients should be referred to a psychiatrist or hospital rather than be managed in primary care (AV 1).

Medications Used in Bipolar Disorder

A wide range of medications are available to treat bipolar disorder. Primary care physicians may be more familiar with some of the drugs used in treating this condition than with others. To help physicians choose among drugs for individual patients, consulting a drug chart can aid in comparing side effects and other properties.

Some agents are FDA-approved for acute phase treatment of mania or depression, and others are FDA-approved for maintenance treatment. In clinical practice, some medications used for bipolar disorder have shown efficacy in research, although they are not indicated by the FDA.

Acute Treatment Recommendations

Manic, hypomanic, or mixed episode. Treatments that can be managed in primary care are shown in a TIMA algorithm for a currently hypomanic/manic episode (either acute euphoric or mixed).1 The first-line treatment for patients in an acute euphoric episode of hypomania or mania is monotherapy with a mood stabilizer (lithium or valproate) or atypical antipsychotic (aripiprazole, quetiapine, risperidone, ziprasidone). For a mixed episode, valproate, aripiprazole, risperidone, and ziprasidone are the first-line treatment options. If symptoms do not respond to the initial medication, olanzapine or carbamazapine can be tried for either type of episode. Although primary care clinicians may be more familiar with carbamazapine, as it is often prescribed for seizures, olanzapine may be the better choice for mania because it controls mania more quickly.


If monotherapy with lithium, valproate, or an atypical antipsychotic fails or is inadequate, 2 of these drugs can be combined. However, 2 atypical antipsychotics should not be combined, and, due to a lack of evidence, aripiprazole and clozapine should not be combined with lithium or valproate.

If partial or no response to the initial combination occurs, 2 different drugs can be combined among lithium, valproate, atypical antipsychotics, carbamazapine, oxcarbazepine, or typical antipsychotics. Again, 2 atypical antipsychotics should not be combined, and clozapine is not recommended.

If treatment still remains unsuccessful or only partially successful, the patient should be referred to a psychiatrist. Referral is necessary for 2 reasons: (1) The longer a patient remains manic, the more likely he or she is to become severely psychotic and require hospitalization. (2) Few primary care practices have the resources to manage this level of treatment; ECT requires consultation, and clozapine requires a year of biweekly and then ongoing monthly blood cell counts before the pharmacy will issue the next prescription.

Depressive episode. Primary care physicians can use another TIMA algorithm to initiate treatment for acute depressive bipolar episodes.1 Before initiating treatment, the physician should establish whether the patient is currently taking lithium or another antimanic medication and whether the patient has a history of severe and/or recent mania. A patient already taking lithium may need a dose increase, which requires careful dose titration to therapeutic blood levels. Lamotrigine can be added if a patient is taking lithium or another antimanic agent. If the patient is not taking an antimanic medication and has a history of severe and/or recent mania, then an antimanic agent and lamotrigine should be prescribed. Lamotrigine monotherapy can be prescribed if the patient has no history of severe or recent mania. Lamotrigine has to be started at a low dose and titrated up over a 2-week period, and results are not immediate. Dose-titration packages are available to aid in this process.

AV 2. Bipolar Disorder: Making a Treatment Change (02:00)

If symptoms do not respond or only partially respond, discontinue the patient’s current medication(s), tapering as needed. Monotherapy with quetiapine or the olanzapine-fluoxetine combination should then be initiated (AV 2).

If only partial response or nonresponse results, a combination of any 2 of the following medications can be started: lithium, lamotrigine, quetiapine, or the olanzapine-fluoxetine combination. Although clinicians may have taken the patient off lithium treatment earlier, it can be reintroduced at this point.

If patients still do not respond or only partially respond to this treatment, they should be referred to a psychiatrist or hospital. Other treatments that may be used include traditional antidepressants, which require a detailed knowledge of drug-drug interactions, as well as ECT and medications that require intensive monitoring.

Maintenance Treatment Recommendations

When a patient with acute mania or depression has been stabilized with a particular medication or combination of medications, that regimen can be maintained as long as it is well tolerated. Medications for maintenance treatment include mood stabilizers, anticonvulsants, and atypical antipsychotics:

  • lithium
  • divalproex
  • lamotrigine
  • carbamazapine
  • aripiprazole
  • olanzapine
  • quetiapine
  • risperidone
  • ziprasidone

Follow-up visit timelines vary depending on the medications prescribed, but generally, after the patient has been stable for 4 to 6 months, follow-up can take place with nonphysician clinicians on staff or over the telephone. Other aspects of maintenance treatment are discussed in more detail by Michael Thase, MD, in "Strategies for Increasing Treatment Adherence in Bipolar Disorder" and "Bipolar Disorder Maintenance Treatment: Monitoring Effectiveness and Safety."

For Clinical Use

  • Consult the TIMA and APA guidelines when treating your patients with bipolar disorder
  • Refer patients to a psychiatrist or hospital when appropriate

Drug Names

aripiprazole (Abilify), carbamazepine (Tegretol, Epitol, and others), clozapine (Clozaril, FazaClo, and others), divalproex sodium (Depakote and others), lamotrigine (Lamictal and others), lithium (Lithobid and others), olanzapine (Zyprexa), olanzapine/fluoxetine combination (Symbyax), oxcarbazepine (Trileptal and others), quetiapine (Seroquel), risperidone (Risperdal and others), ziprasidone (Geodon)


APA = American Psychiatric Association
ECT = electroconvulsive therapy
FDA = Food and Drug Administration
TIMA = Texas Implementation of Medication Algorithms

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  1. Crismon ML, Argo TR, Bendele SD, et al. Texas Medication Algorithm Project Procedural Manual: Bipolar Disorder Algorithms. Texas: Texas Department of State Health Services; 2007. http://www.pbhsolutions.org/pubdocs/upload/documents/TIMABDman2007.pdf. Accessed November 30, 2011.
  2. Suppes T, Dennehy EB, Hirschfeld RMA, et al, for the Texas Consensus Conference Panel on Medication Treatment of Bipolar Disorder. The Texas Implementation of Medication Algorithms: update to the algorithms for treatment of bipolar I disorder. J Clin Psychiatry. 2005;66(7):870–886. Abstract.
  3. American Psychiatric Association. Practice Guideline for the Treatment of Patients with Bipolar Disorder, Second Edition. Published 2002. http://psychiatryonline.org/content.aspx?bookid=28&sectionid=1669577#50051. Accessed November 30, 2011.
  4. American Psychiatric Association. Guideline Watch: Practice Guideline for the Treatment of Patients with Bipolar Disorder, Second Edition. Published 2005. http://psychiatryonline.org/content.aspx?bookid=28&sectionid=1682557#148430. Accessed November 30, 2011.
  5. Connolly KR, Thase ME. The clinical management of bipolar disorder: a review of evidence-based guidelines. Prim Care Companion CNS Disord. 2011;13(4):doi:10.4088/PCC.10r01097. Abstract