Bipolar treatment update: Evidence is driving change in mania, depression algorithms
Texas Medication Algorithm Project will weigh data on atypical antipsychotics in mania and on continuing antidepressants after bipolar depression remits.
The recommendation for sustained-release bupropion is consistent with the algorithm principle to use medications in the most well-tolerated form when accessible and available.
With lamotrigine, review with patients the risk of serious rash. To minimize rash risk, start lamotrigine slowly and follow the recommended titration schedule.
Stage 3: Multiple choices. At this stage, no definitive studies, safety data, or tolerability issues are available to rank the medication choices. The algorithm suggests:
- adding lithium21 or a second antidepressant
- or switching to an alternate antidepressant such as venlafaxine or nefazodone.
If a patient moves to stage 3 because of side effects with one antidepressant class, a different class—preferably with a contrasting side-effect profile—is recommended.
Algorithm 2 Treating depression in bipolar I disorder*
Stage 4: Two antidepressants. To enhance clinical response, the algorithm recommends combining two antidepressants, preferably from different classes. Monitor patients closely for side effects.
Stage 5. Antipsychotic or MAOI. At this stage, the algorithm recommends adding an atypical antipsychotic22 or switching to a monoamine oxidase inhibitor (MAOI).
Early evidence supported the efficacy of MAOIs in bipolar depression. However, the panel ranked MAOIs lower in the algorithm because they are associated with more bothersome side effects than SSRIs and other antidepressants. When using MAOIs, provide patients with dietary restriction guidelines.
Stage 6. Other therapies. Therapies such as ECT or “other” interventions are recommended at this stage. ECT has proven efficacy in bipolar depression and is appropriate for patients with limited medication response. The panel gave ECT a low ranking because of limited availability, lack of patient acceptance, and newer options.
Medication options include experimental treatments with limited evidence, such as inositol, dopamine agonists, stimulants, thyroid supplementation, conventional antipsychotics, and tri-cyclic antidepressants.
Acute to maintenance treatment
Adjunctive treatments for agitation, insomnia, GI upset, sedation, headache, and tremor are recommended in the physician manual supporting the TMAP guidelines (see Related resources). The manual also suggests ways to manage medication side effects and modify the algorithms for inpatients.
Patient and family psychoeducation plays an important role in helping the patient:
- identify prodromal bipolar symptoms
- understand the need to take medications as prescribed.
Continuation treatment. After mania or hypomania remits, continue medication(s) at the effective acute-phase dosages for at least 3 months. Use follow-up visits to enhance patient adherence, detect early symptoms of relapse, and monitor for side effects.
During the late continuation phase, after a period of sustained stability, clinicians can try to simplify the medications. When discontinuing a medication, taper the dosage by no more than 25% per week. If symptoms recur, promptly return to acute-phase treatment. Consider restarting medications and titrating up to the dosage(s) that resulted in remission.
In a depressive episode, continue the antidepressant(s) for 1 to 3 months at the effective acutephase dosage(s). Follow up frequently, and educate patients to watch for symptom recurrence and to communicate with you to assess when medication changes are needed.
Maintenance treatment. Relatively few well-controlled studies on long-term management of bipolar patients were available for the 2000 algorithm update.23 In general, all patients need mood stabilizer(s) to prevent relapse, using the lowest dosage that maintains therapeutic efficacy. Based on new evidence for lamotrigine and atypical antipsychotics—including FDAapproval of olanzapine for bipolar maintenace therapy—we anticipate recommendations will be expanded and more delineated in the 2004 update.
Discontinuing antidepressants after 3 to 6 months of initial treatment is now recommended. However, a recent retrospective case series suggests that continuing antidepressants at least 1 year after initial successful therapy may protect against depressive relapse. During this study, continuing antidepressants more than 3 to 6 months did not appear to increase the risk of switching to mania.24
Should antidepressants be continued or discontinued after successful acute treatment of a bipolar I depressive episode? This is an active area of research and debate as to the most appropriate strategy. The 2004 algorithm update panel will consider recent evidence that supports continuing antidepressants after symptom remission.24
- Texas Medication Algorithm Project algorithms and physician manual. Texas Department of Mental Health and Mental Retardation. https://www.mhmr.state.tx.us/centraloffice/medicaldirector/TIMA.html
- American Psychiatric Association. Practice guidelines for the treatment of patients with bipolar disorder. Am J Psychiatry 2002; 159(4):suppl 2.
- Depression and Bipolar Support Alliance. www.dbsalliance.org
Drug brand names
- Bupropion • Wellbutrin SR
- Carbamazepine • Tegretol
- Citalopram • Celexa
- Clozapine • Clozaril
- Divalproex sodium • Depakote
- Escitalopram • Lexapro
- Fluoxetine • Prozac
- Fluvoxamine • Luvox
- Inositol • Various
- Lamotrigine • Lamictal
- Nefazodone • Serzone
- Olanzapine • Zyprexa
- Oxcarbazepine • Trileptal
- Paroxetine • Paxil
- Quetiapine • Seroquel
- Risperidone • Risperdal
- Sertraline • Zoloft
- Topiramate • Topamax
- Tranylcypromine • Parnate
- Valproic acid • Depakene
- Venlafaxine • Effexor
- Ziprasidone • Geodon
Disclosure
Dr. Shivakumar reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.
