uestion:
Is the patient's lithium level at least 0.8 meq/L or higher?uestion:
Is the patient's lithium level at least 0.8 meq/L or higher?
Help: Most experts consider lithium the treatment of first choice for acute bipolar depression.¹,² Therefore, an increase of lithium (if levels are low) may be the best first option for depression which is breaking through a current lithium regimen in bipolar I disorder. In choosing criteria for a low level, 0.8 meq/L was chosen as the cut-off point because of studies by Gelenberg et al and Keller et al demonstrating that better outcome is seen at 0.8 or higher compared to a levels of 0.4-0.6 meq/L.³
¹Srisuarapanont M, Yatham LN, Zis AP. Treatment of acute bipolar depression: A review of the literature. Can J Psychiatry 1995;40(9):533-544
²Sachs GS. Bipolar mood disorder: practical strategies for acute and maintenance phase treatment. J Clin Psychopharmacol 1996;[suppl 1]:32S-47S.
³Gershon S, Soares JC. Current therapeutic profile of lithium. Arch Gen Psychiatry 1997;54:16-20.
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uestion:
Has the patient had a trial of an SSRI antidepressant or bupropion,
added to the mood stabilizer?
Help: If the patient has a lithium level over 0.8 meq/L, or remains depressed after the lithium level is maintained over 0.8 for several weeks, or if the patient was unable to tolerate a lithium level over 0.8, addition of an antidepressant is recommended. This recommendation is based in part on a recent study that showed that in these clinical circumstances, initiation of antidepressant treatment is better tolerated than adding a second mood stabilizer, although efficacy was comparable.¹ The mood stabilizer should be continued to minimize the risk of antidepressant-induced mania or rapid cycling. The question asks if this has already been tried. If not, it will be recommended, and the comparative merits of SSRIs and bupropion will be discussed.
¹Joffe RT, Young LT, Robb JC, MacQueen GM, Marriott M. A randomized controlled trial of the acute treatment of bipolar depression, Abstract 54. American College of Neuropsychopharmacology 37th Annual Meeting. Las Croabas, Puerto Rico; 1998.
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Add an SSRI or bupropion to the patient's mood stabilizer regimen. All SSRIs seem to be effective for bipolar depression, although the only placebo-controlled study was with fluoxetine.¹ However, for patients with prior histories of antidepressant-induced mania or in whom a later trial of an MAOI can be anticipated, fluoxetine's long half-life (7-10 days for its metabolite norfluoxetine) is a relative disadvantage. Both SSRIs and bupropion seem to have a relatively low tendency to induce cycling into mania.²
Bupropion has a higher risk of seizures, namely about 0.44% at doses up to 450 mgs per day,³ vs 0.1-0.2% for the SSRIs according to the package inserts. The seizure risk of the sustained release form of bupropion is lower (0.1 % at doses of 300 mg/day or below, rising to 0.4% at a dose of 400 mg/day according to the package insert), making it the preferred form for general use.(4) Patients with bipolar disorder taking anticonvulsants are possibly at lower risk, but the use of bupropion is relatively contraindicated in patients with comorbid eating disorders such as bulimia or anorexia nervosa, or with a history of seizures.
A shorter half life SSRI is preferred, such as citalopram, sertraline or paroxetine. Click here for dosing information. If the patient is currently taking carbamazepine, be aware that dosing requirements may be higher due to induction of 3A3,4 metabolism of the SSRI. The SSRI may in turn affect the carbamazepine's 3A3,4 metabolism: for example, sertraline will inhibit it and paroxetine will have only a minor effect. Our drug interaction computer program is available for more detailed cytochrome interaction information.
If the patient is psychotic, inclusion of an antipsychotic is recommended. Review the recommendation about using an antipsychotic.
Recommendation #21 (not psychotic) or #21P (psychotic)
¹Cohn JB, Collins G, Ashbrook E, Wernicke JF. A comparison of fluoxetine, imipramine, and placebo in patients with bipolar depressive disorder. Int Clin Psychopharmacol. 1989;4:313-322.
²Peet M. Induction of mania with selective serotonin re-uptake inhibitors and tricyclic antidepressants. Br J Psychiatry 1994;164:549-550. Sachs GS, Lafer B, Stoll AL, et al. A double-blind trial of bupropion versus desipramine for bipolar depression. J Clin Psychiatry 1994;55:391-393.
³Rosenstein DL, Nelson JC, Jacobs SC. Seizures associated with antidepressants: a review. J Clin Psychiatry 1993;54:289-299
(4) Dunner DL, Zisook S, Billow AA, Batey SR, Johnston JA, Ascher JA. A prospective safety surveillance study for bupropion sustained-resease in the treatment of depression. J Clin Psychiatry. 1998;59:366-373.
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If the level is less than 0.8 meq/L, raise it to that level or above (suggested range 0.8 to 1.2).¹ To make this a meaningful increase, the level should rise at least 0.3 meq/L or more. Thus, for example, if the level is 0.3 meq/L now, it should be raised at least 0.5 meq/L more so that the level rises to at least 0.8. Or, if the level is 0.79 meq/L now, it should be raised at least 0.3 to 1.09 meq/L if the patient can tolerate this increase.
If the patient is psychotic, inclusion of an antipsychotic is recommended. Review the recommendation about using an antipsychotic.
Recommendation #18 (not psychotic) or #18P (psychotic)
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¹Gelenberg A, Kane J, Keller M, et al. Comparison of standard and low serum levels of lithium for maintenance treatment of bipolar disorder. NEJM. 1989;321:1489-1493.