uestion: How severe is the depression?uestion: How severe is the depression?
Help: Goodwin and Jamison propose that in relatively mild bipolar I depressions that are not rapid cycling or mixed, it may be worth trying lithium alone first. On the other hand, if the depression is severe, a more rapid response should be sought through a combination of lithium and an antidepressant, taking the somewhat increased risks of cycling into mania.¹ A modified version of this approach is adopted here.
¹Goodwin FK, Jamison KR. Manic Depressive Illness. New York. Oxford University Press, 1990:532-535.
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Lithium alone is the first line treatment. Adding an antidepressant would probably produce a more rapid or robust effect in many cases, but the patient and physician may prefer to defer this potential advantage, in exchange for the advantages of monotherapy with a mood stabilizer. Lithium dose should be gradually increased as tolerated so as to produce a plasma level of 0.8 meq/L or greater unless response occurs at a lower level.
If you did not read the Help section of the last question, press "back" on your browser and read it now. It explains the reasons for the choice of lithium, and why it is preferred over valproate, carbamazepine, lamotrigine, and other possibilities as the generic first-line choice here. Side effect considerations or patient preferences may lead the to a choice of one of these other options for some patients. ECT is also an important option, which was considered earlier.
If the patient is psychotic, an antipsychotic should be included. Review the recommendation about using an antipsychotic.
Recommendation #20
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The first-line recommendation is to begin both a mood stabilizer (e.g. - lithium or valproate) and an antidepressant at the same time. Since the primary antidepressant effect is expected to come from the antidepressant, there is no clear preference regarding which mood stabilizer to use (lithium or divalproex sodium). Due to its side effect profile, carbamazepine is not considered first line, although there may be reasons why an individual patient would present with a risk to benefit ratio favoring carbamazepine as the choice.
The first-line antidepressants to consider are an SSRI or bupropion.
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 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 IIIA3,4 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.
Recommendation #19
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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