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06. Augmenting With SGAs After Unsatisfactory Response to Lithium in Bipolar Mania

Published on July 1, 2024 Certification expiration date: July 1, 2027

David Osser, M.D.

Associate Professor of Psychiatry - Harvard Medical School

Key Points

If there is no response to lithium, add an SGA for the management of acute, classic mania.
Consider quetiapine first and then risperidone and olanzapine.
Olanzapine is less recommended due to its side effects.
Risperidone is preferred over olanzapine.

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Slides and Transcript

Slide 1 of 12

This is video 6 of the Algorithm for the Psychopharmacology of Acute Mania.

Augmenting With SGAs After Unsatisfactory Response to Lithium in Bipolar Mania Slide 1 of 12

Slide 2 of 12

We are midway through the part of the algorithm that discusses acute treatment of classic mania. And we discussed the initial treatment choices in the last video. So in this video, we discuss what to do after unsatisfactory response to the first recommended treatment which is lithium. So we think the add-on should be with a second-generation antipsychotic.

References:

Osser, D. (2021). Psychopharmacology algorithms. Wolters Kluwer.

Augmenting With SGAs After Unsatisfactory Response to Lithium in Bipolar Mania Slide 2 of 12

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Slide 3 of 12

This addition could be done quickly though giving the first medication more time and using benzodiazepines for sedation is recommended as we discussed in detail in the video on treating mixed mania.

References:

Osser, D. (2021). Psychopharmacology algorithms. Wolters Kluwer.

Augmenting With SGAs After Unsatisfactory Response to Lithium in Bipolar Mania Slide 3 of 12

Slide 4 of 12

Anyway, as noted though, quetiapine comes closest to lithium as a full mood stabilizer that works for mania and depression. The doses are 500 to 600 for mania. It's an FDA-approved add-on to lithium both acutely and for maintenance. It's gotten an FDA approval. So it's the odds on best evidenced add-on to your lithium.

References:

Osser, D. (2021). Psychopharmacology algorithms. Wolters Kluwer.

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Slide 5 of 12

Now, you may wonder, what about adding adding valproate? The evidence that valproate is effective in bipolar mania is weaker than many assume and has been previously assumed and it's been overused we think in part due to very effective marketing by the drug company starting in 1994 when they did their first quite positive study and that got ingrained into the brains of a whole generation of psychiatrists who then taught that to the next generation.

References:

Osser, D. (2021). Psychopharmacology algorithms. Wolters Kluwer.

Augmenting With SGAs After Unsatisfactory Response to Lithium in Bipolar Mania Slide 5 of 12

Slide 6 of 12

But there was a game-changing BALANCE study among other studies that evaluated the long-term effect of adding lithium to valproate. And there was very little, no clinically significant additional benefit from adding valproate to lithium over a two-year period in the BALANCE study. And that's why we do not recommend adding valproate as your second drug to your lithium for acute classic mania.

References:

Geddes, J. R., Rendell, J. M., & Goodwin, G. M. (2002). BALANCE: A large simple trial of maintenance treatment for bipolar disorder. World Psychiatry,1(1), 48–51.

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Slide 7 of 12

So what if you have added the quetiapine or other antimanic agent and you still have an unsatisfactory response? What's the third-line treatment for acute classic mania? Well, as the arrow indicates as you can see if you can visualize our slides, since the two agents with the broadest spectrum of activity have failed, lithium and quetiapine, we now give more consideration to options with efficacy more limited to acute mania and that is the other SGAs like risperidone and olanzapine and we prefer those two.

References:

Osser, D. (2021). Psychopharmacology algorithms. Wolters Kluwer.

Augmenting With SGAs After Unsatisfactory Response to Lithium in Bipolar Mania Slide 7 of 12

Slide 8 of 12

And we would suggest switching the quetiapine to one of these at this point to not have two antipsychotics on board at the same time. Add your risperidone or add your olanzapine instead of your quetiapine. But we also now offer you the option of adding the anticonvulsants – valproate or carbamazepine – at this point. They're third line as we said earlier. We've demoted them to the third choice in this situation. They may have efficacy.

References:

Osser, D. (2021). Psychopharmacology algorithms. Wolters Kluwer.

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Slide 9 of 12

And you could even add valproate here as I said. And if you do, the plasma level suggested is 50 to 125 though no studies have found that level to actually be the therapeutic level for mania. Now, if you do add it to quetiapine, watch for the risk of adding weight gain and triglyceride elevation as in particular had been noted which causes insulin resistance.

References:

Bowden, C. L., Janicak, P. G., Orsulak, P., Swann, A. C., Davis, J. M., Calabrese, J. R., Goodnick, P., Small, J. G., Rush, A. J., Kimmel, S. E., Risch, S. C., & Morris, D. D. (1996). Relation of serum valproate concentration to response in mania. The American Journal of Psychiatry, 153(6), 765–770.
Janicak, P. G., & Rado, J. T. (2011). Quetiapine monotherapy for bipolar depression. Expert Opinion on Pharmacotherapy, 12(10), 1643–1651.

Augmenting With SGAs After Unsatisfactory Response to Lithium in Bipolar Mania Slide 9 of 12

Slide 10 of 12

So in conclusion now, the key points of video 6, we recommend adding a second medication to your initial lithium for the management of acute classic mania and we would choose an SGA. And the SGA we would choose would be quetiapine first and then two others with strong acute effectiveness that could be tried are risperidone and olanzapine.

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Slide 11 of 12

We don't recommend olanzapine due to its side effects. We prefer risperidone over it.

Augmenting With SGAs After Unsatisfactory Response to Lithium in Bipolar Mania Slide 11 of 12

Slide 12 of 12

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Next Section

07. Other Pharmacologic Options and ECT for Managing Bipolar Mania

Learning Objectives:

After completing this activity, the learner will be able to:

Apply an evidence-based psychopharmacology algorithm to effectively treat bipolar mania.
Identify the appropriate circumstances for the use of each medication in the treatment of bipolar mania.
Evaluate the effectiveness of various medication combinations in the management of bipolar mania.

Original Release Date: July 1, 2024

Expiration Date: July 1, 2027

Expert: David Osser, M.D.

Medical Editor: Paz Badía, M.D.

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None of the faculty, planners, and reviewers for this educational activity have relevant financial relationships to disclose during the last 24 months with ineligible companies whose primary business is producing, marketing, selling, re-selling, or distributing healthcare products used by or on patients.

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