Free Section - Video Lectures

08. Node 5: Lithium Augmentation

Published on September 1, 2021 Expired on April 1, 2024

David Osser, M.D.

Associate Professor of Psychiatry - Harvard Medical School

Key Points

After 2 combination trials without a satisfactory response, consider augmentation with lithium.
Use regular levels of lithium.
Continue lithium if it was effective.

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Slides and Transcript

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Hi again everybody. This is Dr. David Osser and I am presenting the algorithm for the psychopharmacology of psychotic depression or major depression with psychotic features. We are on video 8. And in this video, we're going to discuss lithium augmentation of combination therapy, of combination with an antipsychotic and antidepressant for psychotic depression.

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The previous videos have taken you through the evidence on the various possible combinations, which antidepressant to choose, which antipsychotic to choose and which to choose second depending on what you chose first. But if you've had 2 trials and you've had an unsatisfactory response and you're not doing ECT, which we strongly suggest, and you want to keep with pharmacotherapy… We're at node 5 — have you tried adding lithium?

References:

Tang M, Osser DN. (2012). The Psychopharmacology Algorithm Project at the Harvard South Shore Program: 2012 update on psychotic depression. Journal of Mood Disorders, 2(4),167-179.
Hamoda, H. M., & Osser, D. N. (2008). The Psychopharmacology Algorithm Project at the Harvard South Shore Program: An update on psychotic depression. Harvard Review of Psychiatry, 16(4), 235-247.

Node 5: Lithium Augmentation Slide 2 of 10

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Slide 3 of 10

So what evidence do we have on that? Well, not a whole lot. There was a case series of 20 patients that was published in 1986. These were people who were on a tricyclic plus a first-generation antipsychotic and had not done well and they were augmented with lithium. Forty percent had at least a partial, ranging from a partial to a marked response. So, we're not talking about a robust additional response, but a significant number did proceed to further improvement with addition of lithium.

References:

Nelson, J. C., & Mazure, C. M. (1986). Lithium augmentation in psychotic depression refractory to combined drug treatment. The American Journal of Psychiatry, 143(3), 363–366.

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Beyond that, we just have some more case series. Here's one, also old, this one from 1983. Six unresponsive patients to a tricyclic plus antipsychotic got lithium. Three had a dramatic response, so that would be half of them, and 2 more responded gradually.

References:

Price, L. H., Conwell, Y., & Nelson, J. C. (1983). Lithium augmentation of combined neuroleptic-tricyclic treatment in delusional depression. The American Journal of Psychiatry, 140(3), 318–322.

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Slide 5 of 10

And then there is a small Rothschild series from 1993. These were people that he was treating then with fluoxetine plus perphenazine. He was using an SSRI and a first-generation antipsychotic. There were 8 left in his trial that didn't respond. Three of them responded to lithium. So that's also in the 40% area.

References:

Rothschild, A. J., Samson, J. A., Bessette, M. P., & Carter-Campbell, J. T. (1993). Efficacy of the combination of fluoxetine and perphenazine in the treatment of psychotic depression. The Journal of Clinical Psychiatry, 54(9), 338–342.

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Then in 2009, Birkenhager to his big study with venlafaxine, imipramine and venlafaxine-quetiapine, added open-label lithium for 4 weeks to 15 non-responding patients. Remember that? I talked about that a few sessions ago. So, they were finished with that study of those 3 possible treatments. He kept them on their blinded initial medications and started lithium and he adjusted to bring their levels from 0.6 to 1. Nine patients, 60%, had a sustained remission. Remission, not improvement.

References:

Birkenhäger, T. K., van den Broek, W. W., Wijkstra, J., Bruijn, J. A., van Os, E., Boks, M., Verkes, R. J., Janzing, J. G., & Nolen, W. A. (2009). Treatment of unipolar psychotic depression: an open study of lithium addition in refractory psychotic depression. Journal of Clinical Psychopharmacology, 29(5), 513–515.

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Slide 7 of 10

Now, 5 of the 15 were on combination therapy because 2 of those groups were monotherapy and 5 of the 15 were combination. Unfortunately, Dr. Birkenhager did not specify separately whether it was the combination people that responded. These 5 combination people, did they respond to the lithium or was it the monotherapy people that responded? We can't know that from their published data. Still, they had a pretty decent result from adding lithium. It makes you wonder if you could add lithium to monotherapy to get some improvers.

References:

Birkenhäger, T. K., van den Broek, W. W., Wijkstra, J., Bruijn, J. A., van Os, E., Boks, M., Verkes, R. J., Janzing, J. G., & Nolen, W. A. (2009). Treatment of unipolar psychotic depression: an open study of lithium addition in refractory psychotic depression. Journal of Clinical Psychopharmacology, 29(5), 513–515.

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So in short, from this really minimal evidence, we think it's reasonable to add lithium after at least 1 or probably 2 combination therapies of the ones that we've suggested and if ECT is not a serious consideration and you might as well use typical blood levels of lithium. And you might as well continue for longer than 4 weeks and maintain them on it if you do get a good response because we don't have much else in terms of evidence on augmentation strategies. Maybe after a year, you could consider tapering it and see what happens. But if you are fortunate enough to get this long-sought improvement, you might as well keep everything going that you were initiating.

References:

Tang M, Osser DN. (2012). The Psychopharmacology Algorithm Project at the Harvard South Shore Program: 2012 update on psychotic depression. Journal of Mood Disorders, 2(4),167-179.
Hamoda, H. M., & Osser, D. N. (2008). The Psychopharmacology Algorithm Project at the Harvard South Shore Program: An update on psychotic depression. Harvard Review of Psychiatry, 16(4), 235-247.

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Slide 9 of 10

So in conclusion about lithium augmentation, if the patient has had a couple of antipsychotic plus antidepressant trials and still has not responded satisfactorily and ECT is not an option, consider augmentation with lithium. The data are very limited, but it seems you can use regular levels, that is to say, over 0.6 mEq/L at trough. If it was effective, you probably want to continue it since this has been a difficult case of psychotic depression.

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Next Section

09. Node 6: Other Options: ECT, Clozapine, and Methylphenidate