Posted by SalArmy4me on September 9, 2001, at 8:26:18
In reply to They all think i am, but am I?bipolarthatis, posted by emma lee on September 8, 2001, at 23:30:32
Bauer, Michael PhD, MD. Adverse Events and Tolerability of the Combination of Fluoxetine/Lithium Compared With Fluoxetine. Journal of Clinical Psychopharmacology. Apr 1996:
"Furthermore, there have been reports that administrating fluoxetine to patients who are already on lithium therapy can increase the level of lithium in serum. [15] It is not known why this might happen, and controlled studies for its systematic investigation are missing at present. [3] In a noncontrolled study, Breuel and colleagues [16] did not find pharmacokinetic interactions between lithium and fluoxetine after single and repeated fluoxetine administration in 10 healthy young volunteers. A naturalistic study with 50 outpatients showed a small and statistically not significant increase (mean increase, 0.02 mmol/liter) in lithium levels during the fluoxetine phase treatment. [11] Another potentially serious but rare side effect-the "serotonin syndrome"-occurs most commonly in patients who are given serotonergic agents in combination with a monoamine oxidase inhibitor. The most frequent clinical features of the "serotonin syndrome" are changes in mental status, restlessness, myoclonus, hyperthermia, hypertension, diaphoresis, shivering, and tremor. [17] Because lithium enhances the serotonergic transmission, [18] one would expect that serotonergic symptoms may also appear in the course of fluoxetine-lithium combination. There have been single case reports of significant negative interactions between fluoxetine and lithium, including the development of mania, [19] delirium, [20] absence seizures, [21] and "serotonin syndrome." [22]
This study was designed to evaluate adverse events for the combination of fluoxetine/lithium in comparison to fluoxetine alone in larger samples. The study revealed more adverse events in the fluoxetine/lithium group as compared with the fluoxetine group. However, this difference was statistically not significant. The combination of fluoxetine/lithium is accompanied by a slightly increased risk of adverse events (risk ratio, 1.4) such as those of the nervous system (especially nervousness and vertigo) and the metabolic/nutritional system. It must be emphasized that more patients (30.9%) in the fluoxetine/lithium group received an additional antidepressant drug (mostly TCAs) as compared with 14.9% in the fluoxetine group. The higher incidence of such adverse events as vertigo in the combination group may have something to do with the increased use of TCAs in that group. As we have already pointed out, the addition of fluoxetine to a preexisting TCA regimen can result in an acute increase in TCA levels in plasma, as well as excessive fluoxetine levels.
Because "serotonin syndrome" is a rare adverse drug reaction, the failure to observe it in 110 patients cannot be regarded as conclusive. However, we found a 1.5-fold increase in "serotonergic" adverse events in the combination group (20%) as compared with the fluoxetine group (13.6%). This is paralleled by a somewhat increased rate of early treatment termination because of adverse adverse events in the combination (10.0%) as compared with the fluoxetine group (6.4%). Because about one-third of the fluoxetine/lithium patients were also taking concurrent TCAs, it seems likely that the treating physician would probably discontinue the newer agent (fluoxetine) rather than the TCA when side effects occurred. This would result in an artificially high "dropout" rate for fluoxetine-giving the false impression of increased frequency of side effects in the fluoxetine/lithium group. Extrapyramidal side effects were not observed in both groups. In this study, we did not systematically assess lithium levels in serum, which is a limiting factor for the interpretation of data. However, there was no case of lithium toxicity as a reason for stopping the treatment.
Fava, M. Lithium and Tricyclic Augmentation of Fluoxetine Treatment for Resistant Major Depression: A Double-Blind, Controlled Study. Year Book of Psychiatry & Applied Mental Health. 1996(10):462-463, Annual 1996.
"We conclude from this study that, in general, the combination of fluoxetine and lithium is well tolerated. However, although not statistically significant, a combination of the two drugs reacting via a serotonergic mechanism may have a slightly higher incidence of adverse events than a single drug administration. Therefore, patients on the combination of fluoxetine/lithium in particular should be informed about the possibility of such typical adverse events by their physicians in order to improve their coping with and tolerance toward these symptoms; this will thus enhance treatment compliance."The therapeutic management of the refractory depressed patient is one of the most hotly debated topics in clinical management of affective illness. This study is particularly germane and helpful on the issue. They compared 3 widely used clinical strategies to augment antidepressant efficacy: increase the dose of fluoxetine, add lithium to fluoxetine, and add an antidepressant from another class, in this case desipramine, to fluoxetine. Although the subject sample was relatively small and therefore the results must be considered somewhat preliminary, it is interesting to note that increasing the dose of fluoxetine from 20 mg/day to the 40-60-mg range was the superior course of action. Adding desipramine to fluoxetine at 20 mg/day was the least advantageous approach. The addition of low-dose lithium to fluoxetine was the second most useful approach. Thus, if a patient fails to respond to higher-dose fluoxetine treatment, the next phase of treatment might be the addition of lithium to the fluoxetine regimen.-A. Breier, M.D."
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