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Question. I take Luvox 150 mg per day for chronic depression and obsessive anger problems. My psychiatrist is concerned about my sleep habits, which have basically been the same all my life; I cannot sleep at night, I only sleep soundly in the mid-morning hours. He prescribed Ambien to be taken at bedtime and it put me to sleep right away. I was delighted with that result, however, for two or three days after taking even just one dose, all the obsessive anger and intense depression symptoms would reappear, as if the Ambien negated all the beneficial effects of the Luvox. The psychiatrist prescribed trazodone as a sleeping agent, only to be taken as needed. Well, it works occasionally, but when it does work, I sleep not only through the night but most of the next day as well. But it doesn’t detract from the positive effects of the Luvox. I want to know how drugs such as Ambien and over-the-counter decongestants interfere with SSRIs like Luvox, if such interference is common and if these medications have any property that might cause these problems. Can you offer any insight?

Answer. I wish I had some insight that could unify all the various elements of your case, but I’m afraid I don’t. This is partly because of the complexity of your question, and partly because the circumstances as you’ve described them don’t permit a neat pharmacologic “dissection” of the facts, a result of the way you were taking the medications.

First of all, I would have to say that the reactions you describe strike me as uncommon, but that may be because few such interactions have been published, rather than because they don’t occur. However, my guess is that your nervous system is unusually sensitive to either the single agents you list or to some interaction between them. Let’s start with the Ambien. Ambien itself (i.e., taken without any concomitant medications) can, in less than 1% of cases, cause unusual reactions, including visual distortions, aggressive reactions, manic states and panic attacks. We don’t know whether Ambien alone might have given you some problems. Could it have “negated” the effects of the Luvox? I doubt that a single dose of Ambien could have had any significant effect on the total amount of Luvox in your system; however, since both Ambien and Luvox are bound to “carrier proteins” in the blood, it is theoretically possible that the Ambien displaced a large amount of the Luvox from its carrier proteins, caused a sudden (very brief) surge of “free” Luvox in your brain and somehow negated its own beneficial effects.

Something similar can sometimes be seen in patients with obsessive-compulsive conditions, in which the neurotransmitter serotonin is thought to be deficient (as it is in some depressive states). When we give such individuals chemicals that stimulate serotonin receptors in the brain, they sometimes, at first, get worse; perhaps because their serotonin receptors are overly sensitive. Over longer periods of time (i.e., 6-12 weeks) agents like Prozac and Luvox, which also boost serotonin, are thought to gradually “down regulate” the oversensitive serotonin receptors and restore them to their natural state.

So, thinking very theoretically, it is possible that the Ambien displaced the Luvox from its carrier proteins, caused a sudden, brief surge in your nervous system, which overstimulated your serotonergic system for a few days. However, it is also possible that the Luvox and Ambien interfered with each other’s metabolism (elimination) in some way that led to elevated levels of one or both agents. Now, as to antihistamines and decongestants, it is not clear to me whether these agents have caused intense anger and social withdrawal in you when taken alone or only in combination with Luvox. If the former is the case, I would guess that you have an unusual sensitivity to these agents. More specifically, if you have this reaction to medications such as Actifed and Sudafed – but not to diphenydramine – you may have an unusual sensitivity to pseudoephedrine, a stimulant/decongestant found in Actifed and Sudafed. (Diphenhydramine is an antihistamine). Actifed is actually a combination of pseudoephedrine and the antihistamine tripolidine, so it is possible that you react to the tripolidine. I am not aware of any of these antihistamines or decongestants interacting adversely with Luvox; however, two non-sedating prescription antihistamines (terfenadine and astemizole) may have adverse interactions with Luvox, since Luvox may reduce metabolism of these agents.

My suggestion would be to keep a careful record of your reactions to medications and discuss them with a psychopharmacologist; in the mean time, you might want to avoid use of pseudoephedrine-containing medications. By the way, it may be better for your sleep-wake cycle to use the trazodone on a regular basis, in very small doses (e.g., 25 mg), rather than sporadically; it is not habit-forming and the regularity may help stabilize your sleep-wake cycle.