Posted by Sunnely on August 30, 2000, at 19:52:13
In reply to Paxil and Ambien, posted by Sandy Garner on August 28, 2000, at 10:56:06
> The Dr. prescriped Paxil 20 mg and Ambien 10 mg. I was exhausted all day and nearly passed out when taking the Ambien at bedtime. Of a daytime I have amnesia symptons, severe, SEVERE, head aches, nausea and confusion. I feel my world is spinning and disoriented. Is this fromt he two combinations or what.
> SandySandy,
Although these adverse effects can occur with the use of either paroxetine (Paxil) or zolpidem (Ambien) alone, they are probably magnified more by the combined use of these drugs; a form of drug-drug interaction.
I would venture to say that your blood level of Ambien is at toxic level causing these problems. Allow me to explain how this can happen in your case. Based on "pharmacokinetic" drug-drug interaction, Paxil can intensify the pharmacological effects (therapeutic and adverse effects) of Ambien. Paxil is a potent inhibitor of the liver enzyme called CYP2D6. Ambien is primarily metabolized (broken down) by the liver enzyme CYP3A4. Therefore, this practically rules out the role of liver enzymes in these adverse effects caused by the Paxil-Ambien interaction. The "pharmacokinetic" drug interaction involved is most likely the "protein-binding" displacement. Paxil is highly protein-bound (approximately 95%) while Ambien is approximately 92%. The portion of the drug that is not bound to proteins is called "free fraction." Only the "free fraction" of the drug is considered pharmacologically active, exerting both the therapeutic and adverse effects. The protein-bound portion of the drug is considered pharmacologically inactive, therefore does not have any role in its pharmacologic effects.
Since Paxil is highly protein bound, it will displace Ambien from its protein-binding, therefore more unbound or "free fraction" of Ambien is formed, leading to increased side effects and even toxicity. It's like playing "musical chairs." There is not enough proteins available to accomodate both Paxil and Ambien, together. Therefore, the more "powerful" (Paxil) attaches itself to the available proteins much stronger than Ambien, leading to more Ambien portion being displaced ("free fraction").
Aside from the one I described above (protein-binding effect), other risk factors to increased Ambien side effects/toxicity include gender, dose, and the cytochrome enzymes.
Gender seems to play an important role in risk of Ambien toxicity. (I am assuming you are a woman.) Eighty-two percent (82.4%) of Ambien-induced hallucinations (psychosis) reported were among female patients. Women have been found to have a significantly higher blood level of Ambien (40%) than men at equivalent dosages. Therefore, women may experience Ambien toxicity at the same doses that male patients are able to tolerate well.
The dose of Ambien used is also another risk factor. In case reports of Ambien-induced hallucinations (psychosis), they tend to occur more in doses greater than 5 mg per day. There were no reports of hallucinations or psychosis when patients took doses of 5 mg or less.
Finally, the extent of liver enzyme (CYP3A4) inhibition by the concmitantly used drugs with Ambien, is also a risk factor for Ambien toxicity. Any drug that significantly inhibits the action of this liver enzyme could reduce Ambien metabolism, leading to toxic levels. Examples of these drugs are Serzone (nefazodone), Prozac (fluoxetine, norfluoxetine), antibiotics such as erythromycin, azithromycin (Zithromax), clarithromycin (Biaxin), antifungal drugs (Nizoral, Sporanox), cimetidine (Tagamet), and grapefruit juice.
Based on the above analysis, you meet at least 3 (out of 4) risk factors for Ambien toxicity: 1) the use of a highly protein-bound drug (Paxil) along with Ambien; 2) female gender (I assume you are); and 3) the dose is greater than 5 mg per day.
FYI, numerous side effects have been associated with Ambien use. In a review of the clinical trials, central nervous system (CNS) related adverse effects included lightheadedness or dizziness (5.2%), daytime drowsiness (5.2%), headache (3.0%), fatigue (2.4%), memory deficits (1.8%), nightmares (1.6%), confusion (1.6%), and depression (1.2%). The most commonly seen non-CNS related adverse effects included nausea or vomiting (2.5%), falls (2.3%), malaise (1.4%), stomach or abdominal pain (1.1%), and dry or coated mouth (1.1%).
In a later postmarketing study of 1,972 patients treated with Ambien, 8.9% reported adverse effects and 5.2% of patients discontinued treatment. In this study, the most common CNS-related adverse effects were "residual daytime sedation-like symptoms" (3.7%). Delirium, nightmares, and hallucinations were reported in less than 1% of patients.
The daytime amnesia you described seems to occur more commonly with the short half-life hypnotics (sleeper) drug such as triazolam (Halcion) and zolpidem (Ambien). This is called the "morning-after amnesia," wherein you don't remember what you did the night before. This adverse reaction can be frightening sometimes.
I suggest you discuss this problem with your doctor, and the possibility that you are experiencing a drug-drug interaction (Paxil + Ambien), ASAP. I believe you need some dosage adjustments, at least a dose reduction of Ambien.
JMHO (Just my humber opinion).
References:
1. Toner LC, Tsambiras BM, Catalano G, Catalano MC, Cooper MS: Central nervous system side effects associated with zolpidem treatment. Clinical Neuropsychopharmacology 1999;23(1):54-58.
2. Zolpidem-induced delirum. In: Primary Psychiatry, August 2000.
poster:Sunnely
thread:43915
URL: http://www.dr-bob.org/babble/20000822/msgs/44105.html