Citalopram and Luvox also contain the same fluorophenyl compound..

See also Scotchgard for same effects.


Prozac/Paxil Facts
© 2001 - 2005 PFPC

Latest News

Notes & Observations:

   Prozac is a fluorinated drug called "fluoxetine".

   Paxil is a fluorinated drug called "paroxetine" (also called Seroxat, Aropax). These drugs are designed to inhibit the reuptake of serotonin (serotonin reuptake inhibitors - SSRIs) and hence interfere with the biological actions of serotonin, a neurotransmitter.

   Both drugs contain fluorine and chloride. Fluoride is present as a '4-fluorophenyl' compound, part of the 'active' ingredient.

   Fluorophenyl compounds are found as major metabolites in the human organism from Paxil and Prozac, as well as from pesticides as Flusilazole (Anderson et al, 1999), Fluorbenside; FOE 5043 (Christenson et al, 1996), other drugs such as dexfenfluramine ("Redux"; "Fen-Phen" - now withdrawn) (Kalin et al, 2000); Fluvastatin (Top 200 drugs) (Dain et al, 1993); Flutrimazole (skin cream) (Conte et al, 1992); AD-5423 (an anti-psychotic) (Oka et al, 1993), Bay U 3405 (Braun et al, 1990); Cisapride (also now withdrawn from US market), Leflunamide (Arava) etc...

   Fluorophenyl compounds have shown to disturb thyroid hormone activity in several ways, specifically in the liver and at the hypothalamus-pituitary-thyroid (HPT) axis.

Observations: Thyroid Hormones

   In depressed patients receiving paroxetine the T4 level was reduced by 11. 2% (Konig et al, 2000).

   In animals chronic administration of fluoxetine resulted in a decrease in both T4 and T3 levels. The authors reported that the major effect of the drug “seems to be stimulation of TSH synthesis and release via the inhibition of T4-mediated thyroid-pituitary feedback” (Golstein et al, 1983).

   In rat brain, fluoxetine has also been shown to interfere with local T3 metabolism (Eravci et al, 2000; Baumgartner et al, 1994).


   In the 1930s is was first observed that all fluoride compounds, organic and inorganic ones, inhibit thyroid hormones. Prof. Kurt Kraft exposed tadpoles (bufo vulgaris, rana temporaria) to fluoride compounds including sodium fluoride, fluorotyrosine and fluorobenzoic acid (Kraft, 1937). Litzka’s experiments (1937) showed that the thyroid inhibition was due to activity in the liver (similar to PTU). Numerous fluoride compounds were used subsequently as the first line of treatment for hyperthyroidism in various countries, for several decades.

   1940s experiments on animals were conducted by Euler et al. which showed that all fluoride compounds acted upon liver glycogen, the difference being a matter of amplitude (Euler et al, 1949). Some organic compounds caused identical effects in bone and teeth as inorganic fluorides (Euler et al, 1942).

   In 1996, Christensen et al. tested the experimental herbicide FOE 5043 (4-fluorophenyl-containing) specifically on thyroid hormone function in the liver, after earlier tests had  suggested that the observed reduced circulating serum T4 levels were due to extrathyroidal activity.

    "In the liver, the actvity of hepatitic uridine glucoronosyl transferase, a major pathway of thyroid hormone biotransformation in the rat, increased in a statistically significant and dose-dependent manner, conversely hepatitic 5-monodeiodinase [D1] trended downward with dose. Bile flow and bilary excretion of T4 were increased. These data suggests that the functional status of the thyroid and pituitary glands has not been altered by treatment with FOE 5043 and that reductions in circulating levels of T4 are being mediated indirectly through an increase in the biotransformation and excretion of thyroid hormone in the liver."

   Urichuk et al (1997) showed that levels of fluorophenyl metabolites after fluoxetine administration were 10-fold higher in the liver of rats than in brain.


   In the 1940s numerous investigators were of the opinion that - besides being active in liver - organic fluorides could also be causing disturbances at the hypothalamus-pituitary (HP) axis, due to their high affinity for the central nervous system (CNS) (Litzka, 1937, May, 1950).

   Later investigations into such compounds as fluoxetine   confirmed those suspicions (Jackson et al, 1998; Baumgartner et al, 1994; Golstein et al, 1983).

   In humans fluoxetine treatment reduced TRH-induced TSH release in both normal and obese women (Pijl et al, 1993). In a hypothalamic neuronal culture system fluoxetine decreased TRH levels (Jackson et al, 1998). In other tissue (rabbits - colon) it has shown to enhance TRH activity (Horita  & Carino, 1982).

   In humans, fluvoxamine (Luvox) also causes a decreased TSH response in the TRH test, indicating disturbances in the hypothalamus-pituitary-thyroid (HPT) axis. It caused decreased basal TSH levels (De Mendonca et al, 1997).   

   Fluoxetine affects both D2 and D3 deiodinase activities in the rat brain (Eravci et al, 2000; Baumgartner et al, 1994).

   These deiodinases - of which there are three (D1, D2 and D3) - are responsible for T4 to T3 conversion. While D1 is mainly expressed in the liver, kidney and the thyroid, D2 is found in the central nervous system, the pituitary, skeletal muscle and adipose tissue. D3 is responsible for the production of reverse T3 (rT3).

P450 System

   Fluorophenyl compounds are potent inhibitors of the cytochrome P450 (CYP) enzyme system in the liver. 

   Prolonged inhibition of P450 leads to thyroid hormone reduction. Thyroid hormones, in turn, modulate the levels of P450 in the liver, where the majority of thyroid hormone synthesis occurs (T4 ->T3).

Drug Interactions

   Fluoxetine is a known inhibitor of multiple P450 isoenzymes, thus interfering with the metabolism of other substances (Thompson et al, 1997; 2003)

   Fluoxetine thus may potentiate the effects of other drugs manyfold (Daniel et al, 1999a, 1999b). Fluoxetine potently increased (up to 13 times) the concentrations of thioridazine and its metabolites in the plasma (Daniel et al, 1999), due to synergistic pharmacodynamic effects and the influence of fluoxetine on the bioavailability of such compounds.


   Studies in rat liver slices showed intracellular glutathione levels decreased and fluoride ion levels increased in a time and concentration-dependent manner by fluoxetine (Thompson et al, 1997).

   Like the deiodinases, glutathione peroxidase is another selenoprotein-containing enzyme which further modulates iodine metabolism.

   Glutathione peroxidase levels are considered a diagnostic tool in fluoride poisoning - discriminating between mild and severe chronic fluorosis (Guan, 1983).

   Several animal studies show that fluoxetine affects T3 production in various tissue, including brain (Eravci et al, 2000; Lin et al, 1999; Baumgartner et al, 1994; Shelton et al, 1993). .   

   Because of their vast effects on the thyroid hormone system, it is of great importance that anybody wishing to get off such medications as Paxil, Prozac, Luvox etc. does so very gradually.

Other Assorted Prozac Facts

   Infants who were breastfed by mothers taking fluoxetine demonstrated a growth curve significantly below that of infants who were breastfed by mothers who did not take the drug (Chambers et al, 1999).  Newborn mouse pups exposed to paroxetine were more likely to have low birthweights (Rayburn et al, 2000). Low birth weight is related to thyroid status of the mother.

   Fluoxetine has been shown to cause severe liver dysfunction such as hepatitis (Cai et al, 1999; Johnston & Wheeler, 1997; Mars et al, 1991; Friedenberg & Rothstein, 1996).

   Fluoxetine has also been shown to cause secondary hyperthyroidism - originating from pituitary dysfunction (Martinez & Ortiz, 1999).

   Visual hallucinations have been found associated with use of fluoxetine (Bourgeois et al, 1998).

   Dyskinesia has been reported with use of fluoxetine. (Duborvski & Thomas, 1996).

   Fluoxetine showed tumor-promoting activity in rat liver , as did fenfluramine, another fluorophenyl-containing fluoride compound (Lin et al, 1999). [Ed: as does PFOS  - "Scotchgard")].

   Like other, inorganic fluoride compounds, 4-fluorophenyl shows activity upon TXA2/PGA2 receptors (Marcin et al. 1999).


   “A 72-year-old woman developed rhythmic palatal movements, myoclonus, chorea, and possibly dystonia after 2 years of therapy with fluoxetine. On withdrawal of fluoxetine, the movements abated after 5 days and did not recur. A second patient, a 58-year-old man, developed myoclonic jerking and rapid, stereotypic movements of his toes after a year of fluoxetine therapy.” (Bharucha & Sethi, 1996).


Abenhaim L, Moride Y, Brenot F, Rich S et. al. - "Appetite-Suppressant Drugs and the Risk of Primary Pulmonary Hypertension" NEJM 335:609-616 (1996)

Anderson JJ, Shalaby LM, Berg DS - "Metabolism of [(14)C]flusilazole in the goat" J Agric Food Chem 47(6):2439-46  (1999) trieve&db=PubMed&list_uids=10794648&dopt=Abstract

Atan A, Basar MM, Aydoganli L  - "Comparison of the efficacy of fluoxetine alone vs. fluoxetine plus local lidocaine ointment in the treatment of premature ejaculation" Arch Esp Urol 53(9):856-8 (2000) trieve&db=PubMed&list_uids=11196396&dopt=Abstract

Baumgartner A, Dubeyko M, Campos-Barros A, Eravci M, Meinhold H - "Subchronic administration of fluoxetine to rats affects triiodothyronine production and deiodination in regions of the cortex and in the limbic forebrain" Brain Res 635(1-2):68-74 (1994) trieve&db=PubMed&list_uids=8173980&dopt=Abstract

Bharucha KJ, Sethi KD - "Complex movement disorders induced by fluoxetine" Mov Disord 11(3):324-6 (1996) trieve&db=PubMed&list_uids=8723152&dopt=Abstract

Bourgeois JA, Thomas D, Johansen T, Walker DM J - “Visual hallucinations associated with fluoxetine and sertraline” Clin Psychopharmacol 18(6):482-3 (1998) trieve&db=PubMed&list_uids=9864082&dopt=Abstract.

Braun M, Schror K - "Bay U 3405 inhibits cerebral vasospasm induced by authentic thromboxane A2" Stroke 21(12 Suppl):IV152-4 (1990) trieve&db=PubMed&list_uids=2260141&dopt=Abstract

Bross R, Hoffer LJ - "Fluoxetine increases resting energy expenditure and basal body temperature in humans" Am J Clin Nutr 61(5):1020-5 (1995) trieve&db=PubMed&list_uids=7733022&dopt=Abstract

Braun M, Schror K - "Bay U 3405 inhibits cerebral vasospasm induced by authentic thromboxane A2" Stroke 21(12 Suppl):IV152-4 (1990) trieve&db=PubMed&list_uids=2260141&dopt=Abstract
(Bay U 3405)

Chambers CD, Anderson PO, Thomas RG, Dick LM, Felix RJ, Johnson KA, Jones KL - "Weight gain in infants breastfed by mothers who take fluoxetine" Pediatrics 104(5):e61 (1999) trieve&db=PubMed&list_uids=10545587&dopt=Abstract

Choy RK, Thomas JH - "Fluoxetine-resistant mutants in C. elegans define a novel family of transmembrane proteins" Mol Cell 4(2):143-52 (1999) trieve&db=PubMed&list_uids=10488330&dopt=Abstract

Christenson WR, Becker BD, Wahle BS, Moore KD, Dass PD, Lake SG, Van Goethem DL, Stuart BP, Sangha GK, Thyssen JH - "Evidence of chemical stimulation of hepatic metabolism by an experimental acetanilide (FOE 5043) indirectly mediating reductions in circulating thyroid hormone levels in the male rat" Fundam Appl Toxicol 29(2):251-9 (1996) trieve&db=PubMed&list_uids=8742323&dopt=Abstract

Cai Q, Benson MA, Talbot TJ, Devadas G, Swanson HJ, Olson JL, Kirchner JP - "Acute hepatitis due to fluoxetine therapy" Mayo Clin Proc 74(7):692-4 (1999) trieve&db=PubMed&list_uids=10405699&dopt=Abstract

Cisapride Factsheet 1:

Conte L, Ramis J, Mis R, Forn J, Vilaro S, Reina M, Vilageliu J, Basi N - "Percutaneous absorption and skin distribution of [14C]flutrimazole in mini-pigs" Arzneimittelforschung 42(6):847-53 (1992) trieve&db=PubMed&list_uids=1418044&dopt=Abstract

Dain JG, Fu E, Gorski J, Nicoletti J, Scallen TJ - "Biotransformation of fluvastatin sodium in humans" Drug Metab Dispos 21(4):567-72 (1993) trieve&db=PubMed&list_uids=8104114&dopt=Abstract

Daniel WA, Syrek M, Wojcikowski J - "The influence of selective serotonin reuptake inhibitors on the plasma and brain pharmacokinetics of the simplest phenothiazine neuroleptic promazine in the rat" Eur Neuropsychopharmacol 9(4):337-44 (1999) trieve&db=PubMed&list_uids=10422895&dopt=Abstract

Daniel WA, Wojcikowski J - "The role of lysosomes in the cellular distribution of thioridazine and potential drug interactions" Toxicol Appl Pharmacol 158(2):115-24(1999) trieve&db=PubMed&list_uids=10406926&dopt=Abstract

De Mendonca Lima CA, Vandel S, Bonin B, Bechtel P, Carron R - "Maprotiline versus fluvoxamine: comparison of their effects on the hypothalamo-hypophyseal-thyroid axis" Encephale 23(1):48-55  (1997) trieve&db=PubMed&list_uids=9172968&dopt=Abstract

Dihydrolenperone phenyl&hl=en

Dubovsky SL, Thomas M - "Tardive dyskinesia associated with fluoxetine" Psychiatr Serv 47(9):991-3 (1996) trieve&db=PubMed&list_uids=8875667&dopt=Abstract

Eravci M, Pinna G, Meinhold H, Baumgartner A - "Effects of pharmacological and nonpharmacological treatments on thyroid hormone metabolism and concentrations in rat brain" Endocrinology 141(3):1027-40  (2000) FULL TEXT

Euler H, Eichler O, Hindemith H -"Über die Wirkung einiger organischer Fluoride bei chronischer Darreichung" Arch Exp. Path u Pharmakol Bd.206:75-82 (1949)

Euler H, Eichler O - "Über die Wirkung von Fluor in organischer Bindung auf das Zahnsytem der Ratte" Arch Exp Pathol Pharmakol 199:179-187 (1942)


Flusilazole Fact Sheet 1:

Flusilazole Fact Sheet 2: Food Residues: htm

Fluvastin Fact Sheet:

DEXFENFLURAMINE Fen-Phen Withdrawal Notice FDA

Friedenberg FK, Rothstein KD - "Hepatitis secondary to fluoxetine treatment" Am J Psychiatry 153(4):580(1996) trieve&db=PubMed&list_uids=8599417&dopt=Abstract

Goeringer KE, Raymon L, Christian GD, Logan BK -"Postmortem forensic toxicology of selective serotonin reuptake inhibitors: a review of pharmacology and report of 168 cases" J Forensic Sci45(3):633-48 (2000) trieve&db=PubMed&list_uids=10855970&dopt=Abstract

Golstein J, Schreiber S, Velkeniers B, Vanhaelst L - "Effect of fluoxetine, a serotonin reuptake inhibitor, on the pituitary-thyroid axis in rat" Eur J Pharmacol 91(2-3):239-43 (1983) trieve&db=PubMed&list_uids=6413229&dopt=Abstract

Guan ZZ - "An experimental study of blood biochemical diagnostic indices for chronic fluorosis" Zhonghua Yu Fang Yi Xue Za Zhi 25(1):33-5 (1991) trieve&db=PubMed&list_uids=2036910&dopt=Abstract

Henry ME, Moore CM, Kaufman MJ, Michelson D, Schmidt ME, Stoddard E, Vuckevic AJ, Berreira PJ, Cohen BM, Renshaw PF - "Brain kinetics of paroxetine and fluoxetine on the third day of placebo substitution: a fluorine MRS study" Am J Psychiatry 157(9):1506-8 (2000) trieve&db=PubMed&list_uids=10964871&dopt=Abstract

Horita A, Carino MA - “Centrally administered thyrotropin-releasing hormone (TRH) stimulates colonic transit and diarrhea production by a vagally mediated serotonergic mechanism in the rabbit” J Pharmacol Exp Ther 222(2):367-71 (1982)

Hostetter A, Ritchie JC, Stowe ZN - "Amniotic fluid and umbilical cord blood concentrations of antidepressants in three women" Biol Psychiatry 48(10):1032-4 (2000) trieve&db=PubMed&list_uids=11082480&dopt=Abstract

Jackson IM, Luo LG - "Antidepressants inhibit the glucocorticoid stimulation of thyrotropin releasing hormone expression in cultured hypothalamic neurons" J Investig Med 46(9):470-4 (1998) trieve&db=PubMed&list_uids=9861783&dopt=Abstract

Johnston DE, Wheeler DE - "Chronic hepatitis related to use of fluoxetine" Am J Gastroenterol 92(7):1225-6 (1997) trieve&db=PubMed&list_uids=9219808&dopt=Abstract

Kalia M, O'Callaghan JP, Miller DB, Kramer M - "Comparative study of fluoxetine, sibutramine, sertraline and dexfenfluramine on the morphology of serotonergic nerve terminals using serotonin immunohistochemistry" Brain Res 858(1):92-105 (2000) trieve&db=PubMed&list_uids=10700602&dopt=Abstract

Konig F, Hauger B, von Hippel C, Wolfersdorf M, Kaschka WP - "Effect of paroxetine on thyroid hormone levels in severely depressed patients" Neuropsychobiology 42(3):135-8  (2000) trieve&db=PubMed&list_uids=11015031&dopt=Abstract

Kraft K - "Über die Synthese einiger aromatischer Fluorverbindungen" Knoll Research, Chem Ber. 84(2):150-156 (1951)

Kraft K - "Beiträge zur Biochemie des Fluors I.Über den Antagonismus zwischen Fluor und Thyroxin." Hoppe-Seglers Z.Physiol. Chem 245:58 -65 (1937)

Kraft K, Dengel F - "Über die Synthese einiger aromatischer Fluorverbindungen, II. Mitteilung" Chem Ber 85(6):577-582 (1952)

Lin X, Levitsky DA, King JM, Campbell TC - "The promotion effect of anorectic drugs on aflatoxin B(1)-induced hepatic preneoplastic foci" Carcinogenesis 20(9):1793-9 (1999) trieve&db=PubMed&list_uids=10469626&dopt=Abstract

Litzka G - "Die experimentellen Grundlagen der Behandlung des Morbus Basedow und der Hyperthyreose mittels Fluortyrosin" Med Wochenschr 63:1037-1040 (1937)

Marcin Róalski M, Boncler M, Wiclawska B, Watala C - "Molecular and therapeutical aspects of the blood platelet receptors antagonists" Laboratory of Haemostasis and Haemostatic Disorders, Department of Laboratory Diagnostics, Medical University, Lód , Poland

Mars F, Dumas de la Roque G, Goissen P - "Acute hepatitis during treatment with fluoxetine" Gastroenterol Clin Biol 15(3):270-1  (1991) trieve&db=PubMed&list_uids=2044897&dopt=Abstract

Martinez Ortiz JJ - "Hyperthyroidism secondary to antidepressive treatment with fluoxetine" An Med Interna 16(11):583-4 (1999) trieve&db=PubMed&list_uids=10638001&dopt=Abstract

May W - "Die Basedowsche Krankheit" Aulendorf, Sandmeyer & Sohn (1950)

Meuldermans W, Hendrickx J, Lauwers W, Hurkmans R, Mostmans E, Swysen E, Bracke J, Knaeps A, Heykants J - "Excretion and biotransformation of cisapride in rats after oral administration" Drug Metab Dispos 16(3):410-9 (1988) trieve&db=PubMed&list_uids=2900733&dopt=Abstract

Moreau X, Azorin JM, Lejeune PJ, Jeanningros R - "Red blood cell triiodothyronine uptake in unipolar major depression: effect of a chronic antidepressant treatment" Prog Neuropsychopharmacol Biol Psychiatry 24(1):23-35 (2000)

Nargund LV, Hariprasad V, Reedy GR - "Synthesis and anti-inflammatory activity of fluorinated phenyl styryl ketones and N-phenyl-5-substituted aryl-3-p-(fluorophenyl) pyrazolins and pyrazoles" J Pharm Sci 81(9):892-4 (1992) trieve&db=PubMed&list_uids=1432635&dopt=Abstract
"All compounds (0.20 mM) showed ability to denature bovine serum albumin, as observed in in vitro inhibition studies."

Ohta T, Wergedal JE, Matsuyama T, Baylink DJ, Lau KH - "Phenytoin and fluoride act in concert to stimulate bone formation and to increase bone volume in adult male rats" Calcif Tissue Int 156(5):390-7 (1995) trieve&db=PubMed&list_uids=7621347&dopt=Abstract

Oka M, Noda Y, Ochi Y, Furukawa K, Une T, Kurumiya S, Hino K, Karasawa T - "Pharmacological profile of AD-5423, a novel antipsychotic with both potent dopamine-D2 and serotonin-S2 antagonist properties" J Pharmacol Exp Ther 264(1):158-65(1993) trieve&db=PubMed&list_uids=8093723&dopt=Abstract

Oida T, Terauchi Y, Yoshida K, Kagemoto A, Sekine Y - "Use of antisera in the isolation of human specific conjugates of haloperidol" Xenobiotica 19(7):781-93 (1989) trieve&db=PubMed&list_uids=2773512&dopt=Abstract

Pijl H, Koppeschaar HP, Willekens FL, Frolich M, Meinders AE - The influence of serotonergic neurotransmission on pituitary hormone release in obese and non-obese females” Acta Endocrinol (Copenh)128(4):319-24 (1993)

Prozac Data Sheet

Prozac Violence:
Tracy, Ann Blake - “ The Aftermath Of Prozac, Zoloft, Luvox, Fen-Phen, & Many Other Serotonergic Drugs” After.html

Rayburn WF, Gonzalez CL, Christensen HD, Kupiec TC, Jacobsen JA, Stewart JD - "Effect of antenatal exposure to paroxetine (paxil) on growth and physical maturation of mice offspring" J Matern Fetal Med 9(2):136-41 (2000)

Sarich TC, Wright JM - "Hypothyroxinemia and phenytoin toxicity: a vicious circle" Drug Metabol Drug Interact 13(2):155-60 (1996) trieve&db=PubMed&list_uids=8905247&dopt=Abstract

Schuld A, Archelos JJ, Friess E - “Visual hallucinations and psychotic symptoms during treatment with selective serotonin reuptake inhibitors: is the sigma receptor involved?” J Clin Psychopharmacol 20(5):579-80 (2000)

Shelton RC, Winn S, Ekhatore N, Loosen PT - "The effects of antidepressants on the thyroid axis in depression." Biol Psychiatry 33(2):120-6 (1993) trieve&db=PubMed&list_uids=8439600&dopt=Abstract

Thompson DC, Perera K, London R - "Spontaneous hydrolysis of 4-trifluoromethylphenol to a quinone methide and subsequent protein alkylation" Chem Biol Interact 126(1):1-14 (2000) trieve&db=PubMed&list_uids=10826650&dopt=Abstract

Thompson DS, Kirshner MA, Klug TL, Kastango KB, Pollock BG - “A Preliminary Study of the Effect of Fluoxetine Treatment on the 2:16-alpha-Hydroxyestrone Ratio in Young Women” Ther Drug Monit 25(1):125-8 (2003)

Urichuk LJ, Aspeslet LJ, Holt A, Silverstone PH, Coutts RT, Baker GB - “Determination of p-trifluoromethylphenol, a metabolite of fluoxetine, in tissues and body fluids using an electron-capture gas chromatographic procedure” J Chromatogr B Biomed Sci Appl 698(1-2):103-9 (1997)