Prozac
Determination of fluoxetine and norfluoxetine by high-performance liquid chromatography.

Wong SH, Dellafera SS, Fernandes R, Kranzler H.

Department of Laboratory Medicine, University of Connecticut School of Medicine, Farmington 06032.

A high-performance liquid chromatographic assay was developed for a recently introduced atypical antidepressant, fluoxetine and its demethylated metabolite, norfluoxetine. Prior to analysis, aliquots of alkalinized plasma were extracted with n-hexane and isoamyl alcohol, followed by back-extraction with diluted phosphoric acid. These extracts were injected into a 10 microns, reversed-phase C18 column with phosphate and acetonitrile as the mobile phase and detection at 214 nm. Peak height ratios were linearly correlated up to 800 micrograms/l. Acceptable coefficients of variation were demonstrated for both within-run and day-to-day studies. Selected drugs were checked for interference. The assay was used to monitor nine patients receiving 20 to 80 mg of fluoxetine per day. Plasma concentrations of fluoxetine and norfluoxetine ranged from 37 to 301 micrograms/l and 29 to 326 micrograms/l respectively.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2324217&dopt=Abstract fluoxetine Prozac



Prozac
Fluoxetine ingestion: a one year retrospective study.

Spiller HA, Morse S, Muir C.

Deleware Valley Regional Poison Control Center, Philadelphia, PA 19104.

Fluoxetine (PROZAC) is a recently marketed straight chain antidepressant unrelated to the cyclic anti-depressants. There is only limited information on fluoxetine and a single case report on overdose (benign outcome) in the literature. In response to this we performed a 1y retrospective chart review at 2 AAPCC certified poison centers. Forty-four exposures to fluoxetine were reviewed from 1988; 31 cases were treated in a HCF, 2 cases were followed at home by phone and 11 cases were lost to follow up. Thirteen cases with follow up (FU) reported no coingestants; 3 cases reported increased anxiety without cardiovascular (CV) changes, 2 cases presented confused with out CV changes, and 8 cases were asymptomatic. Eight cases with FU had ETOH and/or benzodiazepines as a coingestant and experienced only a decreased level of consciousness that could be explained by the coingestant. Five cases remained asymptomatic with reported coingestants of APAP #3, lorazepam, haloperidol, molindone, alprazolam, propranolol, phenobarbital (level 18.2). Four cases were excluded from the evaluation due to the coingestants involved. No seizures were recorded in this series. Three possible drug reactions occurred; 2 cases had reactions with tranylcypromine (PARNATE), and 1 case with a diagnosis of septicemia had a severe hyperthermic reaction with therapeutic coingestants of mephytoin, verapamil, digoxin and indocin. We believe overdose with fluoxetine present minimal risk of serious cardiovascular or neurological complications.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2327065&dopt=Abstract fluoxetine Prozac



Prozac
Clinical and experimental studies on fluoxetine: effects on serotonin uptake.

Butler J, Leonard BE.

Department of Pharmacology, University College, Galway, Ireland.

A decreased rate of uptake of serotonin (5HT) into platelets is recognized as a possible marker of the depressed state, being normalized only by effective antidepressant treatment. Fluoxetine is a novel antidepressant, with 5HT uptake inhibitory properties. In this study, treatment of depressed patients with fluoxetine for up to 6 months did not normalize the decreased platelet 5HT uptake rates associated with depression, although the patients showed a clinical recovery. The olfactory bulbectomized (OB) rat shows a characteristic hyperactivity in a stressful environment, which can be reversed only by chronic treatment with most antidepressants. OB rats have been found to exhibit a decreased rate of platelet 5HT uptake, similar to depressed patients, which is normalized by chronic antidepressant treatment. However, 3 weeks treatment with fluoxetine failed to reverse the hyperactivity of the OB rat and the decreased rates of uptake of 5HT. We also examined the rate of uptake of serotonin into the synaptosomes of the OB rats, in order to elucidate whether platelet 5HT uptake reflected central activity. Chronic fluoxetine treatment failed to normalize high affinity synaptosomal 5HT uptake in the OB rat. Fluoxetine, therefore, unlike most other antidepressants, does not normalize the decreased rates of platelet 5HT uptake in depressed patients on clinical recovery. OB rats also showed a deficit in their platelet and synaptosomal 5HT uptake rates, following 3 weeks treatment with fluoxetine.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2332607&dopt=Abstract fluoxetine Prozac



Prozac
Effects of the selective serotonin reuptake inhibitor, fluoxetine, on regional gastric contractility.

James AN, Ryan JP, Parkman HP.

Department of Medicine, Temple University School of Medicine, Philadelphia, PA 19140, USA.

Selective serotonin reuptake inhibitors (SSRIs) are increasingly used to treat a variety of disorders but have gastrointestinal side-effects. AIM: To determine the effects of the SSRI, fluoxetine, on gastric smooth muscle contractility. METHODS: Fundic, antral, and pyloric circular muscle contractility of guinea pig muscle strips were measured in vitro. Fluoxetine was added in concentrations from 0.1 nmol L(-1) to 100 mumol L(-1). Receptor antagonists were used to determine the neural pathways involved. RESULTS: Fluoxetine caused concentration dependent contractions, which were greatest in fundus compared with the antrum or pylorus. The contractile effects of fluoxetine in the antrum were reduced by tetrodotoxin, atropine, phentolamine, and the 5-HT(4) receptor antagonist GR 113808. The contractile effects of fluoxetine in the fundus were reduced by atropine, phentolamine, and GR 113808. CONCLUSIONS: Fluoxetine affects gastric contractility with regional variability - contracting the fundus more than the antrum or pylorus. The fluoxetine contractile effect is reduced by tetrodotoxin, atropine, phentolamine, and a 5-HT(4) receptor antagonist. These results suggest fluoxetine interacts with muscarinic, alpha-adrenergic, and serotoninergic receptors and/or ongoing reuptake/release of serotonin in the stomach.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15670267&dopt=Abstract fluoxetine Prozac



Prozac
Adverse consequences of fluoxetine-MAOI combination therapy.

Feighner JP, Boyer WF, Tyler DL, Neborsky RJ.

Feighner Research Institute, La Mesa, Calif.

The authors describe two series of patients: 12 treated simultaneously with fluoxetine and a monoamine oxidase inhibitor and 6 patients started on treatment with an MAOI 10 days or more after stopping fluoxetine treatment. All patients had extremely refractory depression and were treated in open fashion before general knowledge was obtained of the side effects that may accompany the fluoxetine-MAOI combination. During the fluoxetine-MAOI trial, most patients continued to receive other psychotropic combinations that had been partially helpful. The use of fluoxetine and an MAOI, either together or in close succession, was accompanied by a very high incidence of adverse effects, especially the "serotonergic syndrome." This syndrome was characterized by mental status changes, such as hypomania and confusion, and physical symptoms, such as myoclonus, hypertension, tremor, and diarrhea. Because of the high incidence of side effects and the lack of definite efficacy, the concurrent use of fluoxetine and MAOIs should generally be avoided. The long half-lives of fluoxetine and norfluoxetine, as well as the prolonged metabolic effects of MAOIs, may also dispose patients to an interaction if one of the drugs is started soon after stopping the other.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2347858&dopt=Abstract fluoxetine Prozac



Prozac
Obsessive-compulsive disorder: suffering in silence.

Vanin JR.

West Virginia University Health Service.

Obsessions and compulsions vary in frequency and intensity. Many individuals have habits that cause minimal or no disruption of their lives. OCD, however, causes significant distress and interference with daily life. The problem may go unnoticed by anyone except the involved individual, or it may involve family, friends, and acquaintances. The disorder can be disabling, adversely affecting a student personally, socially, and occupationally. Those who are significantly affected by OC symptoms are encouraged to seek treatment. Behavior therapy and medications are extremely beneficial in helping to relieve symptoms of OCD. Clomipramine and fluoxetine (Prozac) are new drugs available in the US that appear to be effective for OCD symptoms. Several other anti-OCD medications may be available in the US within the next few years. It is important that students and others on campus be made aware that OCD is more common than previously recognized, that more persons with OCD are seeking help, and that effective treatment is available. This "secretive," often disabling disorder is more open now, and it is to be hoped that more individuals will take advantage of current, effective evaluation and treatment modalities.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2365928&dopt=Abstract fluoxetine Prozac



Prozac
Fluoxetine trial in borderline personality disorder.

Cornelius JR, Soloff PH, Perel JM, Ulrich RF.

Western Psychiatric Institute and Clinic, University of Pittsburgh, PA 15213.

Borderline personality disorder (BPD) is defined by many of the symptoms associated with serotonin dysregulation, including affective lability, suicidal behaviors, and impulsive aggression, providing an ideal clinical model for studying the treatment of these serious disorders. The recent development of selective serotonin re-uptake inhibitors such as fluoxetine makes it possible to study the role of serotonin in the etiology of affective and behavioral dyscontrol in BPD. In this preliminary medication trial, 5 patients with BPD were treated openly with 20 mg to 40 mg of fluoxetine for 8 weeks, with weekly ratings of symptoms. The findings from this work suggested efficacy for fluoxetine in treating the depressive and impulsive symptoms of patients with BPD. The findings were mixed concerning the efficacy of fluoxetine in treating the hostility and psychotic symptoms of BPD. No evidence for effectiveness was found in the treatment of the anxiety, phobic anxiety, or interpersonal sensitivity of BPD.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2371370&dopt=Abstract fluoxetine Prozac



Prozac
Drug-drug interactions of fluoxetine with tricyclics.

von Ammon Cavanaugh S.

Department of Psychiatry, Rush-Presbyterian-St. Luke's Medical Center, Chicago, IL 60612.

The drug-drug interactions with fluoxetine, a pure serotonergic reuptake blocker with a unique profile of side effects, have not been studied adequately. This preliminary report shows that desipramine and nortriptyline plasma levels are markedly increased at steady state (2 to 11 times) when coadministered with fluoxetine. This appears to be the result of the inhibition of the P450 enzyme system of the liver by fluoxetine, resulting in increased plasma levels of drugs metabolized by this system. Research must promptly address drug-drug interactions with fluoxetine since potentially all psychotropic drugs (except for lithium) and many medically indicated drugs could also have significant drug-drug interactions with fluoxetine.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2388981&dopt=Abstract fluoxetine Prozac