FLUOXETINE

• 0.0 OVERVIEW
• 0.1 LIFE SUPPORT
• A. This overview assumes that basic life support measures have been instituted.
• 0.2 CLINICAL EFFECTS
• 0.2.1 SUMMARY OF EXPOSURE
• A. Doses of 40 to 800 mg produce minimal, if any, symptoms.
• 1. Effects reported in overdose include blurred vision, vomiting, lethargy, dizziness, insomnia, diarrhea, tremors, abdominal pain and rarely seizures.
• 2. Significant cardiovascular toxicity is unusual. Effects have included mild hypertension, tachycardia, and rare cases of junctional rhythm, bigeminy and ventricular tachycardia, and QTc prolongation associated with ventricular tachycardia.
• B. Adverse effects following therapeutic doses, may include seizures; suicidal ideation, mania, and paranoia; extrapyramidal effects; cardiac dysrhythmias; hyponatremia and SIADH; serum sickness or flu-like symptoms; and serotonin syndrome.
• 0.2.4 HEENT
• A. Blurred vision has been a minor side effect of fluoxetine therapy and was also seen in one case after ingestion of 3 grams.
• 0.2.5 CARDIOVASCULAR
• A. Significant cardiovascular toxicity is unusual. Effects have included mild hypertension, tachycardia, ST depression, and rare reports of junctional rhythm, bigeminy and ventricular tachycardia, and QTc prolongation associated with ventricular tachycardia.
• 0.2.7 NEUROLOGIC
• A. OVERDOSE effects, in most patients, include only mild neurological symptoms. However, seizures and coma may occur.
• B. THERAPEUTIC DOSES have been reported to cause dizziness, tremor, restlessness, ataxia, and syncope.
• C. SEROTONIN SYNDROME may develop after overdose or when used therapeutically with other serotonergic agents.
• 0.2.8 GASTROINTESTINAL
• A. Nausea, vomiting, and diarrhea have all been reported.
• 0.2.18 PSYCHIATRIC
• A. Mania and insomnia have been reported as side effects.
• 0.2.20 REPRODUCTIVE
• A. Fluoxetine has no known teratogenic effect in humans; US FDA pregnancy category C.
• 0.2.22 OTHER
• A. Serotonin syndrome may develop when fluoxetine is administered with other serotonergic agents.
• 0.3 LABORATORY/MONITORING
• A. Serum levels are not clinically useful in managing overdose.
• B. Obtain an ECG in symptomatic patients.
• C. Monitor for evidence of serotonin syndrome.
• 0.4 TREATMENT OVERVIEW
• 0.4.2 ORAL/PARENTERAL EXPOSURE
• A. EMESIS: Ipecac-induced emesis is not recommended because of the potential for CNS depression and seizures.
• B. ACTIVATED CHARCOAL: Administer charcoal as slurry (240 mL water/30 g charcoal). Usual dose: 25 to 100 g in adults/adolescents, 25 to 50 g in children (1 to 12 years), and 1 g/kg in infants less than 1 year old.
• C. Ingestions are rarely life threatening; gastric lavage is generally NOT warranted.
• D. SEIZURES: Administer a benzodiazepine IV; DIAZEPAM (ADULT: 5 to 10 mg, repeat every 10 to 15 min as needed. CHILD: 0.2 to 0.5 mg/kg, repeat every 5 min as needed) or LORAZEPAM (ADULT: 4 to 8 mg; CHILD: 0.05 to 0.1 mg/kg).
• 1. Consider phenobarbital if seizures recur after diazepam 30 mg (adults) or 10 mg (children > 5 years).
• 2. Monitor for hypotension, dysrhythmias, respiratory depression, and need for endotracheal intubation. Evaluate for hypoglycemia, electrolyte disturbances, hypoxia.
• 0.5 RANGE OF TOXICITY
• A. Ingestions of 40 to 800 milligrams have generally produced minimal toxicity in adults.
• B. Seizures have been reported in adults after ingestions of 900 milligrams or more.
• 1.0 SUBSTANCES INCLUDED/SYNONYMS
• 1.1 THERAPEUTIC/TOXIC CLASS
• A. Fluoxetine is a straight chain phenylpropylamide which is not structurally related to the tricyclic antidepressants.
• 1.2 SPECIFIC SUBSTANCES

o             Fluoxetine

o             dl-N-methyl-3-phenyl-3-(alpha,alpha,alpha-

o               trifluoro-p-tolyl) oxy)propylamine

o               hydrochloride

o             Fontex

o             LY-110140

o             CAS 54910-89-3

• 1.6 AVAILABLE FORMS/SOURCES
• A. SOURCES
• 1. Fluoxetine is marketed by Dista with the trade name Prozac(R).
• B. USES
• 1. Fluoxetine is used in the treatment of depression, obsessive compulsive disorder, and bulimia nervosa (Prod Info Prozac(R), 1999). It is also used in the treatment of premenstrual dysphoric disorder (Prod Info Sarafem(R), 2000).
• 3.0 CLINICAL EFFECTS
• 3.1 SUMMARY OF EXPOSURE
• A. Doses of 40 to 800 mg produce minimal, if any, symptoms.
• 1. Effects reported in overdose include blurred vision, vomiting, lethargy, dizziness, insomnia, diarrhea, tremors, abdominal pain and rarely seizures.
• 2. Significant cardiovascular toxicity is unusual. Effects have included mild hypertension, tachycardia, and rare cases of junctional rhythm, bigeminy and ventricular tachycardia, and QTc prolongation associated with ventricular tachycardia.
• B. Adverse effects following therapeutic doses, may include seizures; suicidal ideation, mania, and paranoia; extrapyramidal effects; cardiac dysrhythmias; hyponatremia and SIADH; serum sickness or flu-like symptoms; and serotonin syndrome.
• 3.4 HEENT
• 3.4.1 SUMMARY
• A. Blurred vision has been a minor side effect of fluoxetine therapy and was also seen in one case after ingestion of 3 grams.
• 3.4.3 EYES
• A. BLURRED VISION has been a minor side effect of fluoxetine therapy and has been reported after overdose (Prod Info Prozac(R), 1999; Tech Info, 1987).
• 1. CASE REPORT - A 15-year-old girl developed blurred vision after ingesting 900 milligrams of fluoxetine (Braitberg & Curry, 1995).
• B. NYSTAGMUS was noted in one patient who ingested approximately 340 mg (Tech Info, 1987).
• 3.5 CARDIOVASCULAR
• 3.5.1 SUMMARY
• A. Significant cardiovascular toxicity is unusual. Effects have included mild hypertension, tachycardia, ST depression, and rare reports of junctional rhythm, bigeminy and ventricular tachycardia, and QTc prolongation associated with ventricular tachycardia.
• 3.5.2 CLINICAL EFFECTS
• A. DYSRHYTHMIA
• 1. OVERDOSE
• a. CASE REPORT - A 33-year-old healthy man developed a prolonged QRS interval (0.110 seconds) and a QTc interval of (0.458 seconds) within 30 minutes following an overdose of 120 20-mg fluoxetine capsules and 100 500-mg acetaminophen tablets. The QRS narrowed promptly (0.09 seconds) after an intravenous bolus of 50 mEq sodium bicarbonate (Graudins et al, 1997).
• b. CASE SERIES - Of 9 patients reported to have ingested fluoxetine alone, one patient was reported to have ST segment depression (Tech Info, 1987). Of another group of 37 patients, one had a junctional rhythm and the rest of the 23 who had EKG studies showed sinus rhythm (Borys et al, 1990).
• c. CASE REPORT - A patient who ingested fluoxetine with indomethacin had premature ventricular contractions, bigeminy, and ventricular tachycardia, all responsive to lidocaine (Borys et al, 1990).
• d. CASE REPORT - A 22-year-old woman presented to the emergency department with bradycardia (heart rate 59) and QTc prolongation (0.456 seconds) 5 hours after ingesting 1.2 to 1.4 grams of fluoxetine. Bigeminy and further QTc prolongation (0.495 seconds) developed 12 hours after ingestion and deteriorated to ventricular tachycardia responsive to lidocaine and sodium bicarbonate. QTc remained prolonged (0.483 seconds) 4 days after exposure (Hofman & Liu, 1994).
• e. CASE REPORT - A 19-year-old man developed two episodes of atrial flutter, each lasting approximately 15 minutes, after ingesting 140 milligrams of loxapine and 600 milligrams of fluoxetine (Roberge & Martin, 1994).
• 2. THERAPEUTIC USE -
• a. CASE SERIES - ECGs of patients taking fluoxetine showed none of the prolongation of PR and QRS intervals seen with the tricyclics. Fluoxetine in therapeutic doses had no significant clinical effect on the ECG, and two patients, one of whom ingested 1,000 mg and the other 200 mg, had normal ECGs (Fisch, 1985).
• b. CASE SERIES - Spier & Frontera (1991) report that 3 elderly female patients, with underlying life-threatening pulmonary and cardiac disorders, died of cardiac dysrhythmias within 10 days of beginning fluoxetine treatment. A clear relationship between the death of these patients and the start of fluoxetine therapy was not established.
• c. CASE REPORT - A 74-year-old woman developed syncope and Torsades de Pointes requiring cardioversion 3 weeks after being switched from amitriptyline to fluoxetine (Appleby et al, 1995). ECG revealed QTc prolongation. Symptoms stopped when fluoxetine was discontinued but the ECG was not repeated.
• B. BRADYCARDIA
• 1. A slightly decreased heart rate has been seen in both animal and human studies (Fisch, 1985; Ellison et al, 1990; Borys et al, 1990).
• 2. Buff et al (1991) report a case of bradycardia in an elderly woman treated with 20 mg fluoxetine per day. Friedman (1991) suggests that these effects are dose-related and therefore dosage should be reduced in the elderly or patients with a history of cardiac problems.
• C. TACHYCARDIA
• 1. OVERDOSE -
• a. Tachycardia is common after overdose (Feierabend, 1995; Braitberg & Curry, 1995).
• b. CASE SERIES - Fifteen of 87 patients developed tachycardia after overdose with fluoxetine alone (Borys et al, 1992).
• 2. THERAPEUTIC USE -
• a. CASE REPORT - Supraventricular tachycardia and hypotension was associated with maintenance therapy with fluoxetine 20 mg daily in a 54-year-old woman (Gardner et al, 1991). Cardiac symptoms and palpitations have not recurred in 25 months of follow-up. She received verapamil initially, which was discontinued six weeks later.
• D. ECG ABNORMAL
• 1. THERAPEUTIC USE -
• a. CASE REPORT - A 52-year-old man developed ECG changes of broad based T waves and QTc prolongation (0.56 sec) after beginning fluoxetine 40 mg/day. The QTc returned to normal (0.38 sec) 10 days after fluoxetine was discontinued (Varriale, 2001). 3 months after
• E. LACK OF EFFECT
• 1. In contrast with both the tricyclic antidepressants and trazodone, fluoxetine does not cause ORTHOSTATIC HYPOTENSION. Unlike the tricyclics, it does not appear to possess alpha-adrenoceptor blocking properties (Bowsher et al, 1988).
• F. HYPERTENSION
• 1. CASE SERIES - 3 of 37 patients reported for purely fluoxetine poisoning had diastolic blood pressures greater than 100 mmHg and ingestions of 340 to 1500 mg (Borys et al, 1990).
• G. VASCULITIS
• 1. THERAPEUTIC USE -
• a. CASE REPORT - An 83-year-old woman developed pain, swelling and tenderness of her arms with malaise, lethargy, nausea and vomiting three days after beginning fluoxetine therapy. Muscle biopsy showed acute myositis and extensive muscle infarction. Fluoxetine was discontinued and the patient died suddenly on the 7th hospital day of a ruptured abdominal aortic aneurysm. Postmortem muscle biopsy showed muscle necrosis and necrotizing vasculitis of the small and medium sized arteries (Fisher et al, 1999).
• 3.6 RESPIRATORY
• 3.6.2 CLINICAL EFFECTS
• A. INFLUENZA-LIKE SYMPTOMS
• 1. CASE REPORT - A 19-year-old woman developed flu-like symptoms (dyspnea, malaise, myalgias, arthralgia, chill, headache, nasal congestion, cough), along with urticaria, maculopapular rash, and angioedema 2 days following ingestion of 680 mg of fluoxetine.
• a. Although this may have represented a hypersensitivity reaction, another possible explanation is a dose-related phenomenon associated with peak metabolite (norfluoxetine) serum concentrations (Kim & Pentel, 1989).
• B. RESPIRATORY DISORDER
• 1. CASE REPORT - A 62-year-old woman developed cough and dyspnea 4 months after beginning fluoxetine (Gonzales-Rothi et al, 1995). Symptoms resolved when fluoxetine was discontinued and recurred within 5 days when it was restarted. She developed interstitial infiltrates and restrictive lung disease and bronchioalveolar lavage was suggestive of hypersensitivity pneumonitis.
• 3.7 NEUROLOGIC
• 3.7.1 SUMMARY
• A. OVERDOSE effects, in most patients, include only mild neurological symptoms. However, seizures and coma may occur.
• B. THERAPEUTIC DOSES have been reported to cause dizziness, tremor, restlessness, ataxia, and syncope.
• C. SEROTONIN SYNDROME may develop after overdose or when used therapeutically with other serotonergic agents.
• 3.7.2 CLINICAL EFFECTS
• A. SEIZURES
• 1. OVERDOSE
• a. CASE REPORT - Two generalized seizures of 2 to 3 minute duration were seen 9 hours after ingestion of 3 g of fluoxetine. The patient had a plasma concentration of 2461 ng/mL; aspirin and alcohol were co-ingestants in this case. The patient also had a prior history of seizures (Wernicke, 1985).
• b. CASE REPORT - A single generalized seizure occurred 3.5 hours after ingestion of 1,880 mg by a 12-year-old boy (Riddle et al, 1989).
• c. CASE REPORT - A tonic-clonic seizure was observed in a 27-year-old female following co-ingestion of 80 mg fluoxetine and 150 mg phenelzine. This was apparently due to an adverse interaction between these drugs (Chiang & Smilkstein, 1989).
• d. CASE REPORT - One patient who ingested fluoxetine with 2 grams of meprobamate had seizures (Borys et al, 1990).
• e. CASE REPORT - Tonic-clonic seizures developed in a 15-year-old girl 10 hours after ingesting 900 milligrams of fluoxetine (Braitberg & Curry, 1995).
• f. CASE REPORT - A 26-year-old male patient ingested 1200 mg of fluoxetine and developed generalized tonic-clonic seizures approximately 3 hours post- ingestion. EEGs performed 1 and 7 days after the event were normal (Gross et al, 1998).
• 2. THERAPEUTIC USE -
• a. CASE REPORT - An 84-year-old woman was reported to have a single brief generalized seizure 5 days after initiating therapy with fluoxetine 20 mg/day. The patient had no prior history of seizures, but had other concurrent illnesses that may have been contributory (Weber, 1989).
• b. CASE REPORT - Two patients currently taking lithium and fluoxetine in therapeutic doses for depression and suicidal ideation experienced seizures following ingestion of LSD (Jackson & Hornfeldt, 1991).
• B. CNS DEPRESSION
• 1. CASE SERIES - Of 9 patients reported to have ingested fluoxetine alone, one patient who ingested 340 mg was comatose; drowsiness was reported in a 19-year-old who ingested 1000 to 1200 mg (Tech Info, 1987). Drowsiness developed in 14 of 87 patients after overdose with fluoxetine alone (Borys et al, 1992).
• C. ATAXIA
• 1. Ataxia and tremor were side effects seen with some frequency with fluoxetine therapy or overdose (Borys et al, 1992; Wernicke, 1985). Tremor was seen in a 26-year-old who ingested 220 mg/day for 9 days (Tech Info, 1987).
• D. DIZZINESS
• 1. CASE SERIES - Dizziness and blurred vision were reported in 25 percent of patients taking therapeutic dosages of fluoxetine and in 1 of 37 patients after fluoxetine overdose (Borys et al, 1990; Gorman et al, 1987).
• E. CNS STIMULATION
• 1. CASE REPORT - A 4-year-old girl developed hypervigilance, nervousness, psychomotor agitation and abnormal jerking movements after ingesting an unknown quantity of fluoxetine (Feierabend, 1995). This was followed by a several minute period of unresponsiveness.
• F. SYNCOPE
• 1. Syncope has been reported at dosages of 20 to 80 mg/day (Ellison et al, 1990).
• G. SEROTONIN SYNDROME
• 1. Fluoxetine, a potent inhibitor of serotonin uptake, may interact with other pharmaceuticals or circumstances which cause serotonin release. Because of fluoxetine's long half-life which results in significant plasma levels persisting many weeks after fluoxetine discontinuation, caution must be used with concomitant use of serotonin-increasing medications. A wash-out period of at least 5 weeks after discontinuing fluoxetine and beginning a drug which may increase serotonin levels is recommended (Lane et al, 1997).
• a. Serotonin syndrome has been described from fluoxetine interactions with irreversible MAOIs, moclobemide, tryptophan, selegiline, nefazodone, tramadol and lithium (Mitchell et al, 1997; Smith & Wenegrat, 2000; Kesavan & Sobala, 1999).
• 2. SIGNS may include hyperreflexia, hyperthermia, restlessness, diaphoresis, unsteady gait, and myoclonic jerking. It is contrasted with the neuroleptic malignant syndrome, which usually includes rigidity and autonomic dysfunction (Perse et al, 1991).
• 3. CASE REPORT - A 40-year-old woman developed CNS depression, tremors, decerebrate posturing, hyperthermia, hypotension, DIC, metabolic acidosis, rhabdomyolysis, and multiple organ failure after overdose of moclobemide, clomipramine and fluoxetine (Power et al, 1995).
• 4. CASE REPORT - A 39-year-old woman developed mental status changes, diaphoresis, diarrhea and slurred speech one day after discontinuing fluoxetine and clonazepam and starting on venlafaxine and lorazepam. This is reported as a case of serotonin syndrome with the use of fluoxetine which did not involve the concomitant use of a monoamine oxidase inhibitor (Bhatara et al, 1998).
• H. MS-LIKE SYNDROME
• 1. CASE REPORT - Exacerbation of symptoms of multiple sclerosis (arm numbness and grogginess) developed in a 41-year-old woman 10 hours after beginning fluoxetine and progressed over the next 4 days of therapy (Browning, 1990). Symptoms returned to baseline after discontinuing therapy.
• I. DREAMING ABNORMAL
• 1. Vivid nightmares and night terrors have been reported with therapeutic use (Lepkifker et al, 1995).
• J. EXTRAPYRAMIDAL DISORDER
• 1. Extrapyramidal symptoms have been reported in patients taking fluoxetine but are not common (Arya, 1994).
• 2. CASE SERIES - In a series of 5,555 patients taking fluoxetine therapeutically 15 developed extrapyramidal effects (Coulter & Pillans, 1995). Eight of these were taking other drugs which may have contributed to these effects.
• K. HALLUCINATIONS
• 1. CASE REPORT - A 38-year-old man developed a complex visual hallucination, described as a blue-green central disc that nearly filled the visual fields, with a dynamic yellow central portion and peripheral yellow regions and a red vertical bar in the left visual field of both eyes. The visual pattern was present daily on awakening and would last 30 to 40 seconds. The pattern occurred initially with sertraline therapy and recurred when fluoxetine was substituted. It gradually disappeared when both were discontinued and nefazodone was substituted (Bourgeois et al, 1998).
• 3.7.3 ANIMAL EFFECTS
• A. SEIZURES
• 1. Seizure potential was evaluated in animals during high-dose administration. 50% of the animals had seizures with doses near 250 mg/kg in one study and 450 mg/kg in another (Wernicke, 1985).
• 3.8 GASTROINTESTINAL
• 3.8.1 SUMMARY
• A. Nausea, vomiting, and diarrhea have all been reported.
• 3.8.2 CLINICAL EFFECTS
• A. NAUSEA VOMITING
• 1. Nausea is a common mild to moderately severe side effect seen with therapeutic or excessive dosing (Borys et al, 1992; Wernicke, 1985).
• 2. CASE REPORTS - Spontaneous emesis developed in one patient who ingested 900 to 1200 mg, with no reported co-ingestants (Tech Info, 1987), and another who ingested 2000 mg (Moore & Rodriguez, 1990).
• B. DIARRHEA
• 1. CASE SERIES - Diarrhea developed in 38 percent of patients receiving therapeutic doses of fluoxetine for panic attacks and in 2 of 37 patients reported with fluoxetine overdose (Borys et al, 1990; Gorman et al, 1987).
• C. ANOREXIA
• 1. Fluoxetine has been shown to cause anorexia with resultant weight loss in overweight, non-depressed individuals at dosages of 20 to 80 mg/day (Ferguson & Feighner, 1987).
• D. STOMATITS
• 1. CASE REPORT - Two cases of stomatitis related to fluoxetine intake in the treatment of depression are reported. A 24-year-old woman had been taking fluoxetine for 6 months and experienced six recurrent episodes of stomatitis without complete remission between outbreaks. When fluoxetine was discontinued the stomatitis resolved completely. A rechallenge with fluoxetine 7 months later caused the stomatitis to recur. A second case was reported in a 41-year-old female taking fluoxetine and bentazepam. After both drugs were discontinued the stomatitis resolved in two days. She refused rechallenge with fluoxetine (Palop et al, 1997).
• 3.9 HEPATIC
• 3.9.2 CLINICAL EFFECTS
• A. HEPATITIS
• 1. CASE REPORT - A 35-year-old male with histologically severe hepatitis had a positive antibody against hepatitis C, but no hepatitis c viral RNA could be detected by branch chain DNA or reverse-transcription PCR. He did not respond to prednisone therapy but did respond when his fluoxetine was discontinued. In retrospect, researchers found a strong correlation between elevated ALT and fluoxetine dose during the 10 months prior to presentation. They postulate that his chronic hepatitis was due to fluoxetine therapy (Johnston & Wheeler, 1997).
• 2. Several other cases of hepatitis associated with therapeutic fluoxetine use have been reported (Cai et al, 1999; Anon, 1996).
• 3.12 FLUID-ELECTROLYTE
• 3.12.2 CLINICAL EFFECTS
• A. HYPONATREMIA
• 1. Hyponatremia secondary to SIADH has been reported in patients taking therapeutic doses of fluoxetine (Jackson et al, 1995; Flint et al, 1996; Girault et al, 1997; Anon, 1994).
• 3.13 HEMATOLOGIC
• 3.13.2 CLINICAL EFFECTS
• A. PLATELETS ABNORMAL
• 1. Fluoxetine blocks 5-hydroxytryptamine reuptake in platelets and may lead to platelet dysfunction.
• 2. CASE REPORT - Humphries et al (1990) describe a patient with a minor history of bleeding disorder (occasional epistaxis and bruising) who developed a prolonged bleeding time and petechiae while taking fluoxetine 20 mg every other day for two years.
• a. Her platelet count, prothrombin time, and von Willebrand factors were normal, and she was on no medication.
• b. The patient was taken off fluoxetine, and bleeding time returned to normal. After a return to fluoxetine therapy at the same dose, prolonged bleeding time and petechiae again returned.
• B. APLASTIC ANEMIA
• 1. CASE REPORT - A 28-year-old male taking 20 mg fluoxetine twice daily for 6 weeks developed aplastic anemia. The bone marrow biopsy showed hypoplasia with severe depression of megakaryocytes and myeloid cells and moderate depression of erythroid cell line. Fluoxetine was discontinued on the 3rd hospital day and his blood count rose slowly.
• a. Twenty-five days after admission fluoxetine 20 mg once daily was reinstituted, but 5 days later was withdrawn due to a fall in peripheral blood cell counts. His hematological abnormalities returned to normal within 12 days and pancytopenia had not recurred during 6 months follow up (Bosch & Vera, 1998).
• C. ECCHYMOSIS
• 1. CASE REPORT - A 31-year-old woman developed easy bruising with a normal PT, PTT and CBC after beginning fluoxetine. Bleeding time was not assessed. The authors speculated that the bruising was a result of suppression of serotonin-induced platelet aggregation (Pai & Kelly, 1996).
• 3.14 DERMATOLOGIC
• 3.14.2 CLINICAL EFFECTS
• A. URTICARIA
• 1. CASE REPORT - Urticaria was reported in a 48-year-old man who ingested 280 mg over 2 days (Tech Info, 1987).
• B. RASH
• 1. CASE REPORT - Bullous pemphigoid was associated with fluoxetine therapy in a 75-year-old woman; it resolved with discontinuation of fluoxetine (Rault et al, 1999).
• 3.18 PSYCHIATRIC
• 3.18.1 SUMMARY
• A. Mania and insomnia have been reported as side effects.
• 3.18.2 CLINICAL EFFECTS
• A. MANIC REACTION
• 1. CASE SERIES - Fluoxetine appears to have precipitated a case of mania in a susceptible patient taking 80 mg/day (Settle Jr & Settle, 1984). Hypomania was described in 2 patients who ingested 120 mg/day for 7 days and 140 mg/day for 16 days, respectively (Tech Info, 1987), and in another patient who took 140 mg for 36 hours (Chouinard & Steiner, 1986).
• B. INSOMNIA
• 1. Insomnia as well as nervousness and anxiety are common mild to moderately severe side effects seen with therapeutic dosing (Wernicke, 1985). Insomnia and agitation have been described in patients accidentally prescribed higher than recommended doses (140 to 220 mg/day) (Tech Info, 1987).
• C. DEPRESSION PSYCHOTIC
• 1. Suicidal ideation has been associated with fluoxetine treatment.
• 2. Fava & Rosenbaum (1991) studied 1017 patients receiving treatment for depression. 231 of those were treated with fluoxetine alone, and when compared with patients treated with other regimens no significant increase in suicidal episodes was found. Association between fluoxetine and suicide is disputed (Hoover, 1991; Fava & Rosenbaum, 1991).
• 3. CASE SERIES - Masand et al (1991) reported 2 patients without previous history of suicidal ideation, gestures, mania, or hypomania who developed suicidal ideations beginning 3 days to 2 weeks following initiation of fluoxetine therapy for depression. Suicidal ideations disappeared within a week of discontinuing treatment in both patients.
• D. HYPERKINESIA
• 1. CASE SERIES - Rothschild & Locke (1991) report 3 cases in which the patients' suicidal thoughts while on fluoxetine seemed to stem directly from problems with akathisia. Cessation of fluoxetine treatment was associated with elimination of both akathisia and suicidal thoughts.
• E. PSYCHOSIS
• 1. CASE REPORT - Hersh et al (1991) report a case of psychosis in an 11-year-old girl who was given fluoxetine 20 mg for 35 days. The patient had no history of delusional psychosis, but had sustained head trauma five years before and had an abnormal EEG. The patient was normal 3 weeks after cessation of fluoxetine therapy.