Fluoxetine (Prozac)

Fluoxetine was the very first SSRI anti-depressant available in the U.S. and its now available as a very inexpensive generic with the wholesale price of thirty 20 mg. capsules, the standard month’s supply, being only $3.30. It works about as well as other anti-depressants, although dual action anti-depressants like some tricyclics and venlafaxine work slightly better for the average patient.  Venlafaxine is much more expensive, but tricyclics are also fairly inexpensive. 

The majority of people will improve on most anti-depressant medications, and about the same percentage of people on each medication.  However, some people will definitely respond better to one type than another. Unfortunately, there is no test to tell us who is likely to respond on which medicine.  SSRI anti-depressants do help Obsessive Compulsive Disorder, too.  So depressed patients with this type of symptoms might be best started on fluoxetine. For everyone else, it is a question of trying one for several weeks, then trying another if the first didn't help. While some people may respond quickly, others need 8 weeks or even more to respond.

Fluoxetine has been very extensively researched.  For the average patient, starting on 20mg each morning for at least the first eight weeks is ideal.  If there is no response, increasing the dose is probably the best second step, although an earlier increase at two weeks is probably indicated if there is no improvement at all.  Adding thyroid, either right from the beginning and phasing it out or using it for non-responders is another good idea.  Of course, all patients should take fish oil or some other source of omega-3 fatty acids, folate, multivitamins, and selenium as recommended earlier under the Healthy Living section.

While there is very little good research on whether to switch to another SSRI or a different family of medications when there is a lack of response or side-effects.  While each case has to be individually evaluated, in my opinion, the best decision is probably to switch to another family of anti-depressant medications. This might be bupropion, venlafaxine, or a tricyclic like nortriptyline or imipramine. You cannot go directly from an SSRI to an MAO inhibitor because of the danger of a serious interaction between the two families of medicines. Since fluoxetine is so long acting, it will naturally taper itself, taking at least several weeks to get out of the body.  Another option for non-responders might be to try rTMS, trazodone, or lithium.

Suicides: Fluozetine Causes No Increase in Suicide: A prospective study of depression found no increase in suicide compared to other anti-depressants. Andrew Leon, Am J Psychiatry 2/99 156:195-201.

Bupropion (Wellbutrin) as Good as Fluoxetine in DB: In an 8-week DB PC study of 450 patients with depression, fluoxetine 20-60/d did equally well to bupropion 150-400/d and both did better than placebo. There was more sexual dysfunction with fluoxetine. A placebo-controlled comparison of the effects on sexual functioning of bupropion sustained release and fluoxetine. Coleman CC, King BR, et al. Clin Ther 2001 Jul;23(7):1040-58

Buspirone No Added Benefit; Fluoxetine 40/d Faster than 20/d: A randomized open study in Turkey of 120 MDD patients found that patients assigned to buspirone plus fluoxetine actually responded more slowly (40 days average response time) compared to fluoxetine 20mg/d alone (33 days) or fluoxetine 40 mg/d alone (25 days). Faster response in depressive patients treated with fluoxetine alone than in combination with buspirone. Onder E, Tural U. J Affect Disord. 2003 Sep;76(1-3):223-7

Cocaine Addicts: Fluoxetine No Benefit in MDD Cocaine Addicts: DB PC 68 in cocaine rx with MDD. MDD improved in all in 12 weeks. Positive urines for cocaine higher in fluoxetine group. Fluoxetine treatment of cocaine-dependent patients with major depressive disorder. U Tx Houston: Schmitz JM, Averill P, et al. Drug Alcohol Depend 2001 Aug 1;63(3):207-14

Cognitive Behavior Therapy: Fluoxetine Better than CBT, But Both Did Best for Teens: In a DB PC study of 439 depressed teens ages 12-17 comparing twelve weeks of (1) fluoxetine alone (10 to 40 mg/d), (2) CBT alone, (3) CBT with fluoxetine (10 to 40 mg/d), or (4) placebo (equivalent to 10 to 40 mg/d), the placebo and fluoxetine alone were administered double-blind; CBT alone and CBT with fluoxetine were administered unblinded. Compared with placebo, the combination of fluoxetine with CBT was statistically significant (P =.001) on the Children's Depression Rating Scale-Revised. Compared with fluoxetine alone (P =.02) and CBT alone (P =.01), treatment of fluoxetine with CBT was superior. Fluoxetine alone is a superior treatment to CBT alone (P =.01). Rates of response for fluoxetine with CBT were 71.0%; fluoxetine alone, 60.6%; CBT alone, 43.2%; and placebo, 34.8%. Fluoxetine, cognitive-behavioral therapy, and their combination for adolescents with depression: Treatment for Adolescents With Depression Study (TADS) randomized controlled trial. March J, Silva S, Petrycki S, Curry J, Wells K, Fairbank J, Burns B, Domino M, McNulty S, Vitiello B, Severe J; Treatment for Adolescents With Depression Study (TADS) Team. Duke University. JAMA. 2004 Aug 18;292(7):807-20

Duloxetine did Better than Fluoxetine 20/d: In an Eli Lilly-funded study of 173 adults with DSM-IV major depressive disorder. Duloxetine, a dual NE and 5HT reuptake inhibitor, was titrated in the first 3 weeks in a forced-titration regimen from 40 mg (20 mg b.i.d.) to 120 mg/day (60 mg b.i.d.). Duloxetine did better. Duloxetine in the treatment of major depressive disorder: a double-blind clinical trial. Goldstein DJ, Mallinckrodt C, Lu Y, Demitrack MA. J Clin Psychiatry 2002 Mar;63(3):225-31. Ed: Dual action anti-depressants tend to do a little better, although studies funded by the manufacturer tend to exaggerate the benefits of the medicine being promoted.

Fluoxetine Better Than Placebo for Suicidal Ideation: Review of 25 DB PC studies with 4,100 patients. Fluoxetine and concomitant centrally acting medication use during clinical trials of depression: the absence of an effect related to agitation and suicidal behavior. Wernicke JF, Sayler ME, et al. Depress Anxiety 1997;6(1):31-9

Fluvoxamine as Good as Fluoxetine: In a DB PC study of 100 adults with major depression, fluvoxamine was started at 50mg/d and increased to 100-150/d with a mean of 102. Fluoxetine 20/d was increased to a max of 80/d and a mean of 34/d. 7 weeks. HAM-d and HAM-A, and CGI improved equally. Side-effects both mild with half having some headache, 23% and 42% some nausea. UpJohn funded. Rapaport M et al: A comparison of fluvoxamine and fluoxetine in the treatment of major depression. J Clin Psychoph 96;16:373-8, UCSD

Lamotrigine Added to Fluoxetine Helped Depression: In a DB PC study of 23 Bipolar II or Major Depression who had failed at least one course of antidepressants, all received fluoxetine 20 mg/d and half received lamotrigine 25 mg/d titrated up to 100 mg/d for 6 weeks. HAM-D scores decreased to 9.7 for lamotrigine vs. 14.5 for placebo. CGI-I much improved ratings were 85% for lamotrigine vs. 30% for placebo (p=.013). Univ Melbourne. Barbosa L, Berk M, Vorster M: A double-blind, randomized, placebo-controlled trial of augmentation with lamotrigine or placebo in patients concomitantly treated with fluoxetine for resistant major depressive episodes. J Clin Psychiatry 2003;64:403-7. (Lamotrigine is getting some impressive results. However, because of its higher cost and some side-effects, I think these patients should all have first been treated with fish oil, folic acid, exercise, bright light, rTMS, and, if necessary, thyroid supplementation.)

Lithium: Fluoxetine Increase Slightly Better than Low Dose Lithium or Desipramine Augmentation: 101 pt not responding to fluoxetine 20mg QD in 8wk. DB to Fluoxetine 40-60mg DQ, or add Lithium 300-600 or Desipramine 25-50. No signif difference but trend favoring higher dose (high-dose fluoxetine, 42.4%; fluoxetine plus desipramine, 29.4%; fluoxetine plus lithium, 23.5%) with fewer dropouts (9% vs 14%). Trend same in both non-responders and partial responders. Double-blind study of high-dose fluoxetine versus lithium or desipramine augmentation of fluoxetine in partial responders and nonresponders to fluoxetine. MGH, Fava M, Alpert J, et al. J Clin Psychopharmacol 2002 Aug;22(4):379-87

Maprotiline Not as Good as Fluoxetine for Young Women: Lilly study claims in DB 104 MDD men and women 6 weeks women under 44 did better with fluoxetine but others did equally well. Gender differences in the efficacy of fluoxetine and maprotiline in depressed patients: a double-blind trial of antidepressants with serotonergic or norepinephrinergic reuptake inhibition profile. Vienna: Martenyi F, Dossenbach M, Mraz K, Metcalfe S. Eur Neuropsychopharmacol 2001 Jun;11(3):227-32

Mirtazapine = Fluoxetine: Analysis of DB studies comparing the two, 583 MDD pts. No difference altho very slightly faster improvement with mirtazapine 13% vs 8% responders in 1^st week. Does mirtazapine have a more rapid onset than SSRIs? Columbia: Quitkin FM, Taylor BP, Kremer C. J Clin Psychiatry 2001 May;62(5):358-61

Nortriptyline Did Better than Fluoxetine (Prozac) in Small DB: A 48-patient 6-week DB PC study of Major Depression found that nortriptyline 150 mg/d did better than fluoxetine 60 mg/d.  There was no difference in the dropout rate. Tehran Univ. Double-blind comparison of fluoxetine and nortriptyline in the treatment of moderate to severe major depression. Akhondzadeh S, Faraji H, Sadeghi M, Afkham K, Fakhrzadeh H, Kamalipour A. J Clin Pharm Ther. 2003 Oct;28(5):379-84. Ed: Although this is a very small and short study, the outcome is in the expected direction since nortriptyline is more of a dual action anti-depressant, which as a group usually do better than SSRIs, except perhaps in young women.

Nortriptyline and Venlafaxine did Better than Fluoxetine for Melancholia: Two studies have found nortriptyline or venlafaxine did better than fluoxetine. A third retrospective study reports that of nine patients to develop melancholia while already on anti-depressant, all were on an SSRI. They responded quickly to non-SSRI meds. Guadagno, East Tenn State U, APA 5/30/98 Toronto

Reboxetine = Fluoxetine in DB: 381 patients treated with reboxetine 8 to 10 mg/day, fluoxetine 20 to 40 mg/day, or placebo for up to 8 weeks. Both meds helped equally. Reboxetine, a new noradrenaline selective antidepressant available in Europe, is at least as effective as fluoxetine in the treatment of depression. Andreoli V, Caillard V, Deo RS, Rybakowski JK, Versiani M., J Clin Psychopharmacol 2002 Aug;22(4):393-9

Sertraline = Fluoxetine = Paroxetine & Insomnia Pts Improve: no significant differences in acute treatment efficacy and tolerability across fluoxetine, sertraline, and paroxetine in major depressive disorder patients. Improvement in overall depression and in associated insomnia was achieved by most patients regardless of baseline insomnia. DB 284 Pt 10-16 week MDD. MGH, Acute efficacy of fluoxetine versus sertraline and paroxetine in major depressive disorder including effects of baseline insomnia. Fava M, Hoog SL, Judge RA, Kopp JB, Nilsson ME, Gonzales JS.

Tricyclics = Fluoxetine and Both Help Suicidal Ideation: Double-blind, controlled clinical trial data were evaluated to assess a hypothetical relationship between fluoxetine and suicidality (suicidal acts and ideation) in patients with mood (n = 5,655) and non-mood disorders (n = 4,959) (Mantel-Haenszel incidence difference method). In mood disorders, act rates (suicide attempts/completions) were low (treatment differences non-significant). Substantial suicidal ideation emerged less frequently with fluoxetine than placebo and was comparable with fluoxetine and tricyclic antidepressants. Improvement in ideation was greater with fluoxetine than placebo; it was comparable with fluoxetine and tricyclic antidepressants (United States trials) and greater with tricyclic antidepressants than fluoxetine (international trials). In non-mood disorders, no suicides occurred. Act and emergent ideation rates were low (treatment differences non-significant). Evaluation of suicidality during pharmacologic treatment of mood and non-mood disorders. Tollefson GD, Fawcett J, Winokur G, Beasley CM Jr, Potvin JH, Faries DE, Rampey AH Jr, Sayler ME. Ann Clin Psychiatry 1993 Dec;5(4):209-24

Venlafaxine did Better than Fluoxetine for MDD with GAD: DB PC 368 patients with Major Depressive Disoredy of whom 92 also Generalized Anxiety Disorder. Response, defined as > or = 50% decrease in symptoms score, was achieved in 66% and 59% of the comorbid patients for HAM-D and HAM-A, respectively, in the venlafaxine XR group at week 12. This response was higher than that seen with fluoxetine (52% and 45%) or placebo (36% and 24%). Comorbid patients slower to respond. Efficacy of venlafaxine extended release in patients with major depressive disorder and comorbid generalized anxiety disorder. U Alberta, Silverstone PH, Salinas E., J Clin Psychiatry 2001 Jul;62(7):523-9

Venlafaxine (Effexor) and Fluoxetine (Prozac) Only a Little Better than Placebo: In a 6-week DB PC study of 308 outpatients with depression, venlafaxine-immediate release (75-225mg/day; n=102) did a little better than fluoxetine (20-60mg/day; n=104), which did a little better than placebo (n=102). Remission (defined as HAM-D7) rates were 32%, 28%, and 22% for venlafaxine, fluoxetine, and placebo. Few differences between the active treatments attained statistical significance. Side-effects were somewhat less with fluoxetine. A double-blind, placebo-controlled comparison of venlafaxine and fluoxetine treatment in depressed outpatients. Nemeroff CB, Thase ME. Emory University. J Psychiatr Res. 2005 Sep 12. 

Fluoxetine Helpful for Suicidal Substance Abusers: Only 1 DB PC with alcohol or substance abuse has included substantial numbers of suicidal patients. 51 subjects, of whom 20 (39%) had made a suicide attempt in the current depressive episode, 31 (61%) had made a suicide attempt in their lifetime, and 46 (90%) had reported suicidal ideations in the week before hospitalization. Fluoxetine was effective in decreasing but not eliminating both the depressive symptoms (including suicidal ideations) and the level of alcohol consumption among a study group of subjects with comorbid major depressive disorder and alcohol dependence, many of whom displayed suicidal ideations. Cigarette smoking is also significantly decreased by fluoxetine, but the magnitude of the decrease is limited and few of these patients totally quit smoking with fluoxetine treatment alone. Marijuana smoking was also significantly decreased in a subgroup of subjects who demonstrated cannabis abuse and that the magnitude of this improvement was robust. Cocaine abuse acts as a predictor of poor outcome for both depressive symptoms (including suicidality) and level of alcohol use in this population. 1 yr open f/u positive benefits of fluoxetine in decreasing depressive symptoms and level of drinking persist 1 year after entering the treatment program. U Pitt, Treating the substance-abusing suicidal patient. Cornelius JR, Salloum IM, Lynch K, Clark DB, Mann JJ. Ann N Y Acad Sci 2001 Apr;932:78-90; discussion 91-3

Fluoxetine Enteric-Coated = 20mg/d: 501 MDD patients on continuation therapy DB to Fluoxetine 20/d or enteric-coated 90/wk. No difference over 25 week study in efficacy or side-effects. Efficacy and safety of weekly treatment with enteric-coated fluoxetine in patients with major depressive disorder. Dinan TG. J Clin Psychiatry 2001;62 Suppl 22:48-52

Fluoxetine 60/wk = 20/d: Short 7 week study found no difference. Exploring treatment alternatives: weekly dosing of fluoxetine for the continuation phase of major depressive disorder. U Nebraska, Burke WJ, McArthur-Miller DA. J Clin Psychiatry 2001;62 Suppl 22:38-42

Fluoxetine Levels on 20mg/d Not Related to Relapse: Plasma concentrations of fluoxetine and/or its metabolite norfluoxetine, are not correlated with relapse in patients treated with a fixed dose of 20 mg/day fluoxetine. Fluoxetine plasma levels cannot be used to guide relapse-prevention treatment. Part of large DB PC study of 369 patients remitting on fluoxetine 20/d and switched to placebo at various times after initial 12 weeks of therapy. Fluoxetine and norfluoxetine plasma concentrations during relapse-prevention treatment. Brunswick DJ, Amsterdam JD, Fawcett J, Quitkin FM, Reimherr FW, Rosenbaum JF, Beasley CM Jr., J Affect Disord 2002 Apr;68(2-3):243-9

Fluoxetine Prevents Relapses: Lilly study of 140 pt MDD responders in 32 weeks put in DB PC for 48 more weeks. Relapse 20% fluoxetine, 40% placebo. Fluoxetine in the prevention of depressive recurrences: a double-blind study. Gilaberte I, Montejo AL, de la Gandara J, Perez-Sola V, Bernardo M, Massana J, Martin-Santos R, Santiso A, Noguera R, Casais L, Perez-Camo V, Arias M, Judge R; Fluoxetine Long-Term Study Group. J Clin Psychopharmacol 2001 Aug;21(4):417-24

Fluoxetine, SSRIs Good for DM MDD: While TCAs, esp. imipramine, are more effective for diabetic neuropathy at low doses with 81% reponse rate, TCAs tend to increase FBG in depressed diabetics. Six studies of fluoxetine, a selective serotonin reuptake inhibitor (SSRI), at a dose of 60 mg/day pursued up to 12 months that have demonstrated that medication's usefulness in diabetic patients, with reductions in weight (to 9.3 kg), in FPG (to 45 mg%), and in HbA1c (to 2.5%). In studies in comorbid diabetes mellitus and depression, nortriptyline, a norepinephrine reuptake inhibitor that produces increased synaptic catechols, has led to worsening of indices of glucose control. Use of antidepressants in treatment of comorbid diabetes mellitus and depression as well as in diabetic neuropathy. However, several studies show SSRIs and nefazodone effective. U Miami, Goodnick PJ. Ann Clin Psychiatry 2001 Mar;13(1):31-41

Fluoxetine, Paroxetine OK in Elderly: DB PC 242 depressed, average age 75yo. Most of the tested cognitive functions improved. Good antidepressant efficacy was maintained for over 1 year with both drugs, based on the percentage of responders to treatment (patients achieving a HAM-D total score < 10; 60%). Both drugs showed a good tolerability and safety profile. Paroxetine and fluoxetine effects on mood and cognitive functions in depressed nondemented elderly patients. Cassano GB, Puca F, Scapicchio PL, Trabucchi M; Italian Study Group on Depression in Elderly Patients. J Clin Psychiatry 2002 May;63(5):396-402

Fluoxetine No Effect on Suicidal Behavior of Frequent Attempters: Fluoxetine in a dose of 120 mg a week, administered biweekly, had no effect on the recurrence rate, which was maintained at approximately the same rate on fluoxetine (1 every 18.7 days) as with placebo (1 every 17.6 days). In a group of patients with two or more prior episodes of suicidal behavior, there were 18 attempted suicides in the 54 patients treated with fluoxetine and the same number in the 53 patients treated with placebo. Fluoxetine neither raised nor lowered the suicide attempt rate as compared with placebo, providing no evidence to support the drug's role in either suicide provocation or prevention. Since fluoxetine is clearly effective with recurrent major depression, it would appear that recurrent brief depression has a different pharmacology. Lack of efficacy of fluoxetine in recurrent brief depression and suicidal attempts. London, Montgomery DB, Roberts A, Green M, Bullock T, Baldwin D, Montgomery SA. Eur Arch Psychiatry Clin Neurosci 1994;244(4):211-5

Fluoxetine May Help Recurrent Brief Depression: RBD = monthly non-menstrual depression less than 2 weeks for one year, therefore not MDD. Author claims condition is common, 10% of population (sic). SSRIs haven’t done well with RBD suicide attempters. Study of 15 keeping diaries for 28 weeks, put of fluoxetine 20-40/d for 8 weeks. Claims benefit. Fluoxetine treatment in patients with recurrent brief depression. U Vienna, Stamenkovic M, Blasbichier T, Riederer F, Pezawas L, Brandstatter N, Aschauer HN, Kasper S., Int Clin Psychopharmacol 2001 Jul;16(4):221-6

Fluoxetine No Withdrawal Syndrome: A DB trial of 395 patients with 60 switched to placebo for 6 weeks found no worsened or new symptoms of withdrawal, possibly due to the long half-life of the drug. Shorter acting SSRIs have been reported to have problems with abrupt discontinuation. David Michelson, J Clin Psychiatry 11/98 59:544-5. 35% paroxetine patients, 80% amitrip, 33% clomipramine and 32% phenelzine and 55% imipramine reported to have withdrawal. Symptoms are GI, headache, lethargy, sweating, sleep disturbance. Usually brief and mild and can be avoided by tapering. J Clin Psych 59:541

Fluoxetine BIW: Half life 4-6 days and half life active metabolite norfluoxetine 4-16 days. Case of a woman stabilized on lithium 600 bid, olanzapine 5 hs and fluox 10 qd caused mania. Did well with reduction to 10 biw. Megna, Ann Pharmacoth 01;35:45

Recommend 38 week Rx: DB PC by Reimherr of U Utah in Am J Psychiatry 9/98 155:1247 randomizing pts to 24 weeks of fluoxetine or 38 weeks or 62 weeks found relapse high if d/c at 24 week (49% vs. 26%), and after 38 additional weeks (23% vs 9%) but difference became non-signif after total of 62 weeks (16% vs 10%).

Helped Alcoholics with Major Depr: 51 pts Rx DB 12 weeks with decr depression and drinking. Cornelius, Western Psychiatric Inst, Pittsbg, Arch Gen Psychiatry 8/97;54:700

Fluoxetine Sex Dysfunction Not Helped by Mirtaz, Yohimbine, Olanzepine: DB PC 6 wk with females sexually dysfunctional due to fluoxetine treated with augmentation with mirtazepine, yohimbine, or olanzepine all found to be of no benefit. Michelson, J Psyc Res 36:147-52, ’02.

Clonazepam Augmentation of Fluoxetine Limited Value: 80 pt on flouxetine with DB PC of either 0.5-1.0 clonazepam or placebo for three weeks then tapper for two weeks. Clonazepam better at 10 days, but equal at 28 days and thereafter. Funded by LaRoche AJP 98;155:1339

Fluoxetine No Increase Suicidal Behavior: f/u 643 pt. 29% on fluoxetine at some time. They had 56% decr in suicidal behavior vs. untreated. Pts on other anti-depressants had 40% decr. Fluox pts had more prior episodes of depression. Leon, Cornell, Lilly funded, AJP 99;156:195.

Less Infant Wt Gain on Fluoxetine Breast-Feeding: 64 women taking in pregnancy. 21 continued while breastfeeding and others stopped. Those continuing fluoxetine, infants gained 400g less at 12 weeks. Chambers Pediatrics 99;104:e61

Death in 9yo with CYP2D6 Deficiency: Youth on fluoxetine for 3 years at increasingly high doses for Tourette’s and OCD to 100mg/d. Blood level at death extremely high. 7-10% European-Americans genetically deficient in CYP2D6. Sallee, J Child Adol Psychoph 00;10:27

Fluoxetine Increases Risperidone Level 300%: 10 pt on 4-6 mg risperidone rx fluoxetine 20mg/d for depression. Blood levels increased 2-10 fold. Minor decrease in depression (18 to 14) and psychosis (61 to 56). J Clin Psychopharm 02;22:419-23

Fluoxetine Helps Anorexia Nervosa: Ten of 16 (63%) subjects remained on fluoxetine for a year, whereas only three of 19 (16%) remained on the placebo for a year (p =.006). Those subjects remaining on fluoxetine for a year had reduced relapse as determined by a significant increase in weight and reduction in symptoms. U Pitt, Double-blind placebo-controlled administration of fluoxetine in restricting- and restricting-purging-type anorexia nervosa. Kaye WH, Nagata T, Weltzin TE, Hsu LK, Sokol MS, McConaha C, Plotnicov KH, Weise J, Deep D. Biol Psychiatry 2001 Apr 1;49(7):644-52

Fluoxetine Helps OCD in Kids: 7 to 17yos (N = 103) were randomized at a ratio of 2:1 to receive either fluoxetine or placebo. Dosing was initiated at 10 mg daily for 2 weeks, then increased to 20 mg daily. After 4 weeks of treatment, and again after 7 weeks of treatment, non-responders could have their dosage increased by 20 mg daily, for a maximum possible dosage of 60 mg daily. significantly greater improvement in OCD as assessed by the CY-BOCS (p = .026). Well-tolerated. d/c = placebo. McLean. Fluoxetine treatment for obsessive-compulsive disorder in children and adolescents: a placebo-controlled clinical trial. Geller DA, Hoog SL, Heiligenstein JH, Ricardi RK, Tamura R, Kluszynski S, Jacobson JG; Fluoxetine Pediatric OCD Study Team. J Am Acad Child Adolesc Psychiatry 2001 Jul;40(7):773-9

Fluoxetine Helps Fibromyalgia: 12-week, flexible-dose, placebo-controlled trial, fluoxetine was found to be effective on most outcome measures and generally well tolerated in women with fibromyalgia. Fluoxetine dose could vary 10-80mg/d. Average at end of study 45mg/d. Large effect on fibromyalgia pain. A randomized, placebo-controlled, double-blind, flexible-dose study of fluoxetine in the treatment of women with fibromyalgia. Arnold LM, Hess EV, Hudson JI, Welge JA, Berno SE, Keck PE Jr., Am J Med 2002 Feb 15;112(3):191-7

Fluoxetine Helps Migraines: DB PC 6 months 20mg/d, 52 pt. Reduced pain starting in 3^rd month. Migraines without auras. U Naples: Fluoxetine for migraine prophylaxis: a double-blind trial. d'Amato CC, Pizza V, Marmolo T, Giordano E, Alfano V, Nasta A. Headache 1999 Nov-Dec;39(10):716-9

Fluoxetine Markedly Reduces Urine Spraying by Cats: Neutered cats over 1yo DB PC. Spraying decreased 80% by week 2 and 95% by week 7. Minor decrease with placebo. UC Davis Vet, Effects of a selective serotonin reuptake inhibitor on urine spraying behavior in cats. Pryor PA, Hart BL, Cliff KD, Bain MJ., J Am Vet Med Assoc 2001 Dec 1;219(11):1557-61

Fluoxetine Helps Panic: Patients not responding to 20mg eligible to be increased up to 60mg which may have helped. Efficacy of usual antidepressant dosing regimens of fluoxetine in panic disorder: randomised, placebo-controlled trial. Eli Lilly: Michelson D, Allgulander C, Dantendorfer K, Knezevic A, Maierhofer D, Micev V, Paunovic VR, Timotijevic I, Sarkar N, Skoglund L, Pemberton SC.

Fluoxetine Help Binge-Eaters in DB: 60 out-pt DB PC 6 wk 20-80mg fluoxetine (average 71mg). Improvement of binge eating and more wt loss with fluox. A placebo-controlled, randomized trial of fluoxetine in the treatment of binge-eating disorder. U Cinn., Arnold LM, McElroy SL, Hudson JI, Welge JA, Bennett AJ, Keck PE., J Clin Psychiatry 2002 Nov;63(11):1028-33

Fluoxetine 20mg Works Fine: DB 178pt Tianeptine 37.5/d vs fluoxetine 20/d. 75% and 67% response rate. Tianeptine vs fluoxetine in major depression: a 6-week randomized double-blind study. Novotny V, Faltus F.

Fluoxetine Some Benefit with MDD Kids: 200+ children and teens DB PC 8wk fluoxetine 20 QD. 41% vs 20% responded. No significant difference in a 30% response (60% vs 53%). Fluoxetine for acute treatment of depression in children and adolescents: a placebo-controlled, randomized clinical trial. Author says this is first anti-depressant with two positive DB studies with kids. Emslie GJ, Heiligenstein JH, Wagner KD, Hoog SL, Ernest DE, Brown E, Nilsson M, Jacobson JG. J Am Acad Child Adolesc Psychiatry 2002 Oct;41(10):1205-15

Fluoxetine Helps Dysthymia: 140 dysthymics HAM-D >15 rx 20mg/d DB PC and non-responders increased to 40/d at 3 months. At 3 mo 58% Fluox vs 36% placebo response. At 6 mo., response rate 79% with remission rate of 69%. Vanelle J-M et al: Controlled efficacy study of fluoxetine in dysthymia. Br J Psyc 97;170:345-50, Paris.

Fluoxetine Blood Level Unrelated to Effect: 615 pt on long-term fluoxetine found no difference in responders, partial responders, and non-responders in plasma levels of fluoxetine, norfluoxetine, combo, or ratio. No therapeutic window either. Amsterdam J, et al: Fluoxetine and norfluoxetine plasma concentrations in major depression: a multicenter study. Am J Psyc 97;154:963-9, U Penn & Lilly

Fluoxetine-Induced Intrusive Memory Recall: 4 cases with obsessional qualities. Austrlian & NZ J Psyc 97;31:128-30, Robertson A: Fluoxetine and involuntary recall of remote memories.

OK with BCP: 17 DB PC studies with 1700+ women analyzed. No clinical evidence that concomitant use of oral contraceptives and fluoxetine affects the safety or efficacy of either agent. Eli Lilly, Safety and efficacy of fluoxetine in patients who receive oral contraceptive therapy. Koke SC, Brown EB, Miner CM., Am J Obstet Gynecol 2002 Sep;187(3):551-5

Fluoxetine 57mg Helps PTSD: 12 weeks of acute treatment with fluoxetine, 20 to 80 mg/day (N = 226), or placebo (N = 75). Done in war-torn countries. Fluoxetine significantly better at 6 weeks and thereafter. Well tolerated. Eli Lilly, Fluoxetine versus placebo in posttraumatic stress disorder. Martenyi F, Brown EB, Zhang H, Prakash A, Koke SC. J Clin Psychiatry 2002 Mar;63(3):199-206

Fluoxetine = Sertraline for OCD at 24 weeks: 150 OCD moderate to severe DB. Equal improvement at 24 weeks although sertraline better on CGI at 12 weeks. Sertraline and fluoxetine treatment of obsessive-compulsive disorder: results of a double-blind, 6-month treatment study. Bergeron R, Ravindran AV, Chaput Y, Goldner E, Swinson R, van Ameringen MA, Austin C, Hadrava V. J Clin Psychopharmacol 2002 Apr;22(2):148-54

Fluoxetine 20mg, Not 10mg, Helps PMS: 260 women were randomized to fluoxetine 10 mg, fluoxetine 20 mg, or placebo (dosed daily from 14 days before next expected menses through the first full day of bleeding) for three cycles. Both dosages helped mood. Only premenstrual daily fluoxetine 20 mg showed significant treatment advantage over placebo for physical symptoms of breast tenderness (P <.001), bloating (P =.001), and joint/muscle pain (P =.037). Harvard, Premenstrual daily fluoxetine for premenstrual dysphoric disorder: a placebo-controlled, clinical trial using computerized diaries. Cohen LS, Miner C, Brown EW, Freeman E, Halbreich U, Sundell K, McCray S., Obstet Gynecol 2002 Sep;100(3):435-44

SSRIs Effective for PMS: 12 randomised, controlled trials with continuous dose administration of SSRIs and the eight randomised, controlled trials with luteal phase dose administration (from ovulation to menses) are reviewed. All the treatment studies on fluoxetine, sertraline, paroxetine and citalopram have reported positive efficacy. Brown U, Selective serotonin reuptake inhibitors for premenstrual dysphoric disorder: the emerging gold standard? Pearlstein T., Drugs 2002;62(13):1869-85

Some Benefit on Smoking at 30 & 60mg: 989 smokers to 3 dose conditions: 10 weeks of placebo, 30 mg, or 60 mg fluoxetine per day. Smokers received 9 sessions of individualized cognitive-behavioral therapy, and biologically verified 7-day self-reported abstinence follow-ups were conducted at 1, 3, and 6 months posttreatment. Analyses assuming missing data counted as smoking observed no treatment difference in outcomes. Pattern-mixture analysis that estimates treatment effects in the presence of missing data observed enhanced quit rates associated with both the 60-mg and 30-mg doses. Brown U, Multicenter trial of fluoxetine as an adjunct to behavioral smoking cessation treatment. Niaura R, Spring B, Borrelli B, Hedeker D, Goldstein MG, Keuthen N, DePue J, Kristeller J, Ockene J, Prochazka A, Chiles JA, Abrams DB., J Consult Clin Psychol 2002 Aug;70(4):887-96

SSRIs May Increase Self-Injurious via Serotonin Effect: L-type calcium channel activator +/-Bay K 8644 has recently been shown to provoke self-injurious biting in young mice. Since the serotonergic systems have been implicated in the expression of self-injurious behavior in both humans and animals, the present studies tested whether drugs influencing serotonin systems could modify the ability of +/-Bay K 8644 to cause this behavior. The ability of +/-Bay K 8644 to provoke self-biting behavior was increased by the serotonin uptake inhibitor fluoxetine or the monoamine oxidase inhibitor clorgyline. On the other hand, the ability of +/-Bay K 8644 to provoke self-biting was decreased by depletion of serotonin with p-chlorophenylalanine or 5,7-dihyroxytryptamine. These results suggest that the ability of +/-Bay K 8644 to provoke self-injurious behaviors may be mediated by serotonergic influences. Johns Hopkins, Self-biting induced by activation of L-type calcium channels in mice: serotonergic influences. Kasim S, Egami K, Jinnah HA., Dev Neurosci 2002;24(4):322-7

No Effect on Warfarin in Seven: Prospective study of fluoxetine 20/d and prothrombin times Q 3 days first 21 days. Therefore, may only be susceptible individuals affected and measure warfarin or phenytoin blood levels but no need to avoid fluoxetine in these patients. Ford M, et al: Lack of effect of fluoxetine on the hypoprothrombinemic effect of warfarin. J Clin Psychoph 97;17:110

Imipramine Raised Blood Sugar; Fluoxetine (Prozac) Lower It: In a 60 healthy Major Depression patient, 8-week DB PC study, patients on fluoxetine 20-40 mg/day had a decrease in fasting blood sugar (FBS) from 88 to 80 while those on imipramine had an increase from 87 to 97. Ghaeli P, Shahsavand E, Mesbahi M, Kamkar MZ, Sadeghi M, Dashti-Khavidaki S. Tehran University. J Clin Psychopharmacol. 2004 Aug;24(4):386-8