Does fluoxetine have a therapeutic window?

Fichtner, ChristopherG.; Jobe, Thomas H.; Braun, B. H.

doi:10.1016/0140-6736(91)90599-k

Cited by 12 publications

(4 citation statements)

References 6 publications

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“…41 Another intriguing phenomenon involves the concept of a therapeutic window, which was originally applied to nortriptyline, 42 but was subsequently described with SSRI therapy. [43][44][45][46][47] The possibility of paradoxical or no effects occurring above a certain dosage would be in line with the phenomena described with patients with affective disorders and healthy controls. In any event, these effects appear to occur in a very limited percentage of patients treated with antidepressants.…”

Section: Paradoxical Effects Of Antidepressant Drugsmentioning

confidence: 64%

Can Long-Term Treatment With Antidepressant Drugs Worsen the Course of Depression?

Fava¹

2003

J. Clin. Psychiatry

208

130

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Background: The possibility that antidepressant drugs, while effectively treating depression, may worsen its course has received inadequate attention. Method: A review of the literature suggesting potential depressogenic effects of long-term treatment with antidepressant drugs was performed. A MEDLINE search was conducted using the keywords tolerance, sensitization, antidepressive agents, and switching. This was supplemented by a manual search of Index Medicus under the heading "antidepressant agents" and a manual search of the literature for articles pointing to paradoxical effects of antidepressants. Results: A number of reported clinical findings point to the following possibilities: very unfavorable long-term outcome of major depression treated by pharmacologic means, paradoxical (depression-inducing) effects of antidepressant drugs in some patients with mood and anxiety disturbances, antidepressant-induced switching and cycle acceleration in bipolar disorder, occurrence of tolerance to the effects of antidepressants during long-term treatment, onset of resistance upon rechallenge with the same antidepressant drug in a few patients, and withdrawal syndromes following discontinuation of mood-elevating drugs. These phenomena in susceptible individuals may be explained on the basis of the oppositional model of tolerance. Continued drug treatment may recruit processes that oppose the initial acute effects of a drug and may result in loss of clinical effect. When drug treatment ends, these processes may operate unopposed, at least for some time, and increase vulnerability to relapse. Conclusion: The possibility that antidepressant drugs may worsen the course of depression needs to be tested, even though its scientific exploration is likely to encounter considerable methodological and ideological difficulties. The clinical implications of this hypothesis in depression are considerable. Antidepressant drugs are crucial in the treatment of major depressive episodes. However, appraisal of paradoxical effects that may occur in susceptible patients during long-term treatment may lead to more effective use of the drugs.

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Section: Paradoxical Effects Of Antidepressant Drugsmentioning

confidence: 64%

Can Long-Term Treatment With Antidepressant Drugs Worsen the Course of Depression?

Fava¹

2003

J. Clin. Psychiatry

208

130

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“…This phenomenon was first described in five patients in whom fluoxetine had been initially effective, but relapsed despite escalation of the dose to 60-80 mg/day (Diamond et al, 1989). Fichtner et al (1991) reported similar effects in two patients. The first patient responded well to fluoxetine (40 mg/day), but doses of 60 or 80 mg/day led to a deterioration in symptoms, whilst a dose of 20 mg/day produced an inadequate response.…”

Section: Posologymentioning

confidence: 89%

“…Such neurophysiological tolerance may promote a relapse or a recurrence of depression (Post et al, 1992). The reemergence of depressive symptoms following a positive initial response to SSRIs, particularly fluoxetine, has been well documented (Ayd, 1991;Fichtner et al, 1991;Cain, 1992;Leinonen et al, 1993;Rapport and Calabrese, 1993;Fava et al, 1995;Goldberg et al, 1995;McGrath et al, 1995). For example, the study of Michelson et al (1997) suggested that fluoxetine may no longer be effective after 9 months of continuation treatment for depressed outpatients.…”

Section: Loss Of Efficacymentioning

confidence: 93%

Selective serotonin reuptake inhibitors in affective disorders -II. Efficacy and quality of life

Goodnick¹,

Goldstein

1998

J Psychopharmacol

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Since their introduction, the selective serotonin reuptake inhibitors (SSRIs) have become one of the most widely used classes of medication in psychiatry. Their popularity is based on apparent efficacy over a wide range of disorders and a favorable side-effect profile. However, as with any psychotropic medication, considerable data are required to define where a drug works and where it does not. There is now a wealth of evidence demonstrating that SSRIs may differ in their efficacy profiles in certain depressive symptoms, in different subtypes of depression, with respect to their ability to maintain efficacy over time, on broader outcomes such as quality of life, and in the consistency of the usually effective minimum therapeutic dose across the age spectrum and across indications. Although this review includes data on all SSRIs, it focuses on fluoxetine and sertraline, which in addition to being the most widely used SSRIs are also the most widely studied. The relative quantity and quality of data on these two SSRIs means that it is possible to make relatively firm inferences regarding their differential effects on affective symptoms and quality of life.

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“…5-11 Stewart et al 9 wrote about starting fluoxetine therapy in patients who were prone to anxiety or panic at a dosage as low as 2.5 mg. Fichner et al 6 published their careful dose titration of a 46-year-old man with major depression and suicidal ideation. Fluoxetine 20 mg produced agitation and restlessness that improved when the dosage was reduced to 10 mg.…”

Section: A Preventable Dose-related Problemmentioning

confidence: 99%