High Doses of an Enteric-Coated Weekly Formulation of Fluoxetine
High Doses of an Enteric-Coated Weekly Formulation of Fluoxetine
Background: Anew formulation of enteric-coated oral fluoxetine given at a dose of 90mg once weekly has been shown in clinical trials to be well tolerated, safe, effective and associated with very high compliance. It has been approved by regulatory agencies for marketing in the continuation phase of antidepressant therapy. However, literature reports on experience with the once-weekly formulation in clinical practice, especially in patients with substantial medical and psychiatric co-morbidities, are sparse.
Methods: Enteric-coated fluoxetine 90mg was provided in a clinic setting to 39 psychiatric outpatients (aged 18 to 78 years) with a confirmed diagnosis of major depression. A co-morbid medical or psychiatric condition was present in 45.8% of the women and 42.9% of the men; most of these patients were on concomitant medication. Seven patients were previously untreated for depression. The tolerability, efficacy and compliance of once-weekly fluoxetine (90 to 540mg) were evaluated in this patient population utilising data from patient charts.
Results: Of the 32 patients already receiving fluoxetine, 31 were successfully converted from a single daily dose to a single weekly dose (90 to 540mg) and one patient was converted to a divided dosage (twice weekly). The remaining seven patients were started on weekly fluoxetine administration de novo. Presently, all 39 remain in remission from depression, with no changes in affect, co-morbid conditions or compliance. After dosage adjustments to date, this cohort has been monitored and has a cumulative exposure of weekly fluoxetine administration of 7.2 patient-years. No patient has discontinued enteric-coated fluoxetine therapy. No serious adverse events or hospitalisations were reported. There were no new reports of queried events of nausea, headache or sexual dysfunction. There were no new spontaneous reports of nervousness, asthenia, diarrhoea, abnormal thinking or somnolence.
Conclusions: In our clinical experience, enteric-coated fluoxetine, administered at higher doses once or twice weekly, was effective and well tolerated for short-termmaintenance treatment of major depressive disorder. The simple once-or twice-weekly administration could be a convenient alternative for some patients during long-term treatment of depression.
It is well documented that depression is a serious life-threatening illness often requiring long-term treatment, and that the adequacy and duration of antidepressant exposure is less than optimal for many patients. One factor contributing to this undertreatment is the reluctance of the patient to stay on medication for an extended period of time, especially when they are feeling well. Once-weekly drug administration may provide a strategy for enhancing psychological well-being and over-all tolerability, leading to improved compliance.
Fluoxetine is the only orally administered agent capable of providing an antidepressant effect during continuation treatment using less frequent dosage intervals than daily administration; this is due to the long elimination half-lives of the drug and its desmethylated metabolite, norfluoxetine.
Montgomery et al. explored the possibility of using higher doses at less frequent intervals by showing that responsive patients randomly assigned to receive fluoxetine 80mg weekly were as likely to remain well as patients assigned to fluoxetine 60mg daily. Burke et al. subsequently confirmed that 60mg of fluoxetine once a week was a well tolerated and effective continuation treatment regimen. Asimilar finding was recently made in a 501-patient, randomised, multi-centre clinical trial. After 13 weeks of 20mg daily and immediate-release fluoxetine, responders were randomly assigned to receive 20mg of fluoxetine daily, placebo or 90mg of enteric-coated fluoxetine weekly for 25 weeks of double-blind continuation treatment. Relapse rates for patients assigned to fluoxetine 20mg daily or 90mg weekly were significantly lower than those for placebo recipients and did not significantly differ. Tolerability evaluations for the enteric-coated fluoxetine at a once-weekly dose of 90mg were similar to those for the 20mg daily dose. Importantly, however, in another study, once-weekly fluoxetine-treated patients had higher electronically reported compliance rates relative to those receiving once-daily fluoxetine.
As the US Food and Drug Administration recently approved a new enteric-coated weekly formulation of fluoxetine indicated for the continuation treatment of depression, we thought it important to provide our patients with the flexibility and convenience of this newly available formulation of fluoxetine, and here report our experience.
Background: Anew formulation of enteric-coated oral fluoxetine given at a dose of 90mg once weekly has been shown in clinical trials to be well tolerated, safe, effective and associated with very high compliance. It has been approved by regulatory agencies for marketing in the continuation phase of antidepressant therapy. However, literature reports on experience with the once-weekly formulation in clinical practice, especially in patients with substantial medical and psychiatric co-morbidities, are sparse.
Methods: Enteric-coated fluoxetine 90mg was provided in a clinic setting to 39 psychiatric outpatients (aged 18 to 78 years) with a confirmed diagnosis of major depression. A co-morbid medical or psychiatric condition was present in 45.8% of the women and 42.9% of the men; most of these patients were on concomitant medication. Seven patients were previously untreated for depression. The tolerability, efficacy and compliance of once-weekly fluoxetine (90 to 540mg) were evaluated in this patient population utilising data from patient charts.
Results: Of the 32 patients already receiving fluoxetine, 31 were successfully converted from a single daily dose to a single weekly dose (90 to 540mg) and one patient was converted to a divided dosage (twice weekly). The remaining seven patients were started on weekly fluoxetine administration de novo. Presently, all 39 remain in remission from depression, with no changes in affect, co-morbid conditions or compliance. After dosage adjustments to date, this cohort has been monitored and has a cumulative exposure of weekly fluoxetine administration of 7.2 patient-years. No patient has discontinued enteric-coated fluoxetine therapy. No serious adverse events or hospitalisations were reported. There were no new reports of queried events of nausea, headache or sexual dysfunction. There were no new spontaneous reports of nervousness, asthenia, diarrhoea, abnormal thinking or somnolence.
Conclusions: In our clinical experience, enteric-coated fluoxetine, administered at higher doses once or twice weekly, was effective and well tolerated for short-termmaintenance treatment of major depressive disorder. The simple once-or twice-weekly administration could be a convenient alternative for some patients during long-term treatment of depression.
It is well documented that depression is a serious life-threatening illness often requiring long-term treatment, and that the adequacy and duration of antidepressant exposure is less than optimal for many patients. One factor contributing to this undertreatment is the reluctance of the patient to stay on medication for an extended period of time, especially when they are feeling well. Once-weekly drug administration may provide a strategy for enhancing psychological well-being and over-all tolerability, leading to improved compliance.
Fluoxetine is the only orally administered agent capable of providing an antidepressant effect during continuation treatment using less frequent dosage intervals than daily administration; this is due to the long elimination half-lives of the drug and its desmethylated metabolite, norfluoxetine.
Montgomery et al. explored the possibility of using higher doses at less frequent intervals by showing that responsive patients randomly assigned to receive fluoxetine 80mg weekly were as likely to remain well as patients assigned to fluoxetine 60mg daily. Burke et al. subsequently confirmed that 60mg of fluoxetine once a week was a well tolerated and effective continuation treatment regimen. Asimilar finding was recently made in a 501-patient, randomised, multi-centre clinical trial. After 13 weeks of 20mg daily and immediate-release fluoxetine, responders were randomly assigned to receive 20mg of fluoxetine daily, placebo or 90mg of enteric-coated fluoxetine weekly for 25 weeks of double-blind continuation treatment. Relapse rates for patients assigned to fluoxetine 20mg daily or 90mg weekly were significantly lower than those for placebo recipients and did not significantly differ. Tolerability evaluations for the enteric-coated fluoxetine at a once-weekly dose of 90mg were similar to those for the 20mg daily dose. Importantly, however, in another study, once-weekly fluoxetine-treated patients had higher electronically reported compliance rates relative to those receiving once-daily fluoxetine.
As the US Food and Drug Administration recently approved a new enteric-coated weekly formulation of fluoxetine indicated for the continuation treatment of depression, we thought it important to provide our patients with the flexibility and convenience of this newly available formulation of fluoxetine, and here report our experience.
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