K.J. Gregor, J.M. Overhage, S.J. Coons, R.C. McDonald, Selective serotonin reuptake inhibitor dose titration in the naturalistic setting. Clinical Therapeutics 1994; 16(2):306-15.

The Regenstrief Medical Record System was used to analyze the dosing of 2859 patients on fluoxetine, and 460 on sertraline, treated in the outpatient population of a US urban teaching hospital. These patients received 21,079 prescriptions over nine consecutive clinic visits.

This paper was sponsored in part by Eli Lilly & Company. It speculates that fluoxetine may be more economical to use than sertraline - since, over the study period, "the frequency of increases in the prescribed dose of sertraline was nearly three times greater than the frequency of increases in the prescribed dose of fluoxetine." The mean daily dose for all patients receiving fluoxetine was 21 +/- 6mg for the first prescription dispensed and 25 +/- 11mg for the ninth. The corresponding figures for sertraline were 59 +/- 28mg, increasing to 117 +/- 66mg. In addition, a mean 5% of all patients continuing fluoxetine therapy, and 15% of patients on sertraline, had their daily dose increased with each prescription refill during the first nine prescriptions.

Comments from C.W. Barrett, Chief Pharmacist, The Royal London Hospital *

1. In the UK, nine out of ten prescriptions for antidepressants are written by General Practitioners and, to this extent, the paper would not reflect prescribing "in a naturalistic setting".

2. The time period between prescription refills was not recorded and it is not clear it was the same for all patients. No comment is made about the significance of non-compliance, use of other medications during the study period, differences in half-life of the study drugs, or patients' experiences of withdrawal.

3.  Only a small minority of patients had "depression" listed in their medical notes/records - 18% of patients on fluoxetine, and 12% of patients on sertraline. Other diagnoses are not recorded.  There were also significant gender differences involved: 12% of all men and 20% of all women were identified as depressed.

4. High attrition rates were reported, but were not commented upon. Of the sertraline-treated patients, only 8% (38/460) persisted with treatment through to the ninth prescription; the corresponding figure for fluoxetine was 24% (698/2859).

5. The title of the paper refers to "dose titration" which implies a planned increase in dosage until a desired and stable response is achieved, but there is no evidence to confirm this was the case. If it were, then dose reductions would also be counted as "titration", whereas this paper suggests that these resulted from adverse effects or "weaning patients from thereapeutic doses". The data might therefore indicate that other factors were at play, eg drug tolerance; a worsening of the patient's condition; drug ineffectiveness; use of the drug for an associated condition requiring a higher dosage; drug dependence; or even that the drug was making the condition worse.

The paper raises many interesting questions, but few are resolved

* CM writes: The notes above in no way adequately reflect the contribution Chris Barrett has made to this whole project. He made a decisive contribution to getting this research off the ground, in mid 1996, and has given invaluable support and encouragement ever since. I am extremely grateful to him for all he has done and look forward to collaborating further, following his retirement from the Royal London Hospital, in the Spring of this year. .


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