Posted by Larry Hoover on February 25, 2003, at 22:56:11
In reply to Could someone please explain this study,, posted by Jaynee on February 25, 2003, at 21:10:37
> Please excuse my ignorance, but what I get from this study is that 40mg of Celexa works better than 20mg for anxiety. Is this correct? I find this study confusing to understand.
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> Thanks.I'll take a crack at it. First and foremost, though, the focus of the paper is on major depression. Anxiety is a secondary measure, and may be less reliably measured.
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> Psychopharmacology (Berl) 2002 Aug;163(1):20-5 Related Articles, Links
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> Citalopram dose-response revisited using an alternative psychometric approach to evaluate clinical effects of four fixed citalopram doses compared to placebo in patients with major depression.
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> Bech P, Tanghoj P, Andersen HF, Overo K.
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> Psychiatric Research Unit, Frederiksborg General Hospital, Dyrehavevej 48, 3400 Hillerod, Denmark. pebe@fa.dk
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> RATIONALE: Among the many problems in interpreting dose-response studies with antidepressants are the psychometric problems in the identification of true antidepressive effect versus true adverse drug effect.There's a problem finding objective tools for assessing drug efficacy at different doses, as questionnaires that are available don't always seem to ask the right questions, or aren't sensitive enough to reveal dose-responsiveness adequately.
>OBJECTIVES: This study is a re-examination of a dose-response trial with citalopram in order to examine the explanatory ability of using strict psychometric dimensions to measure the wanted and unwanted drug effects of different doses compared to placebo.
They wanted to see how the test scores predicted response when separated into different factors or subscales.
>METHODS: The antidepressive response was measured after 2 and 6 weeks of therapy with the depression subscales of the HAM-D and on the Montgomery-Asberg Depression Scale (MADRS). The patient-reported Symptom Checklist (SCL) sub-scales for depression and anxiety were also examined. Subjective side-effects were measured on serotonin-specific items of the SCL.
In identifiying the questionnaires in use, it's important to recognize that there is only one measure of anxiety. There are three measures of depression. That may make inferences with respect to anxiety less reliable.
>Effect size statistics were used to measure the antidepressive effect (an effect size of 0.30 equals a drug superiority over placebo of 15-20%). Side effects were statistically analysed using baseline-adjusted scores of the individual symptoms.
Self-explanatory, I think.
>RESULTS: The psychometric analysis of the outcome scales showed that the full HAM-D(17), the SCL-56 and the SCL side-effect subscale were multidimensional scales, while the HAM-D and MADRS subscales as well as the SCL-anxiety subscale were most homogeneous, indicating that their total scores are sufficient statistics.
The full HAM-D, the SCL-56, and the SCL side-effect scale require detailed analysis as they measure more than one variable at the same time. In saying that the specified subscales were homogenous, they mean that they are measuring just one trait. Thus, the latter items can be interpreted without detailed analysis, simply by comparing scores.
>When the scales were used as well as the individual serotonin-specific SCL side-effect symptoms, the results showed that after 2 weeks of therapy a clinical response (effect side over 0.30) was only seen for the SCL-anxiety subscale in the citalopram doses of 40 mg and 60 mg daily.
Early results at high dose showed no response in depressive symptoms, while anxiety diminished at the two highest doses studied (presumably not at the lower doses).
>After 6 weeks of therapy response to even 10 mg and 20 mg was seen in the HAM-D and MADRS subscales and in the SCL-anxiety subscale, however, with lower effect sizes than found for 40 mg and 60 mg citalopram daily.
By six weeks time, significant improvement in depressive symptoms was seen at all four doses of citalopram studied. Anxiety was similarly improved.
>The dose of 20 mg citalopram induced side-effects comparable with those seen for 40 mg and 60 mg, while 10 mg was not different from placebo. This was further confirmed by the fact that more patients dropped out on 20 mg than on 10 mg citalopram daily, due to adverse events.
Self-evident?
>CONCLUSION: This psychometric re-examination of a citalopram dose-response trial has shown that the pure antidepressive or antianxiety effects can be observed after 6 weeks of therapy even in a dose of 10 mg daily. However, both 10 mg and 20 mg daily had lower effect sizes than 40 mg and 60 mg daily. At a dose level of 20 mg daily, side effects are more pronounced initially than at 10 mg daily; this should be taken into account clinically when evaluating the overall benefit of the drug. For a highly serotonin-specific drug such as citalopram, both wanted and unwanted effects are dose-related.
The lowest dose possible should be employed, to minimize side effects, but higher doses provided improved relief from symptoms of both depression and anxiety.
If that didn't help, perhaps specific questions?
Lar
poster:Larry Hoover
thread:203845
URL: http://www.dr-bob.org/babble/20030224/msgs/203864.html