Conclusions : According to the published literature , the clinimetric properties of HAM-D6 are superior to those of both the HAM-D17 and MADRS .
Background : In a study aim ed at identifying the items carrying information regarding the global severity of depression , the 6-item Hamilton Depression Rating Scale ( HAM-D6 ) was derived from the original 17-item version of the scale ( HAM-D17 ) .
Since then , the HAM-D6 has been used in a wide range of clinical studies .
We now provide a systematic review of the clinimetric properties of HAM-D6 in comparison with those of HAM-D17 and the Montgomery Asberg Depression Rating Scale ( MADRS ) .
The responsiveness of the different versions of the Hamilton Depression Scale.
In clinical pharmacology , the evidence proving that a drug has a therapeutic effect in a specific medical condition is based on two major elements : superiority of the drug over placebo in r and omized clinical trials within the medical condition under examination , and a systematic relationship between the dose of the drug and the magnitude of the response it elicits . In their overview of antidepressants versus placebo , Khan and Brown ( 1 ) conclude that “ no clear dose-response relationship has been established to date for most of the new antidepressants ” , while the superiority of the antidepressants over placebo in terms of effect size statistics is approximately 0.30 , a level they find “ less than impressive ” . In their review of double-blind , placebo-controlled trials of antidepressants conducted from 1981 to 2008 , Khan et al ( 2 ) observed that the Hamilton Depression Scale ( HAM-D ) had been used as an outcome scale in most of the trials . However , the HAM-D was actually used in two different versions , the 21-item version ( HAM-D-21 ) and the 17-item version ( HAM-D-17 ) . The HAM-D-21 was used in one third of the trials and the HAM-D-17 in two thirds . Unfortunately , authors who use the HAM-D-21 rarely provide information about the results on the HAM-D-17 . Khan and Brown ( 1 ) highlight now that the antidepressant-placebo difference seems to be higher in HAM-D-21 trials compared to the trials in which the HAM-D-17 has been used as outcome measure . This is a tautological finding in so far as the st and ard deviation of this difference is not available , which is the case for most of the trials review ed by Khan et al ( 2 ) . Among the trials collected by Khan et al ( 2 ) it is possible , however , to identify ten publications in which the six-item HAM-D ( HAM-D-6 ) is compared to both HAM-D-17 and HAM-D-21 , or to HAM-D-28 . The HAM-D-6 covers the core symptoms of depression : depressed mood , work and interests , guilt feelings , psychomotor retardation , psychic anxiety , and general somatic ( fatigability ) . These six items have clinical and psychometric validity ( 3 ) . In two of these ten trials , a dose-response relationship was investigated . Fabre et al ( 4 ) showed that sertraline was significantly superior to placebo at all three doses ( 50 , 100 , 200 mg daily ) when using HAM-D-6 , but only at 50 mg daily when using HAM-D-17 . Liebowitz et al ( 5 ) showed that desvenlafaxine was superior to placebo at both 50 and 100 mg daily when using HAM-D-6 , but only at 50 mg daily when using HAM-D-17 . An analysis of all placebo-controlled trials of desvenlafaxine showed that at doses of 200 or 400 mg daily the effect size was negative during the first week of treatment ( superiority of placebo ) when using HAM-D-17 but not when using the HAM-D-6 , implying that the HAM-D-17 includes symptoms which might be side effects of the drug ( 6 ) . In placebo-controlled trials of fluoxetine , over a dose range from 20 to 60 mg daily , the effect size using HAM-D-17 was approximately 0.30 , but when using HAM-D-6 it was approximately 0.40 ( 3 ) . For escitalopram , a dose of 10 mg daily obtained an effect size of 0.38 mg using HAM-D-6 and a dose of 20 mg daily gave an effect size of 0.61 ( 3 ) . Over the past decade , the goal when evaluating the effect of an antidepressant has been the event of remission rather than response ( 7 ) . Remission in major depression is defined as a minimal level of the core symptoms of depression ( 7 ) . The syndrome reflected by the HAM-D-6 is a unidimensional measure for specific drug targets , and a cut-off score below 5 indicates that the individual symptoms of the scale are only present to a very doubtful degree ( remission ) . Khan and Brown ( 1 ) refer to the Sequenced Treatment Alternatives to Relieve Depression ( STAR*D ) as an example of a poor response to citalopram treatment . Indeed , when using the conventional definition of remission ( HAM-D-17 < 8) , only approximately 36 % of the patients  achieved remission . However , when using a HAM-D-6 score of < 5 as the definition of remission , approximately 45 % of the patients in that study achieved remission ( p<0.001 ) ( 8) . From a statistical point of view , failed trials are merely a consequence of insufficient power , as the inability to reject the null hypothesis is inherently associated with low statistical power . This has recently been illustrated in a re- analysis of a failed study which had used the HAM-D-17 to evaluate the effect of erythropoietin as augmentation in patients with treatment-resistant depression ( 9 ) . By focusing on the HAM-D-6 , fewer patients are needed to reject the null hypothesis . Psychometrically , Khan and Brown ( 1 ) correctly focus on the use of the HAM-D-17 as the major factor for the “ less than impressive ” effect size of 0.30 and the lack of a dose-response relationship . However , their solution to go for a larger HAM-D version ( HAM-D-21 ) is not justified . The solution is to go for the brief , clinical ly and psychometrically valid subscale ( HAM-D-6 ) . The use of the HAM-D-6 as outcome measure in placebo-controlled clinical trials of antidepressants increases the effect size to 0.40 , which is indicative of clinical significance . Using the HAM-D-6 as outcome measure , a dose-response relationship has been established for newer antidepressants such as escitalopram and desvenlafaxine . Moreover , fewer patients are then needed to identify antidepressant effect in controlled trials , which has important ethical implication s ( fewer patients need to receive placebo ) . In my opinion , we need to aim at establishing “ dose-remission ” rather than dose-response relationship in future trials of antidepressants . The HAM-D-6 contains the core symptoms of depression by which to define the event of remission
Conclusions : According to the published literature , the clinimetric properties of HAM-D6 are superior to those of both the HAM-D17 and MADRS .
Background : In a study aim ed at identifying the items carrying information regarding the global severity of depression , the 6-item Hamilton Depression Rating Scale ( HAM-D6 ) was derived from the original 17-item version of the scale ( HAM-D17 ) .
Since then , the HAM-D6 has been used in a wide range of clinical studies .
We now provide a systematic review of the clinimetric properties of HAM-D6 in comparison with those of HAM-D17 and the Montgomery Asberg Depression Rating Scale ( MADRS ) .