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David Baxter

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Antidepressant benefit may be apparent sooner
Tuesday, 18 July 2006
TIMOTHY F. KIRN

TORONTO ? Most clinical recommendations advise that patients who start an antidepressant be given 4?6 weeks to see whether they respond and have improvement.

But an analysis of more than 5,000 patients treated in clinical trials with a variety of antidepressants suggests that most patients who respond well start to improve within 2 weeks, Dr. Armin Szegedi said at the annual meeting of the American Psychiatric Association.

?This is a very strong, clinically relevant, and, perhaps to many, a surprising finding,? said Dr. Szegedi, executive director of clinical projects, psychiatry, at Organon International Inc., Rosalind, N.J., in an interview.

The analysis included patients who were treated with six different, selective serotonin reuptake inhibitors, including paroxetine (Paxil) and fluoxetine; two tricyclic antidepressants, amitriptyline and doxepin; and venlafaxine (Effexor), a selective norepinephrine reuptake inhibitor.

Regardless of the kind of drug used, patients showed a notable improvement by 2 weeks, or they had only about a 10%?20% chance of ever responding well, Dr. Szegedi said in a poster presentation given at the meeting.

The general recommendation that patients need to continue a trial of an antidepressant for a full 6 weeks before it is given up as a failure and the patient switched never was based on data, but rather, on expert opinion, Dr. Szegedi said.

And most have assumed that drugs with different mechanisms of action would have different times of onset. ?Unfortunately, the data do not back that up,? he said in the interview.

Instead, his data indicate that physicians might want to consider 2-week trials, saving time and misery, particularly if the patients are at any risk of hurting themselves, he suggested.

The data for the analysis came from several single- or double-blind trials comparing Organon's mirtazapine with other antidepressants in patients with major depression.

The trials used Hamilton Depression Rating Scale (HAMD-17) scores to assess the patients' depression. Improvement in the trials was considered to be a greater than 20% reduction in the score from baseline.

Of 2,655 patients treated with mirtazapine in the trials, 47% had improvement at the end of the first week of treatment, 68% had improvement by the second week, 75% by the third week, 79% by the fourth week, and 83% by the sixth week.

Of 1,306 patients treated with a selective serotonin reuptake inhibitor (SSRI), the percentages showing improvement at those time points were 36%, 63%, 70%, 76%, and 82%.

Of 404 patients treated with a tricyclic, the percentages improved at those time points were 38%, 69%, 78%, 81%, and 85%. Of 189 patients treated with venlafaxine, the percentages improved at those time points were 47%, 72%, 76%, 77%, and 80%. Among the 564 placebo-treated patients from the trials, 31% had improvement in the first week, and 66% had improvement by the sixth week.

The percentages of patients with at least a 50% reduction from baseline on the HAMD-17 were 26% at second week and 58% at the sixth week for mirtazapine, 22% and 59% for an SSRI, 24% and 63% for a tricyclic, and 29% and 51% for venlafaxine.

Moreover, those who had an early improvement did not generally backslide but were highly likely to go on to a stable response or remission, Dr. Szegedi said.

An improvement at 2 weeks predicted with 91% sensitivity those patients treated with mirtazapine who would go on to a later stable response, defined as at least a 50% reduction on the HAMD-17 at both the fourth and sixth weeks, as reported on Dr. Szegedi's poster. Likewise, it predicted a stable response in 88% of the patients on an SSRI, 89% of patients on a tricyclic, and 96% of patients on venlafaxine.
 

Holly

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Interesting clinical recommendations and analysis of patients. I have two questions Doc :?
What do you think is a appropriate respond time, if you are allowed to say?
Does it not depend on the reasons why the antidepressant is being given, and should that be considered in the respond?
 

David Baxter

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There are always individual variations in the way people respond to medications. I have seen patients start to respond the first week. I have also seen patients aho after six weeks say they didn't see any benefits, although often family and friends could see significant imporvement.

The effects of these types of medications can be subtle at first and they are cumulative, so the longer you are on them, the greater the benefits (at least up to a point).

The other thing to remember is that often you will be started on a small dose to help you get used to the medication and avoid side-effects. For example, with Effexor, most people will start at 37.5 mgs. That really is n ot enough to have m uch of an impact. For anxiety disorders, most will need to have the dose increased to at least 75 mgs. For depression, most will need to increase the dose in steps to at least 150 mg. But of course even there individuals will vary.

My best advice is to wait the standard 4 to 6 weeks (unless of course you are experiencing distressing side-effects). If you still not seeing benefits by then, it may be time to try something else.
 

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