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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 8 of 8. This is the beginning of the thread.
Posted by Phillipa on May 10, 2011, at 20:22:25
Probably biased as drug companies were involved for you interest only Phillipa
From Medscape Medical News
Dual Antidepressants May Not Be Better Than Monotherapy
Laurie Barclay, MDAuthors and Disclosures
May 10, 2011 Dual medications for depression increased costs and adverse effects with no benefit to patients and no greater efficacy than monotherapy, according to the results of a single-blind, prospective randomized study reported online May 2 in the American Journal of Psychiatry."Clinicians should not rush to prescribe combinations of antidepressant medications as first-line treatment for patients with major depressive disorder," principal investigator Madhukar H. Trivedi, MD, professor of psychiatry and chief of the Division of Mood Disorders at the University of Texas Southwestern, Dallas, said in a news release. "The clinical implications are very clear the extra cost and burden of two medications is not worthwhile as a first treatment step."
The goal of the Combining Medication to Enhance Depression Outcomes study was to compare antidepressant medication combinations with selective serotonin reuptake inhibitor monotherapy to see whether either combination was associated with increased rate of remission in first-step, acute-phase treatment (12 weeks) and long-term treatment (7 months).
At 6 primary and 9 psychiatric care sites, 665 outpatients with at least moderately severe nonpsychotic chronic and/or recurrent major depressive disorder were enrolled. Using measurement-based care, participants received escitalopram (up to 20 mg/day) plus placebo, sustained-release bupropion (up to 400 mg/day) plus escitalopram (up to 20 mg/day), or extended-release venlafaxine (up to 300 mg/day) plus mirtazapine (up to 45 mg/day).
Remission, defined as ratings of less than 8 and less than 6 on the last 2 consecutive applications of the 16-item Quick Inventory of Depressive SymptomatologySelf-Report, was the main study endpoint. Adverse effect burden, adverse events, quality of life, functioning, and study attrition were secondary endpoints.
At 12 weeks, the treatment groups did not differ in remission rates, response rates (51.6% - 52.4%), or most secondary endpoints. Remission rates were 38.8% for escitalopram-placebo, 38.9% for bupropion-escitalopram, and 37.7% for venlafaxine-mirtazapine.
Similarly, there was no significant difference among groups at 7 months in remission rates (41.8% - 46.6%), response rates (57.4% - 59.4%), and most secondary endpoints. Compared with escitalopram-placebo, venlafaxine-mirtazapine was associated with a higher mean number of serious adverse events (5.7 vs 4.7).
"Neither medication combination outperformed monotherapy," the study authors write. "The combination of extended-release venlafaxine plus mirtazapine may have a greater risk of adverse events."
Limitations of this study include a lack of generalizability to all outpatients with chronic and/or recurrent major depression, possibly insufficient doses used, lack of blinding, and lack of a structured interview to establish axis I diagnoses. In addition, participants were not randomized again or stratified by level of improvement after the acute phase.
"In summary, in outpatients with chronic and/or recurrent major depressive disorder, there appears to be no advantage to either medication combination over escitalopram alone as a first-step treatment for non-resistant depression," the study authors conclude.
The National Institute of Mental Health supported this study. Forest Pharmaceuticals, GlaxoSmithKline, Organon and Wyeth Pharmaceuticals provided the study medications. The study authors report various financial relationships with pharmaceutical studies, as listed in the journal article.
Am J Psychiatry. Published online May 2, 2011
Posted by floatingbridge on May 10, 2011, at 21:58:17
In reply to Dual AD Tx Same As Monotheraphy For MDD, posted by Phillipa on May 10, 2011, at 20:22:25
Has it become a standard practice to treat someone with depression who is medically naive with two meds?
(I'm curious what's being practiced these day since I saw seroquel er being advertised for major depression on television and mags as an antidepressant. That it is called an antidepressant is true enough, but there
is a slippage of language occurring
because in general discussion, most folks think antidepressant = ssri.)Many people (I don't know the statistics)
will remit on the first round. Isn't this correct? Are the *many people* I refer
to experiencing major depression or a
less severe form?(I don't like to see people unnecessarily or overly medicated. It can mess with
the diagnostic process. If circumstances warrant polypharmacy, I have no issue.)I might be misunderstanding this study.
Posted by Phillipa on May 10, 2011, at 22:06:13
In reply to Re: Dual AD Tx Same As Monotheraphy For MDD » Phillipa, posted by floatingbridge on May 10, 2011, at 21:58:17
Honestly who knows as each day something changes. Love Phillipa
Posted by Christ_empowered on May 11, 2011, at 0:26:50
In reply to Re: Dual AD Tx Same As Monotheraphy For MDD » floatingbridge, posted by Phillipa on May 10, 2011, at 22:06:13
I think it might depend on where you're being treated and what the symptoms are. I'm going to a Public Health doc right now, and when I hear people in the waiting room talk about their meds, they'll talk about antidepressants, plural, so I imagine in that setting (trying to cut costs while also avoiding benzos and anything else that might make life more pleasurable), multiple antidepressants might be more common than your typical private practice. I have no idea how people hospitalized for more severe depressive episodes would be treated; I'm guessing these days an atypical would likely be involved.
Posted by bleauberry on May 11, 2011, at 4:55:00
In reply to Dual AD Tx Same As Monotheraphy For MDD, posted by Phillipa on May 10, 2011, at 20:22:25
This study has a number of flaws and possible bias. The one thing that stood out in my mind was how they made a blanket statement concerning dual ADs, when the most appropriate potent dual AD combos were not even used. Not a single TCA in there. I think they put more credence in Wellbutrin than it deserves....it did not pass the test as an antidepressant in other countries. Why use such a lame AD? Remeron isn't exactly a powerhorse either. I'm not saying these meds don't work occasionally, they just don't have the track record or the umph of TCAs or other choices. And along the lines of dual ADs, how come they didn't use Milnacipran. It's a built in dual AD all in one. Except for a couple of the TCAs, it is the only one. Effexor gets the dual AD classification, but in reality is hardly so. When combined with Remeron, their is no evidence that it actually increases NE, contrary to the hype. This whole study looks flawed to me due to weak med choices, or cherry picked med choices.
What ever happened to good ole prozac? Ya know, a lot of ssris have jumped on the band wagon. But personally I have just not seen any perform as well as prozac from a subjective audience point of view. I mention prozac because it actually does have evidence that it increases all three of the major neurotransmitters, where lexapro is just one.
Anyway, I'm just rambling. Don't mind me.
Posted by SLS on May 11, 2011, at 6:02:43
In reply to Re: Dual AD Tx Same As Monotheraphy For MDD, posted by bleauberry on May 11, 2011, at 4:55:00
> This study has a number of flaws and possible bias. The one thing that stood out in my mind was how they made a blanket statement concerning dual ADs, when the most appropriate potent dual AD combos were not even used. Not a single TCA in there. I think they put more credence in Wellbutrin than it deserves....it did not pass the test as an antidepressant in other countries. Why use such a lame AD? Remeron isn't exactly a powerhorse either.
The point of combining antidepressants is to bring about a therapeutic response which is absent when using these drugs separately. Neither drug needs to be globally potent as an antidepressive agent. As an example, buspirone makes a terrible antidepressant. Yet, it can turn someone from a non-responder to a responder. Two drugs need only have complementary mechanisms of action that produce a synergy.Sorry, but Wellbutrin makes an excellent choice as an augmenting agent to SRIs, especially with an SNRI. "Welloft" is a term used by doctors to indicate the synergy they observed between Wellbutrin and Zoloft.
It is my guess that ritanserin, a selective 5-HT2a/b/c antagonist would make a good adjunct to standard antidepressants, despite having very little therapeutic properties on its own. I haven't searched online for any investigations of this idea.
- Scott
Posted by SLS on May 11, 2011, at 6:09:08
In reply to Re: Dual AD Tx Same As Monotheraphy For MDD, posted by bleauberry on May 11, 2011, at 4:55:00
Yup.
I mispoke in my previous post. Sorry.
Ritanserin is a 5-HT2a/c receptor antagonist.
- Scott
--------------------------------------
http://www.ncbi.nlm.nih.gov/pubmed/9194148Prog Neuropsychopharmacol Biol Psychiatry. 1997 May;21(4):671-82.
Ritanserin administration potentiates amphetamine-stimulated dopamine release in the rat prefrontal cortex.
Pehek EA, Bi Y.
SourceDepartment of Psychiatry, Case Western Reserve University, Cleveland, OH, USA.
Abstract1. Administration of serotonin 5-HT2 receptor antagonists increases the basal release of dopamine in the mesocorticolimbic pathway. 2. Treatment with dopamine D2 receptor antagonists increases impulse-dependent basal dopamine release in the nigrostriatal pathway. D2 antagonists also potentiate carrier-mediated increases in DA efflux from this pathway. 3. The present study compared the effects of a 5-HT2A/C antagonist (ritanserin) and a D2 antagonist (haloperidol) on carrier-mediated (amphetamine-induced) DA release in the mesocortical system. 4. In vivo microdialysis was used to recover extracellular fluid from the medial prefrontal cortex of conscious rats. Samples were then assayed for dopamine content by HPLC with electrochemical detection. Haloperidol or ritanserin were administered systemically (i.p.) 30 min before d-amphetamine (5.0 mg/kg i.p.). 5. Results demonstrated that 5.0 mg/kg ritanserin, but not 1.0 mg/kg, potentiated amphetamine-induced DA release in the prefrontal cortex. Similar to previous findings in the striatum, haloperidol (1.0 mg/kg) also augmented amphetamine-stimulated DA efflux in the cortex. 6. These results suggest that 5-HT2 and D2 receptor antagonists increase impulse-mediated dopamine release in the rat prefrontal cortex which in turn potentiates carrier-mediated release.
Posted by bleauberry on May 14, 2011, at 5:20:12
In reply to Re: Dual AD Tx Same As Monotheraphy For MDD » bleauberry, posted by SLS on May 11, 2011, at 6:02:43
I whole heartedly agree with everything you pointed out Scott, and thank you for illustrating. I do believe there were better, less trendy, less politcally correct, meds that were ignored....parnate, clomipramine, milnacipran, nardil, prozac+zyprexa, prozac+ritalin, zoloft+nortriptyline. Now, had they based their conclusions by incorporating those in the study, I would give the study more credence than I currently do.
I am almost always suspect of studies anyway.
> > This study has a number of flaws and possible bias. The one thing that stood out in my mind was how they made a blanket statement concerning dual ADs, when the most appropriate potent dual AD combos were not even used. Not a single TCA in there. I think they put more credence in Wellbutrin than it deserves....it did not pass the test as an antidepressant in other countries. Why use such a lame AD? Remeron isn't exactly a powerhorse either.
>
>
> The point of combining antidepressants is to bring about a therapeutic response which is absent when using these drugs separately. Neither drug needs to be globally potent as an antidepressive agent. As an example, buspirone makes a terrible antidepressant. Yet, it can turn someone from a non-responder to a responder. Two drugs need only have complementary mechanisms of action that produce a synergy.
>
> Sorry, but Wellbutrin makes an excellent choice as an augmenting agent to SRIs, especially with an SNRI. "Welloft" is a term used by doctors to indicate the synergy they observed between Wellbutrin and Zoloft.
>
> It is my guess that ritanserin, a selective 5-HT2a/b/c antagonist would make a good adjunct to standard antidepressants, despite having very little therapeutic properties on its own. I haven't searched online for any investigations of this idea.
>
>
> - Scott
>
This is the end of the thread.
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