Monday, May 30, 2016

Rhetoric and Jargon in Health Care Policy, Part 2: "Evidence Based"

These days we often hear about how a new treatment, or program, or therapy style, is "evidence based."  This gives the listener an impression that the new treatment must be superior in some way.

It is another language construct which has become much more common, especially in mental health care discussions.  Recently, its prevalence has tripled in written language, with a steep increase beginning in about 1993, according to the Google NGram viewer.

 But was does "evidence based" really mean?

We often hear, for example, that cognitive-behavioural therapy (CBT) is "evidence based."  The implications of this statement is that other forms of therapy must not be "evidence based."


It should go without saying that most everything is "evidence based":  

An individual's personal account of their experience is a form of evidence.

A randomized controlled prospective trial of therapy supplies another form of evidence.

An opinion from an expert, or from a mystic, or from a random person on a bus, or from a charlatan, is another  form of evidence.


Ironically, the introduction of the phrase "evidence based" may stifle debate and free thinking about a matter.  It implies that the issue it is describing has already been decided upon.

In psychiatry, the phrase "evidence based" is typically used in the area of CBT research, and in health care policy.  But this can bias opinion away from other therapeutic modalities whose practitioners tend not to advertise themselves with this type of language.

I believe that gathering evidence from prospective, randomized, controlled clinical studies is vitally important--so important, in fact, that we must allow such evidence to cause established opinions about care to actually change.   There are many cautionary tales in medical history, in which good evidence about something new was dismissed by practitioners who were resistant to changing the style of practice they had grown up with.

But in mental health care, the evolving evidence is often much less robust than it seems.  Most studies are of very short duration.   Short-term or superficial care approaches may lead to various symptomatic improvements for many people...but long-term data is often not present.   Also, a great deal of evidence supports the efficiency of  treatments which work for 60-70% of people, but does not support useful options of how to help the other 30-40%.  

Many people may look back and value a short-term course of therapy in some way, but what they really found most valuable and life-changing was something quite different, such as having a dedicated caregiver over a period of many years who didn't practice using modern "evidence-based" methods at all...

It is good to think carefully about evidence, and to be prepared to change our practice accordingly.    But the phrase "evidence based" is often just a slogan, a form of jargon, and a construct which can lead to unwelcome biases in thinking.  Such cognitive short-cuts can often be very efficient, in order to decide on an important matter quickly, but such short-cuts should never be used to make large policy changes in a system.


 




Monday, May 2, 2016

Rhetoric and Jargon in Health Care Policy, Part One: "Stakeholders"


Jargon bothers me.  It reduces the enjoyment and engagement we have with languageIt can be a barrier for others to even understand what is being said.  

The term "stakeholder" is part of contemporary jargon in the area of policy development and corporate planning.  According to the Google NGram viewer, this word was very rarely used before 1975.  Since 1975, its frequency of use in printed language has increased by a factor of 10 000!  The words "stakeholder" or "stakeholders" surpassed the prevalence of the word "honesty" in written language as of the year 2000, and since then the prevalence has almost doubled again!  

Before 1975 "stakeholder" was primarily used as part of legal jargon, including one definition as follows: 

"A stakeholder is a person who is or may be exposed to multiple liability as the result of adverse claims."  
(McKinney, W. M. (1918). McKinney's Consolidated Laws of New York Annotated. West Publishing Company.)

Since 1975, the meaning has evolved to:
"a person or company with a concern or financial interest in ensuring the success of an organization or business"   (Oxford English Dictionary) 
   
The etymology of the word "stake," relates not to its meaning as a sharp wooden stick, but rather to another meaning, dating back to 1540,  as "the money risked on a game of dice."  (Oxford English Dictionary) 


The honourable spirit of the word "stakeholder" has to do with respecting different groups, positions, and points of view while discussing an issue in an organization.  It may invite a shared view of complex systemic matters, as though all the different interested individuals figuratively have "money risked on a game of dice."   It invites group decision making, rather than a dictatorial approach.

My complaint about this word has to do with its reflexive use as part of jargon.  There are connotations of a group of people gathered around in a betting game  (which is literally where the word originates).   There is an image of wealthy property-holders (with "stakes" in the land) debating about real estate dealings.   Another unintended connotation is of a group of people holding sharp sticks, waiting to confront a vampire! 

Finally, I wish that people in a discussion could simply be referred to as people, or by name, rather than as "stakeholders." 

I believe that the honourable spirit of respect, intended by using the word “stakeholder,” is vitally important.  But sometimes jargon brings us farther away, rather than closer, to this honourable spirit.  Many policy discussions can be so laden with this, as to be content-free, muddled doublespeak.

I invite us all to express ourselves in an articulate, engaging manner, while letting go of any need to use jargon.   Jargon can be a divisive tactic in language and debate:  many listeners become inured to it through repetition.  The jargon becomes a short-cut to be persuasive, while not leading the listener with any new thought.  It becomes "filler" in a dialog, which can distance and bore the audience.  This type of rhetoric can fool an uneducated audience into believing that the speaker is bestowing more wisdom than is actually the case.  It can also have a suppressive effect on a dissenting voice, therefore stultifying debate and free thinking. 

In cognitive therapy, we see that our minds can create various types of "inner jargon," which can perpetuate anxious or depressive states.  While cognitive therapeutic theory is laden with its own jargon, one healthy principle it encourages is to practice awareness of our "inner jargon," to "talk back" to it, and to create new, imaginative, constructive, mindful, and reasoned inner dialog or self-talk. 

I believe that cognitive therapy doesn't tend to encourage one thing enough:  to practice expressing our thoughts, or forming new inner dialogue, in a way which is rhetorically beautiful.  

In cognitive therapy, we are encouraged always to garner the courage to offer a dissenting voice!  In the case of cognitive therapy for depression, we must bravely speak back, in our thoughts, to a storm of negative, pessimistic, self-critical thinking. Let us make the "speaking back" full of eloquence, poetry, and beauty.  Let us step away from using jargon or other forms of empty talk. 

We are "stakeholders" of our own minds!   Or, different points of view held in the mind are all "stakeholders" of self.   But perhaps we can let go of the "stakes" and simply work with ideas, without using jargon, in a frank, articulate, compassionate dialogue.  


   


Tuesday, April 26, 2016

E-Mental Health

The whole issue of e-mental health induces quite a bit of resistance in me, which causes me to pause and reflect.

The issue perhaps represents, somehow, a threat to the way I like to practice psychiatry.  Therefore, I may be prone to some biases, and simple resistance to change.

On the one hand, I love gadgetry, and I love technological innovation.  But I also love to practice psychiatry in a way which does not require any gadgetry of any sort.  I like, quite simply, to see my patients regularly, in person.  I am averse to a system which would make this type of practice less possible. 

There is no personal financial reason why e-mental health would need to be opposed.  Seeing patients in person, for an hour at a time, is financially disfavoured in the current system.   E-mental health certainly does not need to pose any threat to the financial well-being of therapists.   It may actually facilitate higher earnings for many therapists. In fact, if anything, there may be a bias towards using more e-mental health, as a therapist may be able to offer these types of services in a zero overhead environment, to large numbers of clients, therefore maximizing financial profit.

I have thought that various e-mental health resources are "impersonal," but I realize that I may need to be a bit more open-minded about this.  I am reminded of my own experience in university, many years ago:


I can think of many examples of courses I took in university, even in medical school, in which attending the lectures was not effective for good learning.  It was often a passive activity, involving a struggle to stay awake;  many professors may have been great experts in their fields, but were not effective, dynamic, or interesting teachers.  It would have been better for my learning to have skipped the lecture and just spent the time reading on my own.   Maybe in-person psychotherapy can be like this, in some cases.  

Nowadays, students often have opportunities to take courses entirely online.  Also, many teaching resources, such as lectures (including those done at famous universities) are available online.  While taking a course online could be less "personal" in many ways, it is not necessarily so.  Personal interaction with a professor or classmates may in some cases be easier online than in an in-person lecture.   It is only the medium which is different.

For many types of psychotherapy, there can be a sort of "curriculum" akin to the material presented in a university course.  This is especially true in CBT (cognitive-behavioural therapy).   In many cases, structured self-learning, possibly with an on-line "curriculum," could be more effective, engaging, and enjoyable than attending in-person appointments.

What are the variables that might determine this?  Individual factors relating to personal needs are obviously relevant here--in many cases of depression or anxiety, it is the CBT-like "curriculum" which is the most important element to be mastered, in order to have relief of symptoms.  It may not necessarily be the case that these patients have a particular need for interpersonal care from a therapist, at least not in an in-person setting.   The optimal way, and even the most enjoyable way, for a person to benefit from this "curriculum" may, just like a student in a university course, be through taking a "CBT course" online.   But, of course, in many cases, the "curriculum" does not really matter so much as the "therapeutic alliance" or the personal experience in a therapy setting. 

Another variable is the therapist's personal style.  This reminds me, once again, of professors I took university courses with long ago.  In some cases, the courses were wonderful, meaningful, engaging, energetic, and delightful experiences, with a professor who was full of love for the subject, enthusiasm, and personal care for the students.   This made the course a joy to attend, even if the subject matter might have been approachable in an on-line or indirect fashion.  

I suspect a similar dynamic can occur in therapy--in order for a one-on-one therapy experience to be worthwhile, or superior to an on-line substitute, there would have to be a meaningful engagement with a therapist, whose style would suit the patient's interest, and kindle the patient's motivations.

Unfortunately, in today's therapy environment, personal sessions are often in short supply.  Courses of therapy are often very time-limited.   There is often, as a result, an excessive focus on simple, trite therapeutic advice, with very little time allowed to form an ongoing therapeutic connection.  If this form of therapeutic encounter is compared with a computer app, I am not surprised that the app has similar effectiveness!  I do see that this type of simple, brief, limited therapeutic encounter is indeed helpful for many people (e.g. with stress-related anxiety or mild, transient depression), but I also see that such an encounter would be very frustrating and ineffectual for many who have a more complex or difficult psychological history.     

Here are some other dynamics to watch for:

1) "the Christmas gift effect."  Sometimes, parents will buy expensive gifts for their children, during the Christmas season.  These parents may not have had much time for the children during the year, and indeed the children may well have been asking for various expensive toys or gadgets.  The expensive gifts are appreciated excitedly -- but they don't really help the children feel better!  They are just more "stuff," and may even condition the children to become more materialistic.   What the children may really desire is to have parents who spend more time with them, attending to them, playing with them, and caring for them.  They don't really want gadgets -- they want care and love.  But in the absence of the care and attention, the children may only identify a wish for more presents or gadgets.  This is what Kahneman might call "miswanting," a distortion of identified desire caused by short-term materialistic reflexes, while longer term substantive needs are unmet.

I am concerned that various examples of e-mental health are a bit like expensive Christmas gift gadgetry.  Everyone is excited about it (not least the vendors who are selling the electronics required for it, or the researchers clamoring to publish journal articles about it), but in the midst of the fray, it may not be noticed that even less time, care, and attention is spent actually caring for patients directly.  More time in front of computer screens, less time in front of other people. 

2) The "curriculum" benefits of e-mental health could be obtained in a variety of other trivial ways.  If CBT curricula were widely available online already (which is ever more the case) or if they were introduced as health care programs during childhood, etc., then e-mental health curricula may have much less measurable impact.  It would be like taking the same university course (which you already passed) a second time.  For this cohort, a more direct, personalized form of care may be even more important.

3) Hidden costs.  While e-mental health ideas may indeed be effective in many situations, or may be equal in some measure of effectiveness to other established treatments, there could be hidden problems.  For example, suppose a cohort of therapists who love providing personalized, direct therapeutic care are compelled to spend their time supervising e-mental health activities (for example, sitting alone in an office, in front of a computer screen) for an expanding proportion of their time.  In this case, perhaps an equal (or greater) number of patients or clients could be seen and helped.  But--those individual clients who would have benefited most by seeing someone in person would not have been seen and helped, because the therapist was sitting in front of a computer screen instead!


Another hidden problem is the detriment to morale caused by compelling people to spend even more time in front of a computer screen, instead of in front of an actual person. An effective psychotherapist (or teacher, or musician, or worker of any type) is one who feels joy and passion and excitement and personal connection for the work. Imagine seeing a therapist or a teacher who appears disconnected, distant, or absorbed with an electronic gadget instead of with a person!   If joy of personal connection is deprived, through the use of supposedly efficient technology, then the effectiveness of the entire system is at risk. 

Furthermore, there could be a selection bias evolving in a therapists' population if this trend continues, favouring those who can tolerate more impersonal interactions as a norm.  Those who are most comfortable with simple personal connection, and less comfortable with technology, may feel more and more uncomfortable with entering into a therapy profession at all.   Yet, those with the highest comfort for personal connection are arguably the most valuable and talented therapists! 

The Golden Rule Question:

In trying to sort out this issue, I think we could ask ourselves a type of "Golden Rule" question:  if it was you yourself, or if it was your partner, your spouse, your mother,  your child, or your closest friend, who needed help for managing serious anxiety, depression, or some other psychological distress--how would you feel about an electronic resource being offered instead of a one-on-one therapist?


As I ask myself this question, I think that it ought not to be either/or.  I suspect, for me, that I would appreciate using various electronic resources.  And I suspect, for me, that it would also depend on the therapist who was available:  would I like that person?  Would that person seem compatible?  Would that person have the time and the  commitment to offer the help needed (possibly over a long period of time)?

If I was told that the use of e-mental health modalities would reduce the total amount of direct in-person time available for clients or patients, this might further demote my enthusiasm for them.  

In a system which is already failing to attend to providing adequate personalized care, I would be worried about a strategy in which even more time, money, and attention was given to a gadget, rather than to a human relationship.   The consequences of such movement away from personalized care affect not only clients or patients, but also the morale and health of the therapist community, and arguably the health of society as a whole. 

But, if e-mental health simply expanded the accessibility of therapy, allowed people trapped at home or in remote locations to access care, allowed playful educational engagement, while still allowing clients and therapists to have direct, personal time in a therapeutic framework, then I think this technology could be embraced in a way which is healthy for all.  

In subsequent posts on this subject, I would like to survey some of the literature on this.  Much of the recent literature is very positive and enthusiastic about e-mental health.  While I am curious, and am sometimes delighted, by some of the ideas, I am also wary about the lack of consideration for the issues described above.  There is a long history in psychiatry, and in medicine generally, of big enthusiastic trends of practice, sometimes following political motives, leading in retrospect to regrettable decrements in care.  

Wednesday, March 9, 2016

Stimulant Medications for treating ADHD: A comparison

ADHD medication is a big business in the world today.  Annual sales of ADHD medication are projected to be 15-20 billion dollars by 2020, increasing at a rate of about 8% per year.   To put this in perspective, this is similar to the value of the worldwide market for fresh vegetables
 ( http://siteresources.worldbank.org/INTPROSPECTS/Resources/GATChapter13.pdf ).

 It is an amount of money that would pay for the salaries of
 400 000 teachers, each of whom paid $50 000 per year. 

 A relevant article to look at about this is by Alan Schwartz, published in the New York Times in 2013:
http://www.nytimes.com/2013/12/15/health/the-selling-of-attention-deficit-disorder.html?pagewanted=all&_r=0

I am not meaning this post to be a discussion of the controversies of ADHD diagnosis.  Instead, this post will focus mainly about ADHD medication.   I think the rising rate of ADHD diagnosis, and the rising rate of stimulant prescription,  is a very concerning trend, particularly if these diagnoses and treatments are offered without attending adequately to other biopsychosocial factors, and particularly if these treatments are being offered under the influence of un-recognized biases due to the financial power and influence of the manufacturers.

On the other hand, the rising awareness and acceptance of ADHD can allow those children, adults, and families who are dealing with ADHD-related issues to feel less stigmatized, judged, and unfairly treated.  In families, knowledge and acceptance of ADHD can help child-rearing practices to be adapted, so as to avoid a harshly punitive stance towards those children with attention problems.  


The newer ADHD medications are, not surprisingly, very popular, frequently prescribed, are often touted as being better than the older medications, and are listed first on medication advice guideline sheets (such as the CADDRA recommendations).

Here is a comparison of costs per day between the different ADHD drugs, looking at a typical full therapeutic dose for an adult.  These cost estimates come from a site called "Pharmacy Compass" which searches for the best local prices for medications at pharmacies.   

1. Newer drugs (CADDRA considers these to be the only "first line" medications):

Adderall XR 30 mg:$3.91 per day
Biphentin 80 mg:$4.36 per day
Concerta 72 mg:$5.92 per day
Vyvanse 60 mg:  $5.14 per day
Strattera 100 mg: $5.51 per day


2. Older drugs (CADDRA considers these "second line"):

Dexedrine spansules 40 mg: $3.59 per day

Ritalin (methylphenidate) 60 mg: $0.81 per day
 Ritalin SR 60 mg $0.66 per day


So we see that the least expensive option is methylphenidate or methylphenidate SR.  Dexedrine is over 5 times as expensive.  Concerta and Vyvanse are about 8 times as expensive, per day.

I mention these expense differences not necessarily in an effort to favour the cheaper medication, but rather to heighten your anticipation that there could be bias in any research results regarding these medications--especially if the research is sponsored by the manufacturers-- due to the huge profit motives involved.


It would be fair to look for studies which carefully and prospectively treat ADHD patients with Ritalin vs. one of the newer medications, in randomized comparisons.

1) Vyvanse vs. Ritalin.  Almost no studies in the literature!  In one study, all they looked at was whether patients stuck to a dosing regimen, in which case the Vyvanse group did "better." (http://www.ncbi.nlm.nih.gov/pubmed/23937642 ) But this measure had nothing to do with the patients actually feeling better or improving more!

A better study compared Vyvanse with Oros-MPH, a long-acting version of Ritalin (though not plain old Ritalin itself!)
[ http://www.ncbi.nlm.nih.gov/pubmed/23801529]

In this study, at first glance it certainly appears that Vyvanse is better!  But looking carefully, one finds statements such as this: "At endpoint, the difference between lisdexamfetamine and OROS-MPH in the percentage of patients with an ADHD-RS-IV total score less than or equal to the mean for their age was not statistically significant." (p.747)   This statement was tucked into the results section but left out of the conclusion.  Looking at side-effects, we find a lower total rate of adverse effects in the Ritalin group.  Reduced appetite, insomnia, and nausea were more common in the Vyvanse group.  Notably, there is a long list of conflicts of interest at the end of this paper, including some of the authors being employees of the Vyvanse manufacturer, and owning stocks in the company!


In conclusion here, there is no doubt that Vyvanse is an effective medication for ADHD.  The dosing regime is very convenient, which may be particularly effective and helpful for many.  But it is not necessarily superior to much cheaper alternatives.  For some people (including many patients I have seen), regular methylphenidate (Ritalin) allows better fine control of symptoms during the course of the day, without being "stuck" with a continuous sustained-release effect.  For others, they certainly do prefer the Vyvanse.  I just think that Vyvanse should not be assumed to be better, as the evidence is very weak that it is, while it is 8 times more expensive than Ritalin!

2) Concerta vs. Ritalin
http://www.ncbi.nlm.nih.gov/pubmed/11389303
This is a good early study, directly comparing the two medications, published in Pediatrics in 2001.  Here is the authors' concise summary: "On virtually all measures in all settings, both drug conditions were significantly different from placebo, and the 2 drugs were not different from each other."   The reason to choose Concerta over Ritalin would be convenience.  The authors do point out that "compliance" is more likely on a long-acting formulation.  But remember that "compliance" is a very, very indirect, and possibly irrelevant, measure of health and well-being!!  Why is it important that there be better "compliance?"   Should the only criteria not be well-being?   Certainly this is not a reason to classify Concerta as "better" or "first line".  Concerta is 9 times more expensive than Ritalin!

3) Adderall vs Ritalin
http://www.ncbi.nlm.nih.gov/pubmed/10103335
In this study, published in Pediatrics in 1999, Adderall comes out as looking better than Ritalin.  But, once again, the study was sponsored by the manufacturer.  On a close look, a couple of problems:  first, the doses of the medications were fixed.  The ritalin doses appear too low, so as not to match the equivalent doses of Adderall given.  At this point, one would usually give Ritalin doses at least twice that of Adderall (i.e. 100% higher) but in this study the Ritalin dose was only 40% higher than the Adderall dose.  In accordance with this under-dosing, the Adderall group not surprisingly had more side effects such as insomnia.

In conclusion, there is no doubt that Adderall XR is a good medication for ADHD.  Many of my patients have preferred it over other alternatives.  But it is not fair, once again, to assume that it is better.  It does not deserve to be considered "first line" while a similarly-effective alternative that is one-sixth the cost is considered "second line."

4) Meta-analytic comparison:
Faraone and Glatt (2010) have published a good meta-analytic review paper, which is worth reading in detail, with particular attention to the data tables and graphs:   http://www.ncbi.nlm.nih.gov/pubmed/20051220
In the conclusion of this paper, the authors state that they "found no significant differences between short- and long-acting stimulant medications."

Addendum:  a recent Cochrane review, published in February 2016 by Punja et al., concludes that there is a lot of evidence that amphetamines reduce core symptoms of ADHD, but cause a variety of problematic side-effects.  They note that there was evidence of a lot of bias in the studies they looked at, with the quality of evidence being low to very low.

Here is a direct quote from their conclusion:   "This review found no evidence that supports any one amphetamine derivative over another, and does not reveal any differences between long-acting and short-acting amphetamine preparations." 



Friday, February 19, 2016

Do Higher Doses of Antidepressants Work Better?

It is common practice in psychiatry to increase the dose of an antidepressant if the standard dose is not helping enough.  Sometimes doses are increased before even finding out if the lower dose is working. 

But it is interesting to consider evidence that higher doses actually do not necessarily work better:

RuhĂ© et al. (2009-2010) have published research on this issue, and conclude that SSRI dose increases do not improve effectiveness.  Their explanation for this is quite simple:  serotonin receptors are already well-occupied at standard doses, and this does not change with dose increases:  
http://www.ncbi.nlm.nih.gov/pubmed/18830236
http://www.ncbi.nlm.nih.gov/pubmed/20862644

In general, it is indeed interesting to see scanty evidence that increasing antidepressant doses lead to improved effectiveness, even for treatment-resistant cases.  

This issue came to my attention upon reading Lam's recent article about using light therapy to treat non-seasonal depression   ( http://www.ncbi.nlm.nih.gov/pubmed/26580307).  Their medication groups used only 20 mg of fluoxetine, without the possibility of increasing the dose.  They cited some old, dated references to support this, such as Altamura et al (1988), and  Beasley (1990):
http://www.ncbi.nlm.nih.gov/pubmed/2196623 
 
A better, more recent article reviewing antidepressant dose vs effectiveness is by Berney (2006):
http://www.ncbi.nlm.nih.gov/pubmed/16156383


In many studies, higher doses may appear to work better, mainly because the dose was increased before the lower dose had a chance to work fully.   The lower dose may well have worked just as well as the higher dose.  Controlled studies comparing different doses do not support the belief that higher doses work better.

So it should not be routine practice to increase antidepressant doses beyond a standard "full dose" which is usually one tablet or capsule daily.    In many cases, the different dosage regimes are likely to be equivalent.  It is relevant to consider that higher doses mainly benefit the pharmaceutical companies, since they are selling more product despite the effectiveness being the same.  Therefore, presentations of research data about antidepressant effectiveness may be biased in favour of higher doses.  An extremely common research design in antidepressant studies is to have "flexible dosing," usually leading to the antidepressant group averaging about twice the standard dose in the end.  This design, even when treatment effects are shown, biases the reader to have the specious conclusion that higher doses are better.

However, there are certainly many individual case reports of higher doses being more useful.  So dose increases may have a role in some cases.

The key point is to question dose increases as a reflexive, routine management strategy for inadequate antidepressant effects.  Alternative strategies include giving the lower dose a longer try, switching to something else, or using some form of augmentation.

Addendum:

Just days after posting this, I see there is a new meta-analysis by Jakubovski et al. in The American Journal of Psychiatry (173:2,pp. 174-183) which suggests that SSRI antidepressants do actually work slightly better at higher doses, peaking at 2.5 times the standard dose (e.g. 50 mg fluoxetine).   They admit that the data show a trade-off between slight improved effectiveness at higher doses, but accompanied by worsened tolerability. 

Yet, it is important to consider that higher doses could reflect a greater placebo effect; some of the research about active placebos show that agents which cause more side effects are likely to have a larger impact on symptoms than inert placebos.  Because antidepressants at higher doses have more side effects, there would be more of this "active placebo" effect.  See my previous post on this subject: http://garthkroeker.blogspot.ca/2009/03/active-placebos.html


It's hard to know what to make of this, other than to probably remain open-minded about the issue.  I think that a better study design for this type of issue is to look at dose comparisons within individual clinical trials, rather than to amass data meta-analytically.   Active placebo comparison groups would also be useful.  For example, agents which would cause very mild side-effects could be used instead of a totally inert placebo, so as to improve the blinding of the studies.    In many individual clinical trials of antidepressants (both new and old) which compare doses or dose ranges within the studies themselves, there are no significant differences in effectiveness.

Another issue, which the authors point out, is that most antidepressant studies have strict inclusion criteria which usually do not match the type of cases one would tend to see clinically most often.  Many studies require a major depressive disorder diagnosis, with limited comorbidities allowed, and with limited past treatment trials, etc.

Meanwhile, it remains reasonable to give a baseline dose of antidepressants an adequate length of time to work, without reflexively increasing the dose on a routine basis.   Dose increases remain an option, with some evidence-based support, but switching or augmentation could often be preferred, depending on patient preference and side-effects.