Sunday, May 14, 2017

Not Taking Antidepressants




I came across this open access article on my Twitter feed that highlights some of the reality of antidepressants that I was trying to get at in my previous post.  I encourage a full reading of the article in order to understand it - specifically how patients were selected from a large commercial database.  In this retrospective study the authors selected patient with a diagnosis of major depressive disorder (MDD) who were taking and antidepressant but only in a specific time interval.  They did this for the purpose of constructing the above survival curve.  They started with a group of 6,562,955 people on antidepressants between 7/1/2003 and 1/1/2014 and ended up excluding all but 527,907.  Exclusions were based on no diagnosis of MDD in the previous 6 months, no prescription of an AD in the previous 6 months, lack of continuous enrollment in the previous 6-12 months, and pharmacological  therapies that included initiating treatment with more than one AD or 3+ ADs or augmenting agents (AA).  The final study population was 527,907 patients.

Two major endpoints were defined as measures of medication adherence - medication possession ratio (MPR) and proportion of days covered (PDC).  PDC was considered the primary measure of adherence due to previous convention.  Calculations were made at 3, 6, 9, and 12 months.  Persistence and adherence were calculated for each major antidepressant class (SSRI, SNRI, TCA, MAOI, and Other).  Adherence and persistence were calculated across all of these dimensions.  Bar graphs are available in the full text.

Adherence and persistence at 6 months was 31-36%.  SNRIs had the highest persistence and adherence rates at 6 months at 37% and TCAs the lowest at 16-17%.  Looking at the Kaplan-Meier survival above the curves were significantly different with the lowest adherence to initial TCA and MAOI therapy.  The curves also show natural break points at 30 and 90 day intervals that correspond to the typical length of prescriptions although most primary care physicians provide a significant number of refills beyond that.

A study like this has obvious limitations and the authors do a good job of explaining them. Most of them had to do with the limitations of using a database like this one with limited granularity.  For example - no data about the status of the prescriber or practice context.  I would have the question of whether adherence was any different among those given and antidepressant based on a screening questionnaire versus more detailed assessment and follow up.  It would also be interesting to see if subjects seeing psychiatrists were any more adherent than than what I am guessing are the majority of patients being see in primary care.  Surrogate markers for psychiatric care could have been devised based on AD and AA combinations but that would be an imperfect marker since most primary care depression guidelines incorporate these strategies.   There was a very minor erratum (2) essentially a typographic error that does not change the main paper.                      

When I look at a study like this, I always ask myself if the study group resembles the people I am currently seeing or have seen.  In this case 64% of the population was female and 81% were covered by commercial insurance.  Twenty-four percent had comorbid anxiety, 24% had comorbid chronic noncancer pain, and 6% had both.  Sertraline has the largest percentage of prescriptions at 18.7% with only about 5.4% of people on bupropion extended release.  I currently see a large number of people on sertraline or citalopram +/- bupropion augmentation.  Despite the FDA warning about maximum doses of citalopram - I still see people on 60 mg/day or > 40 mg/day who are 62 years of age or older.  Both of those situations were flagged in the FDA warning.

I do find that SNRI medication are better tolerated than SSRI and do not hesitate to make that change sooner than later.

Give the limitations this is an interesting study.  At several levels it matches my experience.  At least 20-40% of people do not tolerate SSRIs very well.  I have also found that  SNRIs are effective and more well tolerated than SNRIs.  The major limitation from my perspective is that without the data that the authors refer to - it is really not possible to design a clinical program that optimized adherence or that provides much of a foundation for the differences.  Many psychiatrists have the experience that they see the same people with severe depression for years.  In many cases plasma levels of antidepressants are measure to optimize dosing but they also confirm adherence.  In other cases, the patients are in settings where medications are administered.  A critical dimension in psychiatric practice is the ongoing relationship with the patient.

Looking at how the relationship with the patient and how that effects adherence is needed, but it is obviously a more difficult study to capture in a retrospective database.              


George Dawson, MD, DFAPA



References:

1:  Keyloun KR, Hansen RN, Hepp Z, Gillard P, Thase ME, Devine EB. Adherence and Persistence Across Antidepressant Therapeutic Classes: A Retrospective Claims Analysis Among Insured US Patients with Major Depressive Disorder (MDD). CNS Drugs. 2017 May;31(5):421-432. doi: 10.1007/s40263-017-0417-0. PubMed PMID: 28378157.


2: Keyloun KR, Hansen RN, Hepp Z, Gillard P, Thase ME, Devine EB. Erratum to:Adherence and Persistence Across Antidepressant Therapeutic Classes: A Retrospective Claims Analysis Among Insured US Patients with Major Depressive Disorder (MDD). CNS Drugs. 2017 Apr 27. doi: 10.1007/s40263-017-0435-y. [Epub ahead of print] PubMed PMID: 28451963.



Attribution 1:

The above graphic is directly from reference 1 reposted per terms of the Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) license.  No changes were made to the graphic.  Click on the graphic to enlarge.


Thanks:

To Barney Carroll for putting this reference on his Twitter feed.

Burnout Industry Just Doesn't Get It



I was sent a long list of burnout interventions from a colleague today.  It was quite amazing.  Opinion pieces on Burnout. TED talks on burnout.  Books, videos, and web-based resources on burnout.  All with the message: "Physicians - in the event that you could not figure this out yourself - here is what you can do to alleviate burnout."   The disease model of burnout, except in this case we are not treating with with medication or surgery we are using life style modification.  What is wrong with this picture?

It turns out there is plenty wrong with this picture.  The biggest problem of course is that all of the factors that lead to burnout flow from incompetent management.  We have had a surplus of that in the past 30 years with no end in sight.  I would venture a guess that in all of my time in practice, I have seen about 1 manager who I would consider to be competent.  Nobody working for him was at risk for burnout.  More importantly, the most important protective factor against burnout has also become a casualty of bad management.  That factor is collegiality.  I could regale the reader with stories from my past on how much work I and my teammates did in various medical and surgical settings.  But I think that most people in working settings realize how much better the job and the day goes if they are working with bright, knowledgeable and highly motivated people.  A sense of humor is always a plus and I am convinced that at least some of the physicians I worked with were some of the funniest people I have met anywhere.

Rather than more stories, I will get right to the point about how bad management subverts collegiality.  Very early in the process, managers sold the idea that "there are some slackers in the group and therefore we need to introduce a way to measure productivity."  I was skeptical.  I looked around the room and did not see any slackers.  The statement appeals to those who are competitive by nature or anyone who wants to make sure that everyone is working as hard as they feel they are.  The next part of the process was adapting a very crude systems and after several missed starts applying it to everyone.  Even then I was quick to point out that it looked like 95% of the group was working hard and the only difference were the correction factors applied to the work units.  At that point I was told that this was not an academic exercise and we were now on this system whether I liked it or not.  Over the years, the calculations fluctuated and everybody did the same job, but now we were all cast as competitors rather than  colleagues.  In the end the productivity system was just a manipulation, more hoops to jump through as management made us less and less efficient with a series of roadblocks.

The second step is to set some arbitrary rules about how individual productivity affects the entire group.  In other words, penalize everyone up front and let the group know that this "holdback" in earned wages would be paid out only if everyone  made their productivity requirements.  I have never seen that rule applied to any other group of employees.

The next step is to set up some kind of arbitrary and meaningless employee evaluations.  Solicit random anonymous comments from any staff working with the physician employee and have them defend this one-sided criticism in their annual evaluation as if it is  true.  Have the physician who is working 60-70 hours a week, teaching, and doing independent educational activities select some goal at work that they will quickly forget until the next annual review.  All of the steps so far have served to isolate physicians and create a general paranoia about who might be making negative comments about them.  Paranoia is never good for collegiality.

Top this entire mess off with a primary school disciplinary system with a very low threshold.  Nurse Cratchett says that a physicians was too "curt" with her and suddenly that physician is called into the Chief of Staff's office and told that they are a disruptive physician.   Furthermore, that physician is advised that they have "one strike" against them and if they accumulate two more strikes they are "out".  There is no appeal process or due process.  If Nurse Cratchett complains - it must be legitimate and that conclusion based solely on the opinion of one person and supported by the Chief of Staff - stands.

At this point collegiality is gone and the physicians are further isolated from other non-physician staff.   Anyone can "report" them and that report will be taken seriously whether it is true or not.  The physician-administrators are no longer colleagues but hostile flunkies of the business hierarchy.

The final step was a stroke of genius by the incompetent managers.  For about 30 years managed care companies have had physicians reviewers sitting in a different state - remotely viewing records and telling the physician who is actually treating the patient - that patient must be discharged from the hospital or in some cases treatment for substance use disorders or outpatient psychiatric treatment.  In the last 10 years managers decided to have their own on site case managers, sitting in rounds and team meetings telling the physicians when to discharge patients.  If the physician doesn't go along with them they are reported to the medical director.  That creates additional problems and possibly another accusation of being a disruptive physician.

I have been talking about this sequence of events since I started writing this blog.  I recently encountered some resistance for the first time.  A colleague suggested that since burnout in physicians in other countries exists - there must be more to it than managed care.  I think that misses the point at a couple of levels.  First, it is possible that there are other bad managers - managed care companies certainly don't have a monopoly but they are highly standardized so that the onerous management practices that you find in one will certainly exist in another.  The literature on burnout in other cultures is small at this point and in some cases non-specific.  In other cases there is clear overlap.  But as I think more about this argument it seems lacking.  It seems like finding burnout and bad management practices in other countries can be used to rationalize the existence of ultimate bad management or managed care.  Secondly, bad management of personnel is just one aspect of bad management in general.  Does management ever do anything positive from an intellectual or creativity perspective?  Apart from one physician manager, I have not seen a single positive management outcome after observing a significant number of these people.

In fact,   if managed care administrators could not treat physicians like production workers they would have absolutely nothing going for themselves.  Nothing at all.



George Dawson, MD, DFAPA



References International Physician Burnout:

1: Jesse MT, Abouljoud M, Eshelman A, De Reyck C, Lerut J. Professional interpersonal dynamics and burnout in European transplant surgeons. Clin Transplant. 2017 Apr;31(4). doi: 10.1111/ctr.12928. Epub 2017 Mar 19. PubMed PMID: 28185307.

2: Głębocka A. The Relationship Between Burnout Syndrome Among the Medical Staff and Work Conditions in the Polish Healthcare System. Adv Exp Med Biol. 2016 Dec 31. doi: 10.1007/5584_2016_179. [Epub ahead of print] PubMed PMID: 28039665. 

3: O'Kelly F, Manecksha RP, Quinlan DM, Reid A, Joyce A, O'Flynn K, Speakman M, Thornhill JA. Rates of self-reported 'burnout' and causative factors amongst urologists in Ireland and the UK: a comparative cross-sectional study. BJU Int. 2016 Feb;117(2):363-72. doi: 10.1111/bju.13218. Epub 2015 Jul 30. PubMed PMID: 26178315

4: O'Dea B, O'Connor P, Lydon S, Murphy AW. Prevalence of burnout among Irish general practitioners: a cross-sectional study. Ir J Med Sci. 2016 Jan 23. [Epub ahead of print] PubMed PMID: 26803315. 

5: Tomljenovic M, Kolaric B, Stajduhar D, Tesic V. Stress, depression and burnout among hospital physicians in Rijeka, Croatia. Psychiatr Danub. 2014 Dec;26 Suppl 3:450-8. PubMed PMID: 25536981. 

6: Misiołek A, Gorczyca P, Misiołek H, Gierlotka Z. The prevalence of burnout syndrome in Polish anaesthesiologists. Anaesthesiol Intensive Ther. 2014 Jul-Aug;46(3):155-61. doi: 10.5603/AIT.2014.0028. PubMed PMID: 25078767

7: Kravitz RL. Physician job satisfaction as a public health issue. Isr J Health Policy Res. 2012 Dec 14;1(1):51. doi: 10.1186/2045-4015-1-51. PubMed PMID: 23241419; PubMed Central PMCID: PMC3533582. 

8: Putnik K, Houkes I. Work related characteristics, work-home and home-work interference and burnout among primary healthcare physicians: a gender perspective in a Serbian context. BMC Public Health. 2011 Sep 23;11:716. doi: 10.1186/1471-2458-11-716. PubMed PMID: 21943328; PubMed Central PMCID: PMC3189139

9: McKinlay JB, Marceau L. New wine in an old bottle: does alienation provide an explanation of the origins of physician discontent? Int J Health Serv. 2011;41(2):301-35. Review. PubMed PMID: 21563626.



Saturday, May 6, 2017

Wait A Minute - Is Psychiatry Less Unhinged Than Most Other Specialties?




For the past decade psychiatry has taken far more than its share of hits on conflict of interest from both within and outside of the profession.  There are any number of bloggers that claim their reason for existence is to keep the profession honest.  Needless to say - a smug attitude like that rubs people like me and the majority of my colleagues the wrong way.  But I will go beyond that in terms of conflict of interest and have in many posts on this blog.  Unlike managed care administrators and US Senators, I believe that even physicians are entitled to be paid for the work that they do.  That includes providing CME presentations and doing consulting work - whether or not that includes payment by pharmaceutical companies or medical device manufacturers.  The only reason I do not do that, is to keep my name off the corruption list (implicit) that is currently compiled by an agency of the US government.  That list is episodically analyzed by consumer agencies who think that they are doing somebody a favor by naming any physician who gets reimbursed by industry.  My reasoning is simple - businesses and governments already have a painfully large amount of leverage against physicians -  why provide them with more?  Especially when it involves a good faith effort on your part and somebody is distorting  that effort and doing their best to make it seem like you have done something wrong. More importantly there is the frequent suggestion that a physician is aligned against the interests of their own patients.  I don't think that happens, even if a name is on that list.

This decade long campaign to compile the information has resulted in a difficult to decipher database with many errors.  It takes time to go through the data and sort it out.  It is impossible to try it on a casual basis.  It is a full time job.  The first of these disclosures came out in July of 2015 from ProPublica.   In the article, they looked at the number of days per year that a physician would receive industry payments.  They also looked at the top 20 MDs in each state in terms of payments received and in my home state there were no psychiatrists?  Wait a minute - weren't psychiatrists maligned in the press at the national level by a US Senator and also at state levels as being frequent recipients of pharmaceutical money?  In the most popular post on this blog - I point out that erroneous assumption used by a reporter to criticize the DSM-5 process at the peak of DSM-5 hysteria.  In an attempt to suggest that the DSM-5 may be swayed by the fact that the APA received money from the pharmaceutical industry the author fails to point out that the money received was less than half of what another specialty organization received.  I pointed out in a separate post that the theory that pharmaceutical company money to physicians is tied to pharmaceutical prices is equally flawed.  Taking physicians totally out of the loop results in the most expensive pharmaceuticals in the world in the USA.  That suggests that the monetary influence occurs at the level of Congress and not physicians.

The May 2, 2017 edition of JAMA has a conflict of interest theme.  Many of the articles are editorials with very predictable conclusions.  For the past decade conflict of interest in medicine has been simplified on the one hand in terms of definitions and solutions and politicized on the other.  I abstracted the table at the top of this post from one of the data driven articles (1).  They analyzed data from the CMS National Plan & Provider Enumeration System (NPPES), a database of all allopathic or osteopathic physicians with a national provider number (NPI).  The NPPES records input of all general payments, research payments, and ownership interests of these physicians.  General payments were described as all forms of payments (like speaking fees, food, beverages) other than research payments done under a written protocol.  The ownership interest was presumably in medical concerns but that was not really specified in the article.  The specific listing of specialties is available in the full text of the reference below.  My only focus here is on psychiatry.  I don't think the rankings or specific amounts have any particular meaning.

The abstracted table lists two of the end points in the article -  the percentage of physicians receiving some kind of general payment and the percentage of physicians receiving more that $10,000 per year.  The $10,000 amount was flagged by the the US Department of Health and Human Services as representing "significant conflicts of interest".  In fact, for most physicians who do consulting - it represents about 2 weeks of work.  The news for psychiatry reflected the reality that I am aware of.  Psychiatry was mentioned just twice in the article and both of those mentions were in the above highlighted table.  None of the headlines from the past decade that psychiatrists were getting more money from pharmaceutical companies than anybody else.  A little more than a third of psychiatrists got some kind of general payment with a median value of $171 (median interquartile range of $34 - 442.)  For perspective - I purchase 2 or 3 new textbooks a year that typically range $300-400 apiece.  I also subscribe to the standard online internal medicine text at a cost of $500/year.  I am not saying that the transaction involved textbooks but many do involve educational materials and I am not sure they are not added into this figure.

The second endpoint is the $10,000 figure and psychiatry is lower on this metric with 3.6 % of psychiatrists getting this level of payments.  For context, the upper end of the range for these payments is 11-12% for some specialists and the lower end is at about 1%.   Proceduralists (surgeons and interventionalists like cardiologists) tended to get the highest level of payments usually due to substantial licensing fees and ownership interests in the industry like medical imaging facilities and surgical facilities.

The authors do not draw many conclusions about the data.  They point out that there have been some concerns about accuracy.  In their conclusion section they point to other studies about connections between payments and prescribing patterns that suggest a "subconscious bias" in their decision-making.  In other words, accept a free lunch and start prescribing the medication of the pharmaceutical rep that bought the lunch.  One of the reasons I continue to read these articles is to see if the "subconscious bias" argument has any more evidence to back it up than speculation and rhetoric.  I continue to not see very much.  I have pointed out the flaws in one of their references in a previous post.  In other words there are a number of explanatory factors operating here other than "subconscious bias".  I have not seen any Manchurian candidates among my colleagues.  Physicians use a lot more discretion in prescribing medications than whether or not somebody bought them a piece of pizza.  The easiest way to avoid the brainwashing accusation is to not accept the pizza or payment for an educational presentation.  That is what I and two-thirds of my colleagues do.  When you are squeaky clean according to the US government/CMS, it is easy to develop an unrealistic idea about yourself - as if this hall of shame approach means anything.

The downside of course is that industry and medical education suffers unless there are incentives out there for physicians to do additional work.  If you happen to be a national expert in demand - will you fly back and forth across the country to educate your peers for nothing?  Maybe a time or two but not much beyond that.  If the pharmaceutical or medical device industry needs consultation from an expert - will you go to a multi-billion dollar a year business and provide your expertise for nothing?  There are no academics from any other department in any university that are expected to do that.  Another piece of the equation that is never mentioned is how physicians are reimbursed relative to the pharmaceutical industry.  An asthma specialist can see a patient once or twice a year and during that time prescribe $4,000 to $6,000 worth of inhalers.  That specialist might bill $200-300 for their professional time, but that will be discounted by insurance companies.  An argument can be made that physicians are seriously underpaid for managing expensive products and working for the industry is one way around that.  In other words - if physicians were paid for all of the high volume work that they do - they may be less interested in outside consultation with industry.

There are additional arguments about conflict of interest that nobody seems to talk about.  Physician owned medical facilities are often described as being significant sources of self referral conflict of interest.  But what are the advantages of physician ownership?  Not being managed by non-physicians would seem to be the clear cut advantage.  Would these environments provide higher quality and more professional services?  Would they be more likely to treat physicians fairly and cause less burnout?  Would they be more likely to be able to provide the full spectrum of services that their patients need?  Who has the greater conflict of interest - a physician employee of a managed care company who is paid to ration health care for the company's interest or a physician who owns the business and can provide services based on his or her idea of medical quality?  The evidence that these differences exist is widespread.                      

Finally, how much of this conflict of interest rhetoric focused on physicians is designed to control them and keep them in line?  Although there are always qualifiers about this data including its accuracy, the federal government seems to have upped the ante by their description of the $10,000 marker.  Is this the 21st century equivalent of billing and coding violations from the 1990s?  Those investigations were driven more by politics, convention and rhetoric than any wrongdoing.  I can't think of a better example of that than doing $10,000 worth of consulting work and finding out that your name is now on a list produced by the federal government and some media outlet is implying wrong doing or quid pro quo with pharmaceutical companies.

Those are the facts of the list as I see them.  There has not been much discussion of the article or the theme of this edition.  The data within psychiatry confirms what I have seen and it has never been as shocking to me as it has been typically portrayed either in the media or by groups interested in influencing physicians.

It is not shocking at all.


George Dawson, MD, DFAPA



References:

1:  Tringale KR, Marshall D, Mackey TK, Connor M, Murphy JD, Hattangadi-Gluth JA. Types and Distribution of Payments From Industry to Physicians in 2015. JAMA. 2017 May 2;317(17):1774-1784. doi: 10.1001/jama.2017.3091. PubMed PMID: 28464140.

2:  JAMA May 2, 2017, Vol 317, No. 17, Pages 1707-1812.  This entire issue is about conflict-of-interest and the link is here.


Supplementary 1:

Before sending any inflammatory comments please remember that I don't eat the free lunch or accept industry money from anybody.  Feel free to look that up on any list.

Supplementary 2:

Original form of the table.  I had to convert it to a graphic version at the top of this post.

Per Physician Value of General Payments to Allopathic and Osteopathic Physicians by Specialty in 2015
Percentage of physicians receiving general payments
Percentage of physicians receiving >$10,000
 1.
 1.
 2.
 2.
 3.
 3.
 4.
 4.
 5.
 5.
 6.
 6.
 7.
 7.
 8.
 8.
 9.
 9.
10.
10.
11.
11.
12.
12.
13.
13.
14.
14.
15.
15.
16.
16.
17.
17.
18.  Psychiatry (37.3)
18.
19.
19.
20.
20.
21.
21.  Psychiatry (3.6)
22.
22.
23.
23.
24.
24.
25.
25.
26.
26.


Supplementary 3:

Some additional points of interest from other articles in this supplement:

589,042 of 850,000 active physicians in the US received some type of general payment in 2015 with a mean value of $400 and a median value of $138.

Any physician registered at a sponsored CME event is considered to have received a payment whether they consume provided food or beverages or not.

from:  Steinbrook R. Physicians, Industry Payments for Food and Beverages, and DrugPrescribing. JAMA. 2017 May 2;317(17):1753-1754. doi: 10.1001/jama.2017.2477. PubMed PMID: 28464155.

The threshold for reporting is a $10 transfer to the physician.

"At the same time, most physicians have essentially no meaningful COI."

from:  Lichter AS. Conflict of Interest and the Integrity of the Medical Profession. JAMA. 2017 May 2;317(17):1725-1726. doi: 10.1001/jama.2017.3191. PubMed PMID: 28464163.


          

Saturday, April 29, 2017

When To Not Prescribe An Antidepressant?





I encountered that interesting question just last week.  Antidepressant medications have been around for a long time at this point and they have an increasing number of indications.  Everywhere around the Internet there are algorithms that make prescribing these drugs seem easy and automatic.  Qualify for the vague diagnosis and follow the line to the correct antidepressant. At the same time there is plenty of evidence that their use is becoming less discriminate than in the past, largely due to the use of checklists rather than more thoughtful diagnostic processes.  It is common for me to encounter people who have been put on an antidepressant based on a "test".  When I ask them what that test was it is almost always the PHQ-9 or GAD-7, checklist adaptations of DSM criteria for depression and anxiety that can be completed in a couple of minutes.  There is a significant difference between the checklists and the diagnostic process as I pointed out in a previous post about the sleep question on the checklist compared with more detailed questions about sleep.  The list that follows contains a number of scenarios that will not be accessible by a checklist.  In those cases a more thorough diagnostic assessment may be indicated.

1.  Intolerance of antidepressants - Every FDA package insert for medications includes this warning, usually referring to an allergy or a medical complication from previous use.  In addition to allergic reactions (which are generally rare with antidepressants), there a number of significant problems that preclude their use.  Serotonin syndrome can occur with low doses and initial doses in sensitive individuals.  In the case of the more potent classes of serotonergic medications - the SSRIs as many as 20% of patients will experience agitation, nausea, headaches, and other GI symptoms.  By the time that I see them, they will tell me the list of antidepressants that made them ill and that they cannot take.  It is an easy decision to avoid medications that are known to make the patient ill.

2.  Behavioral intolerance of antidepressants - SSRIs in particular can have the effect of restricting a person's emotional range to a narrow margin.  They will typically say: ""I don't get low anymore but I also don't get as happy as I used to get."  A person who is affected in that way finds that to be a very uncomfortable existence.  Many have been told that they will "get used to it" - a frequently used statement about these medication related side effects.  I have never seen anyone get used to a restricted range of emotion and I tell them to stop it an not resume it.  I avoid prescribing antidepressants form that class and that class is typically SSRIs.

While I am on the topic, I frequently use the following vignette when discussing the concept of "getting used to" side effects:

"Many years ago I treated a man who came to me who had been taking a standard antidepressant for about 7 years.  He was not sure that he was depressed anymore.  He was sure that he had frequent headaches and very low energy.  I recommended that we taper him off the antidepressant and see how he felt.  He came back two weeks later and said: 'Doc - I feel great.  For about the last 6 years I felt like I had the flu every day and that feeling is gone.'  That is my concern about 'getting used to a medication'.  It may mean that what you really get used to is feeling sick.  That is why I encourage everyone that I treat to self monitor for side effects, and if they happen we stop the medicine and try something else."

That advice sounds straightforward but it is not.  I still get people who think that they need to "get used to" a medication and will only tell me in a face-to-face interview.

3.  Lack of a clear diagnosis - many of the people I see were started on an antidepressant during an acute crisis situation like the sudden loss of a significant person in their life or a job or their financial status.  There is no real evidence that antidepressants work for acute crisis situations, but some doctors feel compelled to prescribe a medication because it makes it seem like they are trying to help the patient.  I have also heard the placebo response rationalized for these prescriptions.  A similar cluster of symptoms can be observed along with the associated anxiety, but in the short term the main benefits to be gained will be from medication side effects like sedation rather then any specific therapeutic effect.   The real problem is that the medications don't get stopped when the crisis has passed.  I may be seeing a person who has been taking an antidepressants for ten years because they had an employment crisis or divorce at that time and have been taking the medication ever since.  They have been tolerating the medication well for that time, but it now takes a lot of effort to convince them that they don't need the medication and taper them off of it.

I try to prevent those problems on the front end by not prescribing antidepressants for vague, poorly defined emotional problems or crisis situations where they are not indicated.  In my experience, psychotherapy is a more effective approach and it helps the affected person make sense of what has been happening to them.

4.   An unstable physical illness is present - that can mean a number of things.  The commonest unstable physical illness that I routinely deal with is hypertension with or without tachycardia.  Patients and their doctors will often go to extraordinary lengths to avoid treating hypertension even hypertension that is outside of the most current and most liberal guidelines.  I am told that the person has "white coat hypertension".  How do they know that is all that they have?  Have they ever had a normal blood pressure reading outside of a physician's office?  Would they be willing to purchase their own blood pressure device, monitor their blood pressures at home and bring me the readings?  I have had people become angry at me because of these suggestions, even after a thorough explanation of the rationale.  It is almost like patients expect a psychiatrist to hand them a magical pill that takes care of all of their problems.  As an example the following warning if from the FDA package insert for milnacipran but most antidepressants don't include this warning - even when they might affect blood pressure:

"Elevated Blood Pressure and Heart Rate: Measure heart rate and blood pressure prior to initiating treatment and periodically throughout treatment. Control pre-existing hypertension before initiating therapy with FETZIMA"

There are a number of conditions ranging from glaucoma to angina that need treatment before antidepressants can be safely prescribed.  In some cases I am not happy with the pharmacotherapy for associated medical conditions.  Desiccated thyroid rather than levothyroxine for hypothyroidism is a good example.  Why is desiccated animal thyroid gland being used in the 21st century instead of the specific molecule?  In many cases, I will refer the patient to see a specialist and they will never come back because their real problem has been solved.  I posted about cervical spine disease some time ago after I had a number of patients come in for treatment of depression.  What they really had was insomnia from cervical spine disease and when that chronic pain was addressed their depression resolved completely.

I will run into some situations where I insist the patient see a specialist (generally a Cardiologist) to get an opinion on safety of treatment.  This used to be called "clearance" by the Cardiologist but for some reason that term has fallen out of favor.  I think the "clearing" specialists don't want the designation, but from my perspective the patient is not going to get the antidepressant that we discussed unless the Cardiologist agrees.

5.  The patient prefers not to take the medication - I think that patients are often surprised at how easily they can convince me to not prescribe a medication.  Many expect an argument.  I will supply them with the information they want and direct them to reputable sites on the Internet where they can read as much as they want about the medication.  I am very willing to discuss their realistic and unrealistic concerns.  I will attempt to correct their misconceptions  and also provide them with my real life estimate of how many people tolerate the medication and the common reasons why people stop it.  I fully acknowledge that I cannot predict if a medication will work for them or give them side effects.  At the end of that discussion, if they don't want to try the medicine that is fine with me.  I have absolutely no investment in prescribing medication for a person who does not want it.  If the person has clear reservations, I let them know they don't have to come to a decision right in the office - they can go home and think about it and call me with their decision.  I am never more invested in the medication than the person who is taking it.  I will also provide them with feedback on whether or not their decision seems reasonable or not.

6.   Additional patient preferences -  Many people will talk with me about antidepressants and say that they want to solve their problems with psychotherapy, exercise,  or some other non-medical option.  Many people will also talk about drugs, alcohol, cannabis,  hallucinogens, psychedelics, and other drug based treatments for depression.  I can offer people what is known about the scientific basis of treatments for depression and encourage effective non-medical treatment where it is indicated.  I do not endorse the use of the use of alcohol or street drugs for treatment and let people know that I cannot prescribe antidepressant medication if those other substances are being used.  That includes "medical marijuana".  There is a risk for serotonin syndrome with various combinations of stimulants, hallucinogens, and/or psychedelics in combination with antidepressants.  Some web sites that profess to provide neutral advice to people who want to experiment will often have some posts on how to mix these medications to get enhanced effects.  None of that advice should be considered safe or reliable.  It is an indication to me that the person cannot be expected to take the prescription reliably.

7.  Context - very important consideration.  Seeing a person who has just survived a suicide attempt in the intensive care unit is a much different context than seeing a long  line of people who are dissatisfied with life for one reason or another.  Twenty three years of acute care work taught me that medical interventions are much more likely to work for clear cut severe problems than vaguely defined problems.  There are many people who are looking for a fast solution to difficult problems.  When I suggest to them that environmental factors need to be addressed or that they may benefit from psychotherapy or even more explicitly that psychotherapy will work better for your problem than medications - I am often met with resistance.  Common replies are that they cannot commit that kind of time or energy to psychotherapy.  Since most managed care companies discriminate against psychotherapy - many will tell me that their copays are too expensive.  If I point out that their work schedule or job is the problem - they will give me many reasons why they can't change it.  Treatment becomes conditional - as in - I am hoping that this antidepressant will work because I cannot change my life in any reasonable way and I can't do psychotherapy.

8.  Commitment to treatment - too many people come in and expect the prescription of an antidepressant to not only solve the problems but that nothing else is required of them except to show up for an occasional appointment.  If I want to see medical records like exams, labs, imaging studies, ECGs. EEGs, pharmacy records or other information it is generally not an option.  I need that information before any prescription occurs.  The same is true if I need to order these tests and see the results.  I am quite capable of having a discussion of the costs of these orders and that is why I have a preference for not repeating tests and looking at existing results.  That does not prevent the occasional complaints about how I am interested in making money off the person by ordering basic tests, even though I do not get anything at all for ordering tests.

The other part of treatment does involve agreeing to take the medication reliably and following the other recommendations that can be very basic.  If someone tells me that they are drinking two pots of coffee per day and they are anxious and can't sleep but are unwilling to stop the coffee because: "I know that I can drink two cups of coffee and still fall asleep" - I am probably not going to be able to do much with an antidepressant.  The same is true for somebody binge drinking a 12-pack of beer every night after work.  The effects of common substances like caffeine and alcohol are contrary to the goals of treating anxiety and depression with or without medication.

9.  Mania - it is possible for people who have taken antidepressants for years to become manic either while taking the antidepressant regularly or when the antidepressant has been disrupted.  Even though the incidence of mania from antidepressants is low and the treatment of bipolar disorder depressed includes an antidepressant-atypical antipsychotic combination (olanzapine-fluoxetine combination or OFC) stopping the antidepressant acutely is the best idea.  Many people discover at that point that mood stabilizers seem to work much better for their periods of depression than antidepressants.                              
10.  Misunderstanding the treatment alliance - fortunately treating depression and anxiety is not like treating standard medical problems.  Most office visits for new general medical and surgical problems are one or two visits in duration.  A medication is prescribed and it either works or it doesn't.  When it doesn't the problem either resolves on its own or becomes a chronic problem.  One of the best examples anywhere is acute bronchitis.  Over the past decades - tons of antibiotics have been prescribed for no good reason.  Acute bronchitis generally resolves on its own in young healthy people.  I try to be very clear with people that their response (good or bad) to the medication is in no way guaranteed.  I let them know that these medications are moderately effective at best and then only in the hands of somebody who knows how to rapidly switch them up and in some cases augment them.  Even then there will be some people who do not respond.  The key to all of that treatment is communication and it may require significant patience on the part of the patient.  It may also require more frequent appointments then they anticipated especially is associated problems like suicidal thinking and psychosis are also being addressed.

Those are my thoughts about the question of who I would not prescribe an antidepressant to.  I hope to transform those thoughts into dimensions in a useful graphic.  Feel free to let me know if I missed anything.



George Dawson, MD, DFAPA

Thursday, April 27, 2017

Marvel and Netflix Keep The Antipsychiatry Fake News Alive






I try to exercise an hour a day.  During that time I am either on a treadmill or an exercise bike.  If I am exercising in the house, I am watching television at the same time.  I watch a lot of television at the same time.  Entire series on Amazon, Netflix, or premium channels.  Some of this television can be motivating but even with all of that content bandwidth - I still find myself searching for the occasional independent film because there seems like there is nothing else out there.  About 80% of what I watch is on Netflix and a lot of that is science fiction.  The Marvel series on Netflix is a rich source of superhero type science fiction.  I noticed the latest addition The Iron Fist some time ago, but that name and the visuals were not all that inspiring.  At least until I stopped a very bad film dead in its tracks about 15 minutes in an switched over to Iron Fist.

In the opening moments we see a disheveled young man walking barefoot through New York City.  We find out that his name is Danny Rand.  He appears to be fairly naive.  At one point he announces that he is from a large family who owns a prominent building and the man he is talking to suggests that he should: "Sell the building an buy some shoes."  He tries to get in to the building to talk with Harold Meachum his father's former partner who is currently the head of Rand Enterprises.  He has to fight his way past security.  He encounters the adult Meachum children Ward and Joy.  They tell him that Harold is dead and they doubt his identity.  They say the Rands including Danny were all killed in a plane crash in the Himalayas 15 years ago.  He leaves but Ward Meachum dispatches his security forces to find Danny and beat him up or kill him.  After he dispatches the security guards he breaks into the Meachum home and eventually meets with Joy back at the company headquarters.

This is where several distinctly antipsychiatry themes start to kick in.  Joy drugs Danny and he is taken to what appears to be a small forensic psychiatric hospital.  He awakens there in five point restraints and is advised that he is on a 72 hour hold.  Over the course of that hold he is given many cups of what are supposedly psychiatric medications.  In some cases the orderly forces his mouth open with a tongue blade and pours the cup of capsules and tablets into his mouth.  On other occasions, the orderly comes  in with an absurdly large bottle of medication and draws the medication out of that bottle into a syringe and he is given an injection.  He is told that the medication is given to him so that he will "cooperate".  Cooperate is loosely defined as not becoming aggressive but also in some cases giving up the idea that he is Danny Rand.  In short, he is basically tortured on this inpatient unit.

To make  matters even worse, another patient disguised as a physician with a white coat is alone with him at one point when he is being restrained.  The viewer does not realize it at the time until this patient suggests that Danny kill himself and when that fails he sticks a fork under his chin and says he will kill him if he gives him the word.  The aggressive patient is eventually removed, but later reinstated as Danny's "tour guide" of the unit.  During that tour, he advises Danny of the folly of the 72 hour hold like this: "He was living under a bridge and came in here on a 72 hours hold.  Now he has paranoid personality disorder and he has been here for 5 years.  He was living on the street and came in on a 72 hour hold.  Now he has schizoaffective disorder and has been here for 3 years."  He simultaneously points out the folly of the 72 hour hold and suggests that people are just plucked off the street, labelled and stuck in a locked psychiatric facility for a long time.  In the span of 5 or 10 minutes we have seen a homicidal patient disguised as a doctor, threatening to kill the superhero, and then becoming a tour guide who is an expert commentator on psychiatric injustices!

Dr. Paul Edmonds is the psychiatrist on the floor.  He is pleasantly coercive at first.  He seems generally clueless about assessing acute care psychiatric patients and interacting with them.  He finally catches on that Danny Rand is who he really says that he is and acts professionally for a brief period of time.  He almost gets to the point where he will release Danny, but decides against it when he hears about how Danny is a Warrior Monk who is in possession of the power of the Iron Fist.  At that point Harold Meachum who has been watching all of the events in the psychiatric unit remotely and who has concluded that Danny is the real Danny Rand - sends in his security to take Danny out of the hospital.  In the finale to episode 2, Danny summons the Iron Fist power to dispatch the security guards who were beating him mercilessly and with a single punch - knocks down a large metal door confining him in the hospital.

There are numerous cliches about psychiatric treatment that are obvious in this episode.  The first is that psychiatric treatment is about social control.  In this case the Meachums have a problem when Danny shows up.  He owns 51% of the company stock.  They get him out of the picture by drugging him and taking him to a psychiatric hospital.  I have never seen that happen.  In real life, if a person in the emergency department shows up there drugged and points out that somebody did this to them, the police would be dispatched to pick them up for assault.  The associated dimension here is that the psychiatrist and the hospital are working for the Meachums and doing their bidding at least until Dr. Edmonds finally refuses to provide Joy confidential information on Danny.  In my 23 years of inpatient work, treatment was focused on the best interests of the patient, and confidential information was not provided without consent.  Forced treatment was portrayed in as heavy handed a manner as possible.  The patient was drugged to the point that he was "in control" and in one situation ready to cooperate by accepting a false identity.  Dr. Edmonds also appears to lack skill at two levels.  It takes him too long to find out who Danny really is and them it seems only by a bit of luck.  When he finally does that, he is unable to assess the patient's superhero story (trained warrior monk from the Mother of the Crane order in the mythical K'un-Lun that appears from another dimension once in every 14 years), see it for what it is and release him.  Any inpatient psychiatrist has seen and discharged their share of superheroes.  Delusional or not - treatment depends on local legal convention and the bias is heavily stacked toward no treatment by the courts and business systems.  Businesses don't want anybody spending any length of time in a psychiatric hospital whether they are stable enough for discharge or not.  But I suppose that is a far less dramatic premise than psychiatrists and psychiatric hospitals detaining people and torturing them.

At no point do we see legal representatives and representatives of the court to protect the civil rights of anyone who is on a legal hold or subject to involuntary treatment.  The viewers have to suffer through another skewed treatment of psychiatric care and an unenlightened view of the containment function of psychiatric units.

There is a clear mischaracterization of acute care or inpatient psychiatric units.  Anyone experienced with psychiatric disorders and severe addictions realizes that there are some mental disorders where the person's ability to self correct is gone.  That results in uncharacteristic behaviors that can include aggression, suicide, self-injury, and a long list of high risk behaviors that endanger health and life.  A common example is mania without psychosis.  The manic person can carry on a coherent conversation but may have been hospitalized because his or her judgment and decision-making was greatly impaired by the manic state.  A consistent treatment environment is required to assist that person in getting back to their stable mood and decision-making.  Having an appropriate treatment unit available can prevent life altering events that can be associated with severe mental disorders.  When I refer to a containment effect - it means providing a safe environment for these changes to occur and there are multiple pathways to stability.

I know a lot of people will say it's just a television show.  It is a television show with considerable viewership in a country with meager resources for psychiatric treatment.  It is a television show in a country that is a mill for antipsychiatry fake news.  It is also part of an ongoing process that stigmatizes people with mental illnesses and psychiatrists.  You only have to look as far as network television and Gotham or American Horror Story to find an equally grim depiction. It seems that the default horrifying and anxiety producing storyline is to go back to the old myth of the psychiatrist as bogeyman.

The treatment situation is so desperate that in current politically correct times - people with mental illnesses, their families, and doctors need to be treated realistically just like it would occur with any other disadvantaged minority.            

Get real with portrayals of mental  illnesses, psychiatric treatment, and psychiatrists and drop the unnecessary drama and distortion.  It deters people from seeking the safety and treatment that they need and keeps politicians and the businessmen in charge of medicine and cutting psychiatric services to the bone.

It's the 21st century and it is time to wake up and realize that there is an enlightened approach to these problems.



George Dawson, MD, DFAPA        

 

Sunday, April 23, 2017

Is Diet Soda A Biohazard?









I woke up to a scary story about diet soda several days ago.  At least I thought it was scary.  It was clear at some point the the reporter had lost track of what the story was all about and was talking about regular and diet soda as being interchangeably toxic.  I can see how that might happen, since most of the recent soda scares have focused on regular soda or as it is referred to "sugary" soda.  Sugar is the current hysteria and it must be eliminated.  The media routinely informs us that for years cholesterol and fat were vilified and now we have that all wrong.  Fat and cholesterol are now acceptable and sugar is the villain.  To complicate matters, the message is to consume large quantities of colorful fruits and vegetables - 6 - 8 servings a day.  The problem is those colorful fruits on a serving per serving basis generally contain as much sugar as "sugary" soda.

The latest story was presented as they all are - a news headline rather than a work in progress. News flash - drink diet soda and you will get Alzheimer's Disease or a stroke.  In fact - drink as little as 1 can per day and get a stroke.  A few news outlets, talked about the other part of the story - consuming those sugary drinks in the same study did not increase the risk for dementia or stroke.  But even then it was presented in way to keep the hysteria going: "That does not mean you should start drinking those sugary soft drinks?"  Really - why not?  You just told me they don't cause strokes or Alzheimer's Disease.  Oh that's right - they contain that well known toxin - sugar.

Time for some self-disclosure in the interest of transparency before I get to the real story.  I eat a lot of sugary foods.  I like just about every imaginable kind of desert.  I am generally averse to vegetables unless they have a starchy consistency. I have consumed massive amounts of soda and diet soda in my life time.  I realize that everybody has a story of the outlier who beat the food and health odds.  "Grandpa smoked two packs of cigarettes a day and died at 95 of old age" or "Grandpa ate raw bacon every day and died at 95 of old age."  That is not my point here.  As a physician, more than anybody I know better than to challenge medical common sense and hope to survive it.  I happen to be a health nut who consumes junk food.  I don't eat meat, fat. or cholesterol and I exercise a lot.  If I had to guess where the proclivity for sweet consumption comes in - I would attribute it to the Scandinavian side of my genome - cookies, pies, cakes, donuts with coffee of course.  So I am not here to defend or vilify sugar or artificial sweeteners.  In fact, I would definitely try my hardest to stop consuming this stuff if it was really a biohazard.

With that self disclosure, the real story in this case is easy to find and publicly accessible.  There is not only the original research article but an editorial.  To keep myself honest, I wrote about the article without reading the editorial first. but did read it.  The original article and the editorial are references 1 and 2 respectively and full text is available.  One of the associations I automatically have when dealing with food headlines is the Framingham Study.  This study was big when I was in medical school.  It offered the first exposure to epidemiology and risk factor analysis in cardiovascular pathology.  That was built on in the epidemiology course where several of the professors were experts.  There were board exam questions based on a knowledge of this study.  Generations of physicians have studied papers based on this study and probably react to the cardiovascular risk factor headlines the same way that I do.  I was mildly surprised to see that this study of diet soda and sugar sweetened drinks was based on the Framingham Study.

In this case the researchers looked at the Framingham Heart Study Offspring cohort.  That study began in 1971 with 5124 volunteers.  The participants are studied in examination cycles about every 4 years.  To date that means there have been 9 cycles so far with the last one occurring in 2014.  For the purpose of this study, they looked at the 10 year risk of stroke and dementia beginning with the 7th cycle (1998-2001).  A total of 3539 subjects were available at exam 7 and 3029 completed the Food Frequency Questionnaire (FFQ).  That population was split based on age and other criteria to an arm that was to be analyzed for 10 year risk of of incident stroke (N=2888) and another arm that was to be sampled for 10 year risk of incident dementia.  The FFQ was used to determine total sugary beverage consumption, sugary sweetened soft drink, and artificially sweetened soft drink in various rates of consumption where one can or bottle equaled one drink.  Answers at exam cycle 7 were used to measure recent intake and averaged responses over exams 5,6, and 7 were used to calculate cumulative intake over 7 years.  This was a prospective study, so time to stroke or dementia (using standard definitions) was done over the next ten years (from examination cycle 7).  The total number of events form the article are listed below.  The article contains tables detailing all of the demographic details by cohort and by consumption of sugary or artificially sweetened drinks.  The authors also present 10 year survival curves for both the stroke and dementia cohorts.  About 53% of the sample drank at least 1 artificially sweetened drink per week with 18% drinking more than one per day.

  
Stroke Cohort
Total Events (all strokes)
Ischemic Stroke
Recent Intake
N=2888
97
82
Cumulative Intake
N=2690
87
72

Dementia Cohort
Total Events (all cause dementia)
Alzheimer’s Disease
Recent Intake
N=1442
81
63
Cumulative Intake
N=1356
75
57

The main finding was that consumption of any amount of artificially sweetened soft drinks was associated with risk of stroke in both the case of recent (HR 1.88-2.17) and cumulative intake (HR 1.75-2.20).  Drinking greater than or equal to 1 artificially sweetened soft drink was associated with increased risk of all-cause (HR 2.28) and Alzheimer's dementia (HR 2.48) but only in the cumulative intake mode.

 They controlled for two major variables - hypertension and diabetes mellitus are immediately relevant for both strokes and dementia.  Controlling for diabetes mellitus, intake of artificially sweetened beverages remained a significant predictor of stroke, all cause dementia and Alzheimer's dementia but diabetes was found to be a partial mediator of the effect.  Excluding people with hypertension decreased the effect of artificially sweetened drinks on all strokes.

This was a very well done prospective study.  The HRs for artificially sweetened soda and stroke risk appear to be robust nearly doubling the rate across the board.  There is also a dose related effect with the HRs for subjects drinking ≥ 1/day artificially sweetened drink being a greater rate than those drinking > 0-6 drinks/week.  For dementia, significant HRs were noted only for cumulative intake of ≥ 1/day.  The authors do a good job of listing the limitations of the study. They point out that there were no ethnic minorities and that limits generalizability to populations of non-European decent.  While that is true, it may also be true that the study is not generalizable to other white populations.  They provide the usual disclaimer about causality from observational studies.  They discuss recall bias on the FFQ, but they previously discussed validity of recall of Coke/Pepsi product in the range of 0.81-0.85.  They mentioned undetermined confounding variables.  They also did not adjust for multiple comparisons which is surprising in a study with this many variables.  That seemed to be the weakest methodological link

When I thought a bit more about the study, there was no clear mechanism of why strokes and dementia would be produced by artificial sweeteners.  They discuss theories about how these compounds have been implicated as increasing cardiometabolic risk factors.  The other factor is that several of these compounds have been consumed by the public for over 50 years.  The FDA provides information that some of the compounds have been extensively studied for safety in both animals and humans.  Is it possible that the FDA missed some excessive cardiovascular, cerebrovascular or dementia mortality due to high-intensity sweeteners?  Their approach seems to be to suggest an average daily intake (ADI) of these compounds and suggest that consuming that amount over the course of a lifetime is safe.

The other main factor that affects how physicians think about these studies is whether or not there is supporting or contradictory data.  This paper lists the  Nurses Professional and Health Professionals Follow-Up Study that showed that both artificially sweetened and sugar sweetened soft drinks were both associated with a higher risk of stroke over 28 years of follow up for women and 22 years of follow up for men.  The sample size was large (women N=84085 and men N=43371).  The pooled Relative Risk of stroke was 1.16 and the authors suggest drinking decaffeinated coffee reduced risk.  The authors also listed the Northern Manhattan Study (N=2564) that showed that artificially sweetened soda increased the combined risk of vascular events but not stroke.  In the editorial, the authors list two negative studies.  In the first, there was an association between coronary heart disease and biomarkers of coronary heart disease for sugar sweetened beverages but not artificially sweetened beverages (6).  The second study (7) showed the identical result with risk for sugar sweetened but not artificially sweetened beverages.  

I am always skeptical of the results of studies with many variables and clear-cut effects - at least until they are replicated.  This is a good study that will be quoted for years.  You can't believe what you hear in the media about it - but to physicians and researchers it raises significant questions.  I think that it is useful to known this literature in order to discuss it with people who need to take specific medications that increase their cardiometabolic risk like atypical antipsychotics.

At a personal level, the question is what if anything should be done?  It is clear that although the study points to increased risk, the majority of the research subjects who ingested diet soda did not experience an adverse outcome during the test period.  Doing a basic literature search shows that there are many epidemiological studies looking for various adverse outcomes from artificial sweetener exposure and few positive findings.  I will take it as a sign that I need to get more disciplined in terms of my intake of high intensity sweeteners as well as sugar.  Why take something toxic if there is even a theoretical risk?  The answer of course is preferences over time and those preferences die hard.

Wish me luck.



George Dawson, MD, DFAPA


References:

1: Pase MP, Himali JJ, Beiser AS, Aparicio HJ, Satizabal CL, Vasan RS, SeshadriS, Jacques PF. Sugar- and Artificially Sweetened Beverages and the Risks of Incident Stroke and Dementia: A Prospective Cohort Study. Stroke. 2017 Apr 20. pii: STROKEAHA.116.016027. doi: 10.1161/STROKEAHA.116.016027. [Epub ahead of print] PubMed PMID: 28428346

2: Wersching H, Gardener H, Sacco RL. Sugar-Sweetened and Artificially Sweetened Beverages in Relation to Stroke and Dementia: Are Soft Drinks Hard on the Brain? Stroke. 2017 Apr 20. pii: STROKEAHA.117.017198. doi: 10.1161/STROKEAHA.117.017198. [Epub ahead of print] PubMed PMID: 28428347.

3: Kissela BM, Khoury JC, Alwell K, et al. Age at stroke: Temporal trends in stroke incidence in a large, biracial population . Neurology. 2012;79(17):1781-1787. doi:10.1212/WNL.0b013e318270401d.

4: Barraclough H, Simms L, Govindan R. Biostatistics primer: what a clinician ought to know: hazard ratios. J Thorac Oncol. 2011 Jun;6(6):978-82. doi: 10.1097/JTO.0b013e31821b10ab. Erratum in: J Thorac Oncol. 2011 Aug;6(8):1454. PubMed PMID: 21623277.

5: Bernstein AM, de Koning L, Flint AJ, Rexrode KM, Willett WC. Soda consumption and the risk of stroke in men and women. Am J Clin Nutr. 2012 May;95(5):1190-9. doi: 10.3945/ajcn.111.030205. Epub 2012 Apr 4. PubMed PMID: 22492378.

6: de Koning L, Malik VS, Kellogg MD, Rimm EB, Willett WC, Hu FB. Sweetenedbeverage consumption, incident coronary heart disease, and biomarkers of risk in men. Circulation. 2012 Apr 10;125(14):1735-41, S1. doi: 10.1161/CIRCULATIONAHA.111.067017. Epub 2012 Mar 12. PubMed PMID: 22412070.

7: Fung TT, Malik V, Rexrode KM, Manson JE, Willett WC, Hu FB. Sweetened beverage consumption and risk of coronary heart disease in women. Am J Clin Nutr. 2009 Apr;89(4):1037-42. doi: 10.3945/ajcn.2008.27140. Epub 2009 Feb 11. PubMed PMID: 19211821.




Attribution:

Image at the top is from Shutterstock per their standard license agreement.  Title is:
"Yellow tin for drinks with a symbol of biological danger" by Liusa.


An Experiment (7/29/2017):

Consistent with my above statement - I took a bottle of my current favorite soda and diluted it by 1:1 with carbonated water.  There was no appreciable degradation of flavor or carbonation.  That is a reduction of 190 to 95 calories/16 ounce and 50 g to 25 g sugar (One teaspoon of sugar is 4.2 grams).  I did the same thing with a 3:1 dilution.  It was slightly more watery but still a reasonable taste.

I have used this technique for years with fruit juices in order to avoid the high sugar content and it can clearly be applied to colas with the same result.