Thursday, December 17, 2015

Antidepressants in Pregnancy: Autism Risk?

On December 14, 2015, Boukhris, Sheehy, Mottron, and Berard published a paper in JAMA Pediatrics which described their  study of the association between autism-spectrum disorders and exposure in utero to antidepressants.

They looked at all women who had pregnancies in Quebec between 1998 and 2009.  These 186 165 women have been followed prospectively in the Quebec Pregnancy Cohort (QPC).  The authors looked only at those infants born at full term; all antidepressant exposure was recorded, and there was up to 11 years of follow-up. 

They found that 3.2% of all infants born to this cohort were exposed to antidepressants in utero.  Of those infants who had this exposure, 46 later received a diagnosis of an autistic-spectrum disorder (1 %).  More specifically, among those exposed in the second or third trimester, there were 31 autistic-spectrum diagnoses (1.2 %).   Among those infants with no in utero antidepressant exposure, 1008 later received an autistic spectrum disorder diagnosis (0.7 %).

When the diagnoses were restricted to those made by a neurologist or psychiatrist, the findings remained positive, but with reduced statistical confidence.


Other factors, such as maternal history of psychiatric disorders, mother living alone, maternal gestational diabetes or hypertension, were also positively correlated with the infant later having an autistic-spectrum disorder diagnosis.

A major weakness of the study was that it did not have a detailed analysis or discussion of autistic-spectrum symptoms (even subsyndromally) in the parents or other relatives of the infants.  They state "although our sample size is large, the size decreased substantially in stratified analysis on family history of ASD, which led to decreased statistical power."  And they observe that "those using [antidepressants] were...more likely to have had another child with ASD than those not using ADs", but did not expand on this finding.      The most likely contributing factor towards autism-spectrum phenomena would be the presence of these same phenomena in the family, which would be heritable.   It is possible that the presence of this hereditary factor could have been an underlying cause for the heightened risk which they observed.   This same risk factor could theoretically have contributed to the mothers using antidepressants more frequently during the pregnancy.

Another weakness of the study concerns the use of the "autism spectrum disorder" diagnostic label.  The use of this label is more frequent nowadays.  The degree to which it is appropriately considered a "disorder" could be subject to debate about criteria or severity.  For example, with the "autism spectrum quotient" questionnaire,  criteria such as "I don't like reading fiction,"  "I am fascinated by numbers," and "I would rather go to a library than a party" increase the score towards an autism diagnosis!  It seems much more important to restrict such a label to some kind of marked social, behavioural, or communicative problem, rather than intellectual or recreational preferences.   Enjoyment of libraries should not lead to a DSM label! 

Another related confounding factor could be that someone who has taken antidepressants might be more likely to have their children assessed by someone able to "diagnose."   It could be that if an autism questionnaire was administered to every child in the cohort, then 1.2% (rather than 0.7%) of the entire cohort could meet some "autism spectrum" threshold.  Perhaps the increased incidence in the group who had taken antidepressants is simply due to these mothers having a higher likelihood of asking for their children to be assessed.   In order to determine whether this is true, we would have to ensure that every child in the cohort received the same type of assessment, including the same questionnaires (such as the "autism spectrum quotient").   But in this study, this was certainly not the case. 

While the authors find that SSRIs in particular were associated with increased ASD incidence, with minimal associations from other antidepressant classes, it is notable that there were far too few cases of  non-SSRI antidepressant exposure to make any reliable statement at all about non-SSRI antidepressants.   Therefore, they should remove the implied message that only SSRIs are involved with the association. 

Nevertheless, it is an important study with a very large cohort.  We must be vigilant about the possibility of risks for giving any medications, particularly in pregnancy.

If, in future studies, this difference in autism incidence is found to be directly caused by antidepressant exposure, the evidence here shows that the risk increases from 0.7% to 1.2%.  Posed differently, the probability of not having an autism-spectrum diagnosis changes from 99.3% to 98.8%.


In some cases, the risk of severe depression in pregnancy could outweigh the risk of a treatment causing harm, but this would need to be carefully evaluated and discussed.   A question to ask in this situation would be whether the antidepressant is specifically required for treatment of the depression.  In some cases, it might indeed be very helpful, with a much higher likelihood of depressive symptoms, and various adverse outcomes for mother and child, without it.  But in other cases, despite high depressive severity, the antidepressant might not clearly be an imperative component of the therapy.  Perhaps in some cases other treatment modalities could be sufficient, at least during the pregnancy.  It depends on the specific case or situation.  

I am bothered by the author's concluding remarks in their abstract; the remarks assert causation, despite the findings really being associative:  they say "use of antidepressants...increases the risk of ASD in children."  It would be more appropriate for them to have said, as they were more careful to do elsewhere in the body of the paper, that "there is an association between antidepressant exposure in utero and subsequent ASD diagnosis."

In any case, it is not controversial to assert that all possible non-medication strategies should be optimized in the treatment of depression, particularly in pregnancy.  This includes promotion of healthy lifestyle factors, careful attention to social and community support, and psychotherapy.   



Monday, December 14, 2015

Changes in Psychiatric Culture -- Wait Lists, "Efficiency," and Superficial Care

Psychiatrists are more commonly offering the following services:

1) "Assessment":  This is a single 1-hour interview, yielding an obligatory report with diagnostic label, and treatment advice.  In some places, this single interview is all the psychiatric input that is offered.

The single assessment has rich prececents in other areas of medicine.  For example, a visit to a dermatologist could yield a very accurate and fruitful diagnosis of a specific type of chronic skin disease, leading to a clear set of instructions for safe and effective treatments.  In many cases, it would  not be necessary to see the dermatologist regularly after this assessment, unless the treatment regime was going very poorly.

But psychiatry and dermatology are quite different!   Despite our attempts to have a reductionistic and medicalized diagnostic scheme in psychiatry (e.g. the DSM-V), we see that two different people with the exact same diagnosis frequently do not follow the same pathway of symptom progression. Identical treatments do not work in identical ways with different people.

Furthermore, I believe it is an act of significant hubris to assume that one can effectively "diagnose" someone, with respect to issues touching on a person's entire history of self, character, emotion, and intellect, following a single one-hour visit.   The "first impression" from a first interview can be very important to understand a person's life and problems, but as we all know, first impressions can very, very often be inaccurate or incomplete.  For some people, it could take weeks, months, or even years, to share their story. 


Yet, this pattern of assessments may, on paper, appear to be very efficient.  One could "manage" wait lists much more quickly.  The problem is that a single assessment is actually not very useful, despite yielding an official-looking report which appears useful.   Offering single assessments only is similar to a teacher offering a single day of school to each of 4 000 students, rather than a whole year of daily teaching for a classroom of 20.   Another insidious consequence of the apparently "efficient" pattern of doing multiple "assessments" is that the therapist, or teacher, who may have a great joy and talent for deeply helping people in an ongoing collaborative relationship, may instead not really get to help anyone very much, leading to sinking morale and rising cynicism.  Burnout would probably follow, much more often.  But the paycheque would not go down -- it would actually be higher (in psychiatry, the fees for assessments are about 25% higher than for spending the same length of time offering a follow-up therapy appointment).  

Many of the patients I have seen have had an incredible, audible sigh of relief, when they have discovered that I am actually going to make time to see them regularly!   There is often some sense of surprise that I do not focus on diagnostic labels.   The experience of mental health care, for many, has been one of shuttling between various short-term groups, superficial courses of CBT in a sort of group lecture format, brief one-on-one followup which ends just as a deeper sense of trust is forming, and medication trials with primary care doctors.   

2) "Medication management visits":  In many cases, psychiatrists do not offer what could be called "psychotherapy."  Instead, patients are seen for a few minutes,  to discuss medication doses.   These visits could possibly be more frequent if the patient is not doing as well.  It is understandable to have such visits, for people who are wishing to take medication.  In clinics serving those who have major mental illnesses, who are taking complex medication combinations, this type of service is undeniably important.   Other types of psychotherapy or health care may be happening elsewhere.  But if this is the only style of visit which psychiatrists are offering, it creates a frame in which medication use is implied as a norm.  Why would you have a "medication management visit" if you didn't want or need medication?  From the psychiatrist's point of view, why discuss other matters, such as relationships, goals, dreams for the future, etc. unless it pertains to the medication management plan?  The frame leads to an atrophy of therapeutic skill.  I think it is a serious problem if psychiatric visits are framed with an expectation of medication management, particularly when we know what an incredibly, strongly loaded set of biases exist around medication use and marketing.  The medication management visit framework is surely designed to "optimize" the use of psychiatry, in a setting of long wait lists and shortages of care, but in setting things up this way we are inviting a possible massive deterioration in the quality of care.  I note again, that psychiatrists using the provincial fee schedule receive a large financial gain by seeing larger numbers of patients for briefer, more superficial, medication-oriented visits.  The decrement in the quality of care may tragically not be noticed in the short term, because wait lists would be shorter, appearing to be beneficial. 

Also, "improved" wait list management may cause an external observer to assume that the system has been "fixed," therefore delaying more substantive systemic changes.  

In a further sort of game-theoretical analysis of these evolving trends, I believe that there are even more adverse consequences:   because of the changing culture of the type of psychiatric practice which is considered a norm, the profession itself will attract those who are most comfortable offering this style of service.  Those wishing to do more psychotherapeutic work, or having more skepticism about medicalized psychiatry, would feel ever more part of an eccentric minority, and might choose not to enter a psychiatry residency in the first place.    So psychiatry would become even more "medicalized" with time, in a form of evolutionary selection process.  


Ideas for Positive Change:

1) Wait list management.
a)  The public health system in Canada, and possibly private insurers elsewhere in the world, could simply fund private non-medical psychotherapists.  Therapy visits with a psychologist or other counselor could be covered under the public medical services plan.  This could reduce psychiatry wait lists dramatically, while also helping the many psychotherapists who are ironically struggling to make a living, despite there being a massive population need for their services.  For a large institution such as a university, if there were extra funds to spend on mental health, these funds could be spent on providing service availability with local therapists, personal trainers, music & art therapists, pet therapists, gym memberships, etc., rather than spending money on expensive new buildings and other infrastructure.   People help people.  Buildings don't help people much, despite appearing to do so.  

b) Non-medical psychotherapists could be allowed to prescribe medication, at least in a very limited way.    I am not meaning to suggest this as a way to increase medication use!  I suggest this to defuse the power dynamic which currently exists among psychiatrists and other physicians.   The basics of psychiatric medication prescription do not require many years of medical education to understand and manage safely.  In fact, the many years of  education may simply consolidate a culture of medication use as an often unnecessary norm.  If there would be less pressure on psychiatrists and other physicians as the sole prescribers of medication, then there could be an opportunity for psychiatrists to be less focused on medication, and therefore more focused on therapeutic alliance.

2) Style of Practice
Here, I think it is very simple:  make time for people!  Doctors, make time for your patients!  Be willing to see them!  I am less concerned about what style of psychotherapy or other tactics.   I am more concerned about being present, collaborative, empathic, and available.   We should be well-informed about medications, and about therapy styles such as CBT, but we should focus most of our attention on very basic matters of building rapport, trust, and working alliance, without fear of the relationship being cut off.