How Antidepressants Should be Prescribed

 

As psychiatrists are pressured by various business interests to see more and more patients in less and less time, more and more shortcuts have come into practice. Not a good thing. Especially when it comes to anti-depressant prescribing practices. The drugs have become way over-prescribed, and antipsychotic medications are added to them for "augmentation" far more often than necessary. I’ve spoken about the use of symptom checklists, which are screening tests and not diagnostic tests, being used to make diagnoses.

Another recent development has been companies that offer various “genetic testing” to try to predict which medications might work best in a given patient, or what side effects they are likely to get. For example, GeneSight Psychotropic offers a “pharmacogenomic” test which means that it analyzes how your genes may affect medication outcomes. They say: “The GeneSight test analyzes clinically important genetic variations in your DNA. Results can inform your healthcare provider about how you may break down or respond to certain medications commonly prescribed to treat depression, anxiety, ADHD, and other psychiatric conditions.”  

The problem with these tests is that their predictive validity is actually quite poor – even the company admits that “It is important to note that not all patients who received a GeneSight Psychotropic test experienced improved outcomes.”  According to two docs at the NYU School of Medicine, "The tools were developed using small sample sizes, focusing on specific patient populations...and were not tested in real world settings different from the one in which they were developed."

The tests are IMO a waste of money.

Because people are so complicated biologically, psychologically, and socially, I think a far better way for docs to decide which meds to use is to use pattern recognition: Doing a wide-ranging diagnostic evaluation and looking at what factors suggest certain courses of action.

Let’s start with the diagnosis of major depressive disorder. That diagnosis has to be based on a variety of considerations. Symptoms must be pervasive (almost all day every single day, even if you suddenly win the lottery. I exaggerate, but only slightly) and persistent (at least two straight weeks), and the patient’s functioning and stress responses must be significantly different that their norm. (Antidepressants do not work on chronic unhappiness). All symptoms must take place at the same time – having no appetite on Monday and poor sleep on Thursday does not cut it.

If it’s a patient’s first episode, another big issue is that there is no way for the doc to be absolutely certain that it is not a first episode of bipolar disorder rather than a unipolar depression. This is important because if the doc prescribes an antidepressant to a bipolar patient, it can trigger a manic episode – with disastrous consequences. So what is a doctor to do to make sure that doesn’t happen?

Family history is important, since bipolar disorder usually runs in families. If a patient has a family history, the doctor has to be more careful. The problem is of course that the patient might not know if he or she even has a relative who had a manic episode. So what does a good doctor do? In addition to asking about family history, the doc should carefully review the patient’s history for any symptoms suggestive of the disorder. These symptoms should not have occurred only when the patient was high on cocaine, or during a rage reaction upon having found out that the their spouse and best friend were having an affair!

Next, the doc warns the patient about the bipolar issue, and informs patients that in the event of suddenly feeling revved up, they need to STOP the antidepressant and call the office immediately. This instruction can be given at the same time as the doctor describes all possible major side effects with instructions on what to do should they occur. Then, the doctor needs to have the patient comeback for a scheduled follow up visit, preferably within two weeks.

Now, about picking an antidepressant with which to initiate treatment. As I mention, genetic testing is not particularly valuable. It’s always a bit of a crap shoot because a patient’s presentation may be somewhat atypical, but if the doc takes a complete history, it can suggest which agent to try first. If the patient has some obsessive-compulsive qualities, an SSRI like fluoxetine  or escitalopram is a good first choice. If in addition to that there is a lot of anxiety, the SSRI paroxetine is usually the best choice. If the patient has chronic pain, then duloxetine is usually a good starting point. If sexual side effects are a big concern, buproprion is usually the place to start.

Next, the doctor raises the dose of the medication every three to four weeks until there is a response, or it reaches the maximum dose, or until side effects become too big a problem. At this juncture, the doctor should NOT add another, different class of medicine to “augment” the antidepressant, as is suggested by a lot of Pharma commercials. If there has not been a good response to the first drug, the anti-depressant should be stopped, and a trial of a second antidepressant should come next. And again, if no response, a third one. There are diminishing returns here but eventually most patients will have a decent response. If they do not, then than and only then should an augmentation strategy be instituted. Or the diagnosis may need to be re-evaluated.

Close follow up. Close follow up. Close follow up.

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Family Dysfunction and Mental Health Blog has been selected by Feedspot's panelist as one of the Top 100 Psychology Blogs on the web.

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Are Effects on Brain Development Due to Psychological Trauma in Childhood Permanent?

 

Romanian children who had been stuck in orphanages in which they had almost no direct interactions with their caretakers had been studied extensively by a group of researchers, as described in the book Romania’s Abandoned Children: Deprivation, Brain Development, and the Struggle for Recovery  by Charles A. Nelson, Charles H. Zeanah, and Nathan Fox.

Generally, the longer these children were in the orphanages, and the earlier they got there, the more damage to their cognitive abilities, social skills, and stress tolerance there was later in childhood after they were adopted by foster families. Some of them even showed reduced circumferences of their skulls. Hard to imagine that was not permanent damage. Most affected children did seem to show some recovery in their development after adoption, but did not seem to get back completely to normal. 

They were not followed much past adolescence in the original study. However,  according to a follow-up study described by the BBC, many of these young children adopted by UK families in the early 90s are still experiencing mental health problems even in adulthood (https://www.bbc.com/news/health-39055704).

Despite being brought up by caring new families, this newer long-term study of 165 Romanian orphans found emotional and social problems were commonplace. Initially, all 165 had struggled with developmental delays and malnourishment. While many who spent less than six months in an institution showed remarkable signs of recovery by the age of five or six, children who had spent longer periods in orphanages had far higher rates of social, emotional and cognitive problems during their lives. 

Common issues included difficulty engaging with other people, forming relationships, and problems with concentration and attention levels which continued into adulthood. This group was also three to four times more likely to experience emotional problems as adults, with more than 40% having had contact with mental health services. Despite their low IQs returning to normal levels over time, they had higher rates of unemployment than other adopted children from the UK and Romania.

Interestingly, one in five of them seemed to have been unaffected by the neglect they experienced. A small percentage, to be sure, but if the types of experiences these children had cause permanent brain damage, how is this even possible?

In current literature about the effects on the brain of trauma, the common opinion expressed by experts is that they are irreversible. Brain changes that are seen in various neurological evaluative procedures - such as different brain scans - do not seem to go away.

I, on the other hand, have theorized that the effects of trauma on the brain may be reinforced by continued interactions with primary attachment figures, whether they be natural or adoptive parents. If this is going on, the brain changes would not go away. Neural plastic changes leading to this would not happen.

But, people may say, many of these traumatized Romanian orphans were adopted into loving families! If what I believe may be true actually is true, why do scars remain in 80% of these orphans?

Answering this question definitively is extremely difficult to do. Surely, due to variations in the genetics of the orphans, some may have been more vulnerable to permanent brain damage than others. I mean, smaller skulls? But again, on average, and not in all of them. Also, the experiences of the orphans in the orphanage probably varied significantly, with a few of them possibly exposed to more helpful caretakers than the others.

What is rarely discussed is how difficult it is to raise children who have been traumatized in the way the orphans had been. They were difficult children with huge behavior problems, and how to provide proper boundaries in a loving manner is something that many parents of very normal children have difficulty doing. No matter how well intentioned the parents may be. Some of these parents might get help from knowledgeable family therapists, but most do not. So in some ways, the children may be continuously further traumatized by angry and frustrated parents who don’t have a clue as to how to best interact with them.

In the original study, there was some preliminary evidence that interventions by therapists with the adoptive parents were helpful, but such interventions did not usually take place. Even when they did, the quality of therapy the parents receive could vary widely.

So addressing the family dynamics of these adoptive families of adult survivors of the Romanian orphanage, so that these behavioral and cognitive deficits are no longer being triggered and reinforced, might possibly lead in many cases to a reversal of both the psychological deficits as well as the brain changes caused by the original trauma.

I like to think so.