There’s Something About Pregnant Mary

A recording of the full FDA Panel on SSRIs and Pregnancy is linked to the last post here.  There has been extensive media coverage of this event – and 18 takes on what reporters heard can be found linked to Unsafe Safety Systems on RxISK.  

Roger McFillin was on thin ice, at the recent FDA Panel on SSRIs and pregnancy, when he told us that women have emotions and maybe should not go along with a system that suppresses their emotions by labeling them as a disease for which we have no diagnostic test and no great evidence any medicines work.

If what Roger is referring to are emotions, they are emotions of distress. No woman is going to thank a man for telling them to put up with distress. Or telling them to avoid messages saying they can be helped. See Damsels Dying from Distress or Dysphoria. So do women have diseases or distress?

Disease or Distress?

We have very little evidence pregnant women get a mood disease. Unquestionably some women once got, and still get, Melancholia, which is a medical disease. In contrast to claims often made about no physical basis for psychiatric disorders, Melancholia comes with a medical test, the Dexamethasone Suppression Test (DST). The DST stress tests our cortisol system and semi-establishes the presence or otherwise of melancholia.

Women with melancholia did not go out drinking alcohol, snorting cocaine or engaging in risky activities – the reasons cited now for the need to ensure pregnant women who might be depressed get SSRI antidepressants. Before antidepressants came onstream, there was no evidence linking melancholia – the most severe form of depression – to birth defects.

Women’s bodies defend a pregnancy from infections, starvation, and the raised cortisol found in melancholia. What their bodies have not been equipped by evolution to manage are drugs like alcohol, SSRIs, acetaminophen or anticonvulsants.

Many pregnant women in situations of deprivation, low income etc, have elevated scores on a Hamilton Rating Scale and get diagnosed as depressed. This does not mean they have a disease that is going to respond to antidepressants. Rating scales like this and DSM Diagnostic Criteria are only supposed to be applied after an act of judgement has decided that the person does have a medical disease. Using them without knowing the person is dangerous and risks rendering the person consulting us invisible.

Older tricyclic antidepressants or electroconvulsive therapy (ECT) did, and still can, offer benefits to people with melancholia or endogenous depression, which shades into melancholia.  Before 1990 and the advent of SSRIs, they were not used to treat numbers.

Are we not being more scientific now, ensuring we track changes with a rating scale? Not really – doctors applying Hamilton Rating Scales can score you as getting better when in fact you are becoming homicidal and/or suicidal. An interview does better than a rating scale.

If you are let track your mood on a Quality of Life Scale, which is very similar to the Hamilton scale, then no benefit from an SSRI shows up. Companies went to great trouble to produce QoL scales aimed at showing their SSRIs did much better than older tricyclic antidepressants that have lots of side effects. The QoL scales were quietly abandoned when you rated yourself as worse not better on SSRIs compared to older drugs or placebo.  See Let Them Eat Prozac.

Besides being done in situations of deprivation, the studies now cited as supporting claims that leaving pregnant women untreated causes more problems than treating them were done before we learnt that SSRIs trigger alcohol use in pregnancy, and likely cocaine and amphetamine use also. See Antidepressants, Alcohol and Anne-Marie and Canadian Guidelines on SSRIs and Alcohol Use Disorder. The earlier studies all need revisiting – but this is unlikely to happen.

Distress or Disease?

There is an extraordinary historical twist to these debates about treating nervous problems in pregnancy.  Through to 1990, depression was rare. We had anxiety disorders rather than mood diseases. The difficult point to grasp is that most cases of depression in US office practice involved a condition called neurotic depression.

As the word neurosis tells you, this was viewed as an anxiety disorder, linked to states of deprivation and distress. It was not a disease, and was not viewed as appropriately treated with antidepressants but it could give rise to what was called illness behavior.

In line with company interests to segment the marketplace, in 1980, DSM-III divided a monolithic Anxiety Disorder into multiple different conditions – panic disorder, social anxiety disorder, PTSD etc, This should have been good for business and Upjohn colonized panic disorder, GSK pushed out the social anxiety boat and Pfizer and others claimed PTSD.

In contrast, a bunch of different depressive states – neurotic depression, endogenous depression, melancholia, atypical depression were collapsed down into Major Depressive Disorder.  See The Antidepressant Era.

The depression changes should not have been good for business and were not good for science.

The DST looked like it was going to give clinical psychiatry a diagnostic test making it medically respectable. Created in the 1970s, this test distinguished between the relatively rare Melancholia and much more common Neurotic Depression – distinguished in other words between a depressive disease and an anxiety state.

In line with this, tricyclic antidepressants (TCAs) and ECT can help melancholia and other DST positive states but are not treatments for neurotic depression. SSRIs, in contrast, are ineffective in melancholia or do not work in any states that are DST positive.

Business and Science

What happened next is Business eclipsed Science. The DST and melancholia vanished. Neurotic depression was always where the money was and now rebranded as Major Depressive Disorder was a magnet for the SSRIs.

Companies like Lilly began thumping their chests at their heroism in tackling one of mankind’s greatest afflictions. ‘’’MAJOR depression’’’ rapidly became the second greatest and then the greatest source of disability on the planet and has been getting more and more common the more SSRIs we consume.

The upshot is few women who are pregnant and diagnosed as having Major Depressive Disorder have a depressive disease. The social conditions they are dealing with are not going to respond to an SSRI. Deprivation can lead to low birth weight for their babies and substance abuse disorders in them but these are likely to be compounded by SSRI drugs that cause low birth weight and substance use disorders in both women and pregnant animals.

Depressed and Pregnant

If we want the best for women and their offspring, screening for depression and prescribing SSRI agents is not the best way forward for a number of reasons. The first is that 50% of SSRI takers are unlikely to benefit and therefore they and their offspring can only be harmed by the substantial risks these medicines pose.  In addition, their doctor is likely to diagnose someone who is not suited to an SSRI as treatment resistant and needing double the usual SSRI dose.

Some women will have a disease like melancholia that is more likely to respond to TCAs than other depressive states are likely to respond to SSRIs. TCAs are not risk free but are safer than SSRIs in pregnancy and there is more likely to be a benefit to offset against those risks. Again, however, these women need monitoring and if not responding should have the treatment stopped.

If we want a drug to treat a distressed state, less potent benzodiazepines are likely better than SSRIs. They are much more likely to work than SSRIs, and work instantly, and at present there are fewer indicators that they will cause problems.  This would be a Back to the Future moment – giving women the drug they were given before neurotic depression was rebranded to Major Depressive Disorder.

There’s something about Mary

Finally to come back to Roger and valuing emotions. There is a parallel which might seem extreme. Finnish men in the winter regularly take saunas and rush out and plunge through the thin ice Roger is skating on into freezing water – hoping their blood pressure will rise from a normal 120-80 to something more like 300-200.

Most doctors would faint at the sight of a blood pressure this high, but the Finns do it because maintaining a full range of bodily responses to stress helps us live longer. When our blood pressure doesn’t vary much in response to stress or isn’t let vary by tight blood pressure control, we are more likely to die earlier.

We’ve got incapacitatingly neurotic about variations from the norm – we have a dangerous measurement neurosis. Drug companies are too nervous to advise Finnish men to take a blood pressure medicine before their sauna. They’d be told to get lost. Company doctors would not dare say think of your wife and family if something should happen to you.

But There’s Something about Mary when she gets pregnant that allows companies and others to shamelessly guilt-trip her about her unborn child.  Not forcing chemicals on her is viewed as worse than treating her like a second class citizen.

There are occasional stories about marvelous male soccer players who break a bone in mid-game and play on. The European Women’s Football Championship that finished on Sunday had a woman, Lucy Bronze, who played every, and all of every, game in the tournament with a broken leg. No man has ever done this. Men rarely rise to the motivational heights women are capable of.

In my experience, as regards researching conditions and treatment options including non-treatment, no group of people on earth does more or better research than women who are pregnant or about to get pregnant. Excellent researchers though they are, they are not being helped by drug labels designed to misinform.

As regards balancing risks and benefits, no group is called on to do it more often or for a more important mission or does it better than women who are pregnant or thinking about a pregnancy.

While antidepressant prescribing has risen in pregnancy, most women still opt to stop treatment if they can – See Patterns of Antidepressant Prescribing around Pregnancy.

Given the effects of SSRIs on men, it is not clear the scenes that gave the Something About Mary movie its name would have been possible if the men involved had been on SSRIs.