Treating PMDD without Medications

In an earlier post, we defined PMS and PMDD, and briefly discussed their etiology. Here, we will look into the treatment of PMS/PMDD. While there are many pharmacologic treatments of PMDD, non-pharmacologic approaches may often be considered first. Indeed, just like mild to moderate hypertension is often first treated with lifestyle modifications like exercise and a low-sodium diet, PMS/PMDD is often improved with the following lifestyle modifications:

• regular aerobic exercise 4-5 times a week
• good sleep hygiene, i.e., establishing a consistent sleep schedule 
• dietary changes: limiting alcohol, caffeine, salt, chocolate, red meat, and eating smaller, more frequent meals with complex carbohydrates 
• avoiding stressful activities/ situations during the premenstrual period 

These interventions can often be started in the 2 months (or 2 menstrual cycles) during which a patient is completing the daily symptom ratings needed to confirm a diagnosis of PMDD, and for some women, they may be enough to control their symptoms. 

We have had patients ask us about whether certain vitamins and dietary supplements (like vitamin B6, calcium, magnesium, chasteberry, soy) are helpful for PMS/ PMDD symptoms. For most of these supplements, there is no consistent evidence from research showing that they are are better than placebo, and some may carry risks:   

• vitamin B6; at high doses may lead to peripheral neuropathy and there is only low-quality evidence that it may help with PMDD symptoms, so it is not recommended
• calcium supplementation has benefits beyond those on mood symptoms, but high doses may increase the risk of heart disease 
• soy was found to have reduced physical symptoms but not mood symptoms in women with PMS/ PMDD
• chasteberry (vitex agnus-castus) may also be more helpful for the physical symptoms rather than mood symptoms of PMDD

Some other therapeutic modalities that have been considered in the treatment of PMDD include group or individual psychotherapy, acupuncture, yoga, and bright light therapy. There is little research evidence available for most of these treatments, but bright light therapy in particular has shown some promise, and psychotherapy has shown promise but with small effect sizes. 

Can I take antidepressants while breastfeeding?

Given the high prevalence of postpartum depression in the US (often cited as between 10-15% of postpartum women), and the myriad benefits of breastfeeding for both baby and mother, it's not a surprise that women in our clinic often ask about the safety of breastfeeding while taking antidepressants.

To answer this question, it's important to note that concentrations of psychotropics in breast milk have been found to vary widely. The amount of a psychotropic medication that an infant is exposed to depends on multiple factors, including dosage of the drug, rate of maternal drug metabolism, and frequency and timing of feedings. In the past, a technique called "pumping and dumping" was recommended. However, that has been found to be unnecessary; you can read more about why it is not a good idea to pump and dump in this post.

One of the main ways researchers have investigated antidepressant safety in lactation has been to look at infant plasma (i.e., blood) concentrations. The chart below from Berle and Spigset (2011) shows that of the most commonly prescribed SSRIs, sertraline and paroxetine have the lowest infant plasma concentrations: 

click image to enlarge

Duloxetine (an SNRI) and bupropion (an NDRI) also had undetectable infant plasma levels, but there were fewer mother/ infant pairs studied. The SSRIs fluoxetine and citalopram had higher infant plasma concentrations; it's generally recommended that these be used with caution or avoided during breastfeeding. However, if a woman has been stable on these medications prior to and/ or during pregnancy, it may be fine to continue them during breastfeeding.

Another way to evaluate the safety of medications in lactation has been to look at adverse events. Scalia and Wisner did an extensive literature search to create clinical guidelines for antidepressant use during breastfeeding. They found that sertraline, paroxetine, and nortriptyline are the most evidence-based antidepressants in lactation, because levels are usually undetectable in infants, there have been no reports of short term adverse effects, and findings about them have been consistent among different laboratories. They also created the following decision-tree:

click image to enlarge

As you can see, sertraline and paroxetine are generally considered to be the first-line agents if pharmacological treatment is necessary in lactation. Sertraline is often preferred over paroxetine because of paroxetine's greater anticholinergic side effects (including dry mouth, blurred vision, sedation, constipation, and memory impairment) and its shorter half life/ more significant discontinuation syndrome (marked by flu-like symptoms, insomnia, nausea, imbalance, and anxiety).

Happy Mother's Day.

I've always thought that Mother's Day should be celebrated by ALL women!
For all who haven't had children-- whether by choice or circumstances-- this one's for you:

"Even if she has never birthed a child,
Even if she never comes to do so
Every woman is a mother!
First, of her dolls; then, of her little siblings;
Getting married, she's her husband's mother
before mothering their children.

If childless, she will become an adoptive mother and will give someone else's spawn all her love: nieces and nephews, children of friends, students, animals, a good cause.

How many women weren't chosen to mother
their own children but ended up mothering their own mothers? Or fathers? Grandparents?

Motherhood cannot be suppressed.
Just like a water flow that gets blocked by a stone, it will surely find its way out.

During war, they care for the injured,
even if they wave a different flag
or wear a different uniform.

Motherhood has no borders, colors or preferences.
It's one of those few things that are
sufficient in themselves.

Every woman is a mother!"

On Antipsychotics in Pregnancy and the Problem of Confounding

Second-generation antipsychotics, also known as atypical antipsychotics, are frequently used in psychiatry, prescribed not just for psychotic disorders, but also for treatment of bipolar disorder, and for augmentation of depression or OCD treatment. Studies have shown that there is a very high risk of relapse of psychiatric disorders in pregnancy--for example, women with a history of bipolar disorder who discontinue their medications while pregnant have an 85% chance of recurrence of a mood episode while pregnant, compared to a 37% chance of recurrence when continuing to take their medications. Thus, it's important for women who are taking antipsychotics prior to pregnancy to know about the risks and benefits of continuing these medications while pregnant. Here we will focus on a recent article which looked at how taking antipsychotics in pregnancy may affect maternal and perinatal outcomes.

A large population-based cohort study looked at the question of whether or not antipsychotics affected certain maternal and perinatal health outcomes. It looked at all women who had delivered between April 2003 and December 2012 in Ontario, Canada. Data were collected from multiple linked healthcare administrative databases, which included information about medications women were taking, inpatient and outpatient claims, and demographic information. Antipsychotic exposure was defined as at least 2 consecutive filled prescriptions for an antipsychotic between conception and delivery. There were a total of 41,523 women in the study. Of these women, 1,209 were prescribed an antipsychotic, and 40,314 were not. The women were compared in 2 ways--there was an unmatched cohort, and a matched cohort. In the unmatched cohort, maternal and perinatal outcomes between women who were prescribed an antipsychotic and those who were not were compared directly. In the matched cohort, 1,021 women who were prescribed antipsychotics were matched with 1,021 women who were not, using something called a high dimensional propensity score (HDPS) algorithm.

What is a high dimensional propensity score (HDPS), you ask? It's a method commonly used in pharmaco-epidemiological studies to create less biased estimates of treatment effects. In other words, these epidemiological studies are subject to many confounders--things like age, ethnicity, multiple gestations, multi-parity, pre-existing medical problems like hypertension, diabetes, renal disease, smoking, drug use, other medications, and number of healthcare visits. Many of these confounders are observed, or known (e.g., it's easy to determine age from the databases). Researchers sometimes create a propensity score, which is a summary confounding score. The HDPS algorithm attempts to further minimize residual confounding by also incorporating proxy variables (healthcare diagnoses, procedures, and drug claims), which, when combined, can account for important confounders that are unobserved. This is extremely important, because without controlling for the unobserved confounders, we cannot know if a certain maternal or perinatal outcome is due to medication exposure, or to something else. In fact, women who take medications during pregnancy are often very different from women who do not; they tend to have more severe illness with higher risk of relapse...without controlling for this, we won't know if an outcome is related to a woman's underlying illness (severity), or to the medication she took. And this is how the HDPS is very useful.

Back to the study: the researchers looked at the following maternal medical outcomes: gestational diabetes, hypertensive disorders of pregnancy (gestational hypertension, pre-eclampsia, eclampsia), and venous thromboembolism (VTE), and the following perinatal outcomes: preterm birth (<37 weeks gestation), and extremes of newborn weight (a birth weight <3rd percentile or >97th percentile for the same sex and gestational age). What the researchers found illustrates not only the possible effects of antipsychotics on pregnancy outcomes, but also the importance of controlling for confounding. In terms of maternal outcomes in the matched cohort (where HDPS was used), there were no differences in terms of gestational diabetes, hypertensive disorders of pregnancy, and VTE between women who took antipsychotics in pregnancy and those who did not. However, in the unmatched cohort, there was an increased risk of gestational diabetes and hypertensive disorders in the antipsychotic group. In terms of perinatal outcomes, there were similar differences between the matched and unmatched cohorts. In the matched cohort, the 2 groups had no differences in preterm birth, and extremes of newborn weight. However, in the unmatched cohort without HDPS, the infants exposed to antipsychotics had an increased risk of preterm birth and weight >97th percentile. The study thus shows that when these antipsychotic users were matched with non-users who had similar pre-pregnancy morbidity (e.g., weight,  other medical conditions, diagnoses, and other variables), then the risk was about the same for both groups. Here is an illustration of the potential magnitude of bias that is created by not controlling for confounding variables. However, it also showed that the absolute rates of adverse maternal and perinatal outcomes in antipsychotic users were higher than those in the general population. Thus, for women who require antipsychotics during pregnancy, it's imperative to closely monitor their health before and during pregnancy, paying close attention to diabetes, hypertension, preterm birth and fetal growth.