No Relationship Between SSRIs in Pregnancy and Stillbirths or Neonatal Mortality
Much has been written about the use of selective serotonin reuptake inhibitor (SSRI) antidepressants during pregnancy. In a review of 920,620 births in Denmark (1995 to 2008) that Jimenez-Solem published this year in the American Journal of Psychiatry, no link was found between any of the SSRIs used in any trimester and risk of stillbirth or neonatal mortality. The only exception was a possible association of three-trimester exposure to citalopram and neonatal mortality.
Editor’s Note: These new data may be of importance to women considering antidepressant continuation during pregnancy when there is a high risk for a depressive relapse. A maternal depressive episode (like other stressors such as anxiety or experiencing an earthquake) during pregnancy does convey adverse effects to the child, so appropriate evaluation of the risk/benefit ratio or staying on an antidepressant through a pregnancy is important.
Study Calls Into Question FDA Black Box Warning about Suicide Risk in Youth Taking Antidepressants
In 2004, the Federal Drug Administration issued a “black box warning” about increased risk of suicidal thoughts and behavior in children and adolescents taking selective serotonin reuptake inhibitors (SSRIs). See here for an overview from the National Institute of Mental Health.
An article published in the Archives of General Psychiatry earlier this year analyzed data from studies of fluoxetine and venlafaxine in youth, adults, and geriatric patients to determine if antidepressant use is linked to suicide. The drugs decreased both depressive symptoms and suicidal thoughts and behavior in adults and the geriatric population. They seemed to have no effect on suicidal thoughts or behavior in the youth.
For youths, no significant effects of treatment on suicidal thoughts and behavior were found, although depression responded to treatment. No evidence of increased suicide risk was observed in youths receiving active medication.
Mothers’ SSRI Use May Lead to Increased Risk of Pulmonary Hypertension in Infants
The New York Times summarized findings about the effect of mothers’ antidepressant use on enfants from an article published by Kieler et al. in the British Medical Journal this year.
Researchers have long suspected a link between the use of selective serotonin reuptake inhibitors, or S.S.R.I.’s, and [pulmonary hypertension in babies], but previous studies have been small and inconclusive (with results ranging from there being no link to a six times greater risk).
This research, based on 1.6 million births in Denmark, Finland, Iceland, Norway or Sweden from 1996 to 2007, showed that among women using S.S.R.I.’s, the risk of persistent pulmonary hypertension for infants more than doubled (particularly for use late in pregnancy). It’s still a small risk: 3 in 1000 births, as opposed to 1.2 per 1000 births overall. But it’s a small risk of a serious problem.
Pulmonary hypertension, Dr. Juliette Madan, a pediatrician at the Dartmouth Hitchcock Medical Center explained, is diagnosed when an infant struggles to get enough oxygen into her lungs, and therefore into her bloodstream. The condition can be deadly, although Dr. Madan said that it’s usually treatable — with possible lifelong consequences.
But other research suggests that untreated depression during pregnancy has its own risks, including pre-term birth and low birth weight. Given that, how should a pregnant woman and her doctor weigh the competing risks?
See the New York Times for a discussion on how to balance mother’s health with babies’ health.
Exercise May Improve Cognitive Function in Depression
Tracy L. Greer of the University of Texas Southwestern in Dallas presented an abstract at the 51st Annual Meeting of the National Institute of Mental Health’s New Clinical Drug Evaluation Unit (NCDEU) in 2011 that suggested that exercise improved the cognitive function of patients being treated with selective serotonin reuptake inhibitors (SSRIs) for major depressive disorder.
Thirty-nine participants reported cognitive impairment at baseline. Subjects were randomized to receive antidepressant treatment in the form of an SSRI augmented by either an exercise regimen designed to burn 16 kilocalorie/kg per week (kkw) or one designed to burn 4 kkw. Both exercise regimens resulted in improved response time on a measure of attention, and for the higher intensity (16 kkw) exercise group, there were improvements in response time for visual memory tasks as well as decreased errors on an executive function task.
Editor’s note: There is a somewhat mixed literature on the efficacy of exercise in potentiating antidepressant effects of other treatments. Recent data by Fred Gage and colleagues showed that in animals, exercise increased not only brain-derived neurotrophic factor (BDNF), which seems to be necessary for long-term learning and memory, but also the formation of new neurons (neurogenesis). Gage found that new neurons that migrated to the dentate gyrus of the hippocampus were more excitable than older neurons and were important in a variety of cognitive tasks.
The newer neurons could more precisely distinguish between different stimuli, while the older neurons were sufficient only for discriminating stimuli that were widely and obviously different from each other.
Thus, the increase in new neurons and BDNF that may follow exercise and antidepressant use may be associated with some cognitive improvement in depression, particularly in the realm of response speed and perhaps also in making relatively fine discriminations among relatively similar objects.
While not much evidence for the effect of exercise on cognition has been collected in humans, exercise has many other benefits. Since it is good for cardiovascular fitness and wellbeing, as well as potentially generating new neurons that could play an important role in fine cognitive discriminations, encouraging exercise in depressed patients (especially as their depression improves and they have renewed motivation to engage in exercise regimens) could be of value, even if exercise is not a guaranteed enhancer of antidepressant effects per se.
L-Methylfolate Augments the Antidepressant Effects of SSRIs in Treatment-Resistant Major Depression
Folate occurs naturally in foods such as broccoli
The B vitamin folate has been shown to be a useful augmentation treatment for patients who are nonresponsive or only partially responsive to selective serotonin reuptake inhibitor (SSRI) antidepressants. Treatment with folate works even in those who are not folate-deficient at baseline.
When folate is broken down in the body by reductase enzymes, it turns into the active form L-methylfolate, and crosses the blood-brain barrier. Maurizio Fava and colleagues at Massachusetts General Hospital (MGH) performed two placebo-controlled, randomized studies of L-methylfolate for depression. There was significantly greater improvement when SSRIs were augmented with L-methylfolate than when they were augmented with placebo. The results were significant with the use of 15mg of L-methylfolate, but not with 7.5mg, suggesting dose-related effects. Read more
Treating Generalized Anxiety Disorder
Generalized anxiety disorder (GAD) is a prevalent illness often associated with considerable discomfort and dysfunction. It often co-occurs with bipolar disorder. Traditional treatments of the primary syndrome (occurring in the absence of bipolar disorder) involve serotonin-selective antidepressants and serotonin-noradrenergic reuptake inhibitors such as venlafaxine (Effexor) or duloxitine (Cymbalta). While these are often useful and lead to considerable improvement, they often do not lead to full remission of somatic or accompanying symptoms of insomnia.
Alternative treatment possibilities include the anticonvulsant pregabalin (Lyrica), which has been found effective in four placebo-controlled studies in GAD. A poster presentation by Joshi et al. at the American Psychiatric Association meeting in San Francisco in May 2009 also reported that pregabalin was more effective in reducing sleep disturbance than venlafaxine. Pregabaline is FDA-approved for seizures and fibromyalgia, but not for GAD or pain syndromes. Another treatment possibility is quetiapine (Seroquel), where not only have there been positive efficacy in placebo-controlled studies of patients with GAD, but the patients also experienced improvement in sleep.
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