Tag: antidepressants

No Added Seizure Risk from Antidepressant Use in Pregnancy

Pregnant with ultrasound image
Source: Pixabay

A large Swedish study in the journal Neurology found that pregnant women taking selective serotonin reuptake inhibitors (SSRIs) or selective norepinephrine reuptake inhibitors (SNRIs) during the first trimester of was not linked to an increased risk for neonatal seizures and epilepsy in childhood.

Any increase in seizures or epilepsy is likely due to other factors, the researchers said.

“It’s not likely the medications themselves that are causing the seizures and epilepsy in children, but rather the reasons why these women are taking the medication,” according to Kelsey Kathleen Wiggs, a PhD candidate at Indiana University in Bloomington. There are also the other background factors that differ between women who do and do not use SSRI/SNRIs.

“When it rains, it pours,” Wiggs said. “Women who are taking antidepressants in pregnancy are doing that for lots of different reasons, and they might be at risk for different things than women who aren’t taking those medications in pregnancy.”

An elevated risk for neonatal seizures (risk ratio [RR] 1.41) and epilepsy in early childhood (HR 1.21) among offspring of mothers who used antidepressants in pregnancy.

Adjustment for maternal indications for SSRI/SNRI use and background factors like smoking during pregnancy revealed that they were drivers for both associations: neonatal seizures (RR 1.10); epilepsy diagnosis at 5 years (HR 0.96). Parental history of epilepsy was not found to affect the association.

The findings provide a “conclusive answer” to these concerns with using SSRI/SNRIs during pregnancy, according to Anne Berg, PhD, and Torin Glass, BM, Bch, BAO.

“[SSRI/SNRIs] have been demonstrated to have serotonergic central nervous system effects and are associated with an observable withdrawal syndrome which may be seen in the neonate following in utero exposure,” noted Drs Berg and Glass, in an accompanying editorial.

“The authors understood that with a population-based data registry and huge sample size, they had more than sufficient statistical power to detect even a modest increase in risk,” the editorialists wrote. “They tested this hypothesis and were able to reject it, definitively!”

In order to determine whether antidepressants had a causal association with infant seizures and childhood epilepsy, the researchers analysed data from national Swedish healthcare registries on a total of 1 721 274 children in Sweden born between 1996 and 2011.

Participants were divided into two groups: one group of mothers who reported use of an SSRI (fluoxetine, citalopram, paroxetine, sertraline, fluvoxamine, escitalopram) or SNRI (venlafaxine, duloxetine) during the first trimester of pregnancy (n = 24 308), and another group with no reported antidepressant use (n = 1 696 966).

Source: MedPage Today

Antidepressant Use is No Better Long-Term for Depression

Depression, young man
Source: Andrew Neel on Unsplash

Over time, antidepressant use is not associated with significantly better health-related quality of life, compared to people with depression who do not take the drugs, according to a new study reported in PLOS ONE.

Depression disorder is known to have a significant impact on the health-related quality of life (HRQoL) of patients. While studies have shown the efficacy of antidepressant medications for treatment of depression disorder, these medications’ effect on patients’ overall well-being and HRQoL remains controversial.

Researchers used data on adult patients with depression drawn from the 2005-2015 United States’ Medical Expenditures Panel Survey (MEPS), a large longitudinal study that tracks the health services that Americans use. There were 17.47 million adult patients diagnosed with depression each year over the study, with two years of follow-up, and 57.6% of these received treatment with antidepressant medications.

Use of antidepressants was associated with some improvement on the mental component of SF-12 – the survey tracking health-related quality of life. However, when this positive change was compared to the change in group of people who were diagnosed with depressive disorder but did not take antidepressants, there was no statistically significant association of antidepressants with either the physical (p=0.9595) or mental (p=0.6405) component of SF-12. In other words, the change in quality of life seen among those on antidepressants over two years was not significantly different from that seen among those not taking the drugs.

The study was not able to separately analyse any subtypes or varying severities of depression. Future studies should investigate the use of non-pharmacological depression interventions used in combination with antidepressants, said the researchers.

The authors noted that, “Although we still need our patients with depression to continue using their antidepressant medications, long-term studies evaluating the actual impact for pharmacological and non-pharmacological interventions on these patients’ quality of life is needed. With that being said, the role of cognitive and behavioural interventions on the long term-management of depression needs to be further evaluated in an effort to improve the ultimate goal of care for these patients; improving their overall quality of life.”

Source: ScienceDaily

Duloxetine Flops for Osteoarthritis Pain Relief

Photo by Nino Liverani on Unsplash

A new study found that duloxetine, a medication that is prescribed to treat depression and may also reduce chronic pain, did not benefit patients with hip or knee osteoarthritis.

Off-label uses for duloxetine include chemotherapy-induced peripheral neuropathy and stress urinary incontinence. It is in the Serotonin and norepinephrine reuptake inhibitors (SNRIs) class of medications. 

An open label, cluster randomised trial was conducted in patients experiencing chronic osteoarthritis-related pain in the hip or knee that did not go away with paracetamol and NSAIDs. Of 133 patients, 66 were assigned to duloxetine 60mg/day plus usual care and 66 were assigned to only usual care. 

The findings, published in Arthritis & Rheumatology howed that duloxetine did not lessen WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) pain at 3 months or 12 months. For the subgroup of patients with symptoms of centralised pain no effect of duloxetine was found either.

“There was no clinically relevant effect of duloxetine added to usual care compared to usual care alone for chronic osteoarthritis pain, and it should not be implemented,” the authors concluded.

Source: Wiley

Why Antidepressants Take Weeks to Provide Relief

A healthy neuron.
A healthy neuron. Credit: NIH

The findings of a study published in Science Translational Medicine paint a new picture of how current antidepressant drugs work and suggest a new drug target in depression. As with most drugs, antidepressants were developed through trial and observation. Some 40% of patients with the disorder don’t respond adequately to the drugs, and when they do work, antidepressants take weeks to provide relief. Why this is has remained largely a mystery.

To figure out why these drugs have a delayed onset, the team examined a mouse model of chronic stress that leads to changes in behaviours controlled by the hippocampus. The hippocampus is vulnerable to stress and atrophies in people with major depression or schizophrenia. Mice exposed to chronic stress show cognitive deficits, a hallmark of impaired hippocampal function.

“Cognitive impairment is a key feature of major depressive disorder, and patients often report that difficulties at school and work are some of the most challenging parts of living with depression. Our ability to model cognitive impairment in lab mice gives us the chance to try and understand how to treat these kinds of symptoms,” said Professor Dane Chetkovich, MD, PhD, who led the study.

The study focussed on an ion transporter channel in nerve cell membranes known as the HCN channelPrevious work has shown HCN channels have a role in depression and separately to have a role in regulation of cognition. According to the authors, this was the first study to explicitly link the two observations.

Examination of postmortem hippocampal samples led the team to establish that HCN channels are more highly expressed in people with depression. HCN channel activity is modulated by a small signaling molecule called cAMP, which is increased by antidepressants. The team used protein receptor engineering to increase cAMP signaling in mice and establish in detail the effects this has on hippocampal HCN channel activity and, through that connection, on cognition.

Turning up cAMP was found to initially increase HCN channel activity, limit the intended effects of antidepressants and negatively impact cognition (as measured in standard lab tests).

However, a total reversal took place over a period of some weeks. Previous work by the researchers had established that an auxiliary subunit of the HCN channel, TRIP8b, is essential for the channel’s role in regulating animal behaviour. The new study shows that, over weeks, a sustained increase in cAMP starts to interfere with TRIP8b’s ability to bind to the HCN channel, thereby quieting the channel and restoring cognitive abilities.

“This leaves us with acute and chronic changes in cAMP, of the sort seen in antidepressant drug therapy, seen here for the first time to be regulating the HCN channel in the hippocampus in two distinct ways, with opposing effects on behaviour,” Prof Chetkovich said. “This appears to carry promising implications for new drug development, and targeting TRIP8b’s role in the hippocampus more directly could help to more quickly address cognitive deficits related to chronic stress and depression.”

Source: Vanderbilt University

Can Prozac be Used to Treat Macular Degeneration?

Source: Unsplash

The antidepressant fluoxetine, best known as Prozac, could offer the first treatment for the leading cause of blindness among people over 50, new research from the University of Virginia School of Medicine suggests.

Researchers have found early evidence that the drug fluoxetine may be effective against atrophic (or ‘dry’) age-related macular degeneration, a condition that affects nearly 200 million people worldwide. An analysis based on bench research, mouse models and huge insurance databases concluded that patients taking fluoxetine were less likely to develop atrophic macular degeneration (AMD).

On the strength of their findings, which were published in PNAS, the researchers are urging the investigation of fluoxetine to treat AMD, possibly as an oral pill or slow-release implant in the eye.

“These findings are an exciting example of the promise of drug repurposing, using existing medicines in new and unexpected ways,” said Bradley D. Gelfand, PhD, of UVA’s Center for Advanced Vision Science. “Ultimately, the best way to test whether fluoxetine benefits macular degeneration is to run a prospective clinical trial.”

The researchers believe fluoxetine works by binding with an inflammasome, NLRP3-ASC, which triggers the breakdown of the pigmented layer of the eye’s retina.

After conducting extensive bench research, Dr Gelfand and his team tested fluoxetine and eight other depression drugs in lab mice. Fluoxetine slowed the progression of the disease, but the others did not, the scientists found.

Encouraged by their findings, the researchers looked at fluoxetine use among patients aged over 50 in two enormous insurance databases with over 100 million records. They found that people taking the drug had a “significantly” slower rate of developing dry AMD.

Their approach, which combines bench research with big-data analysis, could lead to faster repurposing of existing drugs.

“Traditional approaches to drug development can be expensive and time-consuming: On average, a new FDA-approved drug takes 10–12 years and costs $2.8 billion (present-day dollars) to develop,” the researchers wrote. “Our identification of the unrecognised therapeutic activity of an existing FDA-approved drug using big data mining, coupled with demonstrating its efficacy in a disease-relevant model, could greatly accelerate and reduce the cost of drug development.”

Dr Gelfand was involved earlier this year in using a similar approach to determine that HIV drugs known as nucleoside reverse transcriptase inhibitors, or NRTIs, may be useful against dry macular degeneration as well.

“While we have had a great deal of success with the approach of using real-world patient data, we may have only begun to scratch the surface of finding new uses for old drugs,” said Dr Gelfand, of UVA’s departments of ophthalmology and biomedical engineering. “It is tempting to think about all the untapped therapeutic potential of medicines sitting on pharmacy shelves.”

Source: University of Virginia