I got the following question from a follower in the context of a broader conversation about their concerns, and since it is a common topic that I am asked about, I thought I would include it here.

In this post, I am going to tackle the discussion of antidepressants, especially SSRIs, and whether they cause memory loss or increase risk of dementia. I commonly have people that tell me they stopped taking antidepressants because they didn’t want to lose their memories. But how valid is that concern? Let’s dig into it.

TL;DR:
Many people are concerned that antidepressants (specifically SSRIs) may cause memory loss, cognitive impairment, or increase the risk of dementia. Current research shows that:

• Short-term SSRI use may cause mild, temporary cognitive changes in some individuals.

• Long-term use is not associated with significant memory loss or cognitive decline.

• Most SSRIs have minimal anticholinergic effects and are not linked to increased dementia risk.

• Paroxetine is an exception, with higher anticholinergic activity and more caution advised in older adults.

• Untreated depression poses a greater risk to cognitive health and is a known contributor to long-term decline.

How Antidepressants Work?

For the purposes of this post, I am going to focus on the most common form of antidepressant medication. However, please keep in mind that there are several others, so this research may not apply equally to all of them.

The most common class of antidepressants are Selective Serotonin Reuptake Inhibitors (SSRIs). Common SSRIs include fluoxetine (Prozac), sertraline (Zoloft), citalopram (Celexa), and escitalopram (Lexapro). As the name suggests, SSRIs primarily target serotonin. Serotonin is a neurotransmitter that helps your brain cells communicate. It is involved in mood, emotional regulation, sleep, appetite, and pain perception. In mental health, low serotonin activity is linked to depression and anxiety.

SSRI medications essentially help increase the amount of serotonin that is available in your brain by preventing the “reuptake” of serotonin in the space between neurons. Typically, when a neurotransmitter like serotonin is released into the synapse (space between neurons), it is sucked back up into the neuron that released it. By preventing that from happening, SSRIs allow that serotonin to instead linger around and potentially bind to serotonin receptors, giving you that relief from depression or anxiety that you need. Over time (typically several weeks), this can provide a reduction in mental health difficulties.

SSRIs are widely considered first-line treatments for both depression and anxiety. Clinical research including randomized controlled trials and meta-analyses (large aggregations of data from multiple studies) have consistently shown that they can significantly reduce symptoms of depression and anxiety when compared to placebo. They are especially effective when combined with psychotherapy, and their side effect profiles are generally well-tolerated.

How do SSRIs Impact Cognitive Abilities?

In the field of neurobiology, it is commonly said that “there is no free lunch.” When you have a medication that causes a primary effect, you almost always have other effects as well, which are called side effects. Not all side effects are bad. Sometimes we use medications specifically for their side effects. For example, a lot of people use SSRIs like escitalopram to prevent premature ejaculation during intercourse. Delayed ejaculation is a side effect, but for those that struggle with premature ejaculation, it’s actually helpful.

So, what are the effects of SSRIs on cognition? The answer is not simple and clear cut. Various clinical experiments have shown that a single dose of an SSRI can produce subtle but measurable cognitive changes. Here’s the thing though – they seem to improve some skills like inhibitory control (not impulsively choosing the wrong answer), weaken other skills (more errors when multitasking/set-shifting), and not impact others (Skandali et al., 2018). These studies suggest that increased serotonin can impact cognitive abilities, but they are unlikely to cause broad deficits in the short-term.

How about long-term impacts? The data here are reassuring. In people without underlying cognitive disorders, generally the research shows minimal impairment on cognitive testing for those using SSRIs over longer periods of time. One study looked at performance of individuals that have been on 20mg of escitalopram for 3-6 weeks vs a placebo group. On cognitive tasks that involve little to no emotional component, such as list memory, attention, and executive functioning tasks, there were no significant differences (Langley et al., 2023).

What People Report Feeling on SSRIs

Despite the normal performance on objective cognitive tests, some participants still report subjective cognitive difficulties, often described as “brain fog”. One study looked at 67 patients that had been treated with SSRIs for over six months, and over 20% of them reported cognitive symptoms like poor concentration, mental fatigue, and forgetfulness. In addition to brain fog, some people describe a feeling of emotional blunting or numbness. These effects were not universal. Some people tolerate the experience of being on SSRIs quite well (Popovic et al., 2015).

How do SSRIs Impact Dementia?

When it comes to dementia, there has been a great deal of research looking at the impact of SSRIs on older adults and those who already have dementia.

Positive Effects

Interestingly, there are several potential positive effects from SSRIs due to the downstream effects that they trigger. For example, SSRIs appear to promote neuroplasticity (ability of the brain to change and reorganize networks) and neuroprotection. This is thought to be caused by increasing brain-derived neurotrophic factor (BDNF), which is a protein that plays a role in survival, function, and growth of neurons in the brain. It contributes to neuroplasticity and the formation of new neurons.

In animal models of Alzheimer’s disease (the most common cause of dementia in adult humans), multiple SSRIs have demonstrated the ability to reduce amyloid-beta plaques and tau tangles, which are both believed to play a central role in the development of Alzheimer’s disease. One SSRI (fluoxetine) was also shown to increase the volume of the hippocampus — the brain structure responsible for memory formation and it also activated BDNF signaling.

SSRIs have also demonstrated anti-inflammatory effects in the brain by impacting certain cytokines (small proteins involved in immune responses) that are thought to contribute to degeneration of neurons (Correia & Vale, 2021).

All of this research suggests that SSRIs may have a neuroprotective effect and might slow degenerative processes in the brain.

Negative Effects

Concerning dementia, there have also been some concerns related to negative mechanisms that could potentially increase risk. The most plausible mechanism for this would be through anticholinergic activity. Acetylcholine is another neurotransmitter that plays a major role in memory, learning, attention, and muscle movement.

Certain medications like antihistamines, muscle relaxers, and some antidepressants lower acetylcholine. For something like a medication for overactive bladder, this is the primary effect as reduced acetylcholine will prevent excessive muscle contractions. For antidepressants, it is more of an unwanted side effect.

The problem for older adults is that exposure to anticholinergic medications over time has been demonstrated to potentially cause confusion, memory issues, drowsiness, and increased risk of falls. Cumulative exposure, especially from multiple medications, has also been linked to a higher risk of dementia.

To be clear, most SSRIs have a minimal anticholinergic effect and would not be very likely to cause these side effects. However, paroxetine (Paxil) is a commonly prescribed SSRI that has been shown to have a significant anticholinergic effect, so this should be used with caution. There are also other forms of antidepressants, like tricyclics that are known to have significant anticholinergic effects. These are often avoided if possible in older adults (Richardson et al., 2018).

Studies on Dementia

A large study from the Netherlands that ran from 2018-2024 followed 5,511 dementia-free older adults for up to 16 years. The investigators compared participants who had used antidepressants to those who never did. After adjusting for potential confounding factors, use of any antidepressant (not just SSRIs) was not associated with a higher risk of developing dementia. They also found no evidence of accelerated brain atrophy through MRI imaging among SSRI users vs non-users (Hofe et al., 2024).

On the other side, there have been some observational studies that have demonstrated associations between SSRI use and cognitive decline in specific circumstances. For example, a 2023 study compared older adults with depression who used antidepressants vs psychotherapy alone. Over a two-year follow-up, the antidepressant group showed a small but statistically significant increase in rates of newly diagnosed dementia as compared to the therapy group. However, as a correlational and retrospective study, there are potential confounding factors. For example, those with more severe functional impacts from depression may be more likely to seek out antidepressants, and these same personal factors may also contribute to an increased risk of developing dementia (Wang et al., 2023).

There have also been a couple studies looking at older women that suggest a possible link between SSRI use and cognitive decline. However, these studies are flawed and do not imply a causation. One study had a mean age of 84, which is quite old and features higher cognitive variability in the first place. Then you recognize that those who are on SSRIs seemed to have greater cognitive impairment. There are a lot of potential outside factors influencing that (Leng et al., 2017).

What About Untreated Depression?

Untreated depression on the other hand can significantly impact memory and other cognitive functions in ways that can even mimic dementia. This is a phenomenon we call “pseudodementia.” In particular, it has been shown that working memory, attention, processing speed, and memory retrieval can all be impacted by depression. Physically, depression has been linked to reduced size of brain structures that are essential in memory.

The good news is that when depression is effectively treated or resolves on its own, the cognitive symptoms also improve. One episode of depression is unlikely to cause persistent changes in someone’s cognitive abilities. However, chronic untreated depression over time appears to be a risk factor for later degenerative diseases like dementia.

In Summary

It’s totally normal to be concerned about how medications might impact your cognitive abilities or your risk of developing dementia. In fact, it’s a good thing to consider your overall health profile and make informed choices that align with your personal goals and needs.

Like most things in medicine, it’s all about balance. Untreated depression is itself a risk factor for cognitive decline and it can lead people to self-medicate in risky ways or disengage from life in ways that increase overall health risks. In that context, the potential risks of medication often pale in comparison to the risks of leaving depression unaddressed.

When we look at the research, here’s what stands out:

• Short-term use of SSRIs may cause subtle cognitive shifts – some positive, some negative, but not broad deficits.

• Long-term SSRI use does not appear to impair cognitive functioning based on objective testing.

• In older adults, SSRIs may offer neuroprotective effects, and concerns about increased dementia risk are largely based on flawed or confounded studies.

• Not all antidepressants are the same. Paroxetine, for example, has stronger anticholinergic effects and is typically avoided in older adults.

Overall, SSRIs are considered safe and well-tolerated when it comes to memory and cognitive health. For most people, untreated depression poses a far greater risk to long-term brain health than carefully managed use of these medications. If you’re on antidepressants or considering them, it’s worth having an open conversation with your doctor about how the risks and benefits align with your individual health picture.

Hope this helps! I’d love to hear your thoughts or questions in the comments.